The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular an...The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.展开更多
The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKS...The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.展开更多
In a recent genome-wide association study, the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer＇s disease in Caucasians. Here, we investigated this association in a large North...In a recent genome-wide association study, the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer＇s disease in Caucasians. Here, we investigated this association in a large Northern Han Chinese cohort consisting of 599 sporadic late-onset Alzheimer＇s disease patients and 598 healthy controls matched for sex and age in a Northern Han Chinese population from Qingdao, China. Genotyping by the polymerase chain reaction-ligase detection reaction revealed that there were significant differences in the genotype （P = 0.017） and allele （P = 0.007） frequencies of the rs2072064 polymorphism between late-onset Alzheimer＇s disease patients and controls. The A allele of this polymorphism was significantly associated with a reduced risk of late-onset Alzheimer＇s disease （odds ratio （OR） = 0.792, 95% confidence interval （CI） = 0.670-0.937, P = 0.007）. When the data were stratified by the apolipoprotein E E4 status, there was a significant difference only among apolipoprotein E E4 non-carriers （genotypic P = 0.001, allelic P = 0.001）. Furthermore, the association between rs2072064 and late-onset Alzheimer＇s disease remained significant by logistic regression analysis after adjustment for age, gender, and the apolipoprotein E E4 carrier status （dominant model： OR = 0.787, 95% CI = 0.619-1.000, P = 0.050; recessive model： OR = 0.655, 95% CI = 0.448-0.959, P= 0.030; additive model： OR = 0.792, 95% CI = 0.661-0.950, P = 0.012）. These findings suggest that SLC26A4 is a susceptibility gene for late-onset Alzheimer＇s disease in a Northern Han Chinese population from the Qingdao area.展开更多
BACKGROUND Colon cancer presents a substantial risk to the well-being of elderly people worldwide.With advancements in medical technology,surgical treatment has become the primary approach for managing colon cancer pa...BACKGROUND Colon cancer presents a substantial risk to the well-being of elderly people worldwide.With advancements in medical technology,surgical treatment has become the primary approach for managing colon cancer patients.However,due to age-related physiological changes,especially a decline in cognitive function,older patients are more susceptible to the effects of surgery and anesthesia,increasing the relative risk of postoperative cognitive dysfunction(POCD).There-fore,in the surgical treatment of elderly patients with colon cancer,it is of pa-ramount importance to select an appropriate anesthetic approach to reduce the occurrence of POCD,protect brain function,and improve surgical success rates.METHODS One hundred and seventeen patients with colon cancer who underwent elective surgery under general anesthesia were selected and divided into two groups:A and B.Group A received Dex before anesthesia induction,and B group received an equivalent amount of normal saline.Changes in the mini-mental state exami-nation,regional cerebral oxygen saturation(rSO2),bispectral index,glucose uptake rate(GluER),lactate production rate(LacPR),serum S100βand neuron-specific enolase(NSE),POCD,and adverse anesthesia reactions were compared between the two groups.RESULTS Surgical duration,duration of anesthesia,and intraoperative blood loss were comparable between the two groups(P>0.05).The overall dosage of anesthetic drugs used in group A,including propofol and remifentanil,was significantly lower than that used in group B(P<0.05).Group A exhibited higher rSO2 values at the time of endotracheal intubation,30 min after the start of surgery,and immediately after extubation,higher GluER values and lower LacPR values at the time of endotra-cheal intubation,30 min after the start of surgery,immediately after extubation,and 5 min after extubation(P<0.05).Group A exhibited lower levels of serum S100βand NSE 24 h postoperatively and a lower incidence of cognitive dysfunction on the 1st and 5th postoperative days(P<0.05).CONCLUSION The use of Dex in elderly patients undergoing radical colon cancer surgery helps maintain rSO2 Levels and reduce cerebral metabolic levels and the incidence of anesthesia-and surgery-induced cognitive dysfunction.展开更多
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been concerning.By retrospectively analyzing the clinical data of EGC p...BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been concerning.By retrospectively analyzing the clinical data of EGC patients,we can better under-stand the status of lymph node metastasis and its impact on survival and prog-nosis.AIM To evaluate the prognosis of EGC patients and the factors that affect lymph node METHODS The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study.There were 561 males and 450 females.The mean age was 58±11 years.The patient underwent radical gastrectomy.The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens.The outcomes were as follows:(1)Lymph node metastasis in EGC patients;(2)Analysis of influencing factors of lymph node metastasis in EGC;and(3)Analysis of prognostic factors in patients with EGC.Normally distributed measurement data are expressed as mean±SD,and a t test was used for comparisons between groups.The data are expressed as absolute numbers or percentages,and the chi-square test was used for comparisons between groups.Rank data were compared using a nonparametric rank sum test.A log-rank test and a logistic regression model were used for univariate analysis.A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis.The Kaplan-Meier method was used to calculate the survival rate and construct survival curves.A log-rank test was used for survival analysis.RESULTS Analysis of influencing factors of lymph node metastasis in EGC.The results of the multifactor analysis showed that tumor length and diameter,tumor site,tumor invasion depth,vascular thrombus,and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC(odds ratios=1.80,1.49,2.65,5.76,and 0.60;95%CI:1.29–2.50,1.11–2.00,1.81–3.88,3.87-8.59,and 0.48-0.76,respectively;P<0.05).Analysis of prognostic factors in patients with EGC.All 1011 patients with EGC were followed up for 43(0–13)months.The 3-year overall survival rate was 97.32%.Multivariate analysis revealed that age>60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC(hazard ratio=9.50,2.20;95%CI:3.31-27.29,1.00-4.87;P<0.05).Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged>60 years and≤60 years were 99.37%and 94.66%,respectively,and the difference was statistically significant(P<0.05).The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42%and 97.92%,respectively,and the difference was statistically significant(P<0.05).CONCLUSION The lymph node metastasis rate of EGC patients was 23.64%.Tumor length,tumor site,tumor infiltration depth,vascular cancer thrombin,and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients.Age>60 years and lymph node metastasis are independent risk factors for EGC prognosis.展开更多
This study was carried out explore the mechanism underlying the inhibition of platelet activation by kelp fucoidans in deep venous thrombosis(DVT)mouse.In the control and sham mice,the walls of deep vein were regular ...This study was carried out explore the mechanism underlying the inhibition of platelet activation by kelp fucoidans in deep venous thrombosis(DVT)mouse.In the control and sham mice,the walls of deep vein were regular and smooth with intact intima,myometrium and adventitia.The blood vessel was wrapped with the tissue and there was no thrombosis in the lumen.In the DVT model,the wall was uneven with thicken intima,myometrium and adventitia.After treated with fucoidans LF1 and LF2,the thrombus was dissolved and the blood vessel was recanalized.Compared with the control group,the ROS content,ET-1 and VWF content and the expression of PKC-βand NF-κB in the model were significantly higher(P<0.05);these levels were significantly reduced following treatments with LF2 and LF1.Compared with H_(2)O_(2)treated-HUVECs,combined LF1 and LF2 treatment resulted in significant decrease in the expression of PKC-β,NF-κB,VWF and TM protein(P<0.05).It is clear that LF1 and LF2 reduces DVT-induced ET-1,VWF and TM expressions and production of ROS,thus inhibiting the activation of PKC-β/NF-κB signal pathway and the activation of coagulation system and ultimately reducing the formation of venous thrombus.展开更多
Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disor...Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.展开更多
BACKGROUND Complement components could contribute to the tumor microenvironment and the systemic immune response.Nevertheless,their role in colorectal cancer(CRC)remains a contentious subject.AIM To elucidate the rela...BACKGROUND Complement components could contribute to the tumor microenvironment and the systemic immune response.Nevertheless,their role in colorectal cancer(CRC)remains a contentious subject.AIM To elucidate the relationship between complement components and CRC risk and clinical characteristics.METHODS Searches were conducted in PubMed,the Cochrane Library,and the China National Knowledge Infrastructure database until June 1,2023.We included cohort studies encompassing participants aged≥18 years,investigating the association between complement components and CRC.The studies were of moderate quality or above,as determined by the Agency for Healthcare Research and Quality.The meta-analysis employed fixed-effects or random-effects models based on the I^(2)test,utilizing risk ratio(RR)and their corresponding 95%confidence interval(CI)for outcomes.Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity.RESULTS Data from 15 studies,comprising 1631 participants that met the inclusion criteria,were included in the meta-analysis.Our findings indicated that protein levels of cluster of differentiation 46(CD46)(RR=3.66,95%CI:1.75-7.64,P<0.001),CD59(RR=2.86,95%CI:1.36-6.01,P=0.005),and component 1(C1)(RR=5.88,95%CI:1.75-19.73,P=0.004)and serum levels of C3(standardized mean difference=1.82,95%CI:0.06-3.58,P=0.040)were significantly elevated in patients with CRC compared to healthy controls.Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis,whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression(P<0.05 for all).Although specific pooled results demonstrated notable heterogeneity,subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies.CONCLUSION Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC,emphasizing the potential significance of monitoring elevated complement component levels.展开更多
BACKGROUND Radical resection of colon cancer under general anesthesia is one of the main treatment methods for this malignancy.However,due to the physiological charac-teristics of elderly patients,the safety of periop...BACKGROUND Radical resection of colon cancer under general anesthesia is one of the main treatment methods for this malignancy.However,due to the physiological charac-teristics of elderly patients,the safety of perioperative anesthesia needs special attention.As anα2-adrenergic receptor agonist,dexmedetomidine(Dex)has attracted much attention from anesthesiologists due to its stabilizing effect on heart rate and blood pressure,inhibitory effect on inflammation,and sedative and analgesic effects.Its application in general anesthesia may have a positive impact on the quality of anesthesia and postoperative recovery in elderly patients undergoing radical resection of colon cancer.METHODS A total of 165 colon cancer patients who underwent radical surgery for colon cancer under general anesthesia at Qingdao University Affiliated Haici Hospital,Qingdao,China were recruited and divided into two groups:A and B.In group A,Dex was administered 30 min before surgery,while group B received an equivalent amount of normal saline.The hemodynamic changes,pulmonary compliance,airway pressure,inflammatory factors,confusion assessment method scores,Ramsay Sedation-Agitation Scale scores,and cellular immune function indicators were compared between the two groups.RESULTS Group A showed less intraoperative hemodynamic fluctuations,better pulmonary compliance,and lower airway resistance compared with group B.Twelve hours after the surgery,the serum levels of TLR-2,TLR-4,IL-6,and TNF-αin group A were significantly lower than those of group B(P<0.05).After extubation,the Ramsay Sedation-Agitation Scale score of group A patients was significantly higher than that of group B patients,indicating a higher level of sedation.The incidence of delirium was significantly lower in group A than in group B(P<0.05).CONCLUSION The use of Dex as an adjunct to general anesthesia for radical surgery in elderly patients with colon cancer results in better effectiveness of anesthesia.展开更多
BACKGROUND With the continuous progress of surgical technology and improvements in medical standards,the treatment of gastric cancer surgery is also evolving.Proximal gastrectomy is a common treatment,but double-chann...BACKGROUND With the continuous progress of surgical technology and improvements in medical standards,the treatment of gastric cancer surgery is also evolving.Proximal gastrectomy is a common treatment,but double-channel anastomosis and tubular gastroesophageal anastomosis have attracted much attention in terms of surgical options.Each of these two surgical methods has advantages and disadvantages,so it is particularly important to compare and analyze their clinical efficacy and safety.AIM To compare the surgical safety,clinical efficacy,and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in proximal gastrectomy.METHODS The clinical and follow-up data of 99 patients with proximal gastric cancer who underwent proximal gastrectomy and were admitted to our hospital between January 2018 and September 2023 were included in this retrospective cohort study.According to the different anastomosis methods used,the patients were divided into a double-channel anastomosis group(50 patients)and a tubular gastroesophageal anastomosis group(49 patients).In the double-channel anastomosis,Roux-en-Y anastomosis of the esophagus and jejunum was performed after proximal gastric dissection,and then side-to-side anastomosis was performed between the residual stomach and jejunum to establish an antireflux barrier and reduce postoperative gastroesophageal reflux.In the tubular gastroesophageal anastomosis group,after the proximal end of the stomach was cut,tubular gastroplasty was performed on the distal stump of the stomach and a linear stapler was used to anastomose the posterior wall of the esophagus and the anterior wall of the stomach tube.The main outcome measure was quality of life 1 year after surgery in both groups,and the evaluation criteria were based on the postgastrectomy syndrome assessment scale.The greater the changes in body mass,food intake per meal,meal quality subscale score,and total measures of physical and mental health score,the better the condition;the greater the other indicators,the worse the condition.The secondary outcome measures were intraoperative and postoperative conditions,the incidence of postoperative long-term complications,and changes in nutritional status at 1,3,6,and 12 months after surgery.RESULTS In the double-channel anastomosis cohort,there were 35 males(70%)and 15 females(30%),33(66.0%)were under 65 years of age,and 37(74.0%)had a body mass index ranging from 18 to 25 kg/m2.In the group undergoing tubular gastroesophageal anastomosis,there were eight females(16.3%),21(42.9%)individuals were under the age of 65 years,and 34(69.4%)had a body mass index ranging from 18 to 25 kg/m2.The baseline data did not significantly differ between the two groups(P>0.05 for all),with the exception of age(P=0.021).The duration of hospitalization,number of lymph nodes dissected,intraoperative blood loss,and perioperative complication rate did not differ significantly between the two groups(P>0.05 for all).Patients in the dual-channel anastomosis group scored better on quality of life measures than did those in the tubular gastroesophageal anastomosis group.Specifically,they had lower scores for esophageal reflux[2.8(2.3,4.0)vs 4.8(3.8,5.0),Z=3.489,P<0.001],eating discomfort[2.7(1.7,3.0)vs 3.3(2.7,4.0),Z=3.393,P=0.001],total symptoms[2.3(1.7,2.7)vs 2.5(2.2,2.9),Z=2.243,P=0.025],and other aspects of quality of life.The postoperative symptoms[2.0(1.0,3.0)vs 2.0(2.0,3.0),Z=2.127,P=0.033],meals[2.0(1.0,2.0)vs 2.0(2.0,3.0),Z=3.976,P<0.001],work[1.0(1.0,2.0)vs 2.0(1.0,2.0),Z=2.279,P=0.023],and daily life[1.7(1.3,2.0)vs 2.0(2.0,2.3),Z=3.950,P<0.001]were all better than those of the tubular gastroesophageal anastomosis group.The group that underwent tubular gastroesophageal anastomosis had a superior anal exhaust score[3.0(2.0,4.0)vs 3.5(2.0,5.0),Z=2.345,P=0.019]compared to the dual-channel anastomosis group.Hemoglobin,serum albumin,total serum protein,and the rate at which body mass decreased one year following surgery did not differ significantly between the two groups(P>0.05 for all).CONCLUSION The safety of double-channel anastomosis in proximal gastric cancer surgery is equivalent to that of tubular gastric surgery.Compared with tubular gastric surgery,double-channel anastomosis is a preferred surgical technique for proximal gastric cancer.It offers advantages such as less esophageal reflux and improved quality of life.展开更多
Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies...Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.展开更多
BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically col...BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates,surgical resection rates,tumor-free survival,and severe adverse events.AIM To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options.METHODS A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese(CNKI,Wanfang,China Biomedical Literature Database)and English(PubMed,Embase)databases was performed.Two system assessors independently screened the studies according to the inclusion and exclusion criteria.Quality evaluation and RESULTS Finally,14 studies were included,six of which were randomized controlled studies.A total of 3797 patients were included,including 1865 in the TNT group and 1932 in the nCRT group.The two sets of baseline data were comparable.The results of the meta-analysis showed that the pCR rate[odds ratio(OR)=1.57,95%confidence interval(CI):1.30-1.90,P<0.00001],T stage degradation rate(OR=2.16,95%CI:1.63-2.57,P<0.00001),and R0 resection rate(OR=1.42,95%CI:1.09-1.85,P=0.009)were significantly greater in the nCRT group than in the nCRT group.There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups.The 5-year OS[hazard ratio(HR)=0.84,95%CI:0.69-1.02,P=0.08]and DFS(HR=0.94,95%CI:0.03-1.39,P=0.74)of the TNT group were similar to those of the nCRT group.CONCLUSION TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.展开更多
BACKGROUND Paramyotonia congenita(PMC)stands as a rare sodium channelopaty of skeletal muscle,initially identified by Eulenburg.The identification of PMC often relies on electromyography(EMG),a diagnostic technique.Th...BACKGROUND Paramyotonia congenita(PMC)stands as a rare sodium channelopaty of skeletal muscle,initially identified by Eulenburg.The identification of PMC often relies on electromyography(EMG),a diagnostic technique.The child’s needle EMG unveiled trains of myotonic discharges with notably giant amplitudes,alongside irregular wave trains of myotonic discharges.This distinctive observation had not surfaced in earlier studies.CASE SUMMARY We report the case of a 3-year-old female child with PMC,who exhibited la-ryngeal stridor,muffled speech,myotonia from birth.Cold,exposure to cool water,crying,and physical activity exacerbated the myotonia,which was relieved in warmth,yet never normalized.Percussion myotonia was observable in bilateral biceps.Myotonia symptoms remained unchanged after potassium-rich food consumption like bananas.Hyperkalemic periodic paralysis was excluded.Cranial magnetic resonance imaging yielded normal results.Blood potassium remained within normal range,while creatine kinase showed slight elevation.Exome-wide genetic testing pinpointed a heterozygous mutation on chromosome SCN4A:c.3917G>A(p.G1306E).After a six-month mexiletine regimen,symptoms alleviated.CONCLUSION In this case revealed the two types of myotonic discharges,and had not been documented in other studies.We underscore two distinctive features:Giant-amplitude potentials and irregular waves.展开更多
BACKGROUND Laparoscopic low anterior resection(LLAR)has become a mainstream surgical method for the treatment of colorectal cancer,which has shown many advantages in the aspects of surgical trauma and postoperative re...BACKGROUND Laparoscopic low anterior resection(LLAR)has become a mainstream surgical method for the treatment of colorectal cancer,which has shown many advantages in the aspects of surgical trauma and postoperative rehabilitation.However,the effect of surgery on patients'left coronary artery and its vascular reconstruction have not been deeply discussed.With the development of medical imaging technology,3D vascular reconstruction has become an effective means to evaluate the curative effect of surgery.AIM To investigate the clinical value of preoperative 3D vascular reconstruction in LLAR of rectal cancer with the left colic artery(LCA)preserved.METHODS A retrospective cohort study was performed to analyze the clinical data of 146 patients who underwent LLAR for rectal cancer with LCA preservation from January to December 2023 in our hospital.All patients underwent LLAR of rectal cancer with the LCA preserved,and the intraoperative and postoperative data were complete.The patients were divided into a reconstruction group(72 patients)and a nonreconstruction group(74 patients)according to whether 3D vascular reconstruction was performed before surgery.The clinical features,operation conditions,complications,pathological results and postoperative recovery of the two groups were collected and compared.RESULTS A total of 146 patients with rectal cancer were included in the study,including 72 patients in the reconstruction group and 74 patients in the nonreconstruction group.There were 47 males and 25 females in the reconstruction group,aged(59.75±6.2)years,with a body mass index(BMI)(24.1±2.2)kg/m^(2),and 51 males and 23 females in the nonreconstruction group,aged(58.77±6.1)years,with a BMI(23.6±2.7)kg/m^(2).There was no significant difference in the baseline data between the two groups(P>0.05).In the submesenteric artery reconstruction group,35 patients were type Ⅰ,25 patients were type Ⅱ,11 patients were type Ⅲ,and 1 patient was type Ⅳ.There were 37 type Ⅰ patients,24 type Ⅱ patients,12 type Ⅲ patients,and 1 type Ⅳ patient in the nonreconstruction group.There was no significant difference in arterial typing between the two groups(P>0.05).The operation time of the reconstruction group was 162.2±10.8 min,and that of the nonreconstruction group was 197.9±19.1 min.Compared with that of the reconstruction group,the operation time of the two groups was shorter,and the difference was statistically significant(t=13.840,P<0.05).The amount of intraoperative blood loss was 30.4±20.0 mL in the reconstruction group and 61.2±26.4 mL in the nonreconstruction group.The amount of blood loss in the reconstruction group was less than that in the control group,and the difference was statistically significant(t=-7.930,P<0.05).The rates of anastomotic leakage(1.4%vs 1.4%,P=0.984),anastomotic hemorrhage(2.8%vs 4.1%,P=0.672),and postoperative hospital stay(6.8±0.7 d vs 7.0±0.7 d,P=0.141)were not significantly different between the two groups.CONCLUSION Preoperative 3D vascular reconstruction technology can shorten the operation time and reduce the amount of intraoperative blood loss.Preoperative 3D vascular reconstruction is recommended to provide an intraoperative reference for laparoscopic low anterior resection with LCA preservation.展开更多
The accurate identification of pathogenic fungi is crucial for diagnosing and treating fungal infections. Recent advancements in molecular biotechnology, phylogenetic analysis, and the requirements of the Melbourne Co...The accurate identification of pathogenic fungi is crucial for diagnosing and treating fungal infections. Recent advancements in molecular biotechnology, phylogenetic analysis, and the requirements of the Melbourne Code have led to changes in the classification and naming of fungi. These changes have caused significant confusion for medical laboratories and clinical personnel. This article summarizes the classification and new names of common pathogenic fungi to enhance fungi identification skills and provide accurate information for clinical diagnosis and treatment.展开更多
Intestinal ischemia/reperfusion(II/R)is a severe clinical circumstance which is frequently apparent in situations including midgut volvulus,superior mesenteric vessels closure and hemorrhagic shock.II/R not only bring...Intestinal ischemia/reperfusion(II/R)is a severe clinical circumstance which is frequently apparent in situations including midgut volvulus,superior mesenteric vessels closure and hemorrhagic shock.II/R not only brings about severe intestinal local damage but also leads to remote organs injury including lung,liver etc[1].Lung injury is the most common and severe complications which manifested as pulmonary susceptibility,respiratory dysfunction,and even acute respiratory distress syndrome(ARDS)[2].展开更多
Objective:Non-small cell lung cancer(NSCLC)patients often experience significant fear of recurrence.To facilitate precise identification and appropriate management of this fear,this study aimed to compare the efficacy...Objective:Non-small cell lung cancer(NSCLC)patients often experience significant fear of recurrence.To facilitate precise identification and appropriate management of this fear,this study aimed to compare the efficacy and accuracy of a Backpropagation Neural Network(BPNN)against logistic regression in modeling fear of cancer recurrence prediction.Methods:Data from 596 NSCLC patients,collected between September 2023 and December 2023 at the Cancer Hospital of the Chinese Academy of Medical Sciences,were analyzed.Nine clinically and statistically significant variables,identified via univariate logistic regression,were inputted into both BPNN and logistic regression models developed on a training set(N=427)and validated on an independent set(N=169).Model performances were assessed using Area Under the Receiver Operating Characteristic(ROC)Curve and Decision Curve Analysis(DCA)in both sets.Results:The BPNN model,incorporating nine selected variables,demonstrated superior performance over logistic regression in the training set(AUC=0.842 vs.0.711,p<0.001)and validation set(0.7 vs.0.675,p<0.001).Conclusion:The BPNN model outperforms logistic regression in accurately predicting fear of cancer recurrence in NSCLC patients,offering an advanced approach for fear assessment.展开更多
AIM:To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy(IVCM).METHODS:This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals.Among th...AIM:To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy(IVCM).METHODS:This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals.Among the glaucoma patients,54 were treated with medication,while 25 remained untreated.Central corneal images were evaluated by IVCM,and then ACCMetrics was used to calculate the following parameters:corneal nerve fiber density(CNFD),branch density(CNBD),fiber length(CNFL),total branch density(CTBD),fiber area(CNFA),fiber width(CNFW),and fractal dimension(CNFrD).The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman’s rank correlation coefficient.RESULTS:The CNFD was reduced in glaucoma groups compared to healthy subjects(P<0.01).Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients.As the number of medications and usage count increased,CNFD,CNBD,CNFL,CTBD,CNFA,and CNFrD experienced a decline,while CNFW increased(all P<0.01).For the brinzolamide-therapy group,there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups(P<0.001).In the absence of medication,CNFD in males was lower than that in females(P<0.05).Among patients under medication therapy,CNFD remained consistent between males and females.CONCLUSION:Antiglaucoma eye drops affect the microstructure of corneal nerves.IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a primary contributor to cancer-related mortality on a global scale.However,the underlying molecular mechanisms are still poorly understood.Long noncoding RNAs are emerging m...BACKGROUND Hepatocellular carcinoma(HCC)is a primary contributor to cancer-related mortality on a global scale.However,the underlying molecular mechanisms are still poorly understood.Long noncoding RNAs are emerging markers for HCC diagnosis,prognosis,and therapeutic target.No study of LINC01767 in HCC was published.AIM To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time.METHODS DESeq2 Package was used to analyze different gene expressions.Receiver operating characteristic curves assessed the diagnostic performance.Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis.The least absolute shrinkage and selection operator(LASSO)-Cox was used to identify the prediction model.Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction,next generation sequencing was performed following LINC01767 over expression(GSE243371),and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out.In vitro experiment in Huh7 cell was carried out.RESULTS LINC01767 was down-regulated in HCC with a log fold change=1.575 and was positively correlated with the cancer stemness.LINC01767 was a good diagnostic marker with area under the curve(AUC)[0.801,95% confidence interval(CI):0.751-0.852,P=0.0106]and an independent predictor for overall survival(OS)with hazard ratio=1.899(95%CI:1.01-3.58,P=0.048).LINC01767 nomogram model showed a satisfied performance.The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways.LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC>0.75.LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line;the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro.CONCLUSION LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。
文摘The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.
基金supported by the National Nature Science Foundation of China,No.32101020(to JL)the Natural Science Foundation of Shandong Province,Nos.ZR2020MC071(to JL),ZR2023MH327(to HZ)+1 种基金the Integrated Project of Major Research Plan of National Natural Science Foundation of China,No.92249303(to PL)the Natural Science Foundation of Qingdao,No.23-2-1-193-zyyd-jch(to HZ)。
文摘The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.
文摘In a recent genome-wide association study, the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer＇s disease in Caucasians. Here, we investigated this association in a large Northern Han Chinese cohort consisting of 599 sporadic late-onset Alzheimer＇s disease patients and 598 healthy controls matched for sex and age in a Northern Han Chinese population from Qingdao, China. Genotyping by the polymerase chain reaction-ligase detection reaction revealed that there were significant differences in the genotype （P = 0.017） and allele （P = 0.007） frequencies of the rs2072064 polymorphism between late-onset Alzheimer＇s disease patients and controls. The A allele of this polymorphism was significantly associated with a reduced risk of late-onset Alzheimer＇s disease （odds ratio （OR） = 0.792, 95% confidence interval （CI） = 0.670-0.937, P = 0.007）. When the data were stratified by the apolipoprotein E E4 status, there was a significant difference only among apolipoprotein E E4 non-carriers （genotypic P = 0.001, allelic P = 0.001）. Furthermore, the association between rs2072064 and late-onset Alzheimer＇s disease remained significant by logistic regression analysis after adjustment for age, gender, and the apolipoprotein E E4 carrier status （dominant model： OR = 0.787, 95% CI = 0.619-1.000, P = 0.050; recessive model： OR = 0.655, 95% CI = 0.448-0.959, P= 0.030; additive model： OR = 0.792, 95% CI = 0.661-0.950, P = 0.012）. These findings suggest that SLC26A4 is a susceptibility gene for late-onset Alzheimer＇s disease in a Northern Han Chinese population from the Qingdao area.
文摘BACKGROUND Colon cancer presents a substantial risk to the well-being of elderly people worldwide.With advancements in medical technology,surgical treatment has become the primary approach for managing colon cancer patients.However,due to age-related physiological changes,especially a decline in cognitive function,older patients are more susceptible to the effects of surgery and anesthesia,increasing the relative risk of postoperative cognitive dysfunction(POCD).There-fore,in the surgical treatment of elderly patients with colon cancer,it is of pa-ramount importance to select an appropriate anesthetic approach to reduce the occurrence of POCD,protect brain function,and improve surgical success rates.METHODS One hundred and seventeen patients with colon cancer who underwent elective surgery under general anesthesia were selected and divided into two groups:A and B.Group A received Dex before anesthesia induction,and B group received an equivalent amount of normal saline.Changes in the mini-mental state exami-nation,regional cerebral oxygen saturation(rSO2),bispectral index,glucose uptake rate(GluER),lactate production rate(LacPR),serum S100βand neuron-specific enolase(NSE),POCD,and adverse anesthesia reactions were compared between the two groups.RESULTS Surgical duration,duration of anesthesia,and intraoperative blood loss were comparable between the two groups(P>0.05).The overall dosage of anesthetic drugs used in group A,including propofol and remifentanil,was significantly lower than that used in group B(P<0.05).Group A exhibited higher rSO2 values at the time of endotracheal intubation,30 min after the start of surgery,and immediately after extubation,higher GluER values and lower LacPR values at the time of endotra-cheal intubation,30 min after the start of surgery,immediately after extubation,and 5 min after extubation(P<0.05).Group A exhibited lower levels of serum S100βand NSE 24 h postoperatively and a lower incidence of cognitive dysfunction on the 1st and 5th postoperative days(P<0.05).CONCLUSION The use of Dex in elderly patients undergoing radical colon cancer surgery helps maintain rSO2 Levels and reduce cerebral metabolic levels and the incidence of anesthesia-and surgery-induced cognitive dysfunction.
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
文摘BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been concerning.By retrospectively analyzing the clinical data of EGC patients,we can better under-stand the status of lymph node metastasis and its impact on survival and prog-nosis.AIM To evaluate the prognosis of EGC patients and the factors that affect lymph node METHODS The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study.There were 561 males and 450 females.The mean age was 58±11 years.The patient underwent radical gastrectomy.The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens.The outcomes were as follows:(1)Lymph node metastasis in EGC patients;(2)Analysis of influencing factors of lymph node metastasis in EGC;and(3)Analysis of prognostic factors in patients with EGC.Normally distributed measurement data are expressed as mean±SD,and a t test was used for comparisons between groups.The data are expressed as absolute numbers or percentages,and the chi-square test was used for comparisons between groups.Rank data were compared using a nonparametric rank sum test.A log-rank test and a logistic regression model were used for univariate analysis.A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis.The Kaplan-Meier method was used to calculate the survival rate and construct survival curves.A log-rank test was used for survival analysis.RESULTS Analysis of influencing factors of lymph node metastasis in EGC.The results of the multifactor analysis showed that tumor length and diameter,tumor site,tumor invasion depth,vascular thrombus,and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC(odds ratios=1.80,1.49,2.65,5.76,and 0.60;95%CI:1.29–2.50,1.11–2.00,1.81–3.88,3.87-8.59,and 0.48-0.76,respectively;P<0.05).Analysis of prognostic factors in patients with EGC.All 1011 patients with EGC were followed up for 43(0–13)months.The 3-year overall survival rate was 97.32%.Multivariate analysis revealed that age>60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC(hazard ratio=9.50,2.20;95%CI:3.31-27.29,1.00-4.87;P<0.05).Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged>60 years and≤60 years were 99.37%and 94.66%,respectively,and the difference was statistically significant(P<0.05).The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42%and 97.92%,respectively,and the difference was statistically significant(P<0.05).CONCLUSION The lymph node metastasis rate of EGC patients was 23.64%.Tumor length,tumor site,tumor infiltration depth,vascular cancer thrombin,and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients.Age>60 years and lymph node metastasis are independent risk factors for EGC prognosis.
基金supported by the Special Fund for Clinical Scientific Research of Shandong Medical Association(No.YXH2020ZX058).
文摘This study was carried out explore the mechanism underlying the inhibition of platelet activation by kelp fucoidans in deep venous thrombosis(DVT)mouse.In the control and sham mice,the walls of deep vein were regular and smooth with intact intima,myometrium and adventitia.The blood vessel was wrapped with the tissue and there was no thrombosis in the lumen.In the DVT model,the wall was uneven with thicken intima,myometrium and adventitia.After treated with fucoidans LF1 and LF2,the thrombus was dissolved and the blood vessel was recanalized.Compared with the control group,the ROS content,ET-1 and VWF content and the expression of PKC-βand NF-κB in the model were significantly higher(P<0.05);these levels were significantly reduced following treatments with LF2 and LF1.Compared with H_(2)O_(2)treated-HUVECs,combined LF1 and LF2 treatment resulted in significant decrease in the expression of PKC-β,NF-κB,VWF and TM protein(P<0.05).It is clear that LF1 and LF2 reduces DVT-induced ET-1,VWF and TM expressions and production of ROS,thus inhibiting the activation of PKC-β/NF-κB signal pathway and the activation of coagulation system and ultimately reducing the formation of venous thrombus.
基金supported by the Qingdao Medical Research Guidance Plan(2020-WJZD049).
文摘Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.
文摘BACKGROUND Complement components could contribute to the tumor microenvironment and the systemic immune response.Nevertheless,their role in colorectal cancer(CRC)remains a contentious subject.AIM To elucidate the relationship between complement components and CRC risk and clinical characteristics.METHODS Searches were conducted in PubMed,the Cochrane Library,and the China National Knowledge Infrastructure database until June 1,2023.We included cohort studies encompassing participants aged≥18 years,investigating the association between complement components and CRC.The studies were of moderate quality or above,as determined by the Agency for Healthcare Research and Quality.The meta-analysis employed fixed-effects or random-effects models based on the I^(2)test,utilizing risk ratio(RR)and their corresponding 95%confidence interval(CI)for outcomes.Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity.RESULTS Data from 15 studies,comprising 1631 participants that met the inclusion criteria,were included in the meta-analysis.Our findings indicated that protein levels of cluster of differentiation 46(CD46)(RR=3.66,95%CI:1.75-7.64,P<0.001),CD59(RR=2.86,95%CI:1.36-6.01,P=0.005),and component 1(C1)(RR=5.88,95%CI:1.75-19.73,P=0.004)and serum levels of C3(standardized mean difference=1.82,95%CI:0.06-3.58,P=0.040)were significantly elevated in patients with CRC compared to healthy controls.Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis,whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression(P<0.05 for all).Although specific pooled results demonstrated notable heterogeneity,subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies.CONCLUSION Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC,emphasizing the potential significance of monitoring elevated complement component levels.
文摘BACKGROUND Radical resection of colon cancer under general anesthesia is one of the main treatment methods for this malignancy.However,due to the physiological charac-teristics of elderly patients,the safety of perioperative anesthesia needs special attention.As anα2-adrenergic receptor agonist,dexmedetomidine(Dex)has attracted much attention from anesthesiologists due to its stabilizing effect on heart rate and blood pressure,inhibitory effect on inflammation,and sedative and analgesic effects.Its application in general anesthesia may have a positive impact on the quality of anesthesia and postoperative recovery in elderly patients undergoing radical resection of colon cancer.METHODS A total of 165 colon cancer patients who underwent radical surgery for colon cancer under general anesthesia at Qingdao University Affiliated Haici Hospital,Qingdao,China were recruited and divided into two groups:A and B.In group A,Dex was administered 30 min before surgery,while group B received an equivalent amount of normal saline.The hemodynamic changes,pulmonary compliance,airway pressure,inflammatory factors,confusion assessment method scores,Ramsay Sedation-Agitation Scale scores,and cellular immune function indicators were compared between the two groups.RESULTS Group A showed less intraoperative hemodynamic fluctuations,better pulmonary compliance,and lower airway resistance compared with group B.Twelve hours after the surgery,the serum levels of TLR-2,TLR-4,IL-6,and TNF-αin group A were significantly lower than those of group B(P<0.05).After extubation,the Ramsay Sedation-Agitation Scale score of group A patients was significantly higher than that of group B patients,indicating a higher level of sedation.The incidence of delirium was significantly lower in group A than in group B(P<0.05).CONCLUSION The use of Dex as an adjunct to general anesthesia for radical surgery in elderly patients with colon cancer results in better effectiveness of anesthesia.
文摘BACKGROUND With the continuous progress of surgical technology and improvements in medical standards,the treatment of gastric cancer surgery is also evolving.Proximal gastrectomy is a common treatment,but double-channel anastomosis and tubular gastroesophageal anastomosis have attracted much attention in terms of surgical options.Each of these two surgical methods has advantages and disadvantages,so it is particularly important to compare and analyze their clinical efficacy and safety.AIM To compare the surgical safety,clinical efficacy,and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in proximal gastrectomy.METHODS The clinical and follow-up data of 99 patients with proximal gastric cancer who underwent proximal gastrectomy and were admitted to our hospital between January 2018 and September 2023 were included in this retrospective cohort study.According to the different anastomosis methods used,the patients were divided into a double-channel anastomosis group(50 patients)and a tubular gastroesophageal anastomosis group(49 patients).In the double-channel anastomosis,Roux-en-Y anastomosis of the esophagus and jejunum was performed after proximal gastric dissection,and then side-to-side anastomosis was performed between the residual stomach and jejunum to establish an antireflux barrier and reduce postoperative gastroesophageal reflux.In the tubular gastroesophageal anastomosis group,after the proximal end of the stomach was cut,tubular gastroplasty was performed on the distal stump of the stomach and a linear stapler was used to anastomose the posterior wall of the esophagus and the anterior wall of the stomach tube.The main outcome measure was quality of life 1 year after surgery in both groups,and the evaluation criteria were based on the postgastrectomy syndrome assessment scale.The greater the changes in body mass,food intake per meal,meal quality subscale score,and total measures of physical and mental health score,the better the condition;the greater the other indicators,the worse the condition.The secondary outcome measures were intraoperative and postoperative conditions,the incidence of postoperative long-term complications,and changes in nutritional status at 1,3,6,and 12 months after surgery.RESULTS In the double-channel anastomosis cohort,there were 35 males(70%)and 15 females(30%),33(66.0%)were under 65 years of age,and 37(74.0%)had a body mass index ranging from 18 to 25 kg/m2.In the group undergoing tubular gastroesophageal anastomosis,there were eight females(16.3%),21(42.9%)individuals were under the age of 65 years,and 34(69.4%)had a body mass index ranging from 18 to 25 kg/m2.The baseline data did not significantly differ between the two groups(P>0.05 for all),with the exception of age(P=0.021).The duration of hospitalization,number of lymph nodes dissected,intraoperative blood loss,and perioperative complication rate did not differ significantly between the two groups(P>0.05 for all).Patients in the dual-channel anastomosis group scored better on quality of life measures than did those in the tubular gastroesophageal anastomosis group.Specifically,they had lower scores for esophageal reflux[2.8(2.3,4.0)vs 4.8(3.8,5.0),Z=3.489,P<0.001],eating discomfort[2.7(1.7,3.0)vs 3.3(2.7,4.0),Z=3.393,P=0.001],total symptoms[2.3(1.7,2.7)vs 2.5(2.2,2.9),Z=2.243,P=0.025],and other aspects of quality of life.The postoperative symptoms[2.0(1.0,3.0)vs 2.0(2.0,3.0),Z=2.127,P=0.033],meals[2.0(1.0,2.0)vs 2.0(2.0,3.0),Z=3.976,P<0.001],work[1.0(1.0,2.0)vs 2.0(1.0,2.0),Z=2.279,P=0.023],and daily life[1.7(1.3,2.0)vs 2.0(2.0,2.3),Z=3.950,P<0.001]were all better than those of the tubular gastroesophageal anastomosis group.The group that underwent tubular gastroesophageal anastomosis had a superior anal exhaust score[3.0(2.0,4.0)vs 3.5(2.0,5.0),Z=2.345,P=0.019]compared to the dual-channel anastomosis group.Hemoglobin,serum albumin,total serum protein,and the rate at which body mass decreased one year following surgery did not differ significantly between the two groups(P>0.05 for all).CONCLUSION The safety of double-channel anastomosis in proximal gastric cancer surgery is equivalent to that of tubular gastric surgery.Compared with tubular gastric surgery,double-channel anastomosis is a preferred surgical technique for proximal gastric cancer.It offers advantages such as less esophageal reflux and improved quality of life.
文摘Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.
文摘BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates,surgical resection rates,tumor-free survival,and severe adverse events.AIM To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options.METHODS A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese(CNKI,Wanfang,China Biomedical Literature Database)and English(PubMed,Embase)databases was performed.Two system assessors independently screened the studies according to the inclusion and exclusion criteria.Quality evaluation and RESULTS Finally,14 studies were included,six of which were randomized controlled studies.A total of 3797 patients were included,including 1865 in the TNT group and 1932 in the nCRT group.The two sets of baseline data were comparable.The results of the meta-analysis showed that the pCR rate[odds ratio(OR)=1.57,95%confidence interval(CI):1.30-1.90,P<0.00001],T stage degradation rate(OR=2.16,95%CI:1.63-2.57,P<0.00001),and R0 resection rate(OR=1.42,95%CI:1.09-1.85,P=0.009)were significantly greater in the nCRT group than in the nCRT group.There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups.The 5-year OS[hazard ratio(HR)=0.84,95%CI:0.69-1.02,P=0.08]and DFS(HR=0.94,95%CI:0.03-1.39,P=0.74)of the TNT group were similar to those of the nCRT group.CONCLUSION TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.
文摘BACKGROUND Paramyotonia congenita(PMC)stands as a rare sodium channelopaty of skeletal muscle,initially identified by Eulenburg.The identification of PMC often relies on electromyography(EMG),a diagnostic technique.The child’s needle EMG unveiled trains of myotonic discharges with notably giant amplitudes,alongside irregular wave trains of myotonic discharges.This distinctive observation had not surfaced in earlier studies.CASE SUMMARY We report the case of a 3-year-old female child with PMC,who exhibited la-ryngeal stridor,muffled speech,myotonia from birth.Cold,exposure to cool water,crying,and physical activity exacerbated the myotonia,which was relieved in warmth,yet never normalized.Percussion myotonia was observable in bilateral biceps.Myotonia symptoms remained unchanged after potassium-rich food consumption like bananas.Hyperkalemic periodic paralysis was excluded.Cranial magnetic resonance imaging yielded normal results.Blood potassium remained within normal range,while creatine kinase showed slight elevation.Exome-wide genetic testing pinpointed a heterozygous mutation on chromosome SCN4A:c.3917G>A(p.G1306E).After a six-month mexiletine regimen,symptoms alleviated.CONCLUSION In this case revealed the two types of myotonic discharges,and had not been documented in other studies.We underscore two distinctive features:Giant-amplitude potentials and irregular waves.
文摘BACKGROUND Laparoscopic low anterior resection(LLAR)has become a mainstream surgical method for the treatment of colorectal cancer,which has shown many advantages in the aspects of surgical trauma and postoperative rehabilitation.However,the effect of surgery on patients'left coronary artery and its vascular reconstruction have not been deeply discussed.With the development of medical imaging technology,3D vascular reconstruction has become an effective means to evaluate the curative effect of surgery.AIM To investigate the clinical value of preoperative 3D vascular reconstruction in LLAR of rectal cancer with the left colic artery(LCA)preserved.METHODS A retrospective cohort study was performed to analyze the clinical data of 146 patients who underwent LLAR for rectal cancer with LCA preservation from January to December 2023 in our hospital.All patients underwent LLAR of rectal cancer with the LCA preserved,and the intraoperative and postoperative data were complete.The patients were divided into a reconstruction group(72 patients)and a nonreconstruction group(74 patients)according to whether 3D vascular reconstruction was performed before surgery.The clinical features,operation conditions,complications,pathological results and postoperative recovery of the two groups were collected and compared.RESULTS A total of 146 patients with rectal cancer were included in the study,including 72 patients in the reconstruction group and 74 patients in the nonreconstruction group.There were 47 males and 25 females in the reconstruction group,aged(59.75±6.2)years,with a body mass index(BMI)(24.1±2.2)kg/m^(2),and 51 males and 23 females in the nonreconstruction group,aged(58.77±6.1)years,with a BMI(23.6±2.7)kg/m^(2).There was no significant difference in the baseline data between the two groups(P>0.05).In the submesenteric artery reconstruction group,35 patients were type Ⅰ,25 patients were type Ⅱ,11 patients were type Ⅲ,and 1 patient was type Ⅳ.There were 37 type Ⅰ patients,24 type Ⅱ patients,12 type Ⅲ patients,and 1 type Ⅳ patient in the nonreconstruction group.There was no significant difference in arterial typing between the two groups(P>0.05).The operation time of the reconstruction group was 162.2±10.8 min,and that of the nonreconstruction group was 197.9±19.1 min.Compared with that of the reconstruction group,the operation time of the two groups was shorter,and the difference was statistically significant(t=13.840,P<0.05).The amount of intraoperative blood loss was 30.4±20.0 mL in the reconstruction group and 61.2±26.4 mL in the nonreconstruction group.The amount of blood loss in the reconstruction group was less than that in the control group,and the difference was statistically significant(t=-7.930,P<0.05).The rates of anastomotic leakage(1.4%vs 1.4%,P=0.984),anastomotic hemorrhage(2.8%vs 4.1%,P=0.672),and postoperative hospital stay(6.8±0.7 d vs 7.0±0.7 d,P=0.141)were not significantly different between the two groups.CONCLUSION Preoperative 3D vascular reconstruction technology can shorten the operation time and reduce the amount of intraoperative blood loss.Preoperative 3D vascular reconstruction is recommended to provide an intraoperative reference for laparoscopic low anterior resection with LCA preservation.
文摘The accurate identification of pathogenic fungi is crucial for diagnosing and treating fungal infections. Recent advancements in molecular biotechnology, phylogenetic analysis, and the requirements of the Melbourne Code have led to changes in the classification and naming of fungi. These changes have caused significant confusion for medical laboratories and clinical personnel. This article summarizes the classification and new names of common pathogenic fungi to enhance fungi identification skills and provide accurate information for clinical diagnosis and treatment.
基金supported by the National Natural Science Foundation of China,[No.81600446]。
文摘Intestinal ischemia/reperfusion(II/R)is a severe clinical circumstance which is frequently apparent in situations including midgut volvulus,superior mesenteric vessels closure and hemorrhagic shock.II/R not only brings about severe intestinal local damage but also leads to remote organs injury including lung,liver etc[1].Lung injury is the most common and severe complications which manifested as pulmonary susceptibility,respiratory dysfunction,and even acute respiratory distress syndrome(ARDS)[2].
基金Supported by Beijing Hope Run Special Fund of Cancer Foundation of China(LC2022C05).
文摘Objective:Non-small cell lung cancer(NSCLC)patients often experience significant fear of recurrence.To facilitate precise identification and appropriate management of this fear,this study aimed to compare the efficacy and accuracy of a Backpropagation Neural Network(BPNN)against logistic regression in modeling fear of cancer recurrence prediction.Methods:Data from 596 NSCLC patients,collected between September 2023 and December 2023 at the Cancer Hospital of the Chinese Academy of Medical Sciences,were analyzed.Nine clinically and statistically significant variables,identified via univariate logistic regression,were inputted into both BPNN and logistic regression models developed on a training set(N=427)and validated on an independent set(N=169).Model performances were assessed using Area Under the Receiver Operating Characteristic(ROC)Curve and Decision Curve Analysis(DCA)in both sets.Results:The BPNN model,incorporating nine selected variables,demonstrated superior performance over logistic regression in the training set(AUC=0.842 vs.0.711,p<0.001)and validation set(0.7 vs.0.675,p<0.001).Conclusion:The BPNN model outperforms logistic regression in accurately predicting fear of cancer recurrence in NSCLC patients,offering an advanced approach for fear assessment.
基金Supported by the National Natural Science Foundation of China(No.82371058)the Natural Science Foundation of Shandong Province(No.ZR2020MH172)+2 种基金the Ophthalmology New Technology Incubation Fund Program(Ophthalmology Incubation Fund Phase II Project[2022]No.[005])Medicine Science and Technology Development Program of Shandong Province(No.202107020108)Qingdao Science and Technology Beneficiary Program(No.24-1-8-smjk-16-nsh).
文摘AIM:To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy(IVCM).METHODS:This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals.Among the glaucoma patients,54 were treated with medication,while 25 remained untreated.Central corneal images were evaluated by IVCM,and then ACCMetrics was used to calculate the following parameters:corneal nerve fiber density(CNFD),branch density(CNBD),fiber length(CNFL),total branch density(CTBD),fiber area(CNFA),fiber width(CNFW),and fractal dimension(CNFrD).The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman’s rank correlation coefficient.RESULTS:The CNFD was reduced in glaucoma groups compared to healthy subjects(P<0.01).Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients.As the number of medications and usage count increased,CNFD,CNBD,CNFL,CTBD,CNFA,and CNFrD experienced a decline,while CNFW increased(all P<0.01).For the brinzolamide-therapy group,there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups(P<0.001).In the absence of medication,CNFD in males was lower than that in females(P<0.05).Among patients under medication therapy,CNFD remained consistent between males and females.CONCLUSION:Antiglaucoma eye drops affect the microstructure of corneal nerves.IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.
基金Supported by Foundation of Qingdao Postdoctoral Innovation Project,No.QDBSH20230101019Funded State Key Laboratory of Marine Food Processing&Safety Control,Qingdao,No.SKL2023M05.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a primary contributor to cancer-related mortality on a global scale.However,the underlying molecular mechanisms are still poorly understood.Long noncoding RNAs are emerging markers for HCC diagnosis,prognosis,and therapeutic target.No study of LINC01767 in HCC was published.AIM To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time.METHODS DESeq2 Package was used to analyze different gene expressions.Receiver operating characteristic curves assessed the diagnostic performance.Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis.The least absolute shrinkage and selection operator(LASSO)-Cox was used to identify the prediction model.Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction,next generation sequencing was performed following LINC01767 over expression(GSE243371),and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out.In vitro experiment in Huh7 cell was carried out.RESULTS LINC01767 was down-regulated in HCC with a log fold change=1.575 and was positively correlated with the cancer stemness.LINC01767 was a good diagnostic marker with area under the curve(AUC)[0.801,95% confidence interval(CI):0.751-0.852,P=0.0106]and an independent predictor for overall survival(OS)with hazard ratio=1.899(95%CI:1.01-3.58,P=0.048).LINC01767 nomogram model showed a satisfied performance.The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways.LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC>0.75.LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line;the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro.CONCLUSION LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.
