BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the ...BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced BTC.However,the efficacy of this treatment for GBC remains unclear.CASE SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative surgery.Following three cycles of therapy,a partial response was observed.After one year of combined therapy,a clinical complete response was successfully achieved.Subsequent maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the patient.The patient experienced tolerable toxicities of reversible grade 2 nausea and fatigue.Tolerable adverse events were observed in the patient throughout the entirety of the treatment.CONCLUSION The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse events.Further research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.展开更多
Objective To investigate whether 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside(TSG)ameliorated polycystic ovary syndrome(PCOS)-like characteristics by inhibiting inflammation.Methods PCOS models were established ...Objective To investigate whether 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside(TSG)ameliorated polycystic ovary syndrome(PCOS)-like characteristics by inhibiting inflammation.Methods PCOS models were established by injecting subcutaneously with dehydroepiandrosterone into female Sprague-Dawley rats,followed by receiving intraperitoneal injection of TSG.The granular cells(GCs)KGN were transfected with small interfering RNAs(si-NC and si-CYP19A1).The cells were preincubated with lipopolysaccharide(LPS)and then treated with or without TSG.The estrous cycle was monitored using vaginal exfoliated cells.The morphology of ovarian follicles was analyzed by H&E staining.ELISA was used to analyze estradiol(E2),testosterone(T),follicle stimulating hormone(FSH),luteinizing hormone(LH),IL-6,TNF-α,AGEs,CRP and Omentin-1 levels in serum.Immunohistochemistry was performed to analyze PCNA and CYP19A1 expressions in the GCs of ovaries.Tunel staining was executed to detect the apoptosis of GCs.Quantitative polymerase chain reaction(qPCR)and Western blot were implemented to measure the expression of CYP19A1 in the ovaries and transfected cells.qPCR was used to analyze the expression of IL-6 and TNF-αin the transfected cells treated with LPS and TSG.Results The estrous cycles were restored in TSG group.Compared with model group,the sinus follicles were reduced and corpus luteums were increased in TSG group.TSG group showed increased E2,and decreased T and LH,compared with model group.Pro-inflammatory factors(IL-6,TNF-α,CRP and AGEs)were decreased,and anti-inflammatory factor(Omentin-1)was increased in TSG group compared with those in model group.TSG could partially inhibit decrease of PNCA-positive GCs and increase of Tunel-positive GCs caused by PCOS.The CYP19A1 expression of GCs in TSG group was upregulated compared with model group.The expressions of IL-6 and TNFαin si-CYP19A1 cells were increased compared with si-NC cells.Compared with cells(si-NC and si-CYP19A1)treated without LPS,the expressions of IL-6 and TNF-αcells were increased,and the expression of CYP19A1 was downregulated in LPS-preincubated cells.Compared with cells treated with LPS,the expression of IL-6 and TNF-αwere decreased,and the expression of CYP19A1 was increased in cells treated with LPS and TSG.Compared with si-NC cells treated with LPS and TSG,the expressions of IL-6 and TNF-αcells were increased in the si-CYP19A1 cells treated with LPS and TSG.Conclusion TSG could alleviate PCOS-like characteristics by increasing the expression of CYP19A1 in GCs to inhibit inflammatory response.展开更多
Biomechanical study of the visual system by ocular response analyzer investigates the inter-structural biological relationships,mechanics,and function of the visual system.This review aimed to investigate the changes ...Biomechanical study of the visual system by ocular response analyzer investigates the inter-structural biological relationships,mechanics,and function of the visual system.This review aimed to investigate the changes in corneal biomechanical parameters with age and sex.The articles published in PubMed between 2000 and 2021 were investigated and critiqued,and valid scientific evidence was collected,reviewed and concluded according to the inclusion and exclusion criteria.Most studies showed that corneal biomechanical changes occur infrequently in children up to the age of 20y,and with increasing age and wider age range,there was a significant decrease in corneal biomechanical indices,especially corneal hysteresis.In children and adults,most studies have shown that these biomechanical indicators,especially corneal resistance factor,were higher in females.Although hormonal changes may contribute to this finding,the role of axial length and other biometric indicators should not be ignored.The axial length,the intraocular pressure,and the corneal thickness are other factors associated with biomechanical parameters that should be taken into account in clinical diagnosis and management especially for patients undergoing refractive surgery as well as keratoconus patients.展开更多
Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune res...Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune responses.Pseudomonas plecoglossicida is a pathogenic bacterium that poses a significant threat to aquatic animal health.However,the regulatory mechanisms of sRNAs in P.plecoglossicida remain unclear.This study focused on sRNA113,previously identified as a potential regulator of the fliP gene,a key component of the lateral flagellar type III secretion system.To investigate the effects of sRNA113on P.plecoglossicida virulence,as well as its role in regulating pathogenic processes and host immune responses,mutant strains lacking this sRNA were generated and analyzed.Deletion of sRNA113 resulted in the up-regulation of lateral flagellar type III secretion system-related genes in P.plecoglossicida,which enhanced bacterial swarming motility,biofilm formation,and chemotaxis ability in vitro.In vivo infection experiments with pearl gentian grouper revealed that sRNA113 deletion enhanced the pathogenicity of P.plecoglossicida.This heightened virulence was attributed to the up-regulation of genes associated with the lateral flagellar type III secretion system,resulting in higher bacterial loads within host tissues.This amplification of pathogenic activity intensified tissue damage,disrupted immune responses,and impaired the ability of the host to clear infection,ultimately leading to mortality.These findings underscore the critical role of sRNA113 in regulating the virulence of P.plecoglossicida and its interaction with host immune defenses.This study provides a foundation for further exploration of sRNAmediated mechanisms in bacterial pathogenesis and hostpathogen interactions,contributing to a deeper understanding of virulence regulation and immune evasion in aquatic pathogens.展开更多
AIM:To assess the visual electrophysiological outcomes in children with functional amblyopia who exhibited poor response to conventional treatment.METHODS:Twenty-one children with functional amblyopia,aged 5.7±2....AIM:To assess the visual electrophysiological outcomes in children with functional amblyopia who exhibited poor response to conventional treatment.METHODS:Twenty-one children with functional amblyopia,aged 5.7±2.1y(range:4-10y),underwent comprehensive ophthalmic and refractive evaluations.Spectral domain-optical coherence tomography(SD-OCT)and multifocal electroretinography(mfERG)were conducted to analyze the macular retinal thickness and the first-order response P1 ring of the mfERG in the amblyopic eye(AE)compared to the fellow good eye(GE).RESULTS:Initially,visual acuity in the AE ranged from 20/800 to 20/40,while the GE exhibited a range of 20/25 to 20/20(P<0.01).After 6mo of treatment,17 patients demonstrated improved visual acuity in the AE to 20/50 or better,while 4 children showed no improvement.SD-OCT revealed comparable macular and optic disc structures between the AE and GE.Prior to treatment,the mfERG P1 ring amplitude was significantly reduced in the AE compared to GE(P<0.05).The AE/GE ratio of P1 ring amplitude showed significant improvement post-treatment.However,a smaller AE/GE ratio before treatment was associated with poorer improvement post-treatment.CONCLUSION:In the management of functional amblyopia,a thorough assessment of amblyopic eye examinations is crucial.Approximately 20%of amblyopic eyes may not achieve significant improvement in visual acuity,despite the absence of detectable organic retinal abnormalities.mfERG may reveal underlying abnormalities.Integrating mfERG into initial assessments or treatment follow-ups can aid in identifying potential hidden retinal defects and predicting the prognosis of the amblyopic eye.展开更多
Agricultural heritage systems have the characteristics of ecological fragility and cultural sensitivity.For a long time,the conservation and sustainable development of agricultural heritage systems have received atten...Agricultural heritage systems have the characteristics of ecological fragility and cultural sensitivity.For a long time,the conservation and sustainable development of agricultural heritage systems have received attention from all sectors.However,there are few measurements of tourism disturbance(TD)and community resilience(CR)in agricultural heritage sites,and research on the relationship between the two is even more lacking.This study selects six villages in the Honghe Hani Rice Terraced System(HHRTS)as examples and constructs an evaluation system for TD and CR.Through questionnaires and in-depth interviews,it explores the response relationship between TD and CR of heritage site,and compares the response relationship of villages in different stages of tourism development.The results indicate that the heritage site's current response relationship between TD and CR shows a positive response type,and the development of tourism has brought positive responses and effects.There are differences in the interactive relationship between TD and CR among communities with different levels of tourism development.In communities with poor tourism development,CR is more susceptible to the impact of TD than other communities.The stability of the relationship between TD and CR response gradually tends to stabilize from poor,good,and moderate tourism development.展开更多
BACKGROUND Although the 2021 Chinese Clinical Practice Guidelines for Enhanced Recovery after Surgery(ERAS)provide recommendations for ERAS in gastrointestinal surgery,the clinical application of standard ERAS nursing...BACKGROUND Although the 2021 Chinese Clinical Practice Guidelines for Enhanced Recovery after Surgery(ERAS)provide recommendations for ERAS in gastrointestinal surgery,the clinical application of standard ERAS nursing models is challenging due to the variety of diseases involved in gastrointestinal surgery and the com-plex factors contributing to patient stress responses.Moreover,stress responses are more severe in older adult patients.Therefore,precision medicine is required to improve the quality of nursing care and promote postoperative recovery in gastrointestinal surgery.and demonstrate nursing benefits through clinical practice.METHODS This randomized clinical trial first established an evidence-based nursing ERAS protocol in older adult patients based on literature related to perioperative nursing measures for gastrointestinal surgery stress response.Next,392 older adult patients who underwent gastrointestinal surgery and were admitted to our hospital between December 2021 and June 2023 were categorized into two groups to receive evidence-based(study group)or conventional(control group)ERAS nursing models,respectively.Intraoperative physiological parameters during surgery and postoperative recovery indicators were compared between the groups.RESULTS Among 64 domestic and international studies,the stress responses of older adult patients mainly included emotional anxiety,sleep disorders,gastrointestinal discomfort,physical weakness,pain,and swelling.The appropriate nursing interventions included comprehensive psychological counseling,pre-and postoperative nutritional support,temperature control,pain management,and rehabilitation training.Compared with the control group,the study group showed lower heart rate,mean arterial pressure,blood glucose level,and adrenaline level;shorter duration of drainage tube placement,time to first flatus,time to first ambulation,and postoperative hospital stay;lower anxiety scores on postoperative day 3;and lower incidences of postoperative infection,obstruction,poor wound healing,and gastrointestinal reactions were lower in the study group(all P<0.05).CONCLUSION The evidence-based nursing measures targeting stress responses based on the conventional ERAS nursing model resulted in stable intraoperative physiological parameters during surgery,promoted postoperative recovery,and reduced the incidence of complications.展开更多
Understanding water dynamics under the effect of climatic conditions is important to improve water sustainability over the medium-and long-term.Clay content can affect soil hydrothermal properties,and hence modify wat...Understanding water dynamics under the effect of climatic conditions is important to improve water sustainability over the medium-and long-term.Clay content can affect soil hydrothermal properties,and hence modify water and heat exchange between soil and atmosphere,e.g.evapotranspiration and infiltration.This work aims to develop a numerical approach to explore the influence of clay content on soil hydrothermal response to the timely climatic conditions in the Lake Chad region,Sahel Region of west-central Africa.The meteorological information at the studied points,i.e.points A and B with a clay content of 8.3%and 25%,during the year 2008 is collected from ERA5-Land hourly data.The numerical results allow for understanding the effect of clay content on the hydrothermal response of the surface soil layer.Specifically,the soil surface temperature under point A is lower than that under point B during the dry season due to the dominant effect of heat conduction.However,the converse tendency is observed during the wet season because of the combined effect of heat conduction and latent heat.The variations of soil volumetric water content are closely related to the timely interaction between the soil and atmosphere,in addition to the hydrothermal properties of soil.Moreover,the outcomes of this work improve the understanding of the heat and water dynamics under the effect of climatic conditions and clay content,and provide further insights into the potential water protection in arid and semi-arid regions in the future.展开更多
Nitrogen(N)enrichment is expected to induce a greater phosphorus(P)limitation,despite the acceleration of soil P cycling.However,the changing patterns in plant P and soil available P after N enrichment,and their regul...Nitrogen(N)enrichment is expected to induce a greater phosphorus(P)limitation,despite the acceleration of soil P cycling.However,the changing patterns in plant P and soil available P after N enrichment,and their regulatory mechanisms,remain poorly understood in alpine meadows.Here,we conducted a field experiment with four N addition rates(0,5,10,and 15 g N m^(-2)yr^(-1))in an alpine meadow,and investigated the P in plants,microorganisms,and soil to determine their patterns of change after short-term N addition.Our results showed that N addition significantly increased plant biomass,and the plant P pool showed a non-linear response to the N addition gradient.Soil available P initially increased and then declined with increasing N addition,whereas the occluded inorganic P decreased markedly.The critical factors for soil available P varied with different N addition rates.At lower N addition levels(0 and 5 g N m^(-2)yr^(-1)),soil acidification facilitated the mobilization of occluded inorganic P to increase soil available P.Conversely,at higher N addition levels(10 and 15 g N m^(-2)yr^(-1)),the elevated soil microbial biomass P intensified the competition with plants for soil P,leading to a decline in soil available P.This study highlights the nonlinear responses of the plant P pool and soil available P concentration to N addition rates.These responses suggest the need for developing ecosystem models to assess different effects of increasing N rates,which would enable more accurate predictions of the plant P supply and soil P cycling under N enrichment.展开更多
The use of ultra-high molecular weight polyethylene(UHMWPE)composite in the design of lightweight protective equipment,has gained a lot of interest.However,there is an urgent need to understand the ballistic response ...The use of ultra-high molecular weight polyethylene(UHMWPE)composite in the design of lightweight protective equipment,has gained a lot of interest.However,there is an urgent need to understand the ballistic response mechanism and theoretical prediction model of performance.This paper explores the ballistic response mechanism of UHMWPE composite through experimental and simulation analyses.Then,a resistance-driven modeling method was proposed to establish a theoretical model for predicting the bulletproof performance.The ballistic response mechanism of UHMWPE composite encompassed three fundamental modes:local response,structural response,and coupled response.The occurrence ratio of these fundamental response modes during impact was dependent on the projectile velocity and laminate thickness.The bulletproof performance of laminate under different response modes was assessed based on the penetration depth of the projectile,the bulging height on the rear face of the laminate,the thickness of remaining sub-laminate,and residual velocity of the projectile.The absolute deviations of bulletproof performance indicator between theoretical value and experimental value were well within 11.13%,demonstrating that the established evaluation model possessed high degree of prediction accuracy.展开更多
BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver surgeons.AIM To determine the benefits of indocyanine green(ICG)fluorescence imaging in...BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver surgeons.AIM To determine the benefits of indocyanine green(ICG)fluorescence imaging in patients with hepatocellular carcinoma(HCC)who underwent laparoscopic hepatectomy during and after surgery.METHODS We retrospectively collected the clinicopathological data of 107 patients who successfully underwent laparoscopic hepatectomy at Zhongshan Hospital(Xiamen),Hehai University from June 2022 to June 2023.Whether using the ICG fluorescence imaging technique,we divided them into the ICG and non-ICG groups.To eliminate statistical bias,a 1:1 propensity score matching analysis was conducted.The comparison of perioperative outcomes,including inflammationrelated markers and progression-free survival,was analyzed statistically.RESULTS Intraoperatively,the ICG group exhibited lower blood loss,a shorter surgical time,lower hepatic inflow occlusion(HIO)frequency,and a shorter total HIO time.Postoperatively,the participation of ICG resulted in a shorter duration of hospitalization(6.5 vs 7.6 days,P=0.03)and postoperative inflammatory response attenuation(lower neutrophil-lymphocyte ratio on the first day after surgery and platelet-lymphocyte ratio on the third day,P<0.05).Although the differences were not significant,the levels of all inflammation-related markers were lower in the ICG group.The rates of postoperative complications and the survival analyses,including progression-free and overall survivals showed no significant difference between the groups.CONCLUSION The involvement of ICG fluorescence imaging may lead to improved perioperative outcomes,especially postoperative inflammatory response attenuation,and ultimately improve HCC patients’recovery after surgery.展开更多
Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical ...Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.展开更多
The Nyctereutes procyonoides is highly regarded in the farming and leather industries because of the high value of its fur,which renders artificial feeding a crucial aspect.However,high-fat diets have always been asso...The Nyctereutes procyonoides is highly regarded in the farming and leather industries because of the high value of its fur,which renders artificial feeding a crucial aspect.However,high-fat diets have always been associated with a variety of digestive disorders.This study aimed to investigate the impact of high-fat diets on the gut microbiota and the mechanisms of gut damage in Nyctereutes procyonoides.16S rRNA sequencing demonstrated that high-fat diets caused diarrhea and intestinal damage through alterations in the gut microbiota:a decrease in the abundance of Firmicutes,an increase in the abundance of Proteobacteria and Actinobacteria,and an increase in the abundance of Enterococcaceae,Escherichia coli-Shigella,Clostridium and Lactobacillus.Subsequently,changes in metabolic path-ways,such as amino and fatty acid pathways,were identified by KEGG and COG enrichment analysis,and the TLR4/NF-κB/NLRP3 inflammatory signaling pathway was shown to be activated by high-fat diets.In addition,high-fat diets lead to the accumulation of ROS and MDA and reduce the activity of the antioxidant enzymes GSH-PX and SOD.C orrespondingly,the levels of proinflammatory cytokines(IL-6,IL-1βand TNF-α)were significantly increased,and the apoptosis and necrosis signaling pathways of colonic cells were detected,causing a dramatic decrease in the expression of intestinal tight junction proteins(Occludin,E-cadherin,ZO-1 and ZO-2).In conclusion,high-fat diets altered the structure of the Nyctereutes procyonoides gut microbiota community and led to colon damage.This study provides new insights into the intestinal health of Nyctereutes procyonoides.展开更多
Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond th...Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.e.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.展开更多
Soil nonlinear behavior displays noticeable effects on the site seismic response.This study proposes a new functional expression of the skeleton curve to replace the hyperbolic skeleton curve.By integrating shear modu...Soil nonlinear behavior displays noticeable effects on the site seismic response.This study proposes a new functional expression of the skeleton curve to replace the hyperbolic skeleton curve.By integrating shear modulus and combining the dynamic skeleton curve and the damping degradation coefficient,the constitutive equation of the logarithmic dynamic skeleton can be obtained,which considers the damping effect in a soil dynamics problem.Based on the finite difference method and the multi-transmitting boundary condition,a 1D site seismic response analysis program called Soilresp1D has been developed herein and used to analyze the time-domain seismic response in three types of sites.At the same time,this study also provides numerical simulation results based on the hyperbolic constitutive model and the equivalent linear method.The results verify the rationality of the new soil dynamic constitutive model.It can analyze the mucky soil site nonlinear seismic response,reflecting the deformation characteristics and damping effect of the silty soil.The hysteresis loop area is more extensive,and the residual strain is evident.展开更多
Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treat...Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.展开更多
BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings pr...BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.展开更多
Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack ...Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).展开更多
Long non-coding RNAs(lncRNAs)function as key modulators in mammalian immunity,particularly due to their involvement in lncRNA-mediated competitive endogenous RNA(ceRNA)crosstalk.Despite their recognized significance i...Long non-coding RNAs(lncRNAs)function as key modulators in mammalian immunity,particularly due to their involvement in lncRNA-mediated competitive endogenous RNA(ceRNA)crosstalk.Despite their recognized significance in mammals,research on lncRNAs in lower vertebrates remains limited.In the present study,we characterized the first immune-related lncRNA(pol-lnc78)in the teleost Japanese flounder(Paralichthys olivaceus).Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein(SARM),the fifth discovered member of the Toll/interleukin 1(IL-1)receptor(TIR)adaptor family.This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor(TLR)signaling pathway.Specifically,SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1βand tumor necrosis factor-α(TNF-α).Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3’untranslated region(UTR),thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination.Furthermore,pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression.During infection,the negative regulators pol-lnc78 and SARM were significantly down-regulated,while pol-miR-n199-3p was significantly up-regulated,thus favoring host antibacterial defense.These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.展开更多
Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding throu...Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding through-thickness assumptions of the field variables are made,and the governing equations are two-dimensional,with the displacements and microrotations of the mid-plane as the unknowns.Once the deformation of the mid-plane is solved,a three-dimensional micropolar elastic field within the plate is generated,which is exact up to the second order except in the boundary region close to the plate edge.As an illustrative example,the bending of a clamped infinitely long plate caused by a uniformly distributed transverse force is analyzed and discussed in detail.展开更多
基金Supported by General Project of Natural Science Foundation of Chongqing,China,No.cstc2021jcyj-msxmX0604Chongqing Doctoral"Through Train"Research Program,China,No.CSTB2022BSXM-JCX0045.
文摘BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced BTC.However,the efficacy of this treatment for GBC remains unclear.CASE SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative surgery.Following three cycles of therapy,a partial response was observed.After one year of combined therapy,a clinical complete response was successfully achieved.Subsequent maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the patient.The patient experienced tolerable toxicities of reversible grade 2 nausea and fatigue.Tolerable adverse events were observed in the patient throughout the entirety of the treatment.CONCLUSION The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse events.Further research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.
文摘Objective To investigate whether 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside(TSG)ameliorated polycystic ovary syndrome(PCOS)-like characteristics by inhibiting inflammation.Methods PCOS models were established by injecting subcutaneously with dehydroepiandrosterone into female Sprague-Dawley rats,followed by receiving intraperitoneal injection of TSG.The granular cells(GCs)KGN were transfected with small interfering RNAs(si-NC and si-CYP19A1).The cells were preincubated with lipopolysaccharide(LPS)and then treated with or without TSG.The estrous cycle was monitored using vaginal exfoliated cells.The morphology of ovarian follicles was analyzed by H&E staining.ELISA was used to analyze estradiol(E2),testosterone(T),follicle stimulating hormone(FSH),luteinizing hormone(LH),IL-6,TNF-α,AGEs,CRP and Omentin-1 levels in serum.Immunohistochemistry was performed to analyze PCNA and CYP19A1 expressions in the GCs of ovaries.Tunel staining was executed to detect the apoptosis of GCs.Quantitative polymerase chain reaction(qPCR)and Western blot were implemented to measure the expression of CYP19A1 in the ovaries and transfected cells.qPCR was used to analyze the expression of IL-6 and TNF-αin the transfected cells treated with LPS and TSG.Results The estrous cycles were restored in TSG group.Compared with model group,the sinus follicles were reduced and corpus luteums were increased in TSG group.TSG group showed increased E2,and decreased T and LH,compared with model group.Pro-inflammatory factors(IL-6,TNF-α,CRP and AGEs)were decreased,and anti-inflammatory factor(Omentin-1)was increased in TSG group compared with those in model group.TSG could partially inhibit decrease of PNCA-positive GCs and increase of Tunel-positive GCs caused by PCOS.The CYP19A1 expression of GCs in TSG group was upregulated compared with model group.The expressions of IL-6 and TNFαin si-CYP19A1 cells were increased compared with si-NC cells.Compared with cells(si-NC and si-CYP19A1)treated without LPS,the expressions of IL-6 and TNF-αcells were increased,and the expression of CYP19A1 was downregulated in LPS-preincubated cells.Compared with cells treated with LPS,the expression of IL-6 and TNF-αwere decreased,and the expression of CYP19A1 was increased in cells treated with LPS and TSG.Compared with si-NC cells treated with LPS and TSG,the expressions of IL-6 and TNF-αcells were increased in the si-CYP19A1 cells treated with LPS and TSG.Conclusion TSG could alleviate PCOS-like characteristics by increasing the expression of CYP19A1 in GCs to inhibit inflammatory response.
基金Supported by Noor Ophthalmology Research Center.
文摘Biomechanical study of the visual system by ocular response analyzer investigates the inter-structural biological relationships,mechanics,and function of the visual system.This review aimed to investigate the changes in corneal biomechanical parameters with age and sex.The articles published in PubMed between 2000 and 2021 were investigated and critiqued,and valid scientific evidence was collected,reviewed and concluded according to the inclusion and exclusion criteria.Most studies showed that corneal biomechanical changes occur infrequently in children up to the age of 20y,and with increasing age and wider age range,there was a significant decrease in corneal biomechanical indices,especially corneal hysteresis.In children and adults,most studies have shown that these biomechanical indicators,especially corneal resistance factor,were higher in females.Although hormonal changes may contribute to this finding,the role of axial length and other biometric indicators should not be ignored.The axial length,the intraocular pressure,and the corneal thickness are other factors associated with biomechanical parameters that should be taken into account in clinical diagnosis and management especially for patients undergoing refractive surgery as well as keratoconus patients.
基金supported by the National Natural Science Foundation of China (32373181)National Key Research and Development Program (2023YFD2400700)+2 种基金Science and Technology Plan Project of Fujian Province (2022L3059)High-quality Development of Marine and Fishery Industry Special Fund Project of Fujian Province (FJHYF-L-2023-5)Open Fund of Fujian Province Key Laboratory of Special Aquatic Formula Feed (TMKJZ2302)。
文摘Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune responses.Pseudomonas plecoglossicida is a pathogenic bacterium that poses a significant threat to aquatic animal health.However,the regulatory mechanisms of sRNAs in P.plecoglossicida remain unclear.This study focused on sRNA113,previously identified as a potential regulator of the fliP gene,a key component of the lateral flagellar type III secretion system.To investigate the effects of sRNA113on P.plecoglossicida virulence,as well as its role in regulating pathogenic processes and host immune responses,mutant strains lacking this sRNA were generated and analyzed.Deletion of sRNA113 resulted in the up-regulation of lateral flagellar type III secretion system-related genes in P.plecoglossicida,which enhanced bacterial swarming motility,biofilm formation,and chemotaxis ability in vitro.In vivo infection experiments with pearl gentian grouper revealed that sRNA113 deletion enhanced the pathogenicity of P.plecoglossicida.This heightened virulence was attributed to the up-regulation of genes associated with the lateral flagellar type III secretion system,resulting in higher bacterial loads within host tissues.This amplification of pathogenic activity intensified tissue damage,disrupted immune responses,and impaired the ability of the host to clear infection,ultimately leading to mortality.These findings underscore the critical role of sRNA113 in regulating the virulence of P.plecoglossicida and its interaction with host immune defenses.This study provides a foundation for further exploration of sRNAmediated mechanisms in bacterial pathogenesis and hostpathogen interactions,contributing to a deeper understanding of virulence regulation and immune evasion in aquatic pathogens.
基金Supported by the National Natural Science Foundation of China(No.82271100)the Jiangsu Science and Technology Support Program(No.BE2022805)the Clinical Skills Enhancement Program of Jiangsu Province Hospital(No.JSPH-MC-2022-24).
文摘AIM:To assess the visual electrophysiological outcomes in children with functional amblyopia who exhibited poor response to conventional treatment.METHODS:Twenty-one children with functional amblyopia,aged 5.7±2.1y(range:4-10y),underwent comprehensive ophthalmic and refractive evaluations.Spectral domain-optical coherence tomography(SD-OCT)and multifocal electroretinography(mfERG)were conducted to analyze the macular retinal thickness and the first-order response P1 ring of the mfERG in the amblyopic eye(AE)compared to the fellow good eye(GE).RESULTS:Initially,visual acuity in the AE ranged from 20/800 to 20/40,while the GE exhibited a range of 20/25 to 20/20(P<0.01).After 6mo of treatment,17 patients demonstrated improved visual acuity in the AE to 20/50 or better,while 4 children showed no improvement.SD-OCT revealed comparable macular and optic disc structures between the AE and GE.Prior to treatment,the mfERG P1 ring amplitude was significantly reduced in the AE compared to GE(P<0.05).The AE/GE ratio of P1 ring amplitude showed significant improvement post-treatment.However,a smaller AE/GE ratio before treatment was associated with poorer improvement post-treatment.CONCLUSION:In the management of functional amblyopia,a thorough assessment of amblyopic eye examinations is crucial.Approximately 20%of amblyopic eyes may not achieve significant improvement in visual acuity,despite the absence of detectable organic retinal abnormalities.mfERG may reveal underlying abnormalities.Integrating mfERG into initial assessments or treatment follow-ups can aid in identifying potential hidden retinal defects and predicting the prognosis of the amblyopic eye.
基金funded by the Natural Science Foundation of China(Grant No.41971264)。
文摘Agricultural heritage systems have the characteristics of ecological fragility and cultural sensitivity.For a long time,the conservation and sustainable development of agricultural heritage systems have received attention from all sectors.However,there are few measurements of tourism disturbance(TD)and community resilience(CR)in agricultural heritage sites,and research on the relationship between the two is even more lacking.This study selects six villages in the Honghe Hani Rice Terraced System(HHRTS)as examples and constructs an evaluation system for TD and CR.Through questionnaires and in-depth interviews,it explores the response relationship between TD and CR of heritage site,and compares the response relationship of villages in different stages of tourism development.The results indicate that the heritage site's current response relationship between TD and CR shows a positive response type,and the development of tourism has brought positive responses and effects.There are differences in the interactive relationship between TD and CR among communities with different levels of tourism development.In communities with poor tourism development,CR is more susceptible to the impact of TD than other communities.The stability of the relationship between TD and CR response gradually tends to stabilize from poor,good,and moderate tourism development.
文摘BACKGROUND Although the 2021 Chinese Clinical Practice Guidelines for Enhanced Recovery after Surgery(ERAS)provide recommendations for ERAS in gastrointestinal surgery,the clinical application of standard ERAS nursing models is challenging due to the variety of diseases involved in gastrointestinal surgery and the com-plex factors contributing to patient stress responses.Moreover,stress responses are more severe in older adult patients.Therefore,precision medicine is required to improve the quality of nursing care and promote postoperative recovery in gastrointestinal surgery.and demonstrate nursing benefits through clinical practice.METHODS This randomized clinical trial first established an evidence-based nursing ERAS protocol in older adult patients based on literature related to perioperative nursing measures for gastrointestinal surgery stress response.Next,392 older adult patients who underwent gastrointestinal surgery and were admitted to our hospital between December 2021 and June 2023 were categorized into two groups to receive evidence-based(study group)or conventional(control group)ERAS nursing models,respectively.Intraoperative physiological parameters during surgery and postoperative recovery indicators were compared between the groups.RESULTS Among 64 domestic and international studies,the stress responses of older adult patients mainly included emotional anxiety,sleep disorders,gastrointestinal discomfort,physical weakness,pain,and swelling.The appropriate nursing interventions included comprehensive psychological counseling,pre-and postoperative nutritional support,temperature control,pain management,and rehabilitation training.Compared with the control group,the study group showed lower heart rate,mean arterial pressure,blood glucose level,and adrenaline level;shorter duration of drainage tube placement,time to first flatus,time to first ambulation,and postoperative hospital stay;lower anxiety scores on postoperative day 3;and lower incidences of postoperative infection,obstruction,poor wound healing,and gastrointestinal reactions were lower in the study group(all P<0.05).CONCLUSION The evidence-based nursing measures targeting stress responses based on the conventional ERAS nursing model resulted in stable intraoperative physiological parameters during surgery,promoted postoperative recovery,and reduced the incidence of complications.
基金the National Natural Science Foundation of China(Grant No.42207171).
文摘Understanding water dynamics under the effect of climatic conditions is important to improve water sustainability over the medium-and long-term.Clay content can affect soil hydrothermal properties,and hence modify water and heat exchange between soil and atmosphere,e.g.evapotranspiration and infiltration.This work aims to develop a numerical approach to explore the influence of clay content on soil hydrothermal response to the timely climatic conditions in the Lake Chad region,Sahel Region of west-central Africa.The meteorological information at the studied points,i.e.points A and B with a clay content of 8.3%and 25%,during the year 2008 is collected from ERA5-Land hourly data.The numerical results allow for understanding the effect of clay content on the hydrothermal response of the surface soil layer.Specifically,the soil surface temperature under point A is lower than that under point B during the dry season due to the dominant effect of heat conduction.However,the converse tendency is observed during the wet season because of the combined effect of heat conduction and latent heat.The variations of soil volumetric water content are closely related to the timely interaction between the soil and atmosphere,in addition to the hydrothermal properties of soil.Moreover,the outcomes of this work improve the understanding of the heat and water dynamics under the effect of climatic conditions and clay content,and provide further insights into the potential water protection in arid and semi-arid regions in the future.
基金funded by the National Natural Science Foundation of China(31971746 and 32171685)。
文摘Nitrogen(N)enrichment is expected to induce a greater phosphorus(P)limitation,despite the acceleration of soil P cycling.However,the changing patterns in plant P and soil available P after N enrichment,and their regulatory mechanisms,remain poorly understood in alpine meadows.Here,we conducted a field experiment with four N addition rates(0,5,10,and 15 g N m^(-2)yr^(-1))in an alpine meadow,and investigated the P in plants,microorganisms,and soil to determine their patterns of change after short-term N addition.Our results showed that N addition significantly increased plant biomass,and the plant P pool showed a non-linear response to the N addition gradient.Soil available P initially increased and then declined with increasing N addition,whereas the occluded inorganic P decreased markedly.The critical factors for soil available P varied with different N addition rates.At lower N addition levels(0 and 5 g N m^(-2)yr^(-1)),soil acidification facilitated the mobilization of occluded inorganic P to increase soil available P.Conversely,at higher N addition levels(10 and 15 g N m^(-2)yr^(-1)),the elevated soil microbial biomass P intensified the competition with plants for soil P,leading to a decline in soil available P.This study highlights the nonlinear responses of the plant P pool and soil available P concentration to N addition rates.These responses suggest the need for developing ecosystem models to assess different effects of increasing N rates,which would enable more accurate predictions of the plant P supply and soil P cycling under N enrichment.
基金supported by the National Key Research and Development of China(Grant No.2022YFB4601901)the National Natural Science Foundation of China(Grant No.12122202)。
文摘The use of ultra-high molecular weight polyethylene(UHMWPE)composite in the design of lightweight protective equipment,has gained a lot of interest.However,there is an urgent need to understand the ballistic response mechanism and theoretical prediction model of performance.This paper explores the ballistic response mechanism of UHMWPE composite through experimental and simulation analyses.Then,a resistance-driven modeling method was proposed to establish a theoretical model for predicting the bulletproof performance.The ballistic response mechanism of UHMWPE composite encompassed three fundamental modes:local response,structural response,and coupled response.The occurrence ratio of these fundamental response modes during impact was dependent on the projectile velocity and laminate thickness.The bulletproof performance of laminate under different response modes was assessed based on the penetration depth of the projectile,the bulging height on the rear face of the laminate,the thickness of remaining sub-laminate,and residual velocity of the projectile.The absolute deviations of bulletproof performance indicator between theoretical value and experimental value were well within 11.13%,demonstrating that the established evaluation model possessed high degree of prediction accuracy.
基金Supported by the Incubation Project of Zhongshan Hospital(Xiamen),Hehai University,No.2019ZSXMYS15the Clinical Research Center for Precision Medicine of Abdominal Tumor of Fujian Province+1 种基金the Key Clinical Specialty Discipline Construction Program of Fujian ProvinceXiamen Medical and Health Guidance Project,No.3502Z20244ZD1103.
文摘BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver surgeons.AIM To determine the benefits of indocyanine green(ICG)fluorescence imaging in patients with hepatocellular carcinoma(HCC)who underwent laparoscopic hepatectomy during and after surgery.METHODS We retrospectively collected the clinicopathological data of 107 patients who successfully underwent laparoscopic hepatectomy at Zhongshan Hospital(Xiamen),Hehai University from June 2022 to June 2023.Whether using the ICG fluorescence imaging technique,we divided them into the ICG and non-ICG groups.To eliminate statistical bias,a 1:1 propensity score matching analysis was conducted.The comparison of perioperative outcomes,including inflammationrelated markers and progression-free survival,was analyzed statistically.RESULTS Intraoperatively,the ICG group exhibited lower blood loss,a shorter surgical time,lower hepatic inflow occlusion(HIO)frequency,and a shorter total HIO time.Postoperatively,the participation of ICG resulted in a shorter duration of hospitalization(6.5 vs 7.6 days,P=0.03)and postoperative inflammatory response attenuation(lower neutrophil-lymphocyte ratio on the first day after surgery and platelet-lymphocyte ratio on the third day,P<0.05).Although the differences were not significant,the levels of all inflammation-related markers were lower in the ICG group.The rates of postoperative complications and the survival analyses,including progression-free and overall survivals showed no significant difference between the groups.CONCLUSION The involvement of ICG fluorescence imaging may lead to improved perioperative outcomes,especially postoperative inflammatory response attenuation,and ultimately improve HCC patients’recovery after surgery.
基金Supported by The European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.
文摘The Nyctereutes procyonoides is highly regarded in the farming and leather industries because of the high value of its fur,which renders artificial feeding a crucial aspect.However,high-fat diets have always been associated with a variety of digestive disorders.This study aimed to investigate the impact of high-fat diets on the gut microbiota and the mechanisms of gut damage in Nyctereutes procyonoides.16S rRNA sequencing demonstrated that high-fat diets caused diarrhea and intestinal damage through alterations in the gut microbiota:a decrease in the abundance of Firmicutes,an increase in the abundance of Proteobacteria and Actinobacteria,and an increase in the abundance of Enterococcaceae,Escherichia coli-Shigella,Clostridium and Lactobacillus.Subsequently,changes in metabolic path-ways,such as amino and fatty acid pathways,were identified by KEGG and COG enrichment analysis,and the TLR4/NF-κB/NLRP3 inflammatory signaling pathway was shown to be activated by high-fat diets.In addition,high-fat diets lead to the accumulation of ROS and MDA and reduce the activity of the antioxidant enzymes GSH-PX and SOD.C orrespondingly,the levels of proinflammatory cytokines(IL-6,IL-1βand TNF-α)were significantly increased,and the apoptosis and necrosis signaling pathways of colonic cells were detected,causing a dramatic decrease in the expression of intestinal tight junction proteins(Occludin,E-cadherin,ZO-1 and ZO-2).In conclusion,high-fat diets altered the structure of the Nyctereutes procyonoides gut microbiota community and led to colon damage.This study provides new insights into the intestinal health of Nyctereutes procyonoides.
基金We acknowledge the funding support from the National Science Fund for Distinguished Young Scholars of National Natural Science Foundation of China(Grant No.42225702)the National Natural Science Foundation of China(Grant No.42077235).
文摘Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.e.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.
基金Major Program of the National Natural Science Foundation of China under Grant No.52192675 and the 111 Project of China under Grant No.D21001。
文摘Soil nonlinear behavior displays noticeable effects on the site seismic response.This study proposes a new functional expression of the skeleton curve to replace the hyperbolic skeleton curve.By integrating shear modulus and combining the dynamic skeleton curve and the damping degradation coefficient,the constitutive equation of the logarithmic dynamic skeleton can be obtained,which considers the damping effect in a soil dynamics problem.Based on the finite difference method and the multi-transmitting boundary condition,a 1D site seismic response analysis program called Soilresp1D has been developed herein and used to analyze the time-domain seismic response in three types of sites.At the same time,this study also provides numerical simulation results based on the hyperbolic constitutive model and the equivalent linear method.The results verify the rationality of the new soil dynamic constitutive model.It can analyze the mucky soil site nonlinear seismic response,reflecting the deformation characteristics and damping effect of the silty soil.The hysteresis loop area is more extensive,and the residual strain is evident.
文摘Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.
文摘BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.
基金supported by the National Natural Science Foundation of China(81825009,82071505,81901358)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2MC&T-B-099,2019-I2M-5–006)+2 种基金the Program of Chinese Institute for Brain Research Beijing(2020-NKX-XM-12)the King’s College London-Peking University Health Science Center Joint Institute for Medical Research(BMU2020KCL001,BMU2019LCKXJ012)the National Key R&D Program of China(2021YFF1201103,2016YFC1307000).
文摘Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).
基金supported by the National Natural Science Foundation of China(42006082)Natural Science Foundation of Jiangsu Province of China(BK20221323)+1 种基金“JBGS”Project of Seed Industry Revitalization in Jiangsu Province(JBGS[2021]034)State Key Laboratory of Developmental Biology of Freshwater Fish(2021KF009)。
文摘Long non-coding RNAs(lncRNAs)function as key modulators in mammalian immunity,particularly due to their involvement in lncRNA-mediated competitive endogenous RNA(ceRNA)crosstalk.Despite their recognized significance in mammals,research on lncRNAs in lower vertebrates remains limited.In the present study,we characterized the first immune-related lncRNA(pol-lnc78)in the teleost Japanese flounder(Paralichthys olivaceus).Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein(SARM),the fifth discovered member of the Toll/interleukin 1(IL-1)receptor(TIR)adaptor family.This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor(TLR)signaling pathway.Specifically,SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1βand tumor necrosis factor-α(TNF-α).Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3’untranslated region(UTR),thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination.Furthermore,pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression.During infection,the negative regulators pol-lnc78 and SARM were significantly down-regulated,while pol-miR-n199-3p was significantly up-regulated,thus favoring host antibacterial defense.These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.
基金Project supported by the National Natural Science Foundation of China (No. 12072337)。
文摘Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding through-thickness assumptions of the field variables are made,and the governing equations are two-dimensional,with the displacements and microrotations of the mid-plane as the unknowns.Once the deformation of the mid-plane is solved,a three-dimensional micropolar elastic field within the plate is generated,which is exact up to the second order except in the boundary region close to the plate edge.As an illustrative example,the bending of a clamped infinitely long plate caused by a uniformly distributed transverse force is analyzed and discussed in detail.
