The atmospheric corrosion monitoring(ACM)technique has been widely employed to track the real-time corrosion behavior of metal materials.However,limited studies have applied ACM to the corrosion protection properties ...The atmospheric corrosion monitoring(ACM)technique has been widely employed to track the real-time corrosion behavior of metal materials.However,limited studies have applied ACM to the corrosion protection properties of organic coatings.This study compared a bare epoxy coating with one containing zinc phosphate corrosion inhibitors,both applied on ACM sensors,to observe their corrosion protection properties over time.Coatings with artificial damage via scratches were exposed to immersion and alternating dry and wet environments,which allowed for monitoring galvanic corrosion currents in real-time.Throughout the corrosion tests,the ACM currents of the zinc phosphate/epoxy coating were considerably lower than those of the blank epoxy coating.The trend in ACM current variations closely matched the results obtained from regular electrochemical tests and surface analysis.This alignment highlights the potential of the ACM technique in evaluating the corrosion protection capabilities of organic coatings.Compared with the blank epoxy coating,the zinc phosphate/epoxy coating showed much-decreased ACM current values that confirmed the effective inhibition of zinc phosphate against steel corrosion beneath the damaged coating.展开更多
Background: Non-radiographic axial spondyloarthritis is a progressive and disabling inflammatory disease affecting young adults, with limited treatment options. TNFi are more efficacious than JAKi and IL1-7i in nr-ax ...Background: Non-radiographic axial spondyloarthritis is a progressive and disabling inflammatory disease affecting young adults, with limited treatment options. TNFi are more efficacious than JAKi and IL1-7i in nr-ax SPA and it has a well-known safety profile over a longer duration. Recently, many IL-17i and JAKi were approved for the treatment of nr-ax SPA;however, data comparing IL1-7i and JAKi in terms of efficacy and safety is lacking. This systematized review aimed to compare the existing efficacy and safety data of JAKi vs IL-17i in the treatment of patients with nr-ax SPA. Methods: A systematic literature search was performed using relevant keywords in many databases. According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA, 2020), relevant articles were included and evaluated in this review. Efficacy and safety data were collected, analyzed and compared through week 52. The first check was done by the end of week 14 and week 16 for upadacitinib and IL-17i respectively. Results: Data from four RCTs evaluating upadacitinib, secukinumab, ixekizumab, and bimekizumab comprising 1425 patients were analyzed. Overall, a comparable efficacy and safety profile were observed across different treatment arms through week 52;however, non-significant variations were encountered in some outcome measures. The primary endpoint among these RCTs (ASAS40 response rate) was met and it was higher in patients treated with bimekizumab 160 mg sc Q 4 weeks in TNFi non responders (48%) and lowest in ixekizumab 80 mg sc Q 4 weeks treated patients, (35%) (p Conclusion: The above-mentioned three IL-17i and the only one JAKi demonstrated comparable safety and efficacy profiles with some minor variations. A head-to-head trial comparing the effectiveness and safety characteristics of JAKi vs IL-17i may be needed in patients with active nr-ax SpA.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment opti...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.展开更多
Purpose: Gastrointestinal stromal tumor (GIST) has been considered radiation-resistant and data on the radiotherapy for GIST in previous studies are lacking. The purpose of this article is to accumulate more experienc...Purpose: Gastrointestinal stromal tumor (GIST) has been considered radiation-resistant and data on the radiotherapy for GIST in previous studies are lacking. The purpose of this article is to accumulate more experience in the application of radiotherapy for GISTs. Materials and methods: Review our own case material and the relevant English literature. Results: A huge pelvic GIST after resistance to tyrosine kinase inhibitors (TKIs) has been well controlled by simultaneous-integrated boost intensity-modulated radiation therapy (SIB-IMRT). The time from the initial shrinkage of the mass and subsequent stabilization to now was more than 18 months. The patient was palliated from the series of symptoms caused by tumor compression and well tolerated to the adverse reactions by radiotherapy. And the previous studies have shown that GISTs had a certain sensitivity to radiotherapy. Conclusion: SIB-IMRT may provide a new means of achieving objective response and prolonging survival in selected GIST patients.展开更多
BACKGROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related disorders.Recent evidence suggests associations between long-term...BACKGROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related disorders.Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes,including greater mortality.AIM To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias.METHODS This retrospective cohort study used data from the TriNetX research network,with electronic health records from multiple healthcare organizations.The study employed a new-user,active comparator design,which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists(H2RA)users among adult cancer patients.Newly prescribed PPIs(esomeprazole,lansoprazole,omeprazole,pantoprazole,or rabeprazole)users were compared to non-users or newly prescribed H2RAs(cimetidine,famotidine,nizatidine,or ranitidine)users.The primary outcome was all-cause mortality.Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects.Multivariable Cox regression models were used to estimate hazard ratios(HRs)and 95% confidence interval(CI).RESULTS During the follow-up period(median 5.4±1.8 years for PPI users and 6.5±1.0 years for non-users),PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year,2 years,and at the end of follow up(HRs:2.34-2.72).Compared with H2RA users,PPI users demonstrated a higher rate of all-cause mortality HR:1.51(95%CI:1.41-1.69).Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure,confirming the robustness of these findings.In a sensitivity analysis,we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs,providing insights into the long-term effects of past PPI use.In addition,at 1-year follow-up,the analysis revealed a significant difference in mortality rates between former PPI users and non-users(HR:1.84;95%CI:1.82-1.96).CONCLUSION PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users.These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible.However,further studies are needed to corroborate our findings,given the significant adverse outcomes in cancer patients.展开更多
BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit t...BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400μmol/L cobalt nanoparticles and 25μmol/L deferiprone),the deferiprone group(25μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P<0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factorα,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factorα,interleukin-1β,and interleukin-6)significantly decreased(P<0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P<0.05),while deferiprone inhibited this effect(P<0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.展开更多
Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma,and neoadjuvant immunotherapy is currently being extensively explored.This reviewhighlights the initial findings and key cl...Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma,and neoadjuvant immunotherapy is currently being extensively explored.This reviewhighlights the initial findings and key clinical therapeutic insights on immune checkpoint inhibitors in the early treatment of muscle-invasive bladder cancer across diverse patient populations.Most available literature consists of clinical investigations involving small sample,single-arm phase Ⅱ trials,with the primary endpoint being the pathologic complete response rate.Early results of immune checkpoint inhibitors in the neoadjuvant treatment of bladder cancer have demonstrated promising efficacy.However,these findings require confirmation in large phase Ⅲ clinical trials,with particular emphasis on long-term survival benefits and identifying patients who respond to treatment.展开更多
A pyrimidine derivative,6-phenyl-2-thiouracil(PT),was synthesized for developing a corrosion inhibitor(CI)applied in the protection of the nickel−aluminum bronze(NAB)in seawater.The anti-corrosion effect of PT was eva...A pyrimidine derivative,6-phenyl-2-thiouracil(PT),was synthesized for developing a corrosion inhibitor(CI)applied in the protection of the nickel−aluminum bronze(NAB)in seawater.The anti-corrosion effect of PT was evaluated by the mass loss experiment,electrochemical tests and surface analysis.The results show that PT exhibits excellent inhibition performance and the maximum inhibition efficiency of PT reaches 99.6%.The interaction mechanism was investigated through X-ray photoelectron spectroscopy(XPS)and molecule dynamics simulation based on the density functional theory(DFT).The S-Cu,Al-N and Cu-N bonds are formed by the chemical interactions,leading to the adsorption of PT on the NAB surface.The diffusion of corrosive species is hindered considerably by the protective PT film with composition of(PT-Cu)_(ads)and(PT-Al)_(ads)on the PT/NAB interface.The degree of suppression is increased with the addition of more PT molecules.展开更多
BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotoni...BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotonin reuptake inhibitors(SSRIs)are frequently used in the treatment of depression;however,their efficacy in addressing major depressive disorder(MDD)in adults following TBI remains uncertain.AIM To investigate the efficacy of SSRIs in the treatment of MDD after TBI.METHODS A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,encompassing studies published until May 2024.This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI.Studies were assessed based sample size,treatment duration,treatment methodologies,severity of brain injury,assessment techniques,and drug response.A random-effects model was used to derive the summary effect size.RESULTS Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment.The eight studies did not exhibit heterogeneity(I^(2)=38%).The depression score for MDD after TBI in the SSRI group decreased more than that in the control group[odds ratio(OR)1.68,95%CI:1.09-2.58,P=0.02].The adverse reactions after treatment included diarrhea,dizziness,dry mouth,nausea,or vomiting.There was no difference in the incidence of adverse reactions after treatment between the two groups(OR 1.16,95%CI:0.78-1.73,P=0.46).These studies did not show significant heterogeneity(I^(2)=44%).CONCLUSION SSRIs may be effective in treating patients with MDD after TBI.Adequately powered,randomized,controlled trials are required to confirm these findings.展开更多
BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of a...BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC,we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.AIM To evaluate the value of postoperative combined therapy(PCT)with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included.Recurrence-free survival(RFS)and overall survival were assessed using propensity score matching and inverse probability of treatment weighting.Cox regression analysis was used to identify factors affecting recurrence,and subgroup analysis was conducted to investigate the impact of medications on different populations.Treatment-related adverse events and liver function measurements were evaluated.RESULTS A total of 150 patients were recruited,of whom 30 underwent PCT and 120 did not.After adjusting for confounders,patients who underwent PCT had better RFS at 6 and 12 months than those who did not(P>0.05).Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting,although the difference was not statistically significant(P>0.05).A maximum diameter of>5 cm,vascular invasion,satellite nodules,and high gamma-glutamyl transferase levels were independent risk factors for recurrence(P<0.05).No significant interaction effects were observed in subgroup analyses.The most prevalent adverse event was hypertension(66.7%).PCT was associated with an increased risk of hepatic impairment which may predict RFS rates(P=0.041).CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT.Hepatic impairment during treatment may indicate recurrence,and close monitoring of liver function and HBV infection is recommended.展开更多
Aqueous zinc-ion batteries are highly favored for their enhanced safety and reduced cost.However,there exist challenges including zinc dendrite,hydrogen evolution,and surface corrosion to be solved.Using electrolyte a...Aqueous zinc-ion batteries are highly favored for their enhanced safety and reduced cost.However,there exist challenges including zinc dendrite,hydrogen evolution,and surface corrosion to be solved.Using electrolyte additives is a highly convenient approach to solving zinc anode-related issues.Inspired by industrial corrosion protection,a trace amount of the corrosion inhibitor urotropine(URT)is used as an electrolyte additive to protect the zinc anode.Theoretical calculation and experimental analysis confirm the adsorption of URT molecules onto the surface of Zn,which inhibits hydrogen evolution.This adsorption further leads to the formation of an inorganic-organic bilayer solid electrolyte interface(SEI)on the surface of the zinc anode,effectively protecting the Zn anode from corrosion,hydrogen evolution and zinc dendrites.The presence of SEI enables symmetrical Zn//Zn cells to exhibit a long cycling performance of 1750 h at 1mA/cm^(2)and an average coulombic efficiency of 99.0%at 1mA/cm^(2)in Zn//Cu cells.After being coupled with polyaniline(PANI),the Zn//PANI full battery displays excellent cycle stability and specific capacity.展开更多
The study conducted by Wang et al,focuses on the role of Rho GTPase activating protein 12(ARHGAP12),in hepatocellular carcinoma(HCC).This research reveals that ARHGAP12 expression,markedly elevated in malignant cells ...The study conducted by Wang et al,focuses on the role of Rho GTPase activating protein 12(ARHGAP12),in hepatocellular carcinoma(HCC).This research reveals that ARHGAP12 expression,markedly elevated in malignant cells of HCC,correlates strongly with adverse outcomes for patients.Furthermore,the study illustrates that ARHGAP12 enhances the ability of HCC cells to invade and contributes to their resistance to tyrosine kinase inhibitors(TKIs)through modulation of the focal adhesion pathway.To comprehensively investigate the relationship between ARHGAP12 and TKI resistance,this study integrates single-cell and bulk RNA sequencing methodologies along with data from tumor immune single-cell hub 2,Gene Expression Omnibus,The Cancer Genome Atlas,CellMiner,Genomics of Drug Sensitivity in Cancer 2,as well as immunohisto-chemical staining and proteomic analyses.Statistical analyses,including the Wilcoxon rank-sum test and receiver operating characteristic curve analysis,were employed to evaluate the correlation between ARHGAP12 expression levels and clinical parameters,as well as drug sensitivity.It is evident that a more profound exploration of the molecular dynamics of HCC,especially those related to re-sistance against TKIs,is essential.展开更多
Heart failure(HF),which falls outside of the historical macrovascular or microvascular categorizations of diabetes complications,has been overlooked for long time in diabetic patients,despite its increasing prevalence...Heart failure(HF),which falls outside of the historical macrovascular or microvascular categorizations of diabetes complications,has been overlooked for long time in diabetic patients,despite its increasing prevalence and mortality.As originally stated in the Framingham studies,diabetes is associated with an increased risk of HF.Subsequent studies not only corroborated these findings but also identified HF as the most frequent first onset of cardiovascular involvement.The paramount role of proper management of common modifiable risk factors such as hypertension,obesity,dyslipidemia and smoking,became rapidly clear.Conversely,the impact of intensive glycemic control was more contentious.A large meta-analysis of randomized controlled trials reported a lack of effect of strict glycemic control as compared to standard care on HF-related outcomes.The considerable heterogeneity of the effect estimate and the higher risk conferred by thiazolidinediones suggested that mechanism of action of antidiabetic drugs played a key role.Furthermore,the safety concerns of pioglitazone led Food and Drug Administration to release a guidance for drug manufacturers stating that cardiovascular risk should be comprehensively evaluated during drug development.Surprisingly,in just a few years,large cardiovascular outcome trials established the beneficial cardiovascular effects of sodium-glucose cotransporter 2 inhibitors.These effects were consistent regardless diabetes and ejection fraction.Therefore,scientific community started to question the glucose-lowering and diuretic properties of sodium-glucose cotransporter 2 inhibitors as the unique mechanisms for improved outcomes.A plenty of preclinical and clinical studies identified several mechanisms besides glucose-lowering effects.However,these mechanistic studies focused on animal models and patients with established HF.If the same mechanisms account for beneficial effects in patients at risk for or with pre-HF is unknown.GrubićRotkvićet al published an interesting work adding data in early stages HF.展开更多
Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tum...Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.展开更多
This article discusses the study by GrubićRotkvićet al on the mechanisms of action of sodium-glucose cotransporter 2 inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and heart failure(HF).T2DM and HF a...This article discusses the study by GrubićRotkvićet al on the mechanisms of action of sodium-glucose cotransporter 2 inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and heart failure(HF).T2DM and HF are highly comorbid,with a significantly increased prevalence of HF in patients with T2DM.SGLT2i exhibit potential in reducing hospitalization rates for HF and cardiovascular mortality through multiple mechanisms,including improving blood glucose control,promoting urinary sodium excretion,reducing sympathetic nervous system activity,lowering both preload and afterload on the heart,alleviating inflammation and oxidative stress,enhancing endothelial function,improving myocardial energy metabolism,and stabilizing cardiac ion homeostasis.Further research and clinical practice will help optimize the use of SGLT2i in HF patients.展开更多
Immunotherapy remains one of the most promising strategies for cancer treatment,with ICIs at the forefront of this innovation1.However,patient response to ICIs is highly variable,highlighting the urgent need to enhanc...Immunotherapy remains one of the most promising strategies for cancer treatment,with ICIs at the forefront of this innovation1.However,patient response to ICIs is highly variable,highlighting the urgent need to enhance their efficacy in clinical settings2.Addressing this challenge is critical for advancing the impact of immunotherapy in oncology.展开更多
Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequentl...Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.展开更多
BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of h...BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.展开更多
Interstitial lung disease(ILD)encompasses diverse conditions,including fibrotic lung diseases characterized by cellular proliferation,interstitial inflammation,and fibrosis.ILD can arise from numerous causes,including...Interstitial lung disease(ILD)encompasses diverse conditions,including fibrotic lung diseases characterized by cellular proliferation,interstitial inflammation,and fibrosis.ILD can arise from numerous causes,including connective tissue diseases(CTDs)such as systemic sclerosis(SSc),rheumatoid arthritis(RA),idiopathic inflammatory myopathy(IIM),Sjögren’s syndrome(SS),and systemic lupus erythematosus(SLE),with SSc,RA,and IIM being more prevalent.The reported prevalence of ILD varies widely across studies owing to differences in inclusion criteria,research methodologies,and follow-up durations.For instance,the prevalence of ILD in SSc can reach 30%,with a 10-year mortality rate of up to 40%.[1]The exact prevalence of rheumatoid arthritis-associated interstitial lung disease(RA-ILD)remains uncertain,ranging from 1%to 58%based on different study methodologies.[2]The global prevalence of ILD in polymyositis and dermatomyositis(PM/DM)is approximately 41%,with a higher prevalence in Asian populations.[3]ILD profoundly affects the treatment approaches,quality of life,morbidity,and mortality in patients with rheumatic diseases.The overlapping pathological and clinical features of ILDs complicate diagnosis and pose significant challenges in the management of CTD-ILDs.展开更多
基金financially supported by the National Natural Science Foundation of China(No.52371049)the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology(YESS,No.2020QNRC001)the National Science and Technology Resources Investigation Program of China(Nos.2021FY100603 and 2019FY101404)。
文摘The atmospheric corrosion monitoring(ACM)technique has been widely employed to track the real-time corrosion behavior of metal materials.However,limited studies have applied ACM to the corrosion protection properties of organic coatings.This study compared a bare epoxy coating with one containing zinc phosphate corrosion inhibitors,both applied on ACM sensors,to observe their corrosion protection properties over time.Coatings with artificial damage via scratches were exposed to immersion and alternating dry and wet environments,which allowed for monitoring galvanic corrosion currents in real-time.Throughout the corrosion tests,the ACM currents of the zinc phosphate/epoxy coating were considerably lower than those of the blank epoxy coating.The trend in ACM current variations closely matched the results obtained from regular electrochemical tests and surface analysis.This alignment highlights the potential of the ACM technique in evaluating the corrosion protection capabilities of organic coatings.Compared with the blank epoxy coating,the zinc phosphate/epoxy coating showed much-decreased ACM current values that confirmed the effective inhibition of zinc phosphate against steel corrosion beneath the damaged coating.
文摘Background: Non-radiographic axial spondyloarthritis is a progressive and disabling inflammatory disease affecting young adults, with limited treatment options. TNFi are more efficacious than JAKi and IL1-7i in nr-ax SPA and it has a well-known safety profile over a longer duration. Recently, many IL-17i and JAKi were approved for the treatment of nr-ax SPA;however, data comparing IL1-7i and JAKi in terms of efficacy and safety is lacking. This systematized review aimed to compare the existing efficacy and safety data of JAKi vs IL-17i in the treatment of patients with nr-ax SPA. Methods: A systematic literature search was performed using relevant keywords in many databases. According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA, 2020), relevant articles were included and evaluated in this review. Efficacy and safety data were collected, analyzed and compared through week 52. The first check was done by the end of week 14 and week 16 for upadacitinib and IL-17i respectively. Results: Data from four RCTs evaluating upadacitinib, secukinumab, ixekizumab, and bimekizumab comprising 1425 patients were analyzed. Overall, a comparable efficacy and safety profile were observed across different treatment arms through week 52;however, non-significant variations were encountered in some outcome measures. The primary endpoint among these RCTs (ASAS40 response rate) was met and it was higher in patients treated with bimekizumab 160 mg sc Q 4 weeks in TNFi non responders (48%) and lowest in ixekizumab 80 mg sc Q 4 weeks treated patients, (35%) (p Conclusion: The above-mentioned three IL-17i and the only one JAKi demonstrated comparable safety and efficacy profiles with some minor variations. A head-to-head trial comparing the effectiveness and safety characteristics of JAKi vs IL-17i may be needed in patients with active nr-ax SpA.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.
文摘Purpose: Gastrointestinal stromal tumor (GIST) has been considered radiation-resistant and data on the radiotherapy for GIST in previous studies are lacking. The purpose of this article is to accumulate more experience in the application of radiotherapy for GISTs. Materials and methods: Review our own case material and the relevant English literature. Results: A huge pelvic GIST after resistance to tyrosine kinase inhibitors (TKIs) has been well controlled by simultaneous-integrated boost intensity-modulated radiation therapy (SIB-IMRT). The time from the initial shrinkage of the mass and subsequent stabilization to now was more than 18 months. The patient was palliated from the series of symptoms caused by tumor compression and well tolerated to the adverse reactions by radiotherapy. And the previous studies have shown that GISTs had a certain sensitivity to radiotherapy. Conclusion: SIB-IMRT may provide a new means of achieving objective response and prolonging survival in selected GIST patients.
文摘BACKGROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related disorders.Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes,including greater mortality.AIM To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias.METHODS This retrospective cohort study used data from the TriNetX research network,with electronic health records from multiple healthcare organizations.The study employed a new-user,active comparator design,which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists(H2RA)users among adult cancer patients.Newly prescribed PPIs(esomeprazole,lansoprazole,omeprazole,pantoprazole,or rabeprazole)users were compared to non-users or newly prescribed H2RAs(cimetidine,famotidine,nizatidine,or ranitidine)users.The primary outcome was all-cause mortality.Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects.Multivariable Cox regression models were used to estimate hazard ratios(HRs)and 95% confidence interval(CI).RESULTS During the follow-up period(median 5.4±1.8 years for PPI users and 6.5±1.0 years for non-users),PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year,2 years,and at the end of follow up(HRs:2.34-2.72).Compared with H2RA users,PPI users demonstrated a higher rate of all-cause mortality HR:1.51(95%CI:1.41-1.69).Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure,confirming the robustness of these findings.In a sensitivity analysis,we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs,providing insights into the long-term effects of past PPI use.In addition,at 1-year follow-up,the analysis revealed a significant difference in mortality rates between former PPI users and non-users(HR:1.84;95%CI:1.82-1.96).CONCLUSION PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users.These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible.However,further studies are needed to corroborate our findings,given the significant adverse outcomes in cancer patients.
文摘BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400μmol/L cobalt nanoparticles and 25μmol/L deferiprone),the deferiprone group(25μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P<0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factorα,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factorα,interleukin-1β,and interleukin-6)significantly decreased(P<0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P<0.05),while deferiprone inhibited this effect(P<0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.
基金supported by Shandong Provincial Natural Science Foundation(ZR2023LZL005)Jinan Science and Technology Development Foundation.
文摘Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma,and neoadjuvant immunotherapy is currently being extensively explored.This reviewhighlights the initial findings and key clinical therapeutic insights on immune checkpoint inhibitors in the early treatment of muscle-invasive bladder cancer across diverse patient populations.Most available literature consists of clinical investigations involving small sample,single-arm phase Ⅱ trials,with the primary endpoint being the pathologic complete response rate.Early results of immune checkpoint inhibitors in the neoadjuvant treatment of bladder cancer have demonstrated promising efficacy.However,these findings require confirmation in large phase Ⅲ clinical trials,with particular emphasis on long-term survival benefits and identifying patients who respond to treatment.
基金supported by the National Natural Science Foundation of China(No.52171069).
文摘A pyrimidine derivative,6-phenyl-2-thiouracil(PT),was synthesized for developing a corrosion inhibitor(CI)applied in the protection of the nickel−aluminum bronze(NAB)in seawater.The anti-corrosion effect of PT was evaluated by the mass loss experiment,electrochemical tests and surface analysis.The results show that PT exhibits excellent inhibition performance and the maximum inhibition efficiency of PT reaches 99.6%.The interaction mechanism was investigated through X-ray photoelectron spectroscopy(XPS)and molecule dynamics simulation based on the density functional theory(DFT).The S-Cu,Al-N and Cu-N bonds are formed by the chemical interactions,leading to the adsorption of PT on the NAB surface.The diffusion of corrosive species is hindered considerably by the protective PT film with composition of(PT-Cu)_(ads)and(PT-Al)_(ads)on the PT/NAB interface.The degree of suppression is increased with the addition of more PT molecules.
文摘BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotonin reuptake inhibitors(SSRIs)are frequently used in the treatment of depression;however,their efficacy in addressing major depressive disorder(MDD)in adults following TBI remains uncertain.AIM To investigate the efficacy of SSRIs in the treatment of MDD after TBI.METHODS A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,encompassing studies published until May 2024.This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI.Studies were assessed based sample size,treatment duration,treatment methodologies,severity of brain injury,assessment techniques,and drug response.A random-effects model was used to derive the summary effect size.RESULTS Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment.The eight studies did not exhibit heterogeneity(I^(2)=38%).The depression score for MDD after TBI in the SSRI group decreased more than that in the control group[odds ratio(OR)1.68,95%CI:1.09-2.58,P=0.02].The adverse reactions after treatment included diarrhea,dizziness,dry mouth,nausea,or vomiting.There was no difference in the incidence of adverse reactions after treatment between the two groups(OR 1.16,95%CI:0.78-1.73,P=0.46).These studies did not show significant heterogeneity(I^(2)=44%).CONCLUSION SSRIs may be effective in treating patients with MDD after TBI.Adequately powered,randomized,controlled trials are required to confirm these findings.
基金Supported by the Key Research and Development Projects of Anhui Province,No.202104j07020048National Key Research and Development Program of China,No.2022YFA1304500.
文摘BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC,we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.AIM To evaluate the value of postoperative combined therapy(PCT)with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included.Recurrence-free survival(RFS)and overall survival were assessed using propensity score matching and inverse probability of treatment weighting.Cox regression analysis was used to identify factors affecting recurrence,and subgroup analysis was conducted to investigate the impact of medications on different populations.Treatment-related adverse events and liver function measurements were evaluated.RESULTS A total of 150 patients were recruited,of whom 30 underwent PCT and 120 did not.After adjusting for confounders,patients who underwent PCT had better RFS at 6 and 12 months than those who did not(P>0.05).Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting,although the difference was not statistically significant(P>0.05).A maximum diameter of>5 cm,vascular invasion,satellite nodules,and high gamma-glutamyl transferase levels were independent risk factors for recurrence(P<0.05).No significant interaction effects were observed in subgroup analyses.The most prevalent adverse event was hypertension(66.7%).PCT was associated with an increased risk of hepatic impairment which may predict RFS rates(P=0.041).CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT.Hepatic impairment during treatment may indicate recurrence,and close monitoring of liver function and HBV infection is recommended.
基金financially supported by Joint Funds of the National Natural Science Foundation of China(No.U22A20140)the National Natural Science Foundation of China(No.22379062)+1 种基金supported by Shenzhen Stable Support Plan Program for Higher Education Institutions Research Program(No.20220816131408001)Shenzhen Science and Technology Program(No.JCYJ20230807091802006)。
文摘Aqueous zinc-ion batteries are highly favored for their enhanced safety and reduced cost.However,there exist challenges including zinc dendrite,hydrogen evolution,and surface corrosion to be solved.Using electrolyte additives is a highly convenient approach to solving zinc anode-related issues.Inspired by industrial corrosion protection,a trace amount of the corrosion inhibitor urotropine(URT)is used as an electrolyte additive to protect the zinc anode.Theoretical calculation and experimental analysis confirm the adsorption of URT molecules onto the surface of Zn,which inhibits hydrogen evolution.This adsorption further leads to the formation of an inorganic-organic bilayer solid electrolyte interface(SEI)on the surface of the zinc anode,effectively protecting the Zn anode from corrosion,hydrogen evolution and zinc dendrites.The presence of SEI enables symmetrical Zn//Zn cells to exhibit a long cycling performance of 1750 h at 1mA/cm^(2)and an average coulombic efficiency of 99.0%at 1mA/cm^(2)in Zn//Cu cells.After being coupled with polyaniline(PANI),the Zn//PANI full battery displays excellent cycle stability and specific capacity.
基金Supported by The National Health Commission's Key Laboratory of Gastrointestinal Tumor Diagnosis and Treatment for the Year 2022,National Health Commission's Master's and Doctoral/Postdoctoral Fund Project,No.NHCDP2022001Gansu Provincial People's Hospital Doctoral Supervisor Training Project,No.22GSSYA-3.
文摘The study conducted by Wang et al,focuses on the role of Rho GTPase activating protein 12(ARHGAP12),in hepatocellular carcinoma(HCC).This research reveals that ARHGAP12 expression,markedly elevated in malignant cells of HCC,correlates strongly with adverse outcomes for patients.Furthermore,the study illustrates that ARHGAP12 enhances the ability of HCC cells to invade and contributes to their resistance to tyrosine kinase inhibitors(TKIs)through modulation of the focal adhesion pathway.To comprehensively investigate the relationship between ARHGAP12 and TKI resistance,this study integrates single-cell and bulk RNA sequencing methodologies along with data from tumor immune single-cell hub 2,Gene Expression Omnibus,The Cancer Genome Atlas,CellMiner,Genomics of Drug Sensitivity in Cancer 2,as well as immunohisto-chemical staining and proteomic analyses.Statistical analyses,including the Wilcoxon rank-sum test and receiver operating characteristic curve analysis,were employed to evaluate the correlation between ARHGAP12 expression levels and clinical parameters,as well as drug sensitivity.It is evident that a more profound exploration of the molecular dynamics of HCC,especially those related to re-sistance against TKIs,is essential.
文摘Heart failure(HF),which falls outside of the historical macrovascular or microvascular categorizations of diabetes complications,has been overlooked for long time in diabetic patients,despite its increasing prevalence and mortality.As originally stated in the Framingham studies,diabetes is associated with an increased risk of HF.Subsequent studies not only corroborated these findings but also identified HF as the most frequent first onset of cardiovascular involvement.The paramount role of proper management of common modifiable risk factors such as hypertension,obesity,dyslipidemia and smoking,became rapidly clear.Conversely,the impact of intensive glycemic control was more contentious.A large meta-analysis of randomized controlled trials reported a lack of effect of strict glycemic control as compared to standard care on HF-related outcomes.The considerable heterogeneity of the effect estimate and the higher risk conferred by thiazolidinediones suggested that mechanism of action of antidiabetic drugs played a key role.Furthermore,the safety concerns of pioglitazone led Food and Drug Administration to release a guidance for drug manufacturers stating that cardiovascular risk should be comprehensively evaluated during drug development.Surprisingly,in just a few years,large cardiovascular outcome trials established the beneficial cardiovascular effects of sodium-glucose cotransporter 2 inhibitors.These effects were consistent regardless diabetes and ejection fraction.Therefore,scientific community started to question the glucose-lowering and diuretic properties of sodium-glucose cotransporter 2 inhibitors as the unique mechanisms for improved outcomes.A plenty of preclinical and clinical studies identified several mechanisms besides glucose-lowering effects.However,these mechanistic studies focused on animal models and patients with established HF.If the same mechanisms account for beneficial effects in patients at risk for or with pre-HF is unknown.GrubićRotkvićet al published an interesting work adding data in early stages HF.
基金Supported by 2021 Key Topic of Qinghai Provincial Health System–Guiding Plan Topic,No.2021-WJZDX-43.
文摘Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.
文摘This article discusses the study by GrubićRotkvićet al on the mechanisms of action of sodium-glucose cotransporter 2 inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and heart failure(HF).T2DM and HF are highly comorbid,with a significantly increased prevalence of HF in patients with T2DM.SGLT2i exhibit potential in reducing hospitalization rates for HF and cardiovascular mortality through multiple mechanisms,including improving blood glucose control,promoting urinary sodium excretion,reducing sympathetic nervous system activity,lowering both preload and afterload on the heart,alleviating inflammation and oxidative stress,enhancing endothelial function,improving myocardial energy metabolism,and stabilizing cardiac ion homeostasis.Further research and clinical practice will help optimize the use of SGLT2i in HF patients.
基金supported by grants from the National Key R&D Program of China(2022YFA1206100 and 2021YFA1201100)the National Natural Science Foundation of China(32271449)+1 种基金CAS Project for Young Scientists in Basic Research(YSBR-036,China)Beijing Natural Science Foundation(Z230008,China).
文摘Immunotherapy remains one of the most promising strategies for cancer treatment,with ICIs at the forefront of this innovation1.However,patient response to ICIs is highly variable,highlighting the urgent need to enhance their efficacy in clinical settings2.Addressing this challenge is critical for advancing the impact of immunotherapy in oncology.
基金Supported by Science and Technology Department of Yunnan Province-Kunming Medical University,Kunming Medical Joint Special Project-Surface Project,No.202401AY070001-164Yunnan Provincial Clinical Research Center Cardiovascular Diseases-New Technology Research for Development Project for Diagnosis and Treatment Cardiovascular Diseases,No.202102AA310002the Key Technology Research and Device Development Project for Innovative Diagnosis and Treatment of Structural Heart Disease in the Southwest Plateau Region,No.202302AA310045.
文摘Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.
基金This study was approved by the ethics committee of the First People’s Hospital of Fuzhou City(No.FZ202103).
文摘BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.
文摘Interstitial lung disease(ILD)encompasses diverse conditions,including fibrotic lung diseases characterized by cellular proliferation,interstitial inflammation,and fibrosis.ILD can arise from numerous causes,including connective tissue diseases(CTDs)such as systemic sclerosis(SSc),rheumatoid arthritis(RA),idiopathic inflammatory myopathy(IIM),Sjögren’s syndrome(SS),and systemic lupus erythematosus(SLE),with SSc,RA,and IIM being more prevalent.The reported prevalence of ILD varies widely across studies owing to differences in inclusion criteria,research methodologies,and follow-up durations.For instance,the prevalence of ILD in SSc can reach 30%,with a 10-year mortality rate of up to 40%.[1]The exact prevalence of rheumatoid arthritis-associated interstitial lung disease(RA-ILD)remains uncertain,ranging from 1%to 58%based on different study methodologies.[2]The global prevalence of ILD in polymyositis and dermatomyositis(PM/DM)is approximately 41%,with a higher prevalence in Asian populations.[3]ILD profoundly affects the treatment approaches,quality of life,morbidity,and mortality in patients with rheumatic diseases.The overlapping pathological and clinical features of ILDs complicate diagnosis and pose significant challenges in the management of CTD-ILDs.
