Amoenucles A-F(1-6),six previously undescribed nucleoside derivatives,and two known analogs(7 and 8)were isolated from the culture of Aspergillus amoenus TJ507.Their structures were elucidated through spectroscopic an...Amoenucles A-F(1-6),six previously undescribed nucleoside derivatives,and two known analogs(7 and 8)were isolated from the culture of Aspergillus amoenus TJ507.Their structures were elucidated through spectroscopic analysis,single-crystal X-ray crystallography,and chemical reactions.Notably,3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety.Of particular significance,the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance(NMR),electric circular dichroism(ECD)calculations,and a hydrolysis reaction,presenting a potentially valuable method for confirming nucleoside structures.Furthermore,1,2,and 5-8 exhibited potential tumor necrosis factorα(TNF-α)inhibitory activities,which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.展开更多
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
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 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
BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as le...BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.展开更多
The study by Lin et al delves into the clinical impact of dapagliflozin,a repre-sentative sodium-glucose cotransporter 2(SGLT2)inhibitor,on chronic heart failure complicated by hyperuricemia.This investigation highlig...The study by Lin et al delves into the clinical impact of dapagliflozin,a repre-sentative sodium-glucose cotransporter 2(SGLT2)inhibitor,on chronic heart failure complicated by hyperuricemia.This investigation highlights dapagliflo-zin’s efficacy in lowering serum uric acid levels,enhancing cardiac function,and reducing cardiovascular events.This work not only provides a comprehensive analysis of dapagliflozin’s sustained benefits in these patients but also introduces novel insights for managing chronic heart failure exacerbated by elevated uric acid.Furthermore,this review examines the potential role of SGLT2 inhibitor in the context of gout,evaluating its mechanisms and clinical application prospects in the management of hyperuricemia,thereby further enriching the medical community’s understanding of SGLT2 inhibitor.展开更多
This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved c...This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved combination therapy can improve the efficacy of advanced gastric cancer(AGC).Pembrolizumab combined with chemotherapy can enhance its sensitivity,and further eliminate tumor cells that develop resistance to chemotherapy.The combination of Pembrolizumab and Trastuzumab targeting human epidermal growth factor receptor 2 showed improved prognosis.The overall toxic effects of Pembrolizumab are significantly lower than traditional chemotherapy,and the safety is controllable.PD-1 inhibitor Pembrolizumab sheds a light on the treatment of AGC and brings new hope to the clinical practice.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
BACKGROUND Cardiovascular diseases and cancer are leading causes of morbidity and mortality.Patients with malignancies are at increased risk for cardiovascular complications including acute coronary syndromes,chemothe...BACKGROUND Cardiovascular diseases and cancer are leading causes of morbidity and mortality.Patients with malignancies are at increased risk for cardiovascular complications including acute coronary syndromes,chemotherapy or radiation therapy related complications and cardiac metastasis.CASE SUMMARY We present a case of a 47-year-old female with metastatic cancer on immuno-therapy presented with anterior ST elevation myocardial infarction followed by emergent percutaneous coronary intervention in the left anterior descending artery.Echocardiography after 72 hours showed thickening of inferior wall and cardiac magnetic resonance depicted inflammation and necrosis attributable to either cardiac metastasis or immunotherapy induced myocarditis.Biopsy was not performed because of treatment with antiplatelet drugs and a definite diagnosis was achieved after probationary administration of high-dose intravenous methyl-prednisolone that led to recovery.CONCLUSION In patients with malignancy,chemotherapy-induced cardiovascular complications and cardiac metastasis are common concerns and may coexist with common acute cardiovascular diseases including acute coronary syndromes.In such cases clinical suspicion aided by multimodality imaging is crucial for the diagnosis.A multidisciplinary team approach is required for prompt initiation of the appro-priate treatment.展开更多
BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immu...BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immune cell activity,affecting the immune system and causing immune-related adverse events.The renal system is sometimes affected by these adverse events.Currently,the literature on ICIs-related glomerular injuries is scarce.CASE SUMMARY We present a patient who developed granulomatosis with polyangiitis(GPA)3 weeks after treatment with the anti-programmed cell death-1 inhibitor,tislel-izumab.The patient experienced proteinuria,hematuria,and acute kidney injury without pulmonary hemorrhage and tested positive for anti-neutrophil cyto-plasmic antibody(ANCA)-cytoplasmic type.Renal biopsy confirmed ANCA-associated vasculitis,and GPA was finally diagnosed.The patient received pulse treatment with glucocorticoids and cyclophosphamide,and renal function improved.After self-discontinuation of the drug,the disease recurred,and the original treatment regimen was continued.However,the patient’s renal function continued to deteriorate.CONCLUSION Glucocorticoids plus cyclophosphamide are effective for treating GPA induced by tislelizumab.However,follow-up and patient education are needed.展开更多
BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose c...BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.展开更多
BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the rol...BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.展开更多
基金supported by the National Natural Science Foundation for Distinguished Young Scholars (No. 81725021)the National Natural Science Foundation of China (Nos.82003633 and 82173705)。
文摘Amoenucles A-F(1-6),six previously undescribed nucleoside derivatives,and two known analogs(7 and 8)were isolated from the culture of Aspergillus amoenus TJ507.Their structures were elucidated through spectroscopic analysis,single-crystal X-ray crystallography,and chemical reactions.Notably,3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety.Of particular significance,the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance(NMR),electric circular dichroism(ECD)calculations,and a hydrolysis reaction,presenting a potentially valuable method for confirming nucleoside structures.Furthermore,1,2,and 5-8 exhibited potential tumor necrosis factorα(TNF-α)inhibitory activities,which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
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.
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 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 the Capital’s Funds for Health Improvement and Research,No.SF202222175.
文摘BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.
文摘The study by Lin et al delves into the clinical impact of dapagliflozin,a repre-sentative sodium-glucose cotransporter 2(SGLT2)inhibitor,on chronic heart failure complicated by hyperuricemia.This investigation highlights dapagliflo-zin’s efficacy in lowering serum uric acid levels,enhancing cardiac function,and reducing cardiovascular events.This work not only provides a comprehensive analysis of dapagliflozin’s sustained benefits in these patients but also introduces novel insights for managing chronic heart failure exacerbated by elevated uric acid.Furthermore,this review examines the potential role of SGLT2 inhibitor in the context of gout,evaluating its mechanisms and clinical application prospects in the management of hyperuricemia,thereby further enriching the medical community’s understanding of SGLT2 inhibitor.
基金Supported by Jilin Provincial Natural Science Foundation,No.YDZJ202401650ZYTS。
文摘This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved combination therapy can improve the efficacy of advanced gastric cancer(AGC).Pembrolizumab combined with chemotherapy can enhance its sensitivity,and further eliminate tumor cells that develop resistance to chemotherapy.The combination of Pembrolizumab and Trastuzumab targeting human epidermal growth factor receptor 2 showed improved prognosis.The overall toxic effects of Pembrolizumab are significantly lower than traditional chemotherapy,and the safety is controllable.PD-1 inhibitor Pembrolizumab sheds a light on the treatment of AGC and brings new hope to the clinical practice.
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BACKGROUND Cardiovascular diseases and cancer are leading causes of morbidity and mortality.Patients with malignancies are at increased risk for cardiovascular complications including acute coronary syndromes,chemotherapy or radiation therapy related complications and cardiac metastasis.CASE SUMMARY We present a case of a 47-year-old female with metastatic cancer on immuno-therapy presented with anterior ST elevation myocardial infarction followed by emergent percutaneous coronary intervention in the left anterior descending artery.Echocardiography after 72 hours showed thickening of inferior wall and cardiac magnetic resonance depicted inflammation and necrosis attributable to either cardiac metastasis or immunotherapy induced myocarditis.Biopsy was not performed because of treatment with antiplatelet drugs and a definite diagnosis was achieved after probationary administration of high-dose intravenous methyl-prednisolone that led to recovery.CONCLUSION In patients with malignancy,chemotherapy-induced cardiovascular complications and cardiac metastasis are common concerns and may coexist with common acute cardiovascular diseases including acute coronary syndromes.In such cases clinical suspicion aided by multimodality imaging is crucial for the diagnosis.A multidisciplinary team approach is required for prompt initiation of the appro-priate treatment.
文摘BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immune cell activity,affecting the immune system and causing immune-related adverse events.The renal system is sometimes affected by these adverse events.Currently,the literature on ICIs-related glomerular injuries is scarce.CASE SUMMARY We present a patient who developed granulomatosis with polyangiitis(GPA)3 weeks after treatment with the anti-programmed cell death-1 inhibitor,tislel-izumab.The patient experienced proteinuria,hematuria,and acute kidney injury without pulmonary hemorrhage and tested positive for anti-neutrophil cyto-plasmic antibody(ANCA)-cytoplasmic type.Renal biopsy confirmed ANCA-associated vasculitis,and GPA was finally diagnosed.The patient received pulse treatment with glucocorticoids and cyclophosphamide,and renal function improved.After self-discontinuation of the drug,the disease recurred,and the original treatment regimen was continued.However,the patient’s renal function continued to deteriorate.CONCLUSION Glucocorticoids plus cyclophosphamide are effective for treating GPA induced by tislelizumab.However,follow-up and patient education are needed.
基金Peking University First Hospital Institutional Review Board(No.2018104).
文摘BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.
基金Supported by the National Research Foundation of Korea Grant Funded by the Korea Government,No.RS-2024-00440477the Korea Institute of Science and Technology Institutional Program,No.2E33111-24-042.
文摘BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.