Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Receptor Protein Tyrosine Phosphatases(RPTPs)are a class of membrane proteins that play a crucial role in cellular signal transduction,primarily responsible for regulating the level of protein tyrosine phosphorylation within cells.They participate in various biological processes such as cell proliferation,differentiation,migration,and apoptosis.As a key group of signal transduction regulators,RPTPs are involved in multiple signaling pathways in the nervous system,such as regulating neuronal development,dendritic and axonal growth,and synapse formation.These functions are crucial for the normal development and maintenance of the nervous system.Studies have shown that RPTPs are involved in the occurrence and development of various neuropsychiatric disorders,such as bipolar disorder,autism,schizophrenia,and restless leg syndrome,and are considered potential therapeutic targets.Several studies are exploring how to regulate their expression and function.Here we review the studies of RPTPs in the nervous system,including their roles in axon guidance,synapse formation,and neuropsychiatric disorders,which helps to understand the functions of RPTPs and provides a basis for finding new therapeutic targets for neuropsychiatric diseases.

This study analyzed the burden and trends in enteric infections in China from 1990 to 2021 from a One Health perspec-tive.Data on mortality associated with enteric infections were extracted from the 2021 Global Burden of Disease(GBD)database.The analysis focused on assessing the mortality rates of enteric infectious diseases attributed to various etiologies and risk factors,along with the age and sex distribution,from 1990 to 2021.Average annual percentage change(AAPC)was used to assess the total changes in disease burden.The age-standardized mortality rate of intestinal infections in China decreased from 9.642/100 000 in 1990 to 0.439/100 000 in 2021,with an AAPC of-57.103%(95%CI:-57.118%to-57.088%).In 2021,Rotavirus,Norovirus,and Crypto-sporidium were the top three etiologies contributing to disease burden,with mortality rates of 1.020/100 000,0.040/100 000 and 0.079/100 000,respectively.A significant variation in etiology distribution was observed across age groups:Rotavirus,Shigella,and Crypto-sporidium dominated among children under 5 years of age,whereas Cryptosporidium,Norovirus,and Clostridioides difficile were more prevalent in older populations.Risk factor analysis indicated that unsafe water sources and poor sanitation accounted for 73.394%of all enteric disease-related deaths.In conclusion,the burden of enteric infections in China markedly declined from 1990 to 2021,and sig-nificant variations in the etiological spectrum and disease burden were observed across age groups.The persistent effects of unsafe wa-ter sources and poor sanitation underscore the need for targeted interventions to further decrease the burden of these diseases.Our find-ings highlight the success of public health interventions in decreasing the burden of enteric infections in China,while emphasizing the need for targeted measures to address disparities in high-risk populations and improve environmental sanitation.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective To compare the pain relief and long-term clinical success rate of vital pulp therapy and root canal treatment in mature permanent teeth with carious irreversible pulpitis.Methods A total of 90 patients diagnosed with carious irreversible pulpitis in mature permanent teeth were collected at Shanghai Stomatological Hospital from Jan 2021 to Jun 2022.They were randomly divided into two groups:test group(n=45)undergoing vital pulp therapy(VPT)and control group(n=45)undergoing root canal treatment(RCT).Pain scores were recorded before treatment,24 hours after operation and 7 days after operation.We conducted clinical evaluation and imaging analysis at 1,6,and 12 months after the surgery,then compared the pain scores and treatment success rates between the two groups.Results Eighty-one patients,including 39 patients in group VPT aged(31.00±1.43)years old and 42 patients in group RCT aged(30.60±1.54)years old,received follow-up for more than 1 year,and the success rate of the test group and control was 97.44%and 95.24%.The pain degree of the two groups was reduced at 24 hours and 7 days after operation(P<0.05),and the pain score of the test group was reduced compared with that in the control group 7 days after operation(P<0.01).Conclusion Compared with root canal treatment,vital pulp therapy for mature permanent teeth with carious irreversible pulpitis can achieve good results in short-term pain evolution and long-term clinical success.

Receptor Protein Tyrosine Phosphatases(RPTPs)are a class of membrane proteins that play a crucial role in cellular signal transduction,primarily responsible for regulating the level of protein tyrosine phosphorylation within cells.They participate in various biological processes such as cell proliferation,differentiation,migration,and apoptosis.As a key group of signal transduction regulators,RPTPs are involved in multiple signaling pathways in the nervous system,such as regulating neuronal development,dendritic and axonal growth,and synapse formation.These functions are crucial for the normal development and maintenance of the nervous system.Studies have shown that RPTPs are involved in the occurrence and development of various neuropsychiatric disorders,such as bipolar disorder,autism,schizophrenia,and restless leg syndrome,and are considered potential therapeutic targets.Several studies are exploring how to regulate their expression and function.Here we review the studies of RPTPs in the nervous system,including their roles in axon guidance,synapse formation,and neuropsychiatric disorders,which helps to understand the functions of RPTPs and provides a basis for finding new therapeutic targets for neuropsychiatric diseases.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

This study analyzed the burden and trends in enteric infections in China from 1990 to 2021 from a One Health perspec-tive.Data on mortality associated with enteric infections were extracted from the 2021 Global Burden of Disease(GBD)database.The analysis focused on assessing the mortality rates of enteric infectious diseases attributed to various etiologies and risk factors,along with the age and sex distribution,from 1990 to 2021.Average annual percentage change(AAPC)was used to assess the total changes in disease burden.The age-standardized mortality rate of intestinal infections in China decreased from 9.642/100 000 in 1990 to 0.439/100 000 in 2021,with an AAPC of-57.103%(95%CI:-57.118%to-57.088%).In 2021,Rotavirus,Norovirus,and Crypto-sporidium were the top three etiologies contributing to disease burden,with mortality rates of 1.020/100 000,0.040/100 000 and 0.079/100 000,respectively.A significant variation in etiology distribution was observed across age groups:Rotavirus,Shigella,and Crypto-sporidium dominated among children under 5 years of age,whereas Cryptosporidium,Norovirus,and Clostridioides difficile were more prevalent in older populations.Risk factor analysis indicated that unsafe water sources and poor sanitation accounted for 73.394%of all enteric disease-related deaths.In conclusion,the burden of enteric infections in China markedly declined from 1990 to 2021,and sig-nificant variations in the etiological spectrum and disease burden were observed across age groups.The persistent effects of unsafe wa-ter sources and poor sanitation underscore the need for targeted interventions to further decrease the burden of these diseases.Our find-ings highlight the success of public health interventions in decreasing the burden of enteric infections in China,while emphasizing the need for targeted measures to address disparities in high-risk populations and improve environmental sanitation.

Objective To compare the pain relief and long-term clinical success rate of vital pulp therapy and root canal treatment in mature permanent teeth with carious irreversible pulpitis.Methods A total of 90 patients diagnosed with carious irreversible pulpitis in mature permanent teeth were collected at Shanghai Stomatological Hospital from Jan 2021 to Jun 2022.They were randomly divided into two groups:test group(n=45)undergoing vital pulp therapy(VPT)and control group(n=45)undergoing root canal treatment(RCT).Pain scores were recorded before treatment,24 hours after operation and 7 days after operation.We conducted clinical evaluation and imaging analysis at 1,6,and 12 months after the surgery,then compared the pain scores and treatment success rates between the two groups.Results Eighty-one patients,including 39 patients in group VPT aged(31.00±1.43)years old and 42 patients in group RCT aged(30.60±1.54)years old,received follow-up for more than 1 year,and the success rate of the test group and control was 97.44%and 95.24%.The pain degree of the two groups was reduced at 24 hours and 7 days after operation(P<0.05),and the pain score of the test group was reduced compared with that in the control group 7 days after operation(P<0.01).Conclusion Compared with root canal treatment,vital pulp therapy for mature permanent teeth with carious irreversible pulpitis can achieve good results in short-term pain evolution and long-term clinical success.

Objective:To provide novel genetic biomarkers for the diagnosis and treatment of sepsis,bioinformatics analysis was used to screen differentially expressed genes and identify Hub genes in sepsis.Methods:Gene Expression Omnibus(GEO)database was used to retrieve gene expression datasets of sepsis and screen for differentially expressed genes(DEGs).Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were used to clarify the molecular mechanism of DEGs,and Hub genes were screened.Results:A total of 361 DEGs were identified,including 163 up-regulated genes and 198 down-regulated genes.Enrichment analysis revealed that these DEGs were primarily involved in antigen processing and presentation,T cell biology,cell adhesion molecules,and T cell receptor signaling pathways.CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1 were determined as optimal diagnostic biomarkers for sepsis.Conclusions:This study elucidated 10 Hub genes(CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1)as potential biomarkers for the diagnosis and treatment of sepsis.However,since the the generalizability of these Hub genes in patients with sepsis remains unvalidated,further experimental verification is still needed in the future.