Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with near...Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.展开更多
BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resist...BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resistance(HOMA-IR)andβ-cell function(HOMA-β)in patients with T2D in a meta-analysis.METHODS Randomized controlled trials(RCTs)comparing SGLT2 inhibitors to placebo in T2D patients,with a minimum treatment duration of 12 weeks,were searched using the PubMed,EMBASE,and Cochrane Library databases.Risk of bias was assessed using the Cochrane Risk of Bias Tool,and the certainty of evidence was evaluated using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)system.Changes in HOMA-IR and HOMA-βwere the outcomes analyzed.Meta-analyses were performed using a random-effects model by incorporating the potential influences of heterogeneity.RESULTS Of 1388 articles identified,24 RCTs met the inclusion criteria.23 of the included studies were double-blind RCTs with low risk of bias.Pooled results including 2272 patients showed that SGLT2 inhibitors significantly reduced HOMA-IR compared to placebo[mean difference(MD)=-0.81,95%confidence interval(CI):-1.11 to-0.52,P<0.001;I2=82%],indicating reduced insulin resistance.Addi-tionally,meta-analysis with 2845 patients suggested that SGLT2 inhibitors significantly increased HOMA-β(MD=7.90,95%CI:5.44-10.37,P<0.001;I2=74%)compared to placebo in patients with T2D,indicating improvedβ-cell function.Based on GRADE assessment,the certainty of evidence was rated moderate for both outcomes due to heterogeneity.Subgroup analyses showed that HOMA-βincreased more substantially in non-Asian studies than in Asian studies(P for subgroup difference<0.01).Subgroup analyses according to the individual medications of SGLT2 inhibitors all showed significant improvement of HOMA-IR and HOMA-β(P all<0.05).No significant publication bias was detected(P for Egger’s test all>0.05).CONCLUSION SGLT2 inhibitors are associated with improvements in insulin resistance andβ-cell function in patients with T2D,although the certainty of evidence is moderate due to heterogeneity.展开更多
The residual stress field induced by surface strengthening processes such as mechanical shot peening and other forms of plastic deformation does not generally exhibit a simple“monotonic”distribution trend.Some resea...The residual stress field induced by surface strengthening processes such as mechanical shot peening and other forms of plastic deformation does not generally exhibit a simple“monotonic”distribution trend.Some researchers have analyzed this fact from a mechanical perspective based on Hertz theory.However,the micro/nano-scale microstructural changes corresponding to the distribution of residual stress fields still appear to be lacking.In this study,we focused on a widely used material in aviation manufacturing,namely nickel-based superalloy GH4169,as our experimental material.We subjected GH4169 alloy to me-chanical strengthening treatment using a shot peening intensity of 0.25 mmA,followed by quantitative testing of micromechanical performance indicators such as microhardness and residual stress.To thoroughly investigate the relationship between micromechanical properties and microstructure changes,we utilized transmission electron microscopy(TEM)to observe and analyze shot-peened materials at different depths.Our findings revealed that the most severe microstructural distortion induced by mechanical shot peening in GH4169 alloy was likely to occur within a depth range of 25 to 75μm.This observation aligns with the actual phenomenon that the maximum microhardness and maximum residual compressive stress did not manifest on the outermost surface of the material.By presenting a detailed analysis of deformation defects such as dislocations,stacking faults,and twinning in different depths of mechan-ically strengthened layers,our study contributes to a deeper understanding and practical application of post-processing technologies based on plastic deformation.展开更多
Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone...Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.展开更多
Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluoro...Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.展开更多
The purpose of the research was to assess the impact of Citizen Development activities on digital transformation. The research identified eight categories that contribute to the success of Low-code No-code (LCNC) proj...The purpose of the research was to assess the impact of Citizen Development activities on digital transformation. The research identified eight categories that contribute to the success of Low-code No-code (LCNC) projects: 1) Strategy;2) Infrastructure;3) Technology;4) Processes & Procedures;5) Governance;6) Culture;7) People;8) Goals & Metrics and selected six critical success factors from these categories: 1) Operational Efficiency;2) Time Savings;3) Timeframe to Realize Value;4) Employee Engagement;5) Participation;6) Number of Sponsored Ideas. End users of the digital transformation efforts through Citizen Development were asked to assess the six critical success measures in terms of performance and importance criteria. The research results identified that focus should be applied to improving “Timeframe to Realize Value”, on “Operational Efficiency”, and on “Time Savings” to deliver success.展开更多
Biliary tract cancer(BTC)is a group of rare malignancies that affect the gallbladder and bile ducts.Although rare,BTC is becoming a significant public health burden in China,particularly among males and older individu...Biliary tract cancer(BTC)is a group of rare malignancies that affect the gallbladder and bile ducts.Although rare,BTC is becoming a significant public health burden in China,particularly among males and older individuals.The increasing trends in BTC incidence and mortality in China are influenced by various demographic,environmental,and lifestyle factors.In this review,we examine available epidemiological data on the incidence,mortality,prognosis,and trends of different BTC subtypes in China.We also discuss the challenges and opportunities for improving the prevention,diagnosis,and management of BTC in China,and identify areas for further research and intervention.The article aims to provide a better understanding of the epidemiological features of BTC in China and to inform public health strategies and clinical practice.展开更多
Canine parvovirus 2(CPV-2)is a highly contagious virus in dogs that typically causes hemorrhagic enteritis and a high mortality rate in unvaccinated puppies.The genetic variability and antigenic diversity of CPV-2 hin...Canine parvovirus 2(CPV-2)is a highly contagious virus in dogs that typically causes hemorrhagic enteritis and a high mortality rate in unvaccinated puppies.The genetic variability and antigenic diversity of CPV-2 hinder its efective prevention of infection by vaccination.To investigate the epidemiology and genetic characteristics of CPV-2 in China,rectal swabs from afected dogs were collected from diferent animal clinics in Kunshan from 2022 to 2023.Preliminary detection and capsid gene sequencing of CPV-2 were performed using previously described primers and protocols.The overall detection rate for CPV-2 was 16.5%(33/200).A signifcant association was found between the CPV-2-positivity and clinical signs,age,breed and vaccination status.Sequence analysis revealed the presence of CPV-2c genotypes in all positive samples,which were genetically similar to other Asian CPV-2c strains.Notably,four key mutations(A5G,F267Y,Y324I and Q370R)were detected in all isolates,and one novel mutation(I447M)was detected in three CPV-2 isolates.These mutations in the CPV-2 strains could impact vaccine efcacy and the efectiveness of the virus immune evasion.Surprisingly,no recombination events were observed between the identifed CPV-2c strains and reference strains from China.Our data revealed that amino acid residues 324,426 and 440 of VP2 may under strong selection pressure.This pattern of genetic variation in the CPV-2 lineage warrants continuous laboratory-based surveillance programs in other parts of China to better understand the pattern of seasonal distribution and association between emerging genotypes and the intensity of disease severity.展开更多
文摘Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.
文摘BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resistance(HOMA-IR)andβ-cell function(HOMA-β)in patients with T2D in a meta-analysis.METHODS Randomized controlled trials(RCTs)comparing SGLT2 inhibitors to placebo in T2D patients,with a minimum treatment duration of 12 weeks,were searched using the PubMed,EMBASE,and Cochrane Library databases.Risk of bias was assessed using the Cochrane Risk of Bias Tool,and the certainty of evidence was evaluated using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)system.Changes in HOMA-IR and HOMA-βwere the outcomes analyzed.Meta-analyses were performed using a random-effects model by incorporating the potential influences of heterogeneity.RESULTS Of 1388 articles identified,24 RCTs met the inclusion criteria.23 of the included studies were double-blind RCTs with low risk of bias.Pooled results including 2272 patients showed that SGLT2 inhibitors significantly reduced HOMA-IR compared to placebo[mean difference(MD)=-0.81,95%confidence interval(CI):-1.11 to-0.52,P<0.001;I2=82%],indicating reduced insulin resistance.Addi-tionally,meta-analysis with 2845 patients suggested that SGLT2 inhibitors significantly increased HOMA-β(MD=7.90,95%CI:5.44-10.37,P<0.001;I2=74%)compared to placebo in patients with T2D,indicating improvedβ-cell function.Based on GRADE assessment,the certainty of evidence was rated moderate for both outcomes due to heterogeneity.Subgroup analyses showed that HOMA-βincreased more substantially in non-Asian studies than in Asian studies(P for subgroup difference<0.01).Subgroup analyses according to the individual medications of SGLT2 inhibitors all showed significant improvement of HOMA-IR and HOMA-β(P all<0.05).No significant publication bias was detected(P for Egger’s test all>0.05).CONCLUSION SGLT2 inhibitors are associated with improvements in insulin resistance andβ-cell function in patients with T2D,although the certainty of evidence is moderate due to heterogeneity.
基金supported by the National Key R&D Program of China(Nos.2023YFE0106500,GLAM)the National Natural Science Foundation of China(Nos.52171073,52075298,51801031)the National Science and Technology Major Projects(Nos.Y2022-VII-0007-0049,J2019-VII-0015-0155,P2023-B-IV-002-001,J2019-IV-0009-0077).
文摘The residual stress field induced by surface strengthening processes such as mechanical shot peening and other forms of plastic deformation does not generally exhibit a simple“monotonic”distribution trend.Some researchers have analyzed this fact from a mechanical perspective based on Hertz theory.However,the micro/nano-scale microstructural changes corresponding to the distribution of residual stress fields still appear to be lacking.In this study,we focused on a widely used material in aviation manufacturing,namely nickel-based superalloy GH4169,as our experimental material.We subjected GH4169 alloy to me-chanical strengthening treatment using a shot peening intensity of 0.25 mmA,followed by quantitative testing of micromechanical performance indicators such as microhardness and residual stress.To thoroughly investigate the relationship between micromechanical properties and microstructure changes,we utilized transmission electron microscopy(TEM)to observe and analyze shot-peened materials at different depths.Our findings revealed that the most severe microstructural distortion induced by mechanical shot peening in GH4169 alloy was likely to occur within a depth range of 25 to 75μm.This observation aligns with the actual phenomenon that the maximum microhardness and maximum residual compressive stress did not manifest on the outermost surface of the material.By presenting a detailed analysis of deformation defects such as dislocations,stacking faults,and twinning in different depths of mechan-ically strengthened layers,our study contributes to a deeper understanding and practical application of post-processing technologies based on plastic deformation.
基金supported by the Ministry of Health National Medical Research Council (to JL)the National University of Singapore (to JJEC)
文摘Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.
基金supported through the Faculty of Medicine and Surgery Award 2021 University of Malta(awarded to K.F).
文摘Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.
文摘The purpose of the research was to assess the impact of Citizen Development activities on digital transformation. The research identified eight categories that contribute to the success of Low-code No-code (LCNC) projects: 1) Strategy;2) Infrastructure;3) Technology;4) Processes & Procedures;5) Governance;6) Culture;7) People;8) Goals & Metrics and selected six critical success factors from these categories: 1) Operational Efficiency;2) Time Savings;3) Timeframe to Realize Value;4) Employee Engagement;5) Participation;6) Number of Sponsored Ideas. End users of the digital transformation efforts through Citizen Development were asked to assess the six critical success measures in terms of performance and importance criteria. The research results identified that focus should be applied to improving “Timeframe to Realize Value”, on “Operational Efficiency”, and on “Time Savings” to deliver success.
文摘Biliary tract cancer(BTC)is a group of rare malignancies that affect the gallbladder and bile ducts.Although rare,BTC is becoming a significant public health burden in China,particularly among males and older individuals.The increasing trends in BTC incidence and mortality in China are influenced by various demographic,environmental,and lifestyle factors.In this review,we examine available epidemiological data on the incidence,mortality,prognosis,and trends of different BTC subtypes in China.We also discuss the challenges and opportunities for improving the prevention,diagnosis,and management of BTC in China,and identify areas for further research and intervention.The article aims to provide a better understanding of the epidemiological features of BTC in China and to inform public health strategies and clinical practice.
基金Kunshan Municipal Government research funding(Grant Number:22KKSGR075).
文摘Canine parvovirus 2(CPV-2)is a highly contagious virus in dogs that typically causes hemorrhagic enteritis and a high mortality rate in unvaccinated puppies.The genetic variability and antigenic diversity of CPV-2 hinder its efective prevention of infection by vaccination.To investigate the epidemiology and genetic characteristics of CPV-2 in China,rectal swabs from afected dogs were collected from diferent animal clinics in Kunshan from 2022 to 2023.Preliminary detection and capsid gene sequencing of CPV-2 were performed using previously described primers and protocols.The overall detection rate for CPV-2 was 16.5%(33/200).A signifcant association was found between the CPV-2-positivity and clinical signs,age,breed and vaccination status.Sequence analysis revealed the presence of CPV-2c genotypes in all positive samples,which were genetically similar to other Asian CPV-2c strains.Notably,four key mutations(A5G,F267Y,Y324I and Q370R)were detected in all isolates,and one novel mutation(I447M)was detected in three CPV-2 isolates.These mutations in the CPV-2 strains could impact vaccine efcacy and the efectiveness of the virus immune evasion.Surprisingly,no recombination events were observed between the identifed CPV-2c strains and reference strains from China.Our data revealed that amino acid residues 324,426 and 440 of VP2 may under strong selection pressure.This pattern of genetic variation in the CPV-2 lineage warrants continuous laboratory-based surveillance programs in other parts of China to better understand the pattern of seasonal distribution and association between emerging genotypes and the intensity of disease severity.
