Objective:To study evolutionary relationship of the 5'untranslated regions(5'UTRs) in low passage dengue3 viruses(DEN3) isolated from hospitalized children with different clinical manifestations in Bangkok dur...Objective:To study evolutionary relationship of the 5'untranslated regions(5'UTRs) in low passage dengue3 viruses(DEN3) isolated from hospitalized children with different clinical manifestations in Bangkok during 24 year-evolution(1977-2000) comparing to the DEN3prototype(H87).Methods:The 5'UTRs of these Thai DEN3 and the H87 prototype were amplified by RT-PCR and sequenced.Their multiple sequence alignments were done by Codon Code Aligner v 4.0.4 software and their RNA secondary structures were predicted by MFOLD software.Replication of five Thai DEN3 candidates comparing to the 1187 prototype were done in human(HepG2) and the mosquito(C6/36) cell lines.Results:Among these Thai DEN3,the completely identical sequences of their first 89 nucleotides,their high-order secondary structure of 5'UTRs and three SNPs including the predominant C90 T,and two minor SNPs including A109 G and A112 G were found.The C90 T of Thai DEN3.Bangkok isolates was shown predominantly before 1977.Five Thai DEN3 candidates with the predominant C90 T were shown to replicate in human(HepG2) and the mosquito(C6/36) cell lines better than the H87 prototype.However,their highly conserved sequences as well as SNPs of the 5'UTR did not appear to correlate with their disease severity in human.Conclusions:Our findings highlighted evolutionary relationship of the completely identical 89 nucleotide sequence,the high-order secondary structure and the predominant C90 T of the 5'UTR of these Thai DEN3 during 24 year-evolution further suggesting to be their genetic markers and magic targets for future research on antiviral therapy as well as vaccine approaches of Thai DEN3.展开更多
目的 探讨芪蛭益肾胶囊联合八段锦治疗早期糖尿病肾病患者的临床疗效及对其24 h尿白蛋白排泄率的影响。方法 选取2023年1月—2023年12月在南京医科大学附属苏州医院就诊的260例早期糖尿病肾病患者作为研究对象,采用随机数字表法分为对...目的 探讨芪蛭益肾胶囊联合八段锦治疗早期糖尿病肾病患者的临床疗效及对其24 h尿白蛋白排泄率的影响。方法 选取2023年1月—2023年12月在南京医科大学附属苏州医院就诊的260例早期糖尿病肾病患者作为研究对象,采用随机数字表法分为对照组和观察组,每组130例。对照组在常规用药基础上进行八段锦锻炼,观察组在对照组治疗的基础上服用芪蛭益肾胶囊治疗。治疗6个月后,观察比较两组患者中医证候积分、临床疗效、不良反应情况,治疗前后血糖指标[空腹血糖(Fasting blood glucose,FBG)、餐后2 h血糖(2-hour postprandial blood glucose,2 h PBG)、糖化血红蛋白(Glycosylated hemoglobin,HbA1c)]、肾功能指标[24 h尿液总蛋白定量(24-hour urine total protein,24 h UTP)、血尿素氮(Blood urea nitrogen,BUN)浓度、24 h尿液蛋白排泄速率(24-hour urinary protein excretion rate,24 h UPER)]、血清炎症因子[C反应蛋白(C-reactive protein,CRP)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)]水平。结果 治疗后两组患者中医证候积分均较治疗前降低,差异有统计学意义(P<0.05);且观察组中医证候积分较对照组明显降低,差异有统计学意义(P<0.05)。两组患者治疗前后FBG、2 h PBG、HbA1c水平比较,差异无统计学意义(P>0.05)。治疗后两组患者24 h UTP、BUN、24 h UPER水平较治疗前降低,差异有统计学意义(P<0.05);且观察组24 h UTP、BUN、24 h UPER水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者CRP、TNF-α、IL-6水平均较治疗前降低,差异有统计学意义(P<0.05);且观察组CRP、TNF-α、IL-6水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后观察组治疗总有效率74.62%(97/130)明显高于对照组60.77%(79/130),差异有统计学意义(P<0.05)。治疗期间,两组患者不良反应总发生率比较,差异无统计学意义(P>0.05)。结论 芪蛭益肾胶囊联合八段锦治疗早期糖尿病肾病,能有效控制血糖水平,改善肾功能和血清炎症指标,提高治疗效果,且安全性良好。展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics...BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.展开更多
Background:The phenomenon of multimorbidity in chronic diseases among the elderly is prevalent,and its significant association with depression poses a serious threat to the physical and mental health of older adults.C...Background:The phenomenon of multimorbidity in chronic diseases among the elderly is prevalent,and its significant association with depression poses a serious threat to the physical and mental health of older adults.Current research on the associations between 24-hour movement behaviors(including physical activity,sedentary behavior,and sleep)and depression has largely been confined to examining the effects of single behaviors,overlooking the intrinsic compositional nature and interrelationships among these behaviors.Therefore,it is necessary to investigate the integrated effects of 24-hour movement behaviors on depression in older adults with multimorbidity from a holistic,compositional perspective.Methods:From November 2024 to April 2025,a total of 226 older adult patients with multimorbidity were recruited from a tertiary hospital in Changzhou City.Data were collected using a general information questionnaire,the International Physical Activity Questionnaire–Short Form(IPAQ-SF),the Pittsburgh Sleep Quality Index(PSQI),and the Patient Health Questionnaire-9(PHQ-9).Compositional data analysis and isotemporal substitution models were employed for statistical analysis.Results:The mean daily durations of Light-Intensity Physical Activity(LPA),Moderate-to-Vigorous Physical Activity(MVPA),Sedentary Behavior(SB),and Sleep(SLP)in older adults with multimorbidity were 402.48 min,12.04 min,511.52 min,and 458.68 min,respectively.The prevalence of depressive symptoms was 37.6%.Compositional data analysis revealed that SB was positively associated with depression(βSB=1.005,P=0.006),while SLP was negatively associated with depression(βSLP=−1.736,P<0.001).No statistically significant associations were found between MVPA or LPA and depression(P>0.05).In the 10-minute isotemporal substitution model,replacing SB with any other behavioral component was associated with a decrease in depression scores.Conversely,substituting SLP with either LPA or SB resulted in an increase in depression scores,while substituting SLP with MVPA led to a decrease in depression scores.The dose-response analysis revealed that,among the isotemporal substitution effects,replacing SB with SLP and replacing SLP with MVPA were the substitution pathways associated with the most rapid decline in depression scores,representing the greatest beneficial health effects.Conclusion:The prevalence of depression is notably high among older adults with multimorbidity.Reducing daily sedentary behavior(SB),maintaining adequate sleep(SLP),and increasing moderate-to-vigorous physical activity(MVPA)can improve depressive symptoms and enhance overall health in this population.展开更多
基金supported by two research grants of Associate Professor Dr.W.Attatippaholkun:Grant No.493-5600-G-00-3461,Program in Science and Technology Cooperation,Human Capacity Development,Bureau for Global Programs,Field Support and Research,US Agency for International Development,Washington,DCThe Royal Golden Jubilee-Ph.D Program,Thailand Research Fund,Thailand
文摘Objective:To study evolutionary relationship of the 5'untranslated regions(5'UTRs) in low passage dengue3 viruses(DEN3) isolated from hospitalized children with different clinical manifestations in Bangkok during 24 year-evolution(1977-2000) comparing to the DEN3prototype(H87).Methods:The 5'UTRs of these Thai DEN3 and the H87 prototype were amplified by RT-PCR and sequenced.Their multiple sequence alignments were done by Codon Code Aligner v 4.0.4 software and their RNA secondary structures were predicted by MFOLD software.Replication of five Thai DEN3 candidates comparing to the 1187 prototype were done in human(HepG2) and the mosquito(C6/36) cell lines.Results:Among these Thai DEN3,the completely identical sequences of their first 89 nucleotides,their high-order secondary structure of 5'UTRs and three SNPs including the predominant C90 T,and two minor SNPs including A109 G and A112 G were found.The C90 T of Thai DEN3.Bangkok isolates was shown predominantly before 1977.Five Thai DEN3 candidates with the predominant C90 T were shown to replicate in human(HepG2) and the mosquito(C6/36) cell lines better than the H87 prototype.However,their highly conserved sequences as well as SNPs of the 5'UTR did not appear to correlate with their disease severity in human.Conclusions:Our findings highlighted evolutionary relationship of the completely identical 89 nucleotide sequence,the high-order secondary structure and the predominant C90 T of the 5'UTR of these Thai DEN3 during 24 year-evolution further suggesting to be their genetic markers and magic targets for future research on antiviral therapy as well as vaccine approaches of Thai DEN3.
文摘目的 探讨芪蛭益肾胶囊联合八段锦治疗早期糖尿病肾病患者的临床疗效及对其24 h尿白蛋白排泄率的影响。方法 选取2023年1月—2023年12月在南京医科大学附属苏州医院就诊的260例早期糖尿病肾病患者作为研究对象,采用随机数字表法分为对照组和观察组,每组130例。对照组在常规用药基础上进行八段锦锻炼,观察组在对照组治疗的基础上服用芪蛭益肾胶囊治疗。治疗6个月后,观察比较两组患者中医证候积分、临床疗效、不良反应情况,治疗前后血糖指标[空腹血糖(Fasting blood glucose,FBG)、餐后2 h血糖(2-hour postprandial blood glucose,2 h PBG)、糖化血红蛋白(Glycosylated hemoglobin,HbA1c)]、肾功能指标[24 h尿液总蛋白定量(24-hour urine total protein,24 h UTP)、血尿素氮(Blood urea nitrogen,BUN)浓度、24 h尿液蛋白排泄速率(24-hour urinary protein excretion rate,24 h UPER)]、血清炎症因子[C反应蛋白(C-reactive protein,CRP)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)]水平。结果 治疗后两组患者中医证候积分均较治疗前降低,差异有统计学意义(P<0.05);且观察组中医证候积分较对照组明显降低,差异有统计学意义(P<0.05)。两组患者治疗前后FBG、2 h PBG、HbA1c水平比较,差异无统计学意义(P>0.05)。治疗后两组患者24 h UTP、BUN、24 h UPER水平较治疗前降低,差异有统计学意义(P<0.05);且观察组24 h UTP、BUN、24 h UPER水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者CRP、TNF-α、IL-6水平均较治疗前降低,差异有统计学意义(P<0.05);且观察组CRP、TNF-α、IL-6水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后观察组治疗总有效率74.62%(97/130)明显高于对照组60.77%(79/130),差异有统计学意义(P<0.05)。治疗期间,两组患者不良反应总发生率比较,差异无统计学意义(P>0.05)。结论 芪蛭益肾胶囊联合八段锦治疗早期糖尿病肾病,能有效控制血糖水平,改善肾功能和血清炎症指标,提高治疗效果,且安全性良好。
基金National Natural Science Foundation of China,No.82003223and China Postdoctoral Science Foundation,No.2020M671398.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.
基金supported by the 2025 Jiangsu Province Graduate Student Practice Innovation Program(No.SJCX25_1696)the 2024 Changzhou University Educational Research Project(No.GJY2024009).
文摘Background:The phenomenon of multimorbidity in chronic diseases among the elderly is prevalent,and its significant association with depression poses a serious threat to the physical and mental health of older adults.Current research on the associations between 24-hour movement behaviors(including physical activity,sedentary behavior,and sleep)and depression has largely been confined to examining the effects of single behaviors,overlooking the intrinsic compositional nature and interrelationships among these behaviors.Therefore,it is necessary to investigate the integrated effects of 24-hour movement behaviors on depression in older adults with multimorbidity from a holistic,compositional perspective.Methods:From November 2024 to April 2025,a total of 226 older adult patients with multimorbidity were recruited from a tertiary hospital in Changzhou City.Data were collected using a general information questionnaire,the International Physical Activity Questionnaire–Short Form(IPAQ-SF),the Pittsburgh Sleep Quality Index(PSQI),and the Patient Health Questionnaire-9(PHQ-9).Compositional data analysis and isotemporal substitution models were employed for statistical analysis.Results:The mean daily durations of Light-Intensity Physical Activity(LPA),Moderate-to-Vigorous Physical Activity(MVPA),Sedentary Behavior(SB),and Sleep(SLP)in older adults with multimorbidity were 402.48 min,12.04 min,511.52 min,and 458.68 min,respectively.The prevalence of depressive symptoms was 37.6%.Compositional data analysis revealed that SB was positively associated with depression(βSB=1.005,P=0.006),while SLP was negatively associated with depression(βSLP=−1.736,P<0.001).No statistically significant associations were found between MVPA or LPA and depression(P>0.05).In the 10-minute isotemporal substitution model,replacing SB with any other behavioral component was associated with a decrease in depression scores.Conversely,substituting SLP with either LPA or SB resulted in an increase in depression scores,while substituting SLP with MVPA led to a decrease in depression scores.The dose-response analysis revealed that,among the isotemporal substitution effects,replacing SB with SLP and replacing SLP with MVPA were the substitution pathways associated with the most rapid decline in depression scores,representing the greatest beneficial health effects.Conclusion:The prevalence of depression is notably high among older adults with multimorbidity.Reducing daily sedentary behavior(SB),maintaining adequate sleep(SLP),and increasing moderate-to-vigorous physical activity(MVPA)can improve depressive symptoms and enhance overall health in this population.