Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives ...Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.展开更多
Microcystin-LR(MC-LR),the most prevalent and diverse cyanotoxin produced by harmful cyanobacterial blooms,has been linked to gastrointestinal toxicity.Therefore,we conducted a case-control study across four regions in...Microcystin-LR(MC-LR),the most prevalent and diverse cyanotoxin produced by harmful cyanobacterial blooms,has been linked to gastrointestinal toxicity.Therefore,we conducted a case-control study across four regions in China to investigate this relationship.Inflammatory bowel disease(IBD)cases(219)were matched with healthy controls(438)based on age and gender and conditional logistic regression models and Restricted cubic splines were used to evaluate the association between MC-LR exposure and IBD risk.We used quantitative real-time polymerase chain reaction to measure the expression levels of inflammatory factors.The levels of protein expression in the colorectum were determined using Western blotting(WB).Compared to the lowest quartile of serum MC-LR levels,the adjusted odds ratios and 95%confidence intervals(CI)for the highest quartiles of serum MC-LR levels were 5.51(2.70,11.21).The RCS was shown the association between serum MC-LR levels and IBD risk was nonlinear(Pnonlinear<0.001).In the animal experiments,MC-LR resulted in colorectal injury via the PI3K/AKT signaling pathway.Our study provides the evidence that serum MC-LR exposure is significantly associated with the risk of IBD in China.Animal study results indicate that MC-LR probably causes IBD via the PI3K/AKT signaling pathway.展开更多
Background Blastocystis hominis(Bh)is zoonotic parasitic pathogen with a high prevalent globally,causing opportunistic infections and diarrhea disease.Human immunodeficiency virus(HIV)infection disrupts the immune sys...Background Blastocystis hominis(Bh)is zoonotic parasitic pathogen with a high prevalent globally,causing opportunistic infections and diarrhea disease.Human immunodeficiency virus(HIV)infection disrupts the immune system by depleting CD4^(+)T lymphocyte(CD4^(+)T)cell counts,thereby increasing Bh infection risk among persons living with HIV(PLWH).However,the precise association between Bh infection risk and HIV-related biological markers and treatment processes remains poorly understood.Hence,the purpose of the study was to explore the association between Bh infection risk and CD4^(+)T cell counts,HIV viral load(VL),and duration of interruption in antiviral therapy among PLWH.Methods A large-scale multi-center cross-sectional study was conducted in China from June 2020 to December 2022.The genetic presence of Bh in fecal samples was detected by real-time fluorescence quantitative polymerase chain reaction,the CD4^(+)T cell counts in venous blood was measured using flowcytometry,and the HIV VL in serum was quantified using fluorescence-based instruments.Restricted cubic spline(RCS)was applied to assess the non-linear association between Bh infection risk and CD4^(+)T cell counts,HIV VL,and duration of interruption in highly active antiretroviral therapy(HARRT).Results A total of 1245 PLWH were enrolled in the study,the average age of PLWH was 43 years[interquartile range(IQR):33,52],with 452(36.3%)being female,50.4%(n=628)had no immunosuppression(CD4^(+)T cell counts>500 cells/μl),and 78.1%(n=972)achieved full virological suppression(HIV VL<50 copies/ml).Approximately 10.5%(n=131)of PLWH had interruption.The prevalence of Bh was found to be 4.9%[95%confidence interval(CI):3.8-6.4%]among PLWH.Significant nonlinear associations were observed between the Bh infection risk and CD4^(+)T cell counts(Pfor nonlinearity<0.001,L-shaped),HIV VL(Pfor nonlinearity<0.001,inverted U-shaped),and duration of interruption in HARRT(Pfor nonlinearity<0.001,inverted U-shaped).Conclusions The study revealed that VL was a better predictor of Bh infection than CD4^(+)T cell counts.It is crucial to consider the simultaneous surveillance of HIV VL and CD4^(+)T cell counts in PLWH in the regions with high level of socioeconomic development.The integrated approach can offer more comprehensive and accurate understanding in the aspects of Bh infection and other opportunistic infections,the efficacy of therapeutic drugs,and the assessment of preventive and control strategies.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071426,81873784Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(all to DF)。
文摘Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.
基金National Natural Science Foundation of China(U23A20492)Hunan Province Key Research and Development Projects(2022SK2089)Huxiang Youth Talent Program(2021RC3107).
文摘Microcystin-LR(MC-LR),the most prevalent and diverse cyanotoxin produced by harmful cyanobacterial blooms,has been linked to gastrointestinal toxicity.Therefore,we conducted a case-control study across four regions in China to investigate this relationship.Inflammatory bowel disease(IBD)cases(219)were matched with healthy controls(438)based on age and gender and conditional logistic regression models and Restricted cubic splines were used to evaluate the association between MC-LR exposure and IBD risk.We used quantitative real-time polymerase chain reaction to measure the expression levels of inflammatory factors.The levels of protein expression in the colorectum were determined using Western blotting(WB).Compared to the lowest quartile of serum MC-LR levels,the adjusted odds ratios and 95%confidence intervals(CI)for the highest quartiles of serum MC-LR levels were 5.51(2.70,11.21).The RCS was shown the association between serum MC-LR levels and IBD risk was nonlinear(Pnonlinear<0.001).In the animal experiments,MC-LR resulted in colorectal injury via the PI3K/AKT signaling pathway.Our study provides the evidence that serum MC-LR exposure is significantly associated with the risk of IBD in China.Animal study results indicate that MC-LR probably causes IBD via the PI3K/AKT signaling pathway.
文摘Background Blastocystis hominis(Bh)is zoonotic parasitic pathogen with a high prevalent globally,causing opportunistic infections and diarrhea disease.Human immunodeficiency virus(HIV)infection disrupts the immune system by depleting CD4^(+)T lymphocyte(CD4^(+)T)cell counts,thereby increasing Bh infection risk among persons living with HIV(PLWH).However,the precise association between Bh infection risk and HIV-related biological markers and treatment processes remains poorly understood.Hence,the purpose of the study was to explore the association between Bh infection risk and CD4^(+)T cell counts,HIV viral load(VL),and duration of interruption in antiviral therapy among PLWH.Methods A large-scale multi-center cross-sectional study was conducted in China from June 2020 to December 2022.The genetic presence of Bh in fecal samples was detected by real-time fluorescence quantitative polymerase chain reaction,the CD4^(+)T cell counts in venous blood was measured using flowcytometry,and the HIV VL in serum was quantified using fluorescence-based instruments.Restricted cubic spline(RCS)was applied to assess the non-linear association between Bh infection risk and CD4^(+)T cell counts,HIV VL,and duration of interruption in highly active antiretroviral therapy(HARRT).Results A total of 1245 PLWH were enrolled in the study,the average age of PLWH was 43 years[interquartile range(IQR):33,52],with 452(36.3%)being female,50.4%(n=628)had no immunosuppression(CD4^(+)T cell counts>500 cells/μl),and 78.1%(n=972)achieved full virological suppression(HIV VL<50 copies/ml).Approximately 10.5%(n=131)of PLWH had interruption.The prevalence of Bh was found to be 4.9%[95%confidence interval(CI):3.8-6.4%]among PLWH.Significant nonlinear associations were observed between the Bh infection risk and CD4^(+)T cell counts(Pfor nonlinearity<0.001,L-shaped),HIV VL(Pfor nonlinearity<0.001,inverted U-shaped),and duration of interruption in HARRT(Pfor nonlinearity<0.001,inverted U-shaped).Conclusions The study revealed that VL was a better predictor of Bh infection than CD4^(+)T cell counts.It is crucial to consider the simultaneous surveillance of HIV VL and CD4^(+)T cell counts in PLWH in the regions with high level of socioeconomic development.The integrated approach can offer more comprehensive and accurate understanding in the aspects of Bh infection and other opportunistic infections,the efficacy of therapeutic drugs,and the assessment of preventive and control strategies.
