Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Objective To develop and validate a prediction model to identify high-risk individuals who are at-risk to develop acute liver injury(ALI)within 180 days in new statin users,and to support early clinical intervention.Methods Data were sourced from the Yinzhou Regional Health Information Platform,covering statin initiators aged 18 years and older from January 1,2010,to October 31,2021.The dataset was divided into a derivation cohort and a temporal validation cohort based on the time of statin initiation.Predictors were selected using LASSO regression,and the model was constructed using the extreme gradient boosting(XGBoost)algorithm combined with cost-sensitive learning.Model performance was evaluated using Brier scores,Harrell's C-index,and calibration curves.Results A total of 126,440 statin initiators were included,with 90,542 in the derivation cohort and 35,898 in the validation cohort.Within 180 days of initial statin use,412(0.33％)patients developed ALI,including 305(0.34％)in the derivation cohort and 107(0.30％)in the validation cohort.The final model incorporated 16 predictors,which included demographic characteristics,lifestyle factors,family history,medical history,statin use,and concomitant medication use.The model demonstrated excellent overall performance[Brier score=0.0043,95％CI(0.0038,0.0049)],discrimination[Harrell's C-index=0.761,95％CI(0.725,0.794)],and calibration in internal validation.In temporal validation,the model also performed well[Brier score=0.0044,95％CI(0.0036,0.0052),Harrell's C-index=0.703,95％CI(0.614,0.781)].Conclusion This study develope and validate a prediction model for ALI in statin users,providing clinicians with a reliable tool for individualized risk assessment.This model can help achieve risk stratification and reduce the occurrence of ALI.

Objective:To survey the relationship among parents'rearing style,family conformity and obsess-ive-compulsive symptoms in patients with obsessive-compulsive disorder(OCD).Methods:Totally 216 patients di-agnosed with OCD were recruited(59 cases of mild obsessive-compulsive symptoms,121 cases of moderate obsess-ive-compulsive symptoms,36 cases of severe obsessive-compulsive symptoms).They were assessed with the Yale-Brown Obsessive-Compulsive Disorder Scale(Y-BOCS),Egma Minnen av Bardndosna Uppforstran(EMBU),and Family Accommodation Scale for Obsessive-Compulsive Disorder-Patient Version(FAS-PV).Results:The severe obsessive-compulsive symptom group had the lowest positive parenting style scores.Conversely,they had the high-est negative parental rearing scores and total FAS-PV scores(Ps＜0.01).The ordered logistic regression results showed that male patients had less severe obsessive-compulsive symptoms(OR=0.22).Patients with lower years of education(OR=0.87)and positive parental rearing scores(OR=0.98,0.97)had more severe obsessive-com-pulsive symptoms.Conversely,higher negative paternal rearing scores(OR=1.02)and total FAS-PV scores(OR=1.04)were associated with more severe obsessive-compulsive symptoms.Conclusion:This study suggests that the severity of obsessive-compulsive symptoms is related to parental rearing style and family accommodation.Patients with severe obsessive-compulsive symptoms are more likely to feel negative paternal rearing style and higher level of family compliance,and less likely to feel positive parental rearing style.

Objective:To survey the relationship among parents'rearing style,family conformity and obsess-ive-compulsive symptoms in patients with obsessive-compulsive disorder(OCD).Methods:Totally 216 patients di-agnosed with OCD were recruited(59 cases of mild obsessive-compulsive symptoms,121 cases of moderate obsess-ive-compulsive symptoms,36 cases of severe obsessive-compulsive symptoms).They were assessed with the Yale-Brown Obsessive-Compulsive Disorder Scale(Y-BOCS),Egma Minnen av Bardndosna Uppforstran(EMBU),and Family Accommodation Scale for Obsessive-Compulsive Disorder-Patient Version(FAS-PV).Results:The severe obsessive-compulsive symptom group had the lowest positive parenting style scores.Conversely,they had the high-est negative parental rearing scores and total FAS-PV scores(Ps＜0.01).The ordered logistic regression results showed that male patients had less severe obsessive-compulsive symptoms(OR=0.22).Patients with lower years of education(OR=0.87)and positive parental rearing scores(OR=0.98,0.97)had more severe obsessive-com-pulsive symptoms.Conversely,higher negative paternal rearing scores(OR=1.02)and total FAS-PV scores(OR=1.04)were associated with more severe obsessive-compulsive symptoms.Conclusion:This study suggests that the severity of obsessive-compulsive symptoms is related to parental rearing style and family accommodation.Patients with severe obsessive-compulsive symptoms are more likely to feel negative paternal rearing style and higher level of family compliance,and less likely to feel positive parental rearing style.

Objective To develop and validate a prediction model to identify high-risk individuals who are at-risk to develop acute liver injury(ALI)within 180 days in new statin users,and to support early clinical intervention.Methods Data were sourced from the Yinzhou Regional Health Information Platform,covering statin initiators aged 18 years and older from January 1,2010,to October 31,2021.The dataset was divided into a derivation cohort and a temporal validation cohort based on the time of statin initiation.Predictors were selected using LASSO regression,and the model was constructed using the extreme gradient boosting(XGBoost)algorithm combined with cost-sensitive learning.Model performance was evaluated using Brier scores,Harrell's C-index,and calibration curves.Results A total of 126,440 statin initiators were included,with 90,542 in the derivation cohort and 35,898 in the validation cohort.Within 180 days of initial statin use,412(0.33％)patients developed ALI,including 305(0.34％)in the derivation cohort and 107(0.30％)in the validation cohort.The final model incorporated 16 predictors,which included demographic characteristics,lifestyle factors,family history,medical history,statin use,and concomitant medication use.The model demonstrated excellent overall performance[Brier score=0.0043,95％CI(0.0038,0.0049)],discrimination[Harrell's C-index=0.761,95％CI(0.725,0.794)],and calibration in internal validation.In temporal validation,the model also performed well[Brier score=0.0044,95％CI(0.0036,0.0052),Harrell's C-index=0.703,95％CI(0.614,0.781)].Conclusion This study develope and validate a prediction model for ALI in statin users,providing clinicians with a reliable tool for individualized risk assessment.This model can help achieve risk stratification and reduce the occurrence of ALI.

Objective: To investigate the incidence density of adult sleep disorders (SD) in Yinzhou District, Ningbo City, Zhejiang Province from 2017 to 2023, so as to provide insights into formulating the control measures of SD. Methods: The electronic health records of permanent residents aged 18 years and over in Yinzhou District from 2017 to 2023 were collected through the Yinzhou Regional Health Information Platform. New cases of SD were diagnosed for the first time a year after establishing health records. The incidence density was estimated using Poisson distribution. The temporal, population and regional distribution characteristics of new cases of SD were analyzed using a descriptively epidemiological method. Results: From 2017 to 2023, there were 1 255 129 permanent residents aged 18 years and over in Yinzhou District, with a total observed person-time of 6 292 884 person-years and a median of 5.67 (interquartile range, 3.74) person-years. There were 165 490 new cases of SD, including 67 095 males (40.54%) and 98 385 females (59.46%). The incidence density of SD in Yinzhou District from 2017 to 2023 was 26.30/1 000 person-years, with no significant trend observed (P>0.05). The incidence density of SD was higher in females than in males (29.63/1 000 person-years vs. 22.57/1 000 person-years, P<0.05). The highest incidence density of SD was observed in individuals aged 70 to <80 years (63.30/1 000 person-years), and the lowest was in individuals aged 18 to <30 years (7.24/1 000 person-years). The incidence density of SD in individuals aged 30 years and over was higher than that in individuals aged 18 to <30 years (all P<0.05). The incidence density of SD was 32.03/1 000 person-years in individuals with junior high school education or below, which was higher than individuals with senior high school/technical secondary school education (25.93/1 000 person-years) and college degree and above (18.87/1 000 person-years, all P<0.05). Dongliu Street, Dongjiao Street, and Baihe Street had relatively higher incidence densities of SD, at 45.11/1 000 person-years, 42.87/1 000 person-years and 40.16/1 000 person-years, respectively. Conclusions From 2017 to 2023, there was no significant trend in the incidence density of SD in Yinzhou District. Higher incidence density were observed in females, the elderly, and individuals living in central urban areas.

Objective:To investigate whether hepatitis B virus X protein (HBx) mediates the podocyte injury through reactive oxygen species (ROS) /nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathway.Methods:HBx-overexpressing lentivirus was transfected into renal podocytes of mouse to mimic the pathogenesis of hepatitis B virus-associated glomerulonephritis. Podocytes were divided into the following five groups: blank control group (no special treatment), negative control group (transfected with control lentivirus), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+NLRP3 siRNA group (transfected with HBx overexpression lentivirus and NLRP3 siRNA), and HBx overexpression+ROS inhibitor group (transfected with HBx overexpression lentivirus and adding ROS inhibitor). The morphological changes of podocytes were observed with electron microscope. The generation of ROS was detected by dichlorodihydrofluorescein diacetate assay (DCFH-DA). Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to detect caspase-1 activity, and the levels of lactate dehydrogenase, interleukin (IL)-1β and IL-18. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression levels of mRNA and protein of pyroptosis-related protein, such as NLRP3, apoptosis-associated speck-like protein containing card (ASC), caspase-1, IL-1β and IL-18. TUNEL staining and flow cytometer were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression levels of desmin and nephrin.Results:After successful infection of podocytes with HBx-overexpressing lentivirus, pyroptosis-related morphological changes in the cells were observed under electron microscope. The level of ROS in the HBx overexpression group was significantly higher compared to the negative control group ( P<0.05). Hoechst 33342 staining revealed condensed nuclei in the HBx overexpression group. TUNEL staining and flow cytometer demonstrated that podocytes underwent increased pyroptosis in the HBx overexpression group. The mRNA and protein expression levels of pyroptosis-related proteins such as NLRP3, ASC, caspase-1, IL-1β and IL-18 were up-regulated upon HBx overexpression (all P<0.05). Caspase-1 enzyme activity, lactate dehydrogenase and desmin expression levels were enhanced after HBx overexpression (all P<0.05). However, NLRP3 knockdown or addition of ROS inhibitors attenuated the pyroptosis and increased expression levels of pyroptosis-related proteins caused by HBx overexpression (all P<0.05). Conclusion:ROS/NLRP3 pathway plays an important role in HBx-induced podocyte pyroptosis.

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.