Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

OBJECTIVES: To construct vocal recognition classification models using 6 machine learning algorithms and vocal emotional characteristics of individuals with subthreshold depression to facilitate early identification of subthreshold depression. METHODS: We collected voice data from both normal individuals and participants with subthreshold depression by asking them to read specifically chosen words and texts. From each voice sample, 384-dimensional vocal emotional feature variables were extracted, including energy feature, Meir frequency cepstrum coefficient, zero cross rate feature, sound probability feature, fundamental frequency feature, difference feature. The Recursive Feature Elimination (RFE) method was employed to select voice feature variables. Classification models were then built using the machine learning algorithms Adaptive Boosting (AdaBoost), Random Forest (RF), Linear Discriminant Analysis (LDA), Logistic Regression (LR), Lasso Regression (LRLasso), and Support Vector Machine (SVM), and the performance of these models was evaluated. To assess generalization capability of the models, we used real-world speech data to evaluate the best speech recognition classification model. RESULTS: The AdaBoost, RF, and LDA models achieved high prediction accuracies of 100%, 100%, and 93.3% on word-reading speech test set, respectively. In the text-reading speech test set, the accuracies of the AdaBoost, RF, and LDA models were 90%, 80%, and 90%, respectively, while the accuracies of the other 3 models were all below 80%. On real-world word-reading and text-reading speech data, the classification models using AdaBoost and Random Forest still achieved high predictive accuracies (91.7% and 80.6% for AdaBoost and 86.1% and 77.8% for Random, respectively). CONCLUSIONS Analyzing vocal emotional characteristics allows effective identification of individuals with subthreshold depression. The AdaBoost and RF models show excellent performance for classifying subthreshold depression individuals, and may thus potentially offer valuable assistance in the clinical and research settings.
Humans ; Machine Learning ; Emotions ; Depression/diagnosis* ; Algorithms ; Voice ; Support Vector Machine ; Male ; Female

OBJECTIVES: To investigate the therapeutic mechanism of Wendan Decoction for phlegm syndrome in rats with metabolic syndrome (MS). METHODS: Forty Wistar rats were randomly divided into normal control group (n=8) and 3 phlegm syndrome model groups (induced by high-fat, high-sugar, and high-salt feeding and a single-dose intraperitoneal STZ injection; n=24) treated with daily gavage of saline, Wendan Decoction (3.6 g/kg), or metformin (0.1 g/kg) for 4 weeks. General conditions and glucose and lipid metabolism parameters of the rats were monitored, and serum LPS, liver histopathology, hepatic expressions of FXR, CYP7A1 and FGFR4 and ileal expressions of FXR and FGF15 were examined. Gut microbiota structure was analyzed using 16S rDNA sequencing, and serum bile acids were quantified with UHPLC-MS/MS. RESULTS: The rat models of phlegm syndrome exhibited severe hepatic steatosis and necrosis, increased body weight, abdominal circumference, Lee's index, FBG, FINS, HOMA-IR, TG, TC, LDL and LPS, and decreased HDL level. The abundance of Bacteroidetes, Megamonas, and Bacteroides in gut microbiota increased while Firmicutes, Lachnospiraceae_NK4A136_group, isohyodeoxycholic acid, and glycohyodeoxycholic acid decreased significantly; hepatic FXR and FGFR4 expressions and ileal FXR and FGF15 expressions decreased while hepatic CYP7A1 expression increased significantly in the rat models. Treatment with Wendan Decoction effectively alleviated hepatic pathology, reduced body weight and abdominal circumference, improved glucose and lipid metabolic profiles and gut microbiota structure, and reversed the changes in hepatic and ileal protein expressions. Correlation analysis revealed that Firmicutes and Lachnospiraceae_NK4A136_group were positively correlated while Bacteroidetes, Megamonas and Bacteroides were negative correlated with the levels of isohyodeoxycholic acid and hyodeoxycholic acid. CONCLUSIONS Wendan Decoction can significantly improve metabolic profiles in rats with phlegm syndrome of MS possibly by regulating the intestinal flora-bile acid axis to modulate the intestinal flora structure and maintain bile acid homeostasis via the FXR signaling pathway.
Animals ; Gastrointestinal Microbiome/drug effects* ; Metabolic Syndrome/microbiology* ; Bile Acids and Salts/metabolism* ; Rats, Wistar ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Male ; Fibroblast Growth Factors/metabolism* ; Liver/metabolism* ; Cholesterol 7-alpha-Hydroxylase/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism*

Objective:To establish an environmental management strategy for the prevention of ventilator-associated pneumonia from the perspective of etiological characteristics and to verify its application effect.Methods:Based on a sampling survey, this study constructed preventive management strategies for ventilator-associated pneumonia by blocking pathogen characteristics from the perspective of both colonization and infection management in patients. From July 2021 to June 2023, a non-synchronous randomized controlled study was conducted, including a control group of 59 cases and an experimental group of 57 cases from ICU of Tianjin Teda Hospital, all of them were mechanically ventilated patients. The effectiveness of the strategy was confirmed.Results:In the control group, there were 35 males and 24 females, with an average age of (46.97 ± 18.84) years. In the experimental group, there were 39 males and 18 females, with an average age of (47.49 ± 13.85) years. During the study period, there were 9 cases of ventilator-associated pneumonia (VAP) in the control group and 2 cases in the experimental group, the difference between the two groups was statistically significant (exact odds ratio=0.031). The duration of mechanical ventilation in the experimental group (122.41 ± 18.36) h, which was shorter than that in the control group (187.62 ± 18.05) h, and the difference was statistically significant ( t=19.28, P<0.05). The length of ICU stay in the experimental group was (8.38 ± 0.79) d, in the control group was (10.99 ± 1.10) d, the difference between them was statistically significant ( t=14.66, P<0.05). On the 7th day, there were 7 cases of positive pathogenic bacteria in sputum culture in the experimental group, which was significantly different from the 29 cases in the control group ( χ2=16.73, P<0.05). Conclusions:The vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics can reduce the incidence of VAP, shorten the duration of mechanical ventilation and ICU stay, and reduce the pathogen load in the sputum of mechanically ventilated patients on the 7th day.

Objective:To investigate the association and predictive value of serum biomarkers with carotid atherosclerosis(CAS)in the elderly population.Methods:The data used in this study were obtained from the China Hainan Centenarian Cohort Study(CHCCS), a prospective cohort that includes elderly individuals from community populations in Hainan Province.The baseline survey was conducted between 2014 and 2019.A total of 737 elderly individuals aged 80 to 100 were included in the analysis.The study examined various factors including questionnaires, physical examination data, liver and kidney function indicators(albumin, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and glomerular filtration rate), blood cell counts(red blood cells, white blood cells, platelets, neutrophil count, lymphocyte count, and monocyte count), inflammatory markers(high-sensitivity C-reactive protein), and lipid metabolism markers(total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein AI, and apolipoprotein B).The objective was to explore the lipids of serum biomarkers and diagnostic performance of carotid atherosclerosis.Results:The prevalence of CAS in the elderly population was found to be 80.7%.Spearman's correlation analysis and a fully adjusted multivariate logistic regression model were used to examine the relationship between CAS and various factors in elderly patients.Result showed that systolic blood pressure, heart rate, and serum apolipoprotein B levels were significantly correlated with CAS[ OR(95% CI): 1.012(1.004-1.021), 0.998(1.011-1.024); 15.796(4.914-50.772), respectively; all P<0.001].Additionally, ROC curve analysis demonstrated that the combined application of serum apolipoprotein B, systolic blood pressure, and heart rate improved the predictive value of CAS in the elderly(Area under the curve: 0.820, 95% CI: 0.782-0.858; Sensitivity: 78.8%; Specificity: 86.8%; Positive likelihood ratio: 5.97; Negative likelihood ratio: 0.24). Conclusions:Our study discovered that serum apolipoprotein B is an autonomous risk factor for CAS among the elderly.The utilization of a specific set of biomarkers, in conjunction with other risk markers, holds potential as a promising strategy for evaluating CAS in the elderly population.

Objective To establish the drug use evaluation(DUE)criteria for aspirin enteric-coated tablets and provide a reference for the rationally clinical application of aspirin enteric-coated tablets.Methods DUE criteria for aspirin enteric-coated tablets were established from three aspects of indications,medications and medication results with reference to drug instructions of aspirin enteric-coated tablets,related guidelines,expert consensus and literature,and through Delphi method.A retrospective analysis was conducted to evaluate the medical records of patients who took aspirin enteric-coated tablets from January 2021 to June 2022 in Fuqing Hospital affiliated to Fujian Medical University.Results A total of 1 071 medical records were included.683 cases fully met the DUE criteria,with a rational rate of 63.77％.Irrational drug use mainly included inappropriate indications(6.26％),off-label drug use without approval(28.48％),contraindications(1.03％),inappropriate usage and dosage(1.68％),drug interactions with potential clinical significance(0.65％)and other inappropriate drug use(2.71％).Conclusion The established DUE standard for aspirin enteric-coated tablets has strong scientific practicability and feasibility.The irrational rate of aspirin enteric-coated tablets in this hospital is high.Corresponding intervention measures should be formulated to ensure the safety of clinical medication.

Objective:To investigate the association between regional white matter hyperintensity (WMH) volumes and cognitive impairment in Parkinson′s disease (PD) patients.Methods:The consecutive samples of PD cohort between October 2018 and August 2019 from the Department of Movement Disorders, Beijing Tiantan Hospital, Capital Medical University were retrospectively analyzed. Demographic and disease profiles, three-dimensional brain magnetic resonance imaging data were collected. Cognition was evaluated by Mini-Mental State Examination (MMSE), and mood was evaluated by Hamilton Anxiety Scale and Hamilton Depression Scale (HAMD). According to the MMSE score, patients were divided into PD with dementia group and PD without dementia group. WMH volume was automatically calculated using unidentified bright objects detector pipeline based on anatomical autonomic labeling atlas. Firstly, demographic and disease profiles, and WMH total volume were compared between groups with and without dementia. Then, partial correlation analysis [false discovery rate (FDR) corrected] and principal component (PC) regression analysis were used to assess the association between regional WMH volumes and the MMSE score.Results:Compared with PD without dementia group, PD with dementia group showed significantly higher WMH volume [5 125 (2 727, 13 718) mm 3vs 3 214 (1 959, 7 205) mm 3, Z=-2.256, P=0.024]. After adjusting for age, low density lipoprotein, cholesterol, and HAMD score, partial correlation analysis (FDR corrected) showed that WMH volumes in the right calcarine ( r=-0.204, PFDR-corrected=0.034), the right fusiform ( r=-0.180, PFDR-corrected=0.046), the right lingual ( r=-0.146, PFDR-corrected=0.047), the left middle temporal ( r=-0.168, PFDR-corrected=0.047), the left inferior parietal lobes ( r=-0.145, PFDR-corrected=0.047) and the right inferior parietal lobes ( r=-0.148, PFDR-corrected=0.047) were significantly associated with MMSE score. PC regression analysis demonstrated that MMSE score was significantly associated with PC2 ( B=-0.632, 95% CI -1.222--0.041, P=0.036), PC13 ( B=-1.384, 95% CI -2.155--0.613, P=0.001), and PC14 ( B=-0.913, 95% CI -1.599--0.227, P=0.009); PC2, PC13 and PC14 were mainly composed of temporo-parieto-occipital WMHs in the posterior brain, and the related WMH components accounted for 9.668% of WMH variance. Conclusions:The posterior WMH burden may be associated with cognitive impairment in PD patients. However, WMH burden may not be the main contributor to cognitive impairment in PD patients.

Objective To investigate the interventional effect and mechanism of a novel ampelopsis hydrogel on dampness-heat accumulation syndrome of gouty arthritis. Methods A total of 90 patients with gouty arthritis who met the diagnostic criteria of western medicine and were differentiated as damp-heat accumulation syndrome of traditional Chinese medicine(TCM) were randomly divided into treatment group, control group and blank group, with 30 patients in each group. The blank group was treated with etoricoxib only, the control group was treated with etoricoxib combined with ampelopsis hydrogel, and the treatment group was treated with etoricoxib combined with external application of ampelopsis hydrogel. The clinical efficacy, time to symptom improvement, safety, comfort, changes in syndrome scores of TCM, serum inflammatory factors[C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), erythrocyte sedimentation rate (ESR)], NF-κB signaling pathway-related proteins, Visual Analogue Scale (VAS) scores for pain, and joint mobility were compared among the three groups before and after treatment. Results The total effective rates in the treatment group and control group were 93.33% and 90.00%, respectively, which were higher than 70.00% in the blank group (P < 0.05). The time for improvement of pain, redness, tenderness, and limited joint mobility in the treatment group was shorter than that in the control group and blank group (P < 0.05). After 7 days of treatment, the TCM syndrome score in the treatment group was lower than that in the control group and blank group, and the levels of serum CRP, TNF-α, and ESR and the expressions of NF-κB signalingpathway-related proteins P50 and P65 in the treatment group and control group were lower than those in the blank group (P < 0.05). After 7 days of treatment, the VAS score in the treatment group was lower than that in the control group and blank group, and the comfort score in the treatment group was higher than that in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions among the three groups (P>0.05). Conclusion The effect of ampelopsis hydrogel in treating gouty arthritis is better than that of ampelopsis paste, and its mechanism may be related to the regulation of the NF-κB pathway and inhibition of inflammatory factor expression. The hydrogel is easy to use, hygienic, and comfortable, and is expected to become a safe, effective, and convenient external medicine for gouty arthritis.

A patient with SARS-CoV-2 infection was adimitted to Shanghai Shibei hospital of Jing'an District in early 2023. According to the patient's complaits， clinical manifestations， physical symptoms， laboratory examination， radiological image results， plus lumbar puncture， the patient was diagnosed with novel coronavirus encephalitis. The patient was discharged from the hospital after a combined treatment of Chinese and western medicine.

Objective:To investigate and analyze on the basic skills level of health literacy and its influencing factors in permanent residents in Fujian province in 2020.Methods:In this cross-sectional study, from April to November in 2020, 3 304 urban and rural permanent residents aged 15-69 years in 13 counties (cities or districts) in Fujian province were selected by stratified multistage cluster sampling and random sampling for household questionnaire survey. Based on “Health literacy of Chinese citizens—basic knowledge and skills”, the questionnaire included three aspects: basic knowledge and concept, healthy lifestyle and behavior and basic skills. There were 50 questions in total, including 12 questions about basic skills with a total score of 16 points. A score of 13 points and above was considered as having basic skills. A total of 3 304 questionnaires were issued and reclaimed, and among which 3 250 questionnaires were valid. According to the data of the Sixth National Census in 2010 in Fujian province and the basic data collected in the monitoring process, the basic weight, no response and post-stratification adjustment of the samples were made to obtain the representative data of the province. The χ2 test and multivariate logistic regression were applied to analyze the influencing factors of basic skill level of health literacy in permanent residents in Fujian province in 2020. Results:According to the weighted data, the basic skill level of health literacy in permanent residents in Fujian province in 2020 was 26.02%, and it was higher in urban area than that in rural area (35.00% vs 20.15%). It was higher in people aged 25-34 years (35.36%), people with high education level (college/undergraduate and above 47.20%), civil servants (47.49%), medical personnel (44.00%), people with chronic diseases (27.04%) and people with good health condition (31.31%), respectively (all P<0.05). Among the 12 questions on basic skills, the correct rate in 6 questions was ≥50%. The question with the highest correct rate was “The correct practices after the occurrence of severe infectious diseases in the local area” (88.2%), and the question with the lowest correct rate was “Correctly identify drugs with‘OTC’ printed on the label”(28.7%). Education level (illiterate/less literate, OR=0.036, 95% CI: 0.018-0.073; primary school, OR=0.091, 95% CI: 0.053-0.155; junior high school, OR=0.230, 95% CI: 0.148-0.357; senior high school/vocational high school/technical secondary school, OR=0.351, 95% CI: 0.232-0.532; college/undergraduate and above, OR=1.000) was positively correlated with the basic skill level of residents′ health literacy ( P<0.001). Conclusions:The overall level of basic health skills in permanent residents in Fujian province in 2020 is relatively high, educational level is a positive correlation factor.