Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

This study investigates the material basis and mechanism of Arisaematis Rhizoma Preparatum in the treatment of chronic obstructive pulmonary disease(COPD) using animal experiments, component analysis, network pharmacology, and molecular docking. A mouse model of COPD was constructed by cigarette smoke and lipopolysaccharide(LPS). Blood gas analysis was performed to measure the pH and partial pressure of carbon dioxide(PCO_2) in the blood of the mice. Lung tissue sections were analyzed using HE staining, and the effects of Arisaematis Rhizoma Preparatum water extract on inflammatory factors(TNF-α, IL-6, and IL-1β) and the PI3K/AKT signaling pathway in the lung tissue of COPD model mice were studied by qPCR and Western blot. The composition of the Arisaematis Rhizoma Preparatum water extract was analyzed using UPLC Q-Exactive Orbitrap MS. The SwissTargetPrediction database was used to predict the targets of the chemical components in Arisaematis Rhizoma Preparatum. GeneCards, OMIM, TTD, PharmGKB and DrugBank disease databases were used to screen for COPD targets, and the potential targets of Arisaematis Rhizoma Preparatum in treating COPD were identified. A protein-protein interaction(PPI) network of intersection targets was constructed and analyzed using the STRING database and Cytoscape 3.9.0, and core genes were screened. GO functional analysis and KEGG pathway enrichment analysis were performed using R language, and molecular docking verification was conducted using AutoDock Vina software. The results of the animal experiments showed that Arisaematis Rhizoma Preparatum water extract improved pulmonary ventilation function in COPD model mice, reduced lung inflammatory cells, decreased alveolar cavities, and improved lung tissue condition. The levels of inflammatory factors TNF-α, IL-6 and IL-1β were decreased, and the phosphorylation levels of PI3K and AKT were inhibited. Fifty-two chemical components were identified from Arisaematis Rhizoma Preparatum, and 440 intersection targets related to COPD were found. Nine key components were screened, including hydroxyphenylethylamine, L-tyrosine, L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, methyl azelate, zingerone, 6-gingerol, linoleamide, and linoleoyl ethanolamine. Five core targets were identified, including AKT1, TNF, STAT3, ESR1, and IL1B. The PI3K/AKT pathway was identified as the key pathway for the treatment of COPD with Arisaematis Rhizoma Preparatum. Molecular docking results showed that 75% of the binding energies of key components and core targets were less than-5 kcal·mol~(-1), indicating good binding affinity. In conclusion, Arisaematis Rhizoma Preparatum may improve pulmonary ventilation function, enhance lung pathological morphology, and reduce pulmonary inflammation in COPD model mice by inhibiting the PI3K/AKT signaling pathway and downregulating TNF-α, IL-6, and IL-1β inflammatory factors. The material basis may be associated with L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, zingerone and 6-gingerol, and AKT1 and TNF may be the primary targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rhizome/chemistry* ; Humans ; Molecular Docking Simulation ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Signal Transduction/drug effects* ; Lung/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Interleukin-6/immunology*

Aging is characterized by a gradual deterioration of the physiological integrity of cells,tissues,and or-gans,resulting in a decrease in the body's physiological functions and an acceleration of the onset of age-related diseases,ultimately leading to death.The aging of the liver,which is a critical metabolic organ,is closely linked to various chronic liver diseases,such as hepatitis,liver fibrosis,and cirrhosis,and it ex-acerbates their prognosis and is a primary risk factor for their development at all stages.Therefore,a comprehensive understanding of the causes,mechanisms,and potential therapeutic targets associated with liver aging holds significant clinical importance for delaying or potentially reversing liver aging and for treating chronic liver diseases.Stem cells,which are potential anti-aging agents,present a promising and effective alternative for managing liver aging.In this review,we systematically assess the driving factors,characteristics,and underlying mechanisms of liver aging.We then discuss the current status of the use of stem cells to mitigate liver senescence and address related liver diseases.The review reveals that a stem cell-based approach represents a promising therapeutic strategy for combating liver aging and associated diseases.

OBJECTIVE:External fixators and plate internal fixation are commonly used treatments for comminuted distal radius fractures,each with its own advantages and disadvantages in clinical practice. To systematically evaluate the clinical efficacy and safety of external fixator and plate internal fixation in the treatment of comminuted distal radius fractures,and to provide a basis for the development of guidelines for the diagnosis and treatment of distal radius fractures with integrated traditional Chinese and Western medicine. METHODS:PubMed,Web of Science,Embase,Cochrane Library,China National Knowledge Infrastructure,China Biomedical Literature Database,VIP,andWanFang databases were systematically searched to include randomized controlled trials on external fixators and internal plate fixation for the treatment of comminuted distal radial fractures published from October 2013 to October 2023. The literature was screened according to the inclusion and exclusion criteria. Review Manager was used for literature quality evaluation and meta-analysis.RESULTS:(1) Eight articles were included,including 4 in Chinese and 4 in English,with a total sample size of 648 cases,including 328 cases in the external fixation stent group and 320 cases in the internal fixation plate group. (2) At 3 months after operation,the internal fixation plate group was superior to the external fixation stent group in the range of dorsal extension,palmar flexion and supination. At 12 months after operation,the grip strength,palmar inclination,palmar flexion,pronation and supination in the internal fixation plate group were better than those in the external fixation stent group. The postoperative infection in the internal fixation plate group was better than that in the external fixation stent group,and there was no statistical difference in other outcome indicators.CONCLUSION:Eight evidences showed that in the choice of treatment for comminuted distal radius fracture,both external fixation stent and incision plate internal fixation had good therapeutic effect,and plate internal fixation was better than other factors. However,for some special patients with highly severe comminuted distal radius fractures,poor bone quality,severely contaminated open fractures,and soft tissue swelling that did not allow incision surgery,external fixation was the first choice. The results of this study have limitations,and more high-quality,large-sample,multi-center randomized controlled trials are needed in the future,emphasizing the observation of long-term efficacy and other secondary indicators,and supplementing and optimizing the current research results.

OBJECTIVE:External fixators and plate internal fixation are commonly used treatments for comminuted distal radius fractures,each with its own advantages and disadvantages in clinical practice. To systematically evaluate the clinical efficacy and safety of external fixator and plate internal fixation in the treatment of comminuted distal radius fractures,and to provide a basis for the development of guidelines for the diagnosis and treatment of distal radius fractures with integrated traditional Chinese and Western medicine. METHODS:PubMed,Web of Science,Embase,Cochrane Library,China National Knowledge Infrastructure,China Biomedical Literature Database,VIP,andWanFang databases were systematically searched to include randomized controlled trials on external fixators and internal plate fixation for the treatment of comminuted distal radial fractures published from October 2013 to October 2023. The literature was screened according to the inclusion and exclusion criteria. Review Manager was used for literature quality evaluation and meta-analysis.RESULTS:(1) Eight articles were included,including 4 in Chinese and 4 in English,with a total sample size of 648 cases,including 328 cases in the external fixation stent group and 320 cases in the internal fixation plate group. (2) At 3 months after operation,the internal fixation plate group was superior to the external fixation stent group in the range of dorsal extension,palmar flexion and supination. At 12 months after operation,the grip strength,palmar inclination,palmar flexion,pronation and supination in the internal fixation plate group were better than those in the external fixation stent group. The postoperative infection in the internal fixation plate group was better than that in the external fixation stent group,and there was no statistical difference in other outcome indicators.CONCLUSION:Eight evidences showed that in the choice of treatment for comminuted distal radius fracture,both external fixation stent and incision plate internal fixation had good therapeutic effect,and plate internal fixation was better than other factors. However,for some special patients with highly severe comminuted distal radius fractures,poor bone quality,severely contaminated open fractures,and soft tissue swelling that did not allow incision surgery,external fixation was the first choice. The results of this study have limitations,and more high-quality,large-sample,multi-center randomized controlled trials are needed in the future,emphasizing the observation of long-term efficacy and other secondary indicators,and supplementing and optimizing the current research results.

OBJECTIVE To establish a method for determining the contents of clopidogrel(CLP),clopidogrel carboxylate(CLP-C),clopidogrel acyl-β-D-glucuronide(CLP-G)and contents of clopidogrel active metabolite(CAM)in rat plasma,and to investigate their in vivo pharmacokinetic characteristics.METHODS The Shisedo CAPCELL ADME column was used with a mobile phase consisting of water and acetonitrile(both containing 0.1%formic acid)in a gradient elution.The flow rate was 0.4 mL/min,and the column temperature was maintained at 20℃.The injection volume was 2 μL.The analysis was performed in positive ion mode using electrospray ionization with multiple reaction monitoring.The ion pairs for quantitative analysis were m/z 322.1→211.9(for CLP),m/z 308.1→197.9(for CLP-C),m/z 322.1→154.8(for CLP-G),m/z 504.1→154.9[for racemic CAM derivative(CAMD)].Six rats were administered a single intragastric dose of CLP(10 mg/kg).Blood samples were collected before medication and at 0.08,0.33,0.66,1,2,4,6,10,23 and 35 hours after medication.The established method was used to detect the serum contents of various components in rats.Pharmacokinetic parameters were then calculated using WinNonlin 6.1 software.RESULTS The linear ranges for CLP,CLP-C and CAMD were 0.08-20.00,205.00-8 000.00,and 0.04-25.00 ng/mL,respectively(r≥0.990).The relative standard deviations for both intra-day and inter-day precision tests were all less than 15%,and the relative errors for accuracy ranged from-11.68%to 14.40%.The coefficients of variation for the matrix factors were all less than 15%,meeting the requirements for bioanalytical method validation.The results of the pharmacokinetic study revealed that,following a single intagastric administration of CLP in rats,the exposure to the parent CLP in plasma was extremely low.Both the area under the drug concentration-time curve(AUC0-35 h)and the peak concentration of the parent CLP were lower than those of its metabolites.The AUC0-35 h of the active metabolite CAM was approximately 43 times that of CLP,though it had a shorter half-life(2.53 h).The inactive metabolite CLP-C exhibited the highest exposure level,but it reached its peak concentration the latest and was eliminated slowly.The AUC0-35 h of CLP-G was about four times that of CAM,and its half-life was similar to that of CLP-C.CONCLUSIONS This study successfully established an liquid chromatography-tandem mass spectrometry method for the determination of CLP and its three metabolites,and revealed their pharmacokinetic characteristics in rats.Specifically,the parent drug CLP was rapidly eliminated,while the inactive metabolites CLP-C and CLP-G exhibited long half-lives,and active metabolite CAM displayed a transient exposure pattern.

Objective To investigate the effect of chronic psychological stress on testicular cell senescence in rats and the role of glucocorticoid receptor(GR)in the process.Methods Thirty-two male SD rats(4～6 weeks old,weighing 120～140 g)were randomly assigned into dimethyl sulfoxide(DMSO)group,mifepristone(RU486)group,chronic unpredictable mild stress(CUMS)group,and CUMS+RU486 group.DMSO of 0.5 ml/(kg·d)was injected subcutaneously into the rats of DMSO group.After the rats of the CUMS group were exposed to CUMS,mifepristone of 1 mg/(kg·d)was given to the rats of the RU486 group and CUMS+RU486 group.All the above 4 groups were inflicted for 42 consecutive days.After modeling,the psychological stress status of rats was evaluated with animal behavioral experiments.Computer-aided sperm analysis(CASA)system was used to detect sperm density.ELISA was employed to measure the serum levels of corticosterone(CORT),sex hormones and inflammation factors.The contents of malondialdehyde(MDA),H2O2,NAD+/NADH and ATP in the testicular tissues were tested with corresponding reagent kits.Western blotting was utilized to detect protein levels of[3-gal,p16,and GR in testicular tissue,and transmission electron microscopy was used to observe mitochondrial structure of spermatogenic cells.Results Compared with the DMSO group,the sperm density,serum levels of testosterone(T),luteinizing hormone(LH)and follicle stimulating hormone(FSH)were decreased while those of CORT and estradiol(E2)were increased in the CUMS group(all P＜0.001).Serum pro-inflammatory factors IL-6 and TNF-α concentrations were increased while anti-inflammatory factor IL-10 concentration was decreased in the CUMS group than the DMSO group(all P＜0.05).And,ATP content and NAD+/NADH ratio were decreased while MDA and H2O2 levels were elevated in testicular tissues in the CUMS group(all P＜0.05).Moreover,the protein levels of testicular cell aging markers β-gal,p16 and GR were significantly enhanced in the CUMS group(all P＜0.01),accompanied by swelling and vacuolization of mitochondrial structures in spermatogenic cells.RU486 treatment effectively improved sperm density and increased CORT level and down-regulated the testicularβ-gal,p16 and GR protein level(all P＜0.05).Conclusion Chronic psychological stress induces testicular damage in rats,presenting declines in sperm density and CORT level,which is possibly associated with GR-mediated cell senescence.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.