Ductular reaction （DR） refers to the adaptive pathological changes that occur after hepatobiliary injury， and it is essentially a repair response involving the proliferation， fibrosis， and inflammation of biliary epithelial cell （BEC）. With the understanding of the biological function of BEC， the potential value of DR in disease prognosis and treatment has gradually become a research hotspot. This article systematically reviews the molecular mechanism of DR， its potential as a therapeutic target， and future development directions， as well as novel therapies suggested by targeting these molecular mechanisms， in order to provide a new direction for overcoming current bottlenecks in the treatment of bile duct diseases.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the action and molecular mechanism of modified Tongluo Tangtai Formula（MTLTT） on myelin damage in diabetic peripheral neuropathy （DPN） based on network pharmacology and in vitro experiments. MethodsThe chemical components of the MTLTT were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database and literature， and the component targets were collected from the SwissTargetPrediction database. The targets of DPN were collected from the GeneCards， OMIM， Disgenet， and GEO databases. Gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses were performed using the Metascape database， and a network diagram was constructed using Cytoscape software. The binding actions of core components with glycogen synthase kinase 3 beta （GSK-3β） and β-catenin were analyzed by Autodock Vina. An in vitro DPN model was established by high glucose-induced Schwann cells and dorsal root ganglion cells （SCs/DRGs）. The ultrastructural morphological changes of SCs and DRGs were observed by scanning electron microscope（SEM）， and the expressions of myelin-associated glycoprotein （MAG） and myelin basic protein （MBP） were detected by immunofluorescence staining. The mRNA and protein expression levels of MAG， MBP， myelin protein 0 （P0）， peripheral myelin protein 22 （PMP22）， and Wnt/β-catenin signaling pathway-related protein β-catenin， GSK-3β， Wnt family member 3α （Wnt3α）， and Wnt inhibitory factor-1 （Wif-1） were detected by real-time polymerase chain reaction （Real-time PCR） and Western blot. ResultsNetwork pharmacology analysis revealed that MTLTT components may treat DPN via the Wnt signaling pathway， involving key proteins such as GSK-3β， β-catenin and Wif-1. The molecular docking results indicate that atropine， apigenin， baicalein， isoflavanone， and albiflorin have good binding activity with GSK-3β， and that all 13 core components have stable binding activity with β-catenin. Cell experiments showed that compared with the blank group， SCs and DRGs in the model group exhibited severe morphological and structural abnormalities such as disintegration， shrinkage and axonal rupture， while these abnormal changes were improved after MTLTT intervention. Immunofluorescence results indicated that the fluorescence intensity of MAG and MBP was markedly decreased in the model group relative to the blank group（P<0.01）， while MTLTT treatment obviously upregulated the expression of MAG and MBP compared with the model group （P<0.01）. Real-time PCR and Western blot assays revealed that the expression levels of myelin-related molecules MAG， MBP， P0 and PMP22 were significantly reduced in the model group （P<0.05，P<0.01）， and MTLTT remarkably increased their expression levels （P<0.05）. In the Wnt/β-catenin signaling pathway， the mRNA levels of GSK-3β， Wif-1 and Wnt3α were elevated and β-catenin mRNA expression was declined in the model group （P<0.01）. Meanwhile， the protein expressions of GSK-3β and Wif-1 were upregulated， whereas those of Wnt3α and β-catenin were downregulated （P<0.01）. Compared with the model group， MTLTT at different doses reduced the mRNA and protein levels of GSK-3β and Wif-1 to varying degrees （P<0.05）， and distinctly enhanced the protein expression of Wnt3α and β-catenin（P<0.01）. ConclusionMTLTT can alleviate high glucose-induced myelin damage. Its protective mechanism may promote myelin repair by upregulating the expression of MAG， MBP， P0 and PMP22， and the therapeutic effect is possibly associated with the activation of Wnt/β-catenin signaling pathway.

BackgroundThe global prevalence of depressive disorders is high， with a significant treatment gap remaining. Escitalopram oxalate， as a commonly used antidepressant in clinical practice， has a single target and is prone to cause adverse reactions such as gastrointestinal discomfort. The traditional Mongolian medicine Zadi-5 pills has a multi-target anti-depression mechanism and unique advantages such as improving the intestinal flora. However， there is currently a lack of randomized controlled trial evidence for the combined treatment of first-episode depression， along with insufficient research on its metabolic safety and potential drug interactions. ObjectiveTo explore the efficacy and safety of Zadi-5 pills combined with escitalopram oxalate in the treatment of the first-episode depression， so as to provide references for Mongolian medicine in depression management. MethodsA randomized controlled trial was conducted. A total of 103 patients with first-episode depression who were treated in the outpatient or inpatient departments of the Inner Mongolia Autonomous Region Mental Health Center from January 2023 to December 2024 and met the diagnostic criteria for depressive episode as defined in International Classification of Diseases， tenth edition （ICD-10） were included. Random numbers were generated using the RAND function in Excel software， and the patients were divided into the study group （n=52） and the control group （n=51）. Both groups received escitalopram oxalate treatment， starting from 5 mg/d and gradually increasing to 20 mg/d. The study group additionally received Zadi-5 pills， 13 pills per day. The treatment duration for both groups was 6 weeks. Before treatment and at the 2^nd， 4^th， and 6^th weeks of treatment， the severity of depressive symptoms was evaluated using the Hamilton Depression Scale-24 item （HAMD-24）. At these time points， blood was collected on an empty stomach at 7∶00 for the detection of liver function （aspartate aminotransferase， alanine aminotransferase）， triglycerides， and the blood concentration of escitalopram oxalate. ResultsA total of 100 patients completed the study， with 50 cases in the study group and the control group. The results of the repeated measures ANOVA showed that the interaction effect between group and time in the HAMD-24 score was statistically significant （F _interaction= 18.070， P<0.01）. At the end of the 4^th and 6^th weeks of treatment， the HAMD-24 score of the study group was lower than those of the control group （P<0.05）. At each time point after treatment， the reduction rate of the HAMD-24 score in the study group was higher than those of the control group， and the differences were all statistically significant （P<0.05）. The interaction effect between the triglyceride level groups and time was statistically significant （F_interaction=3.381， P<0.05）.After treatment， the triglyceride levels in the study group showed a downward trend， while those in the control group showed an upward trend. There was no statistically significant interaction effect between the groups and time for liver function （aspartate aminotransferase and alanine aminotransferase） and the blood concentration of escitalopram oxalate （P>0.05）. ConclusionCompared with escitalopram oxalate treatment alone， the combination of Zadi-5 pills and escitalopram oxalate is more effective in treating the first-episode depression， without increasing the risk of liver damage. The combined medication may have a potential beneficial effect on lipid metabolism. ［Funded by Inner Mongolia Autonomous Region Health Science and Technology Planning Project （number， 202202107）］

The zebrafish model has attracted much attention due to its strong reproductive ability, short research cycle, and ease of maintenance. It has always been an important vertebrate model system, often used to carry out human disease research. Its motor behavior features have the advantages of being simpler, more intuitive, and quantifiable. In recent years, it has received widespread attention in the study of traditional Chinese medicine(TCM)for the treatment of sleep disorders, neurodegenerative diseases, fatigue, epilepsy, and other diseases. This paper reviews the characteristics of zebrafish motor behavior and its applications in the pharmacodynamic verification and mechanism research of TCM extracts, active ingredients, and TCM compounds, as well as in active ingredient screening and safety evaluation. The paper also analyzes its advantages and disadvantages, with the aim of improving the breadth and depth of zebrafish and its motor behavior applications in the field of TCM research.
Zebrafish/physiology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Drug Evaluation, Preclinical/methods* ; Animals ; Sleep Wake Disorders/physiopathology* ; Epilepsy/physiopathology* ; Neurodegenerative Diseases/physiopathology* ; Fatigue/physiopathology* ; Behavior, Animal/physiology* ; Motor Activity/physiology*

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
Animals ; Male ; Penile Induration/drug therapy* ; Rats ; Transforming Growth Factor beta1/metabolism* ; Disease Models, Animal ; Fibrin ; Penis/drug effects* ; Polidocanol/administration & dosage* ; Rats, Sprague-Dawley ; Polyethylene Glycols/administration & dosage* ; Injections

Background The decline of physical activity in the elderly due to aging may increase the risk of sarcopenia. Currently, there is a lack of evidence from large natural populations on the relationship between PA and sarcopenia. Objective To explore the relationship between PA and sarcopenia in the elderly aged 60 years and above in 10 provinces (autonomous regions) of China. Methods Data were retrieved from the 2022—2023 round of the China Development and Nutrition Health Impact Cohort. Personal basic information and PA data were collected by questionnaire survey. Skeletal muscle mass was measured by bio-electrical impedance analysis, muscle strength was measured using a grip dynamometer, and physical performance was reflected by 6-meter walk speed. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used to diagnose sarcopenia. Light physical activity (LPA) duration, moderate-to-vigorous physical activity (MVPA) duration, and total physical activity volume were calculated. A total of 3326 residents aged ≥60 years with complete data were selected as the survey participants. Multiple logistic regression models and restricted cubic splines (RCS) were used to assess the association between PA duration/volume and sarcopenia. Results In 10 provinces (autonomous regions) of China, the prevalence of sarcopenia in the elderly aged 60 years and above was 5.5% (95%CI: 4.7%, 6.2%). The logistic regression analysis showed that compared with the elderly reporting 0-7.0 h·week⁻¹ in LPA duration, the risk of sarcopenia in the elderly with LPA duration of >14.0-21.0 h·week⁻¹ was reduced by 51% (OR=0.49, 95%CI: 0.26, 0.96). Compared with the elderly with total physical activity ≥15.0 metabolic equivalent of task (MET)-h·week⁻¹, those with <7.5 MET-h·week⁻¹ had a 2.24-fold increased risk of sarcopenia (OR=2.24, 95%CI: 1.17, 4.29). The RCS results found that LPA duration and total physical activity volume each showed a nonlinear dose-response relationship with the risk of sarcopenia (P_overall<0.05, P_non-linear<0.05). Compared with the elderly with an LPA duration of 0 h· week⁻¹, the risk of sarcopenia in the elderly with an LPA duration of 12.6 h· week⁻¹ was the lowest (OR=0.42, 95%CI: 0.21, 0.83). Compared with the elderly with a total physical activity volume of 15.0 MET-h· week⁻¹, the elderly with a total physical activity volume of 46.0 MET-h· week⁻¹ had the lowest risk of sarcopenia (OR=0.57, 95%CI: 0.38, 0.84). There was no statistically significant association between weekly MVPA duration and the risk of sarcopenia (P>0.05). Conclusion Increasing weekly LPA duration and total physical activity volume would help to reduce the risk of sarcopenia.

OBJECTIVE To compare the efficacy and safety of different daily doses of aspirin in the prevention of preeclampsia （PE）. METHODS The case-control studies and prospective randomized controlled trials on aspirin with daily dose ≥ 100 mg （trial group） vs. ＜100 mg （control group） in the prevention of PE were retrieved from PubMed， Medline， Embase， the Cochrane Library， CNKI， China Biomedical Literatue Database and Wanfang Data from base-building to January 2025. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 literatures were included， involving 3 052 pregnant women. Meta-analysis showed the incidence of PE [RR＝0.63， 95%CI （0.53，0.76）， P＜0.000 01]， gestational hypertension [RR＝0.69， 95%CI （0.50，0.94），P＝0.02]， preterm birth [RR＝0.56， 95%CI （0.47，0.66）， P＜0.000 01]， and intrauterine growth retardation [RR＝0.73，95%CI （0.61，0.87），P＝0.000 5] in trial groups were significantly lower than control group. The incidence of postpartum hemorrhage between the two groups had no statistically significant difference [RR＝1.17， 95%CI （0.90，1.53），P＝0.25]. Subgroup analysis showed that the incidence of PE in Chinese pregnant women taking 150 mg of aspirin was significantly higher than taking 100 mg of aspirin [RR＝3.40， 95%CI （1.29， 8.93）， P＝0.01]； but there was no significant difference between the two groups in the incidences of postpartum hemorrhage， preterm birth （P＞0.05）. CONCLUSIONS Aspirin with daily dose ≥100 mg is more effective in preventing PE than daily dose ＜100 mg， with lower rates of gestational hypertension， preterm birth， and intrauterine growth retardation. It does not increase the risk of postpartum hemorrhage. For pregnant women in China， daily dose 100 mg of aspirin may be more effective in preventing PE than 150 mg.