ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

It is believed that there is a pathogenesis of yang deficiency in polycystic ovary syndrome （PCOS） infertility， and it is concluded that warm-yang method has a better effect in improving endometrial abnormality， enhancing the quality of follicles， correcting endocrine disorders， and resolving or alleviating clinical symptoms in PCOS infertility. Based on Yanghe Decoction （阳和汤）， a representative traditional Chinese medicine decoction for warming yang， Yanghe Xiaonang Decoction （阳和消囊汤） was formulated， combining with warm medicinals according to symptoms， and aerobic exercise was also advocated to help generate and develop yang qi， in order to provide ideas for clinical treatments.

ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

Objective Based on a clinical cohort study of repeated ketamine infusions for treatment-resistant depression(TRD),this study aimed to examine differences in brain-derived neurotrophic factor(BDNF)methylation among patients with varying therapeutic responses and explore its potential role in predicting treatment efficacy.Methods A retrospective analysis was conducted on peripheral plasma BDNF levels in 83 patients with TRD before and after a 2-week course of ketamine treatment(6 injections total).The Montgomery-Asberg depression rating scale(MADRS)was used to assess treatment efficacy.BDNF methylation levels were compared between responder group and non-responder group.The effect of methylation of the target CpG site on transcriptional activity was verified by using the dual luciferase reporter gene system.Results In patients with TRD who completed six repeated ketamine infusions,the responder group showed significant improvements compared to baseline levels in both MADRS scores(25.20±7.54 vs.8.10±5.32,P<0.01)and plasma BDNF concentrations[8.74(5.26,13.46)ng/mL vs.16.59(7.41,24.46)ng/mL,P<0.01].At baseline,35 CpG sites within the BDNF gene displayed significant methylation differences between response groups(P<0.05).Two CpG sites(rs1240718851 and cg06260077)located in the BDNF promoter region demonstrated a hypermethylation-low expression correlation,and dual-luciferase reporter assays confirmed that one of these sites functionally modulates BDNF expression.Conclusions The plasma BDNF concentration in TRD patients increases with the remission of depressive symptoms.The regulation of BDNF gene expression by methylation can predict the antidepressant efficacy of repeated intravenous ketamine.

Aiming at the problems of tongue diagnosis instruments relying on manual operation,uneven illumination,color distortion and lack of dynamic information,an automated operation black box tongue diagnosis instrument based on machine vision is proposed.This instrument utilizes machine vision technology and image processing algorithms to achieve automatic positioning and automatic acquisition of tongue manifestations.High-resolution camera technology enables the acquisition of 3-second dynamic videos and high-quality static images.The performance test results show that,based on the dual-camera geometric projection calibration algorithm,the average time for tongue recognition is less than 0.15 seconds.The diffuse reflection light source improves the gray uniformity to 76.74%,and the maximum color difference in color reproduction degree is 19,which is better than the industry standard value of 25.The developed tongue diagnosis instrument will promote the objective,efficient and precise acquisition of tongue diagnosis in traditional Chinese medicine.

BACKGROUND:Cannabidiol has anti-inflammatory,antioxidant,and other pharmacological effects,and has no mental activity,so the research in liver disease is increasing day by day,but its effect on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells is not clear.OBJECTIVE:To investigate the effect of cannabidiol on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells and its possible mechanism of anti-hepatic fibrosis.METHODS:(1)In vitro experiment:Rat hepatic stellate cell line(HSC-T6)was selected and cultured in six groups.The control group was routinely cultured for 24 hours.The simple drug group was cultured with cannabidiol for 24 hours.The modeling group was cultured with transforming growth factor β1 for 24 hours.The modeling+low-dose drug group,the modeling+high-dose drug group,and the modeling+positive control group were cultured with transforming growth factor β1 for 24 hours,1,5 μmol/L cannabidiol and silymarin were cultured for 24 hours.After culture,the mRNA expression of α-smooth muscle actin and type Ⅰ collagen,the levels of interleukin 1β and tumor necrosis factor α,and the protein expression of type Ⅰ collagen and transforming growth factor β1/Smad signal transduction pathway were detected in each group.(2)In vivo experiments:C57BL/6J mice were randomly divided into five groups with eight mice in each group.Models were not established in the sham operation group.The liver fibrosis models were established by biliary ligation in the modeling group,the modeling+low-dose drug group,the modeling+high-dose drug group,and the modeling+positive control group.At 3 weeks after the modeling,4,8 mg/kg cannabidiol or silymarin were injected intraperitoneally,once a day,for 7 consecutive days.After administration,the liver function,liver pathological morphology,expression levels of α-smooth muscle actin,type Ⅰ collagen,and transforming growth factor β1/Smad signal transduction pathway related protein were detected in each group.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with the control group,mRNA expression of α-smooth muscle actin and type Ⅰ collagen,interleukin 1β and tumor necrosis factor α,and protein expression of type Ⅰ collagen,transforming growth factor β1 and p-Smad2/3 in HSC-T6 cells were increased(P<0.05),while Smad7 protein expression was decreased(P<0.05)in the modeling group.Two doses of cannabidiol could improve the above changes in HSC-T6 cells induced by transforming growth factor β1,and the improvement was more obvious in the modeling+high-dose drug group.(2)In vivo experiment:Compared with sham operation group,the activities of serum alanine aminotransferase and aspartate aminotransferase were increased(P<0.05),inflammatory cell infiltration and collagen content in liver tissue were increased(P<0.05),and the transforming growth factor β1/Smad signal transduction pathway was activated;α-smooth muscle actin and type Ⅰ collagen expression levels were increased(P<0.05)in the modeling group.Two doses of cannabidiol could reduce the changes of the above indexes in the modeling mice,and the effect was more obvious in the modeling+high-dose drug group.(3)It is indicated that cannabidiol inhibits hepatic fibrosis by suppressing the activation of transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells.

Objective:To evaluate left ventricular systolic function in patients with systemic scleroderma (SSc) with normal left ventricular ejection fraction using pressure-strain loop (PSL) .Methods:To collect 30 patients with SSc who were treated in the Rheumatology and Immunology Department of Jining Medical University from January 2022 to March 2024 as the observation group, 30 healthy volunteers were selected as the control group after 1:1 matching with the observation group according to the age ±3 years old and the same gender. Clinical and ultrasound data were collected, PSL was used to evaluate and compare the differences between the two groups in left ventricular longitudinal strain (GLS), global work index (GWI), global useful work (GCW), global useless work (GWW) and global work efficiency (GWE), and the statistically significant variables were analyzed by multivariate logistic regression to analyze the independent predictors of early left ventricular function impairment in patients with SSc,and constructed receiver operating characteristic (ROC) curve to analyze the predictive value of GLS, GWI, GCW, GWW and GWE in early left ventricular function impairment in SSc patients.Results:Compared with the control group, the observation group GLS,GWI, GCW and GWE decreased( P<0.05), while the GWW increased( P<0.05). Multivariate logistic regression analysis showed that GLS[ OR(95% CI)=0.51(0.26, 1.02), P=0.055]、GWI[ OR(95% CI)=1.00(0.99, 1.01), P=0.969)、GCW[ OR(95% CI)=1.00(0.99, 1.02), P=0.771]、GWW[ OR(95% CI)=0.90(0.81, 1.01), P=0.075]and GWE[ OR(95% CI)=0.02(0.00, 0.55), P=0.022], in which GWE had the highest significance in predicting left ventricular myocardial work in SSc patients. ROC curve showed that compared with GLS, GWI, GCW and GWW, the area under GWE curve (0.953) was the largest, and the sensitivity of GWE≤94% to predict myocardial damage in SSc patients was 80.0%, and the specificity was 93.3%. The results of the repeatability test showed that the reproducibility of the intra-observer and inter-observer measurements was good. Conclusion:The PSL provides a new method for the quantitative assessment of early left ventricular systolic function impairment in patients with SSc, and GWE can be used as a sensitive index to predict early left ventricular systolic function impairment in patients with SSc.

Objective To explore the diagnostic value of MRI radiomics analysis in mild carpal tunnel syndrome(CTS).Methods Seventy patients with mild CTS and 86 healthy volunteers who underwent wrist MRI examination were retrospectively selected.MRI fat-suppressed proton density weighted imaging(PDWI)were imported into 3D Slicer software,and the region of interest(ROI)delineation was performed by two radiologists independently.The 830 radiomics parameters were extracted,including first-order fea-tures,shape features,texture features,and wavelet-transform features.Radiomics parameter selection was performed through observer intraclass correlation coefficient(ICC),correlation analysis,and multivariate logistic regression.Five diagnostic models were estab-lished,including logistic regression,support vector machine,naive Bayes,decision tree,and random forest.Receiver operating charac-teristic(ROC)curve was used to analyze the diagnostic efficiency of the models.Results Seven radiomics features were selected for inclusion in the diagnostic models.The logistic regression model demonstrated the best performance,with an area under the curve(AUC)of 0.91[95%confidence interval(CI)0.86-0.96],a sensitivity of 88.63%,and a specificity of 89.00%in the training group.In the test group,the AUC was 0.92(95%CI 0.85-0.97),with a sensitivity of 90.48%and a specificity of 84.62%.Conclusion MRI radiomics analysis can be used to diagnose mild CTS,and the logistic regression model demonstrates superior diagnostic per-formance.

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

Objective To explore the changes and influencing factors in patients' gastrointestinal symptoms and food tolerance before and after laparoscopic sleeve gastrectomy(LSG),and to provide a reference for the development of targeted gastrointestinal symptoms management program.Methods A convenience sampling method was used to select 125 patients who underwent LSG in the bariatric and metabolic surgery department of a tertiary-level hospital in Xuzhou City from June to November 2023 for a prospective observational study.The general information questionnaire,food tolerance questionnaire and Gastrointestinal Symptom Rating Scale(GSRS)were used to investigate at preoperative,3 months after surgery,and 6 months after surgery.Two-factor repeated measures variance analysis and generalized linear mixed model(GLMM)was used to analyze the influencing factors of gastrointestinal symptoms.Results 116 valid questionnaires were collected,and the GSRS scores of LSG patients at 3 time points were 21.67±5.80,23.28±4.33,and 21.22±3.18 respectively;the incidence rates of food intolerance were 0,32.75％,and 28.45％respectively.The patients' symptoms of bowel sounds,dysphagia,constipation,and dry stool were worse after surgery than before surgery(all P＜0.05),and the symptoms of bad breath,diarrhea,loose stools,and the need to defecate immediately were alleviated compared with symptoms before surgery(all P＜0.05).GLMM results showed that short meal times,poor food tolerance,and high school/technical secondary school education were risk factors for increasing gastrointestinal symptoms(all P＜0.05).Conclusion LSG could increase the prevalence of gastrointestinal symptoms such as dysphagia,dyspepsia,constipation and food intolerance.Medical staff should pay attention to the assessment of gastrointestinal symptoms in LSG patients,especially for patients with short meal time and poor food tolerance,strengthen postoperative follow-up,build targeted treatment and care plan,and prevent and reduce such uncomfortable symptoms.