ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes （T2DM）. MethodsA 12-week randomized， placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group （40 cases） was administered with Astragali Radix Granules， while the control group （40 cases） received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 （GLP-1） levels were measured using enzyme-linked immunosorbent assay （ELISA）. Glucose metabolism indicators including fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG），glycated albumin（GA）， and glycated hemoglobin （HbA1c） were evaluated. Pancreatic function was evaluated using fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， and C-peptide area under the curve （AUC_cp）. Traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators， compared with the baseline， both groups exhibited significantly lower FPG， 2 h PG， GA and HbA1C （P<0.01），while FCP， 2 h CP and AUC_cp were significantly higher （P<0.01）. Compared with the control group after the treatment， the observation group showed significantly lower FPG， 2 h PG， GA and HbA1C（P<0.05， P<0.01），and significantly higher FCP， 2 h CP and AUC_cp （P<0.05， P<0.01）， indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota， no significant differences were detected in the Chao1， Shannon and Simpson indexes of the two groups compared with their respective baselines. However， compared with the post-treatment control group， the observation group demonstrated significant increases in the Chao1， Shannon and Simpson indexes （P<0.05， P<0.01）. The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups， indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level， compared with the baseline， both groups showed a significant increase in the relative abundance of Bacteroidota（P<0.01）. The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment （P<0.01）. Compared with the post-treatment control group， the observation group had a significantly higher relative abundance of Bacteroidota（P<0.01）. No significant difference was found in Firmicutes/Bacteroidota （F/B） ratio between the two groups after treatment， and other phyla showed no significant differences. At the genus level， compared with the baseline， the observation group exhibited a significant increase in Bacteroides （P<0.01） and a significant decrease in Escherichia-Shigella （P<0.01）， whereas no significant difference was seen in the control group . Compared with the control group after treatment， the observation group after treatment had a significantly higher relative abundance of Bacteroides （P<0.01）. No significant differences were seen in other genera. Linear discriminant analysis （LDA） identified potential characteristics taxa： in the observation group， Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level， in the control group， Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes， F/B ratio and Fusobacterium， and negatively correlated with Bacteroidota， Proteobacteria， Bacteroides and Escherichia-Shigella. In terms of clinical efficacy， compared with the control group， the total effective rate of the observation group was significantly higher （P<0.05）. Compared with the baseline， the scores for shortness of breath， fatigue， weakness， spontaneous sweating and reluctance to speak significantly decreased in both groups （P<0.01）. Compared with the control group after treatment， the score for weakness was significantly lower in the observation group （P<0.01），indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety， compared with the baseline， alanine aminotransferase （ALT） levels significantly decreased in both groups （P<0.05，P<0.01），indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control， possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.

Objective:Primary sclerosing cholangitis (PSC) is a rare autoimmune disease. This study aims to describe the baseline characteristics and clinical outcomes of Chinese PSC patients and explore risk factors associated with prognosis, addressing the lack of long-term prognostic analysis in China.Methods:Clinical data of PSC patients were retrospectively collected from May 2009 to June 2023 in Beijing Friendship Hospital Affiliated to Capital Medical University, and patient follow-up was conducted through outpatient visits, telephone calls, and medical record reviews. The Cox proportional hazards model and the Kaplan-Meier method were employed to identify risk factors and estimate transplant-free survival.Results:A total of 65 PSC patients were enrolled, with male patients accounting for 50.8% and an average age of onset of 44 years. The disease types primarily included large duct PSC (57.9%) and whole duct PSC (22.8%). Most patients (78.5%) sought medical attention due to symptoms, with common clinical manifestations including jaundice (32.3%), fatigue (23.1%), abdominal discomfort (21.5%), pruritus (16.9%), and fever (10.8%). A total of 19 patients (29.2%) had concomitant ulcerative colitis. Compared to large duct PSC or whole duct PSC, small duct PSC showed a lower proportion of concomitant ulcerative colitis ( P<0.001) and milder baseline disease severity. After a median follow-up of 29 months (interquartile range: 11,53), 19 patients experienced liver transplantations and/or liver disease-related deaths. The overall 2-year and 5-year transplant-free survival rates for PSC patients were 76.0% and 59.5%, respectively. Elevated bile acid levels were identified as an independent risk factor for poor outcomes in PSC patients. Conclusion:The study population of Chinese PSC patients predominantly consisted of middle-aged males, characterized by a low ratio of asymptomatic cases, a low incidence of associated inflammatory bowel disease, and a low rate of transplant-free survival. Elevated bile acid level was identified as an independent risk factor for poor outcomes in PSC patients.

ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang （DGLHT） on patients with type 2 diabetes mellitus （T2DM） complicated by atherosclerotic cardiovascular disease （ASCVD） at high risk， focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation （FMD）， atherogenic index of plasma （AIP）， and triglyceride-glucose index （TyG）， and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B （MyD88/NF-κB） signaling pathway. MethodsThe clinical study was a single-center， double-blind， and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT， while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks， with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD， AIP， TyG， and small dense low-density lipoprotein cholesterol （sdLDL-C） index were compared. Human umbilical vein endothelial cells （HUVECs） were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction （Real-time PCR） and Western blot . ResultsAfter 12 weeks of treatment， the AIP in the treatment group significantly decreased compared with that before the treatment （P<0.05）. Compared with the control group， the treatment group showed significant improvements in FMD and TyG （P<0.05）. Additionally， the treatment group demonstrated significant reductions in two-hour postprandial glucose （2 hPG）， glycated albumin （GA）， triglycerides （TG）， apolipoprotein E （Apo E）， and sdLDL-C （P<0.05）. Analysis of traditional Chinese medicine （TCM） syndrome efficacy indicated that in the treatment group， Yin deficiency and fire excess syndromes， including dry throat and mouth （P<0.05）， excessive thirst （P<0.01）， tidal fever and night sweats （P<0.05）， and dry stools （P<0.05）， improved. Compared with the control group， the treatment group showed significant improvements in symptoms of dry throat and mouth （P<0.05） and excessive thirst （P<0.01）. TCM syndrome scores significantly decreased （P<0.01）， and the overall efficacy rate was 56.67%， significantly higher than the 10.34% observed in the control group （P<0.01）. At the cellular level， increasing concentrations of DGLHT led to decreased messenger ribonucleic acid （mRNA） levels of pro-inflammatory cytokines interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， and interleukin-1-beta （IL-1β） in lipopolysaccharide （LPS）-stimulated HUVECs （P<0.01）， with significant reductions in the high-concentration group （P<0.01）. DGLHT may inhibit the expressions of MyD88 and phosphorylated （p）-NF-κB p65 proteins in a concentration-dependent manner. ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Objective To analyze correlation of endolymphatic hydrops (EH) in the inner ear with age in Meniere’s disease (MD) patients. Methods A retrospective analysis were underwent in 101 definite unilateral MD patients. They were divided into young-age (＜18 years old) group, middle-age (18-45 years old) group and elder-age (＞45 years old) group. All patients underwent inner ear three-dimensional inversion-recovery with real reconstruction (3D-real IR) imaging 4 hours after intravenous gadolinium injection. EH rates among different groups were compared. Results The positive rates of EH in the young-age group, middle-age group and elder-age group were 68.2% (15/22), 54.5% (18/33) and 56.5% (26/46), respectively (P＝0.567). There was no difference in the positive rates of EH in vestibule and cochlea among three groups. There was no difference in the rates of mild and significant EH in vestibule and cochlea among three groups. Conclusions Age might not be related to the occurrence of EH in the inner ear in MD patients.

The paper reviews the evolution of the theory related to meridians and zangfu organs during the Warring States, Qin and Han dynasties, so as to reveal the rules and value of its development. By analyzing historical documents, especially Zubi Shiyimai Jiujing (Moxibustion Classics of Eleven Meridians of Legs and Arms), Yinyang Shiyimai Jiujing (Moxibustion Classic on Eleven Yin and Yang Meridians), Laoguanshan bamboo medical slips of Han Dynasty and lacquer figure of meridian points, the evolutionary stages, i.e. the germination, development, and maturity of meridian-zangfu theory, are explored. In the time of the Warring States, Qin and Han dynasties, the meridian-zangfu related theory was developed from the germination to the maturity. In the classics of the early time, Zubi Shiyimai Jiujing and Yinyang Shiyimai Jiujing demonstrated the preliminary relationship between meridians and zangfu organs, focusing on the physiological connection and pathogenesis of three yin meridians of foot and zangfu organs. In the literature of Laoguanshan bamboo medical slips of Han Dynasty and lacquer figure of meridian points, the physiological connection between the yin meridians of hand and foot, and five zang organs, as well as the related diseases were further clarified; additionally, the meridian-zangfu theory had been developed in the field of diagnosis and treatment. In the era of Chapter of Meridians in Lingshu (Miraculous Pivot), there were up to 31 descriptions relevant with the connection of meridian distribution and zangfu physiological functions. It marks the construction of the "circular" flow of meridians and the interior-exterior communication of zang and fu organs; and enriches the knowledge in diseases, diagnosis and treatment with meridians and zangfu organs involved. The review on the evolution of the meridian-zangfu theory is conductive to supplementing and improving the development history of this theory of early time, and further recognizing its development rules and value. The maturity of this theoretical system not only links the meridians with the five zang and six fu organs, but also provides an important theoretical basis for the diagnosis and treatment of traditional Chinese medicine.
Meridians ; Humans ; History, Ancient ; China ; History, Medieval ; History, 19th Century ; History, 20th Century ; History, 18th Century ; History, 17th Century ; History, 16th Century ; Medicine, Chinese Traditional/history*

OBJECTIVE To evaluate the economic burden of the intensive care unit(ICU)patients due to hospital-associated multidrug-resistant organisms(MDROs)infections based on propensity score matching(PSM)so as to provide evidence-based bases for prevention and control of hospital-associated MDROs infection and improvement of utilization efficiency of medical resources.METHODS A total of 2118 patients who were hospitalized in Zibo Central Hospital from Jan.1,2023 to Dec.31,2024 and conformed to the inclusion and exclusion criteria were re-cruited as the research subjects.The patients with hospital-associated MDROs infections were matched in a 1∶1 ratio by PSM(with the clamp value 0.02).Totally 309 pairs were successfully matched.The length of hospital stay and the costs were observed and compared between the MDROs group and the non-MDROs group.RESULTS The MDROs group was with the length of hospital stay 14.00 days longer than the non-MDROs group after the matching(Z=-5.750,P＜0.001),with the total cost of hospitalization increased by 91,420.84 yuan(Z=-8.271,P＜0.001).With the respect to the medical treatment expenses,the expenses of the MDROs group were higher than those of the non-MDROs group,covering the cost of medical service,therapeutic procedures,nursing,western medicine and TCM,and there were significant differences(P＜0.05).Among the differences in the costs between the two groups,the difference in the cost of western medicine was the most signif-icant(22,182.91 yuan),followed by the cost of clinical laboratory test for diagnosis(19,529.60 yuan)and the cost of therapeutic procedures(16,333.50 yuan).CONCLUSIONS The hospital-associated MDROs infections may lead to the extension of hospital stay length of the ICU patients,which then increases the economic burden.There-fore,it is necessary to strengthen the multidisciplinary collaboration and formulate corresponding measures so as to reduce the risk of such infections among the ICU patients.

Objective:To investigate the relationship between sarcopenic obesity(SO), defined by various obesity indicators, and mortality risk in older adults based on a prospective cohort from multiple nursing homes.Methods:Sarcopenia was diagnosed according to the 2019 consensus of the Asian Working Group for Sarcopenia.Obesity was defined using six different indicators: waist circumference(WC), waist-hip ratio(WHR), waist-height ratio(WHTR), body mass index(BMI), visceral fat area(VFA), and percentage of body fat(PBF).A prospective cohort of adults aged 60 and above was established across 15 nursing homes in Zigong City, with annual follow-ups on survival status conducted over two consecutive years.Cox proportional hazards regression models were employed to analyze the association between SO, defined by different obesity indicators, and mortality risk, calculating hazard ratios( HR)and their 95% confidence intervals( CI). Results:A total of 695 older adults were included in the study, of whom 67.1% were male.During the 2-year follow-up period, 88 participants died.The prevalence of SO as defined by WC, WHR, WHTR, BMI, VFA, PBF was found to be 17.6%, 30.1%, 48.9%, 3.0%, 28.3%, and 58.7%, respectively.When SO was defined using WC, WHR, WHTR, BMI, and VFA, there was no statistically significant difference in mortality rates between the SO and non-SO groups.However, when defined by PBF, the SO group exhibited a significantly higher mortality rate compared to the non-SO group(16.9% vs.6.6%, P<0.01).Cox proportional hazards regression analysis revealed that, compared to the non-SO group, the SO group defined by PBF had a significantly increased mortality risk( HR=2.81, 95% CI: 1.67-4.73, P<0.001).After adjusting for potential confounding factors, the mortality risk for the SO group remained significantly higher than that of the non-SO group( HR=1.97, 95% CI: 1.14-3.38, P=0.015). Conclusions:The prevalence of SO varies significantly across different obesity indicators.SO defined by PBF is significantly associated with mortality risk in nursing home residents.This study provides new evidence for further optimizing the diagnostic criteria for SO in this population.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.