This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

The objective assessment of hearing loss is one of the critical components in forensic clini-cal research.Auditory brainstem response(ABR)is an important method for objectively assessing hearing levels.It is divided into various types based on different stimulus signals,each with its own characteris-tics and applications.Among them,narrow-band Chirp ABR,due to its frequency specificity,fulfills the basic requirements for objective assessment of forensic audiology,promising to be an important method of objective hearing assessment in forensic medicine.This article reviews the development history,charac-teristics and clinical applications of Chirp ABR,and envisions its application prospects in forensic audi-tory identification.

AIM To study the chemical constituents from the leaves of Drynaria fortunei(Kunze)J.Sm.and their antioxidant activity.METHODS ODS-AG-HG,Sephadex LH-20 and semi-preparative HPLC were used for separation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH mothod.RESULTS Fifteen compounds were isolated and identified as kaempferol-3-O-neohesperidoside(1),dihydrodehydrodiconiferyl alcohol(2),kaempferol-3,7-di-O-α-L-rahmnoside(3),astragalin(4),loliolid(5),trichothecene analogue(6),2,2-[bis-4-(2,3-dihydroxypropoxy)phenyl]propane(7),maculatin(8),trichothecin(9),4-[(Z)-but-2-enoyloxy]-8-chloro-12-hydroxy-7,13-epoxytrichothec-9-ene(10),8-deoxy-trichotecin(11),β-sitosterol(12),daucosterol(13),afzelin(14),samwinol(15).The IC50 values of the leaf and rhizome extracts against DPPH free radicals were(0.072±0.005),(0.287±0.012)mg/mL,respectively.CONCLUSION Compounds 1,2,5-11,15 are isolated from this plant for the first time.The leaves of D.fortunei exhibit strong antioxidant activity.

Objectives:To evaluate the incidence of neurological complications following left ventricular assist device(LVAD)implantation and to investigate related risk factors.Methods:A retrospective analysis was conducted on 151 patients who underwent LVAD implantation at Fuwai Hospital between June 2017 and September 2024.Clinical characteristics and postoperative survival outcomes were compared between patients with and without neurological complications.Results:Neurological complications occurred in 21 patients(13.9%)postoperatively,15 cases were ischemic strokes,5 cases were symptomatic intracranial hemorrhages or subarachnoid hemorrhages,and 1 case was transient ischemic attack(TIA).The total incidence of neurological complications was 0.08 events per person-year(EPPY),ischemic stroke was 0.06 EPPY and hemorrhagic stroke was 0.02 EPPY.Compared with patients without neurological complications,patients with neurological complications had a higher proportion of preoperative aortic regurgitation and tricuspid regurgitation,lower triglyceride levels,a lower rate of concurrent left atrial appendage resection and a higher rate of concurrent aortic valve replacement surgery.Multivariate cox regression analysis revealed that higher preoperative triglyceride levels(HR=0.21,95%CI:0.08-0.56,P=0.002)were associated with neurological complications.The median follow-up time was 508.0(186.5,931.5)days,12 out of 15 cases of ischemic stroke experienced no long-term sequelae,while 3 patients had varying degrees of residual deficits.All 5 patients with hemorrhagic stroke died,with 2 deaths directly attributed to hemorrhage.Kaplan-Meier survival curve analysis indicated that patients with neurological complications had a significantly lower survival rate(log-rank P=0.005).Conclusions:Neurological complications after LVAD implantation are predominantly ischemic strokes.Although less frequent,hemorrhagic strokes are associated with worse outcomes.Higher preoperative triglyceride levels is associated with neurological complications.

Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P＜0.01),higher apoptosis rate of neurons in the CA1 re-gion(P＜0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P＜0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P＜0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P＜0.05),lower apoptosis rate of neurons in the CA1 region(P＜0.01),significantly lower protein expression levels of A β42 and GFAP(all P＜0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P＜0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.

Objective:To discuss the risk factors for postoperative venous thromboembolism (VTE) in patients undergoing pancreatic surgery.Methods:The clinical data of 488 patients who underwent pancreatectomy at the First Affiliated Hospital of Harbin Medical University from Jan 2016 to Sep 2024 was retrospectively analyzed.Results:One hundred and sixteen patients (23.8%) developed VTE after pancreatic surgery. Logistic analysis showed that advanced age, abdominal surgery history, high preoperative white blood cell count, high platelet lymphocyte ratio (PLR), distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration were risk factors.Nomogram prediction model based on the above risk factors was constructed and the area under the ROC curve was subsequently measured to be 0.781 (95% CI: 0.731-0.830). Conclusion:The prevention and control of VTE should be strengthened for patients undergoing pancreatic surgery with advanced age, abdominal surgery history, high preoperative white blood cell count, high PLR, distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration.

Objective To investigate the effect of cordyceps sinensis(CS)on the activation of fibroblasts through IL-6 trans-signaling pathway and its specific mechanism in the treatment of renal fibrosis.Methods Renal fibrosis mouse model was established by unilateral ischemia/reperfusion(UIR),and the mice were administered intragastrically CS,soluble glycoprotein 130 Fc(sgp130Fc)or Hyper-IL-6.Masson's trichrome staining was utilized to identify tubulointerstitial fibrosis.PAS staining was utilized to assess the extent of renal injury.Western blot was employed to analyze the expression levels of fibrosis markers[alpha-smooth muscle actin(α-SMA),fibronectin(FN)]and proteins associated with IL-6 trans-signaling pathway[phosphorylated signal transducer and activator of transcription 3(p-STAT3),soluble interleukin-6 receptor(sIL-6R)].The expression and localization of proteins were additionally detected by immunohistochemistry,immunofluorescence and qPCR.The effect of cordyceps sinensis extract cordycepin on IL-6 trans-signaling in fibroblasts was further investigated in vitro.Results The results from in vivo experiments showed that administration of CS during the chronic phase demonstrated a beneficial protective impact on inflammation and fibrosis in the affected kidney,and serum creatinine levels and collagen deposition were decreased.Western blot analysis revealed a decrease in the expression levels of α-SMA,FN,as well as IL-6 trans-signaling pathway protein p-STAT3,sIL-6R in the treatment group.Additionally,the mRNA expression levels of chemokines monocyte chemoattractant protein-1(MCP-1)and C-X-C motif chemokine ligand 12(CXCL12)were also decreased in the CS treatment group.Additionally,Hyper-IL-6 can partially counteract the therapeutic effects of CS.In vitro experiments further demonstrated that cordycepin inhibited the secretion of IL-6 from NRK-52E.Combined treatment of recombinant IL-6 and sIL-6R protein activated NRK-49F,leading to a significant increase in α-SMA,FN,and p-STAT3 expression levels.Cordycepin or sgp130Fc treatment significantly inhibited the proliferation of fibroblasts induced by IL-6 trans-signaling pathway.Conclusion CS can significantly reduce IL-6 secretion by renal tubular epithelial cells and inhibit the activation of IL-6 trans-signaling pathway in fibroblasts,thereby ameliorating renal interstitial fibrosis.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.