ObjectiveTo investigate the risk factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients， to construct a clinical predictive model， and to provide a reference for predicting rebleeding in the early stage， reducing the incidence rate of rebleeding， and improving the clinical outcome of patients. MethodsA retrospective analysis was performed for the clinical data of 194 liver cirrhosis patients with gastroesophageal variceal bleeding who received initial endoscopic therapy at Department of Gastroenterology， The Second People’s Hospital of Lanzhou， from January 1， 2021 to May 31， 2025. According to whether rebleeding occurred within 1 year after endoscopic therapy， the patients were divided into rebleeding group and non-rebleeding group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The patients enrolled were randomly divided into a training set and a validation set at a ratio of 7∶3. In the training set， the Lasso regression analysis was used to obtain optimal predictive variables， and the factors that might affect prognosis were included in the univariate and multivariate Logistic regression analyses to identify independent predictive factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients， which were used to construct a nomogram model. In both the training set and the validation set， the receiver operating characteristic （ROC） curve and the calibration curve were used to assess the discriminatory ability and calibration of the model， and decision curve analysis and the clinical impact curve were used to assess the clinical practicability of the model. ResultsAmong the 194 liver cirrhosis patients with esophageal and gastric varices， 116 （59.79%） experienced rebleeding within 1 year after endoscopic therapy， with 76 patients in the training set and 40 patients in the validation set. In the training set， the Lasso regression analysis and the univariate and multivariate Logistic regression analyses showed that etiology of liver cirrhosis （odds ratio ［OR］=3.540， 95% confidence interval ［CI］： 1.520 — 7.150， P<0.001）， Child-Pugh class （OR=3.560， 95%CI： 1.380 — 9.500， P=0.019）， severity of esophageal and gastric varices （OR=8.190， 95%CI： 3.568 — 17.850， P=0.026）， and main portal vein diameter （OR=2.954， 95%CI： 1.349 — 15.030， P=0.044） were independent predictive factors for rebleeding of esophageal and gastric varices in liver cirrhosis patients. A nomogram model was constructed based on the above independent predictive factors. The ROC curve analysis showed that this model had an area under the ROC curve of 0.845 （95%CI： 0.778 — 0.912） in the training set and 0.801 （95%CI： 0.798 — 0.868） in the validation set. The model had an index of concordance of 0.832 in the training set and 0.820 in the validation set， suggesting that the model had a good discriminatory ability. The Hosmer-Lemeshow test showed P values of 0.320 and 0.550 in the training set and validation set， respectively， the calibration curve indicated that the predicted probabilities of the nomogram model were in good concordance with the actual observed probabilities， suggesting that the model had good calibration. The decision curve analysis and the clinical impact curve showed that the model had good clinical utility. ConclusionThe nomogram model based on etiology of liver cirrhosis， Child-Pugh class， severity of esophageal and gastric varices， and main portal vein diameter has a certain clinical value in predicting the risk of rebleeding from esophageal and gastric varices in liver cirrhosis.

ObjectiveTo explore the mechanism by which aerobic exercise improves hippocampal neuroinflammation and learning and memory ability in brain-aged mice via interferon regulatory factor 7 (IRF7). MethodsA total of 60 male specific pathogen-free (SPF) C57BL/6J mice were enrolled in the experiment, including 30 young mice (2 months old) and 30 naturally aging mice (12 months old). Young mice and old mice were respectively randomly assigned to four groups: young control group (group C, n=15), young exercise group (group CE, n=15), and aging control group (group A, n=15), aging exercise group (group AE, n=15). Mice in the exercise groups received an 8-week continuous treadmill aerobic exercise intervention, while control mice were kept under routine feeding without exercise intervention. After the intervention, Barnes maze and Y-maze behavioral tests were performed to comprehensively assess the learning and memory abilities of each group of mice. Transmission electron microscopy was used to observe the ultrastructural morphological changes of hippocampal synapses. Western blot assay was utilized to detect the protein expression and phosphorylation levels of Janus kinase 1 (JAK1), signal transducer and activator of transcription 1 (STAT1), as well as the expression of postsynaptic density protein 95 (PSD95). Immunofluorescence staining was applied to quantify the fluorescence intensity of ionized calcium-binding adapter molecule 1 (IBA1) in hippocampal tissues. The expression levels of inflammatory cytokines including interferon-α (IFN-α), interferon-β (IFN-β), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA expression level of IRF7, and DNA methylation assay was further conducted to analyze the methylation level of the IRF7 gene in mouse hippocampus. ResultsAt the molecular level, compared with group C, the protein expression levels of JAK1, STAT1, p‑JAK1, and p‑STAT1 in group A were significantly increased (P<0.05), whereas PSD95 expression was decreased (P<0.05). ELISA assays showed that the levels of IFN‑α, IFN‑β, TNF‑α, and IL‑1β were significantly elevated in group A (P<0.001). RT‑PCR analysis revealed that, compared with group C, the mRNA expression of IRF7 in group A was markedly upregulated (P<0.000 1), while the CpG methylation rate of the IRF7 promoter was significantly reduced (P<0.05). In contrast, all the above parameters in the AE group showed improvements relative to those in group A. Immunofluorescence staining indicated positive IBA1 expression in the brain tissues of group A mice. Exercise intervention reversed these abnormal changes. ConclusionIn aged mice, aerobic exercise induces hypermethylation of the IRF7 promoter region, suppresses IRF7 expression and activation of the downstream IFN‑I/JAK1/STAT1 signaling pathway, accompanied by alleviated neuroinflammation, improved learning and memory, and ameliorated brain aging-related phenotypes.

ObjectiveTo explore the mechanism through which Gantou Fumu decoction （GDFMT）-containing serum inhibits the activation of hepatic stellate cells. MethodsSerum pharmacology techniques were employed to prepare GDFMT-containing serum samples. Rat hepatic stellate cells （HSCT6） were randomly allocated into three groups： Control， penicillamine （90 mg·kg^-1）， and GDFMT （6.8 g·kg^-1）. Cell viability was assessed by the cell counting kti-8 （CCK-8） assay， intracellular ROS levels were determined by flow cytometry using the DCFH‑DA fluorescent probe and while extracellular collagen Ⅰ （ColⅠ） levels were quantified via enzyme linked immunosorbent assay （ELISA）. Intracellular α-smooth muscle actin （α-SMA） expression was visualized through immunofluorescence staining. Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to evaluate alterations in the expression of nuclear factor-erythroid 2-related factor 2 （Nrf2）， glutamate cysteine ligase， catalytic （GCLC）， glutamate-cysteine ligase， modifier subunit （GCLM）， Kelch-like ECH-associated protein 1 （Keap1）， NAD（P）H：Quinone oxidoreductase 1 （NQO1）， and heme oxygenase-1 （HO-1）. Genetic knockdown of Nrf2 was achieved through small interfering （siRNA） transfection to validate pathway specificity. ResultsCCK-8 data indicated that under the selected experimental conditions， culturing HSCT6 cells with 10% （volume fraction） GDFMT-containing serum for 48 h demonstrated equivalent effect in inhibiting HSCT6 cell proliferation compared with culturing HSCT6 cells with 10% （volume fraction） penicillamine-containing serum for 36 h， with no statistically significant difference between the two groups. After treatment of HSCT6 cells with siRNA-mediated Nrf2 gene transfection technique， the inhibitory effect of GDFMT on the activation process of HSCT6 cells was significantly weakened. After HSCT6 cells were cultured with GDFMT-containing serum for 48 h， the flow cytometry with a fluorescence probe showed that the content of reactive oxygen species （ROS） in the cells was significantly reduced. After the expression level of the Nrf2 gene in HSCT6 cells was knocked down by siRNA transfection， the content of ROS increased （P<0.01）， indicating that GDFMT significantly reduced the ROS level in activated HSCT6 cells， and this effect strictly depended on the integrity of the Nrf2 pathway. Quantitative analysis by ELISA showed that the synthesis of ColⅠ in the HSCT6 cell culture system treated with GDFMT-containing serum for 48 h was lower than that in the control group （P<0.01）. After the Nrf2 gene level of HSCT6 cells was knocked down by siRNA transfection， the ColⅠ concentration in the culture supernatant increased （P<0.01）. The results of α-SMA detection by IF method showed that compared with the normal group， GDFMT-containing serum reduced the expression of α-SMA （P<0.01） and the protein level of α-SMA in HSCT6 cells was increased （P<0.01） after siRNA-mediated Nrf2 silencing， suggesting that Nrf2 signaling pathway may be involved in regulating the phenotypic transformation process of the cells. Real-time PCR and Western blot results showed that GDFMT-containing serum reduced the protein level of α-SMA （P<0.01） and enhanced the gene and protein levels of Nrf2 in the nucleus and GCLC， HO-1， Keap1， GCLM， and NQO1 in the cytoplasm of HSCT6 cells （P<0.05， P<0.01）. After the Nrf2 gene level of HSCT6 cells was knocked down by siRNA transfection， the protein level of α-SMA was increased （P<0.01）， and the levels of GCLC， GCLM， Keap1， NQO1， and HO-1 were decreased （P<0.05， P<0.01）. These results indicated that GDFMT-containing serum successfully triggered the Nrf2 signaling pathway of HSCT6 cells. ConclusionThe anti-hepatic fibrosis effect of 10%GDFMT was equivalent to that of penicillamine. In addition， GDFMT can inhibit HSC activation and reduce oxidative stress damage by activating the Nrf2/antioxidant response element （ARE） pathway， as manifested by the up-regulated expression of Nrf2 and downstream antioxidant genes （GCLC， GCLM， HO-1， Keap1， and NQO1） and reduced secretion of ROS， α-SMA， and ColⅠ.

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

Objective To explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson's disease(PD)through fecal microbiota transplantation.Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Fecal microbiota from both the model group and the curcumin(Cur)-treated group(80 m g/kg)were collected and analyzed.The experiment involving fecal microbiota transplantation was structured into four distinct groups,fecal microbiota solvent transplantation group(FMTcon),model fecal microbiota transplantation group(FMTmodel),MPTP-induced model group(model),and model group subjected to fecal microbiota transplantation following curcumin treatment(model+FMTCur).The motor skills of the mice were assessed by using rod rotation,pole climbing experiment,and open field tests.Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase(TH)-positive neurons in the substantia nigra of the brain.Additionally,the gene expression of tumor necrosis factor-α(TNF-α)in the midbrain of mice was analyzed,alongside the protein expression of nuclear factor-κB(NF-κB)and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3).Results The subacute PD animal model in mice was successfully established,and fecal microbiota were separated and gathered.The model group exhibited significant motor impairment,as evidenced by a shortened rod rotation time(P＜0.05),prolonged pole climbing time(P＜0.05),significantly reduced total movement distance within the open field(P＜0.001),and decreased time spent in the central zone(P＜0.01).The relative expression level of TH+neurons in the substantia nigra was significantly reduced(P＜0.01).Moreover,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with significant elevations in protein expression of NF-κB(P＜0.001),phosphorylated NF-κB(p-NF-κB)(P＜0.01),NLRP3(P＜0.001),and Caspase-1(P＜0.01).The transplanted model microbial group(FMTmodel)also exhibited motor impairment,manifested by a trend of shortened rod rotation time,prolonged pole climbing time,a significant decrease in total movement distance within the open field(P＜0.01),and a trend of shortened time spent in the central zone.The relative expression level of TH+neurons in the substantia nigra decreased significantly(P＜0.05).Additionally,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with notable elevations in the protein expression of NF-κB(P＜0.05),and Caspase-1(P＜0.01).Treatment with curcumin in the fecal microbiota transplantation group of mice(model+FMTCur)showed improvements in motor abilities,evidenced by shortened pole climbing time(P＜0.05),significantly prolonged rod rotation time(P＜0.01),and extended time spent in the central zone(P＜0.05).The relative expression level of TH+dopaminergic neurons in the substantia nigra increased significantly(P＜0.05).Moreover,mRNA expression of TNF-α in the midbrain decreased significantly(P＜0.01),along with notable reductions in the protein expression of NF-κB(P＜0.001),p-NF-κB(P＜0.01),NLRP3(P＜0.05),and Caspase-1(P＜0.01).Conclusion Fecal microbiota transplantation in PD model mice can induce behavioral deficits,damage TH+neurons in the substantia nigra,and trigger neuroinflammation in the brain.Subsequent curcumin treatment can ameliorate these deficits,reverse damage to TH+neurons,reduce neuroinflammatory factors,and decrease the expression of NF-κB and NLRP3 pathways.This preliminary evidence suggests that curcumin may improve Parkinsonian behavioral deficits in mice by modulating the gut microbiota.

Abelmoschi Corolla, the dried corolla of Abelmoschus manihot, has anti-inflammatory, antioxidant, and anti-fibrosis activities. Its chemical constituents mainly include flavonoids, organic acids, steroids, and polysaccharides. This study reviewed the research progress in the chemical constituents and pharmacological activities of Abelmoschi Corolla in recent 20 years. According to the concept of quality marker(Q-marker), the Q-markers of Abelmoschi Corolla were predicted from plant phylogeny, chemical constituent specificity, traditional efficacy, chemical constituent measurability, and absorbed constituents. The primary Q-markers for Abelmoschi Corolla were anticipated to include quercetin-3'-O-β-D-glucopyranoside, gossypetin-8-O-β-D-glucuronide, isoquercetin, myricetin,quercetin, and hyperoside, with the aim of providing reference data for improving the quality evaluation system of Abelmoschi Corolla.
Abelmoschus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Flowers/chemistry* ; Humans ; Animals ; Quality Control ; Flavonoids/chemistry*

Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Objective:To prepare the nanodrug paclitaxel dimer(PTX2)-loaded nanoparticles(NPs)using the block copolymer 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol 2000,(DSPE-PEG2000),and to explore the killing effect of PTX2 NPs on the human lung cancer A549 cells and its influence on apop to tis.Methods:The PTX2 NPs were prepared using nanoprecipitation method.Dynamic light scattering(DLS)was employed to determine the particle size distribution,and transmission electron microscope(TEM)was used to observe the ultrastructure of the nanoparticles.After treatment of 0 and 10 mmol·L-1 dithiothreitol(DTT),dialysis method was used to evaluate the in vitro drug release profile of PTX2 NPs.The cell counting kit-8(CCK-8)method was used to assess the survival rates of the A549 cells after treated with PTX2 and PTX2 NPs with different concentrations(0.000 1,0.001 0,0.010 0,0.100 0,and 1.000 0 μmol·L-1).The A549 cells were divided into control group,PTX2 group,and PTX2 NPs group.Live/dead staining method was used to detect the survival of the A549 cells in various groups,and flow cytometry was used to detect the apoptotic rates of the A549 cells in various groups.Results:The mean hydrodynamic diameter of PTX2 NPs was determined to be 144.7nmbyDLS.TheTEM imaging confirmed uniform spherical morphology of PTX2 NPs.In a reductive environment,the PTX2 NPs exhibited continuous drug release with total paclitaxel(PTX)release of 84％within 72 h.The results of CCK-8 method showed that both PTX2 and PTX2 NPs inhibited the proliferation of A549 cells in a dose-dependent manner.When the concentrations of PTX＜0.01 μmol·L-1,compared with PTX2 group,the survival rates of A549 cells in PTX2 NPs group were significantly decreased(P＜0.01 or P＜0.001).The live/dead staining results showed that compared with PTX2 group,the number of red fluorescence-labeled dead cells in PTX2 NPs group was increased.The flow cytometry results demonstrated that compared with control group and PTX2 group,the apoptotic rates of the A549 cells in PTX2 NPs group were significantly increased(P＜0.05 orP＜0.01).Conclusion:The PTX2-loaded nanoparticles PTX2 NPs are successfully prepared which exhibits responsive drug release and demonstrates a more significant killing effect on the human lung cancer A549 cells compared to PTX2.