ObjectiveTo investigate the risk factors for bleeding within 5 days and 2 weeks after endoscopic variceal ligation （EVL） or endoscopic cyanoacrylate injection （ECI） for the treatment of esophagogastric varices in patients with liver cirrhosis， as well as the safety of EVL/ECI in patients with thrombocytopenia. MethodsA total of 489 patients with liver cirrhosis and esophagogastric varices who underwent EVL/ECI in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2018 to December 2023 were enrolled as subjects， and according to the presence or absence of bleeding after surgery， they were divided into bleeding group and non-bleeding group. The risk factors for bleeding within 5 days and 2 weeks after surgery were analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups， and the chi-square test or the continuity-corrected chi-square test was used for comparison of categorical data between groups； the receiver operating characteristic （ROC） curve was plotted to determine the cut-off value of MELD score； a multivariate logistic regression analysis was used to identify the independent risk factors for postoperative bleeding. ResultsThere were no significant differences in the bleeding rates within 5 days and 2 weeks after EVL/ECI between the 386 patients with a platelet count of ≥50×10⁹/L and the 103 patients with a platelet count of （25 — 49）×10⁹/L （5 days： 1.94% vs 2.85%， P=0.870； 2 weeks： 2.91% vs 4.92%， P=0.544）. The overall bleeding rate was 2.66% （13/489） and 4.50% （22/489）， respectively， within 5 days and 2 weeks after EVL/ECI. The multivariate logistic regression analysis showed that MELD score was an independent risk factor for bleeding within 5 days （odds ratio ［OR］=3.726， 95% confidence interval ［CI］： 1.214 — 11.429， P=0.021） and 2 weeks （OR=5.760， 95%CI： 1.779 — 18.651， P=0.003） after EVL/ECI， while hemoglobin （Hb） was a protective factor against bleeding within 5 days （OR=0.972， 95%CI： 0.948 — 0.996， P=0.025） and 2 weeks （OR=0.976， 95%CI： 0.957 — 0.995， P=0.016） after surgery； portal vein tumor thrombus （OR=2.667， 95%CI： 1.000 — 7.117， P=0.050） was an independent risk factor for bleeding within 2 weeks after surgery， while platelet count ［（25 — 49）×10⁹/L］ was not a risk factor for postoperative bleeding （P>0.05）. ConclusionBoth EVL and ECI have good safety in patients with liver diseases and grade 3 thrombocytopenia. MELD score is an independent risk factor for bleeding within 5 days and 2 weeks after EVL/ECI， while Hb is a protective factor； portal vein tumor thrombus is an independent risk factor for bleeding within 2 weeks after surgery.

OBJECTIVE To investigate the prevalence and influencing factors of potentially inappropriate medication （PIM） among the elderly in nursing homes in Urumqi based on three PIM screening tools， and to compare the applicability of different tools. METHODS A cross-sectional study design was adopted. Elderly individuals from six nursing homes in Urumqi were selected as the research subjects from May 2021 to September 2023. Demographic characteristics， disease burden and medication records of the elderly were collected. PIM screening was performed using the Chinese PIM criteria （2024 edition）， the American Geriatrics Society （AGS） Beers criteria （2023 edition）， and the Screening Tool of Older Person’S Prescriptions（STOPP）/Screening Tool to Alert to Right Treatment（START） （2023 edition）. Fleiss’s Kappa test was used to assess the consistency among the three screening tools， and multivariate Logistic regression was used to analyze the influencing factors of PIM. RESULTS The prevalence of PIM screened by the Chinese PIM criteria was 47.4% （323/682）， by the AGS Beers criteria was 43.4% （296/682）， and by the STOPP criteria was 50.9% （347/682）. The consistency among the three screening tools was low （Fleiss’s Kappa＝0.12， P ＜0.001）. Multivariate Logistic regression analysis showed that all three screening tools indicated that polypharmacy， aspirin use and psychotropic drug use were independent risk factors for PIM among elderly in nursing houses （all OR＞1， P ＜0.05）. CONCLUSIONS The prevalence of PIM among the elderly in nursing homes in Urumqi is relatively high. Polypharmacy， aspirin use and psychotropic drug use are common independent risk factors for PIM. There are differences in screening results among the three tools with low consistency. The Chinese PIM criteria can serve as a first-line tool for PIM screening in nursing homes.

Multi-target analgesics with minimal side effects and high efficacy are a key research focus in addressing the global pain crisis. Using a molecular networking approach, five pairs of potent analgesic alkaloid enantiomers were isolated from the roots of Anacyclus pyrethrum (A. pyrethrum). Their structures were elucidated by comprehensive spectroscopic data analysis, including LR-HSQMBC and ¹H-¹⁵N HMBC, quantum ¹³C NMR DP4+ and ECD calculations, and single-crystal X-ray diffraction analysis. Anacyphrethines A (1) and B (2) are highly conjugated and polymethylated 6/6/6/6/5/7/5/5-fused octacyclic tetraazabic alkaloids possessing an unprecedented 8,14,18,24-tetraaza-octacyclo[16.8.2.1^1,23.0^4,28.0^5,17.0^9,16.0^11,15.0^21,27] nonacosane motif. Their biosynthetic pathways are proposed involving key aldol, hydroamination, and Schiff base reactions. All isolates showed potent analgesic effects in vivo. Even at a lower dose of 0.2 mg/kg, (±)-1 and (+)-1 still exhibited more potent analgesic activities than morphine. Interestingly, the racemic mixture (±)-1 showed stronger analgesic effect than either pure enantiomer alone at higher doses of 5 and 1 mg/kg; while, (±)-1 showed significant analgesic activities comparable to (+)-1 at lower doses of 0.2 and 0.04 mg/kg. (+)-1 had stronger analgesic effect than (-)-1 at five tested does. Further tests on 44 analgesic-related targets demonstrated that (+)-1 showed significant inhibitory effects against many ion channels such as TRPM8, Kv1.2, Kv1.3, and Ca_v2.1 with IC₅₀ values of 1.10 ± 0.26, 4.20 ± 0.07, 2.20 ± 0.24, and 10.40 ± 0.69 μmol/L, respectively, while (-)-1 primarily inhibited TRPC6, Kv1.2, and Kv1.3 ion channels with IC₅₀ values of 0.81 ± 0.05, 0.91 ± 0.04, and 1.50 ± 0.13 μmol/L, respectively, without affecting the opioid receptors, suggesting their non-opioid analgesic potentials. The molecular dockings provided structural guidance to develop potent non-opioid analgesics.

ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group， a model group， a sulfasalazine group （0.6 g·kg^-1）， and low-， medium-， and high-dose Xielitang groups （1.67， 3.34， 6.68 g·kg^-1）. After treatment for 42 d， the colon length was recorded， and the disease activity index （DAI） score was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. Hematoxylin-eosin （HE） staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor （FXR）， small heterodimer partner （SHP）， liver receptor homolog-1 （LRH-1）， cholesterol 7α-hydroxylase （CYP7A1）， and fibroblast growth factor receptor 4 （FGFR4） in liver and FXR， sodium-dependent bile acid transporter （ASBT）， and fibroblast growth factor 15 （FGF15） in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover， ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group， the model group showed significantly decreased colon length， IL-10 content， α-diversity index， abundance of Firmicutes and Lactobacillus， and content of deoxycholic acid （DCA） and lithocholic acid （LCA） （P<0.01）， significantly increased DAI score， IL-6 and TNF-α content， abundance of Bacteroidetes， and the content of cholic acid （CA）， chenodeoxycholic acid （CDCA）， and taurocholic acid （TCA） （P<0.05， P<0.01）， significantly down-regulated protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. In addition， the structure of colonic mucosa was destroyed， and inflammatory cells infiltrated in the model group. Compared with the model group， Xielitang could significantly increase the colon length， IL-10 content， α-diversity index， the abundance of Firmicutes and Lactobacillus， and DCA and LCA content （P<0.05， P<0.01）， decrease DAI score， abundance of Bacteroidetes， and the content of IL-6， TNF-α， CA， CDCA， and TCA （P<0.01）， up-regulate the protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and down-regulate the protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis， regulating intestinal flora imbalance， and maintaining bile acid homeostasis.

Esophagogastric variceal bleeding is a common complication and the leading cause of death in advanced liver cirrhosis， and endoscopic variceal ligation （EVL） and endoscopic cyanoacrylate injection （ECI） are commonly used treatment strategies. Thrombocytopenia is one of the most common hematological complications in liver cirrhosis， and patients with severe thrombocytopenia have the potential risk of bleeding， which may affect treatment decision-making by clinicians and endoscopists. This article reviews the evolution of guidelines and clinical research advances regarding EVL/ECI in China and globally， in order to provide a basis for decision making among clinicians.

To investigate the mechanism of Qitu Erzhi Decoction(QTEZ) in ameliorating chemotherapy-induced myelosuppression and the focus of its decomposed formulae on the effects of hematopoietic cells of the three lineages, respectively. Ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of QTEZ intestinal absorption liquid and obtain the target sites, which were intersected with chemotherapy-induced myelosuppression targets collected from several databases, including OMIM, and an interaction network was established based on network pharmacology for Gene Ontology(GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Hematopoietic stem cells of mice were taken after intraperitoneal injection of 5-fluorouracil for myelosuppression modeling and randomly divided into the model group, Qitu Erzhi group, Astragali Radix-Angelicae Sinensis Radix group, Ligustri Lucidi Fructus-Ecliptae Herba group, Psoraleae Fructus-Cuscutae Semen group, and positive drug group, which were given the corresponding traditional Chinese medicine intestinal absorption liquid and the positive drug granulocyte colony-stimulating factor, respectively. The normal hematopoietic stem cells were taken as the control group and were given the intervention of normal saline. The proliferation of hematopoietic progenitor cells of three lineages was observed by flow cytometry, and the cell cycle and colony formation assay were observed. Western blot was used to verify the effect of QTEZ on the pathway proteins including phosphoinositide 3-kinase(PI3K), phosphorylated PI3K(p-PI3K), protein kinase B(AKT), and phosphorylated AKT(p-AKT). RT-qPCR and Western blot were used to detect the effects of QTEZ on cell cycle-related targets such as CDK inhibitor 1(P21), cyclin D1(CCND1), and cyclin-dependent kinase 4(CDK4). The results showed that a total of 158 components were identified by QTEZ, and 375 component and disease intersecting targets were obtained, 21 core components and 40 core targets were obtained after constructing the network, and GO and KEGG enrichment showed signaling pathways such as PI3K/AKT. QTEZ and its decomposed formulae could promote the 5-fluorouracil-blocked cell cycle to resume operation, and all of them had different degrees of restoration effects on the set of colonies, among which QTEZ had the best restoration effect, and the Astragali Radix-Angelicae Sinensis Radix group had a focused effect on colony forming unit-erythrocyte. Western blot results indicated that there was no significant difference in the expression levels of pathway proteins among the groups. RT-qPCR and Western blot results showed that QTEZ could down-regulate P21 and up-regulate the protein and mRNA expression of CDK4 and CCND1. In conclusion, QTEZ and its decomposed formulas can exert a protective effect on hematopoietic stem cells with 5-fluorouracil-induced myelosuppression by promoting the normal operation of the cell cycle and colony formation, and the mechanism may be related to the down-regulation of the cell cycle-related targets of P21 and the up-regulation of CDK4 and CCND1. In addition, Astragali Radix-Angelicae Sinensis Radix can have a targeted protective effect on erythrocytes.
Animals ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Mice ; Fluorouracil/adverse effects* ; Male ; Antineoplastic Agents/adverse effects* ; Hematopoietic Stem Cells/cytology* ; Humans ; Signal Transduction/drug effects*

Objective:To investigate the protective effects of resveratrol (RSV) on human sperm cryopreservation and explore its underlying protective mechanisms.Methods:A total of 165 normal fresh semen samples were collected from the Reproductive Medicine Center, Department of Obstetrics and Gynecology and Human Sperm Bank of the First Affiliated Hospital of Anhui Medical University between December 2022 and December 2024. Among them, 65 samples were used to obtain semen parameters before and after conventional freezing. Each sample of the other 104 samples was mixed at a 2∶1 volume ratio with cryoprotectant containing 0, 10 -?, 10 -?, or 10 -? mol/L RSV, followed by cryopreservation in liquid nitrogen for 24 h. Post-thaw assessments included routine sperm parameters, sperm DNA fragmentation index (DFI) evaluated by sperm chromatin dispersion assay, reactive oxygen species (ROS) levels measured via flow cytometry, RSV and nuclear factor erythroid 2-related factor 2 (NRF2) interactions examined by molecular docking and cellular thermal shift assay (CETSA), NRF2 protein contents analyzed by immunofluorescence and Western blotting, mRNA levels of NRF2 and downstream antioxidant proteins Heme Oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) quantified by qRT-PCR and effects of NRF2 inhibitor ML385 on sperm parameters. Results:Compared with fresh samples, conventional cryopreservation significantly reduced sperm motility (all P<0.001). The addition of 10 -? mol/L RSV significantly improved the percentage of forward motile sperm after freezing (26.98%±8.98% vs. 19.61%±8.03%, P<0.001) while reducing DFI (9.84%±3.81% vs. 15.06%±4.22%, P<0.001) and ROS levels ( P<0.001) compared with the post-freezing group without the addition of RSV. Both molecular docking analysis and CETSA confirmed that RSV interacted with NRF2. Notably, sperm cryopreserved with 10 -? mol/L RSV exhibited significantly higher contents of NRF2 and its downstream effectors HO-1 and NQO1 compared with the post-freezing group without the addition of RSV (all P<0.001). This protective effect was markedly attenuated by co-treatment with the NRF2 inhibitor ML385, as evidenced by a significant decline in sperm motility ( P<0.001). Conclusion:RSV exerts cryoprotective effects likely through NRF2-mediated antioxidant pathways, reducing oxidative stress and enhancing post-thaw sperm quality.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Aim To analyze the incidence of major adverse cardiovascular and cerebrovascular events(MACCE)in patients with different types of acute coronary syndrome(ACS)undergoing coronary artery rotational atherec-tomy(RA)within two years.Methods 268 patients with ACS who underwent RA in the Department of Cardiology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School of Nanjing University,between November 2011 and December 2022 were retrospectively included.According to whether ST-segment elevation myocardial infarction(STEMI)occurred,they were divided into 25 cases in the ST-segment elevation myocardial infarction(STEMI)group and 243 cases in the non-ST-segment elevation acute coronary syndrome(NSTE-ACS)group.The NSTE-ACS group included unstable angina pectoris(UAP)and non-STEMI(NSTEMI).The basic information and intraoperative data related to percutaneous coronary intervention(PCI)in the two groups were collected,and the occurrence of MACCE(including car-diovascular death,non fatal myocardial infarction,worsening heart failure,ischemic stroke and target vessel revasculariza-tion)within two years after RA was followed up and analyzed.Results Compared with the NSTE-ACS group,the STEMI group had a higher incidence of MACCE and cardiovascular mortality during the two-year follow-up period(10.3％and 0.4％vs.28.0％and 8.0％;P＜0.05).There was no statistical difference between the incidence of target vessel revascularization,nonfatal infarction,ischemic stroke and worsening heart failure between the two groups(P＞0.05).According to subgroup analysis based on enrollment periods,the results showed that over time(2011-2017 compared to 2018-2022),the incidence of MACCE in all patients within two years after RA showed a decreasing trend(18.97％vs.6.58％).Combined with previous studies,gender,hypertension,diabetes,renal insufficiency,smoking and left ven-tricular ejection fraction(LVEF)were included in the Cox regression model.It was found that the use of intravascular ul-trasound(IVUS)was an independent factor to reduce the incidence of MACCE in ACS patients within two years after RA(HR=0.333,95％CI:0.153～0.723,P＜0.01).Kaplan-Meier analysis showed that among ACS patients undergoing RA,the cumulative incidence of MACCE events was higher in the STEMI group than that in the NSTE-ACS group(P＜0.05).Conclusion STEMI patients have a higher incidence of MACCE and cardiovascular mortality within two years after RA compared to NSTE-ACS patients,and the use of IVUS during RA surgery can reduce the incidence of MACCE in ACS patients after RA.

Aim To analyze the incidence of major adverse cardiovascular and cerebrovascular events(MACCE)in patients with different types of acute coronary syndrome(ACS)undergoing coronary artery rotational atherec-tomy(RA)within two years.Methods 268 patients with ACS who underwent RA in the Department of Cardiology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School of Nanjing University,between November 2011 and December 2022 were retrospectively included.According to whether ST-segment elevation myocardial infarction(STEMI)occurred,they were divided into 25 cases in the ST-segment elevation myocardial infarction(STEMI)group and 243 cases in the non-ST-segment elevation acute coronary syndrome(NSTE-ACS)group.The NSTE-ACS group included unstable angina pectoris(UAP)and non-STEMI(NSTEMI).The basic information and intraoperative data related to percutaneous coronary intervention(PCI)in the two groups were collected,and the occurrence of MACCE(including car-diovascular death,non fatal myocardial infarction,worsening heart failure,ischemic stroke and target vessel revasculariza-tion)within two years after RA was followed up and analyzed.Results Compared with the NSTE-ACS group,the STEMI group had a higher incidence of MACCE and cardiovascular mortality during the two-year follow-up period(10.3％and 0.4％vs.28.0％and 8.0％;P＜0.05).There was no statistical difference between the incidence of target vessel revascularization,nonfatal infarction,ischemic stroke and worsening heart failure between the two groups(P＞0.05).According to subgroup analysis based on enrollment periods,the results showed that over time(2011-2017 compared to 2018-2022),the incidence of MACCE in all patients within two years after RA showed a decreasing trend(18.97％vs.6.58％).Combined with previous studies,gender,hypertension,diabetes,renal insufficiency,smoking and left ven-tricular ejection fraction(LVEF)were included in the Cox regression model.It was found that the use of intravascular ul-trasound(IVUS)was an independent factor to reduce the incidence of MACCE in ACS patients within two years after RA(HR=0.333,95％CI:0.153～0.723,P＜0.01).Kaplan-Meier analysis showed that among ACS patients undergoing RA,the cumulative incidence of MACCE events was higher in the STEMI group than that in the NSTE-ACS group(P＜0.05).Conclusion STEMI patients have a higher incidence of MACCE and cardiovascular mortality within two years after RA compared to NSTE-ACS patients,and the use of IVUS during RA surgery can reduce the incidence of MACCE in ACS patients after RA.