ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

In recent years， traditional Chinese medicine （TCM） has achieved significant progress in the treatment of inflammatory bowel disease （IBD）. A comprehensive literature search was conducted covering the period from January 1， 2010， to December 30， 2024， across Chinese databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP China Science and Technology Journal Database， and the Chinese Biomedical Literature Service System， as well as international databases such as PubMed， Web of Science， and Embase. The clinical applications and mechanistic studies of TCM in IBD were systematically reviewed. The current status of TCM research on the etiology and pathogenesis of IBD， innovative clinical practices， and multimodal therapeutic approaches， including Chinese herbal formulas， single herbs or active compounds， acupuncture， herbal retention enema， and acupoint application， were summarized， together with their synergistic effects when combined with western medical treatments. The development and application of Chinese patent medicines for IBD are undergoing a profound transition from efficacy validation to mechanistic exploration. Mechanistic studies on the effects of TCM in IBD mainly focus on regulating gut microbiota homeostasis， repairing the intestinal mucosal barrier， and modulating intestinal immune balance. Furthermore， future research directions for TCM-based IBD management are proposed， including the establishment of TCM diagnostic and treatment models， expanding integrated applications of external and internal TCM therapies， innovating personalized treatment strategies， and advancing drug development. These efforts aim to provide insights for the standardized and precision-oriented development of TCM in the diagnosis and treatment of IBD.

Objective To explore the effectiveness of the cumulative sum (CUSUM) and the exponentially weighted moving average (EWMA) for early warning of influenza epidemic using two datasets of reported influenza cases and influenza-like illness (ILI) cases. Methods Using the reported cases of influenza and ILI in Daxing District, Beijing, from week 23 of 2018 to week 22 of 2024 as data sets, the CUSUM and EWMA models were established, respectively. The positive rate of influenza etiology was used as the ^“gold standard^”, and the Youden index was used as the evaluation index to compare the early warning effect of the two models under different data sets and different parameters. Results In CUSUM, the optimal Youden indices of the reported influenza cases set and the ILI cases set were 0.751 and 0.635, respectively. In EWMA, the optimal Youden indices of the reported influenza cases set and the ILI cases set were 0.544 and 0.464, respectively. The optimal EWMA and CUSUM models could both issue early warning signals in advance of the ^“gold standard^”. Conclusion In the influenza epidemic early warning in Daxing District, Beijing, the CUSUM model established with the reported cases of influenza can achieve good early warning effects, but the model parameters need to be dynamically adjusted according to the local epidemic characteristics.

Plant-derived extracellular vesicles (PDEVs) are nanoscale extracellular vesicles secreted by plant cells, characterized by a lipid bilayer structure. These vesicles carry a variety of bioactive molecules, including proteins, nucleic acids, and lipids, and play essential roles in intercellular communication and physiological regulation in plants. Compared to animal-derived extracellular vesicles, PDEVs offer several advantages, such as a broad range of sources, high biocompatibility, low immunogenicity, and low production costs. Furthermore, PDEVs have demonstrated remarkable potential as natural nanocarriers for drug delivery, due to their ability to efficiently traverse biological barriers, such as the blood-brain barrier, making them promising candidates for drug delivery systems. This review systematically elaborates on the complex composition of PDEVs, which consists of lipids, proteins, and nucleic acids, the typical structural characteristics of their lipid bilayers ranging from 30 to 150 nm, and their versatile loading capabilities as drug carriers, efficiently encapsulating various types of therapeutic agents such as hydrophilic small molecules, hydrophobic drugs, nucleic acids, and proteins. We systematically summarize the recent advancements in strategies for enhancing the loading efficiency of PDEVs, which include methods such as co-incubation, ultrasound-assisted loading, electroporation, freeze-thaw cycles, and microfluidic technology. These techniques are evaluated based on their underlying principles, suitable drug types, and their respective advantages. In addition to loading strategies, we focus on the engineered approaches to achieve targeted delivery using PDEVs, such as genetic engineering modifications, chemical ligand conjugation, membrane fusion technology, and polyethylene glycol (PEG) modification. We discuss the mechanisms of these strategies in enhancing targeting efficiency, prolonging in vivo circulation time, and improving therapeutic efficacy. Further, this review highlights the application of PDEVs in various disease models, including tumor, skin inflammation, metabolic disorders, and neurodegenerative diseases, showcasing their therapeutic potential as multifunctional delivery platforms. The ability of PDEVs to encapsulate diverse therapeutic agents and target specific tissues or cells opens up new avenues for the treatment of complex diseases, offering advantages over conventional drug delivery systems. However, despite the promising applications of PDEVs, several challenges remain in their development and clinical translation. These challenges include variability in source materials, standardization of preparation processes, quality control, scalability of production, and the need for clinical validation. To overcome these obstacles, the integration of advanced technologies such as artificial intelligence-assisted design and multi-omics analysis is proposed as a way to facilitate the precise development of PDEVs. These emerging technologies hold the potential to further enhance the precision and effectiveness of plant-based drug delivery systems, ultimately advancing the field of precision medicine. In conclusion, the use of PDEVs as a platform for drug delivery represents a promising area of research with the potential to revolutionize therapeutic strategies. Their ability to encapsulate and deliver a wide variety of bioactive molecules, along with their inherent advantages in biocompatibility and versatility, makes them a valuable tool in the development of more efficient and targeted therapeutic interventions. Continued research and innovation in this field will pave the way for the clinical implementation of PDEVs in the treatment of various diseases, offering new hope for more effective and sustainable therapeutic options.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To investigate the efficacy of preprocedural intracoronary injections of adenosine and sodium nitroprusside in patients with intravascular ultrasound-attenuated plaques(AP).Methods In total,200 patients with AP detected using intravascular ultrasound(IVUS)at Shijiazhuang People's Hospital from January 1,2022,to January 1,2024,were selected and randomly divided into conventional treatment and pretreatment groups,with 100 patients in each group.The conventional treatment group underwent standard percutaneous coronary intervention(PCI)procedures,whereas the pretreatment group underwent intracoronary injection of sodium nitro-prusside and adenosine through a guiding catheter prior to PCI.The observation parameters included intraoperative no-reflow(NR)inci-dence,post-PCI TIMI myocardial perfusion frame count(TMPFC),perioperative myocardial infarction(PMN),and 6-month major adverse cardiac and cerebrovascular events(MACCE).Results The pretreatment group exhibited a significantly lower intraoperative NR inci-dence,reduced postoperative TMPFC,and attenuated PMN severity than the conventional treatment group(P＜0.05).Conclusion Pre-procedural intracoronary administration of adenosine and sodium nitroprusside through a guiding catheter can effectively reduce PCI-re-lated NR occurrence,improve post-PCI TMPFC,and mitigate PMN in patients with AP,although no significant improvement in MACCE incidence can be observed at the 6-month follow-up.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To explore the clinical,radiological,and arthroscopic outcomes of anterior cru-ciate ligament(ACL)reconstruction combined with posterior tibial slope(PTS)reducing osteotomy in patients with increased PTS and excessive anterior tibial subluxation(ATS)due to primary ACL inju-ry.Methods This retrospective study included patients who underwent ACL reconstruction between 2016 and 2022 in our department.The inclusion criteria were PTS≥15° and ATS≥6 mm,and all pa-tients received ACL reconstruction combined with PTS reducing osteotomy with a follow-up of more than 2 years.Before and after the operation,they were assessed KT-1000 side-to-side difference(KT SSD),pivot shift grade,Lachman test,anterior tibial subluxation of the medial and lateral compart-ments(ASMC and ASLC),magnetic resonance imaging(MRI),and arthroscopic findings of associat-ed injuries.Moreover,graft laxity was defined as graft laxity observed on MRI or arthroscopy,KT SSD>3 mm,or pivot>1+,while graft failure was defined as graft rupture on MRI or arthroscopy,KT SSD>5 mm,or pivot>2+.Meanwhile,clinical outcomes were compared preoperatively and post-operatively,and graft status and associated injuries were described.Results A total of 30 patients were included,with an average age of 31 years,and 23%of female.The inter-observer reliability for mea-surements of PTS and ATS was greater than 0.80.Compared to preoperative values,postoperative PTS(18.2° vs.6.8°,P<0.001),KT SSD(7.8 mm vs.1.2 mm,P<0.001),ASLC(7.5 mm vs.4.5 mm,P=0.002),and ASMC(5.0 mm vs.2.7 mm,P=0.034),all showed significant improvements.In addi-tion,the proportion of patients with postoperative pivot grade of 2+to 3+(73.3%vs.6.7%,P<0.001)and Lachman grades Ⅱ-Ⅲ(70%vs.3.3%,P<0.001)reduced significantly.At the last follow-up,the incidence of graft laxity was 20%,and that of the graft failure was 13.3%.Among all pa-tients,1 patient(3.3%)had graft roof impingement or cyclops lesion,and 3(10%)suffered from concomitant cartilage injury,with 4(13.3%)undergoing intercondylar notchplasty due to intercondylar notch hyperplasia.However,no complications related to osteotomy,such as infection,non-union,or fixation failure,were observed.Conclusion Over a follow-up period of at least 2 years,for primary ACL injury patients with steep PTS and excessive ATS,combined ACL reconstruction with PTS reduc-ing osteotomy improves knee stability,but significantly reduces PTS,the incidence of severe pivot grade,anterior tibial subluxation in both medial and lateral compartments,and delays the occurrence of graft laxity and failure.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P＜0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P＜0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.

OBJECTIVE To investigate the therapeutic effect of Qingchang Huazhuo Formula(QCHZF)on mice with ulcerative colitis(UC)and the influences of fecal metabolites based on non-targeted metabolomics to investigate the mechanism of action of QCHZF in the treatment of UC.METHODS UC mice were induced by dextran sulfate sodium salt(DSS)and were administered with QCHZF.During the experiment,the body weight,stool characteristics and blood in stool were recorded daily,and the disease activity index(DAI)was calculated.At the end of the experiment,the length of colon was measured,colonic tissue damage in mice were ob-served by hematoxylin-eosin and alcian blue staining,mRNA expression levels of inflammatory factors,IL-6,IL-18 and IL-1β,and intestinal barrier factors,ZO-1 and Muc2,were detected in colon tissues via qPCR method,and protein expression level of intestinal barrier,Muc2,was detected with immunofluorescence.Fecal metabolite changes in mice were detected employing un-targeted metabo-lomics and analyzed by MetaboAnalyst 5.0 for metabolic pathway enrichment.RESULTS QCHZF significantly alleviated colitis symptoms,increased body weight,decreased DAI score,reversed colonic shortening,inhibited inflammatory factors expression,im-proved colonic tissue structure disorders,increased the number of goblet cells,and restored the intestinal barrier in UC mice,regulated 58 metabolites,mainly involving pathways of methionine and cysteine metabolism,purine metabolism,steroid hormone biosynthesis,vitamin B6 metabolism,tryptophan metabolism and primary bile acid pathways.CONCLUSION QCHZF can improve colitis symp-toms,repaire the intestinal barrier and modulate fecal metabolites and related metabolic pathways in UC mice.