OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

Objective: To conduct a scoping review on the types, construction methods and predictive performance of health literacy prediction models based on machine learning methods, so as to provide the reference for the improvement and application of such models. Methods: Publications on health literacy prediction models conducted using machine learning methods were retrieved from CNKI, Wanfang Data, VIP, PubMed and Web of Science from inception to May 1, 2024. The quality of literature was assessed using the Prediction Model Risk of Bias ASsessment Tool. Basic characteristics, modeling methods, data sources, missing value handling, predictors and predictive performance were reviewed. Results: A total of 524 publications were retrieved, and 22 publications between 2007 and 2024 were finally enrolled. Totally 48 health literacy prediction models were involved, and 25 had a high risk of bias (52.08%), with major issues focusing on missing value handling, predictor selection and model evaluation methods. Modeling methods included regression models, tree-based machine learning methods, support vector machines and neural network models. Predictors primarily encompassed factors at four aspects: individual, interpersonal, organizational and society/policy aspects, with age, educational level, economic status, health status and internet use appearing frequently. Internal validation was conducted in 14 publications, and external validation was conducted in 4 publications. Forty-two models reported the areas under the receiver operating characteristic curve, which ranged from 0.52 to 0.983, indicating good discrimination. Conclusion Health literacy prediction models based on machine learning methods perform well, but have deficiencies in risk of bias, data processing and validation.

ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

BACKGROUND:The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans. OBJECTIVE:To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months. METHODS:Eight healthy female Hartley guinea pigs in each age group of 1,6,10,14,16,and 18 months old were selected.The quadriceps femoris was taken for hematoxylin-eosin staining,and the total knee joint was stained with hematoxylin-eosin and toluidine blue.The histopathology of the cartilage,subchondral bone,synovium,meniscus,and muscles were observed under light microscope.Mankin's score and synovitis score were compared,and the correlation analysis was conducted. RESULTS AND CONCLUSION:As the guinea pig age increased,the Mankin's score increased(P<0.05),and the pathological score of synovitis also gradually increased(P<0.05),and there was a significant positive correlation between the two(r=0.641,P<0.001).The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%,and the incidence of meniscus injury was 37.5%.In addition,osteophyte and narrowing of the joint space were observed,and only a few guinea pigs had inflammation in the quadriceps femoris.To conclude,guinea pigs develop significant cartilage defects,synovial inflammation,subchondral bone lesions,meniscus injury,osteophyte formation,and joint space narrowing as they age,all of which are similar to the pathological processes of primary knee osteoarthritis in humans,making it an ideal model of spontaneous knee osteoarthritis.

BackgroundStudents in secondary vocational health school are at the age of puberty and prone to depressive symptoms. Peer victimization and social media addiction are found to be crucial in influencing the development of depression， and positive mental health has been proven to alleviate depressive symptoms， whereas there remains a striking lack of research on the mediating role of positive mental health and social media addiction in the relationship between peer victimization and depressive symptoms among secondary vocational health school students. ObjectiveTo explore the relationship between peer victimization and depressive symptoms and investigate the mediating role of positive mental health and social media addiction， so as to provide references for the prevention of depression among secondary vocational health school students. MethodsFrom October to December 2020， a cluster sampling framework was utilized to recruit 7 307 students from a secondary vocational health school in Luzhou City， Sichuan Province. Assessments were performed using Multidimensional Peer Victimization Scale （MPVS）， Warwick-Edinburgh Mental Well-being Scale （WEMWBS）， Bergen Social Media Addiction Scale （BSMAS） and Patient Health Questionnaire Depression Scale-9 item （PHQ-9）. Spearman correlation analysis was calculated to determine correlations between scores of scales， Process 4.0 was employed to test the mediation effect， and the bias-corrected Bootstrap procedure was used to test the significance of the mediation effect. ResultsA total of 7 044 （96.40%） valid questionnaires were collected. And 4 391（62.34%）students were found to have depressive symptoms. Correlation analysis revealed that PHQ-9 score was positively correlated with BSMAS score and MPVS score （r=0.404， 0.506， P<0.01）. WEMWBS score was negatively correlated with PHQ-9 score， BSMAS score and MPVS score （r=-0.587， -0.259， -0.358， P<0.01）. BSMAS score was positively correlated with MPVS score （r=0.328， P<0.01）. Positive mental health played a mediating role in the relationship between peer victimization and depressive symptoms， with an indirect effect value of 0.130 （95% CI： 0.119~0.141）， accounting for 30.81% of the total effect. Social media addiction also mediated the relationship between peer victimization and depressive symptoms， with an indirect effect value of 0.052 （95% CI： 0.045~0.059）， accounting for 12.34% of the total effect. Positive mental health and social media addiction exhibited a chained mediation effect on the relationship between peer victimization and depressive symptoms， with an indirect effect value of 0.012 （95% CI： 0.010~0.014） and accounting for 2.84% of the total effect. ConclusionPeer victimization can affect the presence of depressive symptoms among secondary vocational health school students both directly and indirectly through either separate or chained mediation of positive mental health and social media addiction.

In tracheal resection and reconstruction, a technically demanding, complex, and high-risk procedure, management of the anastomotic site significantly impacts postoperative outcomes and long-term quality of life. However, comprehensive studies detailing perioperative anastomotic management strategies in tracheal reconstruction remain scarce. This review summarizes perioperative management strategies for tracheal reconstruction, covering preoperative assessment, surgical techniques, and other key aspects. It also highlights future research directions and challenges, aiming to provide clinicians with a systematic guide to perioperative management in tracheal reconstruction.

ObjectiveThis study aims to explore the effects of Huangqin Qingre Chubi capsules-containing serum on the expression of CircRNA_0001543/nuclear factor-kappa B （NF-κB） in co-cultured peripheral blood mononuclear cells （PBMCs） and human fibroblast-like synoviocytes （FLSs） from patients with ankylosing spondylitis （AS）. MethodsVenous blood was collected from patients with AS to isolate PBMCs. FLSs were co-cultured with AS patients' PBMCs， and FLSs were harvested after co-culture for subsequent experiments. The normal control group consisted of normal FLSs， while the model group comprised co-cultured AS PBMCs and FLSs to simulate AS pathology. The Huangqin Qingre Chubi capsules group involved adding Huangqin Qingre Chubi capsules-containing serum to the co-cultured cells（6.48 g·kg^-1）. To investigate the effect of HQC-containing serum on the viability of co-cultured cells， and the experiment was divided into the following groups based on the dilution concentration： blank group， 10% HQC group， 20% HQC group， and 30% HQC group.To study the influence of the optimal concentration of HQC-containing serum on cytokine and pathway indicators in each group， the experiment was divided into three groups： normal group， model group， and optimal concentration HQC-containing serum group.For the validation of the transfection efficiency of the CircRNA_0001543 interference plasmid， the experiment was divided into the following groups： blank group， si-NC group （with transfection reagent）， si-circ_0001543-1 group （with transfection reagent and interference plasmid No. 1 targeting circ_0001543）， si-circ_0001543-2 group （with transfection reagent and interference plasmid No. 2 targeting circ_0001543）， and si-circ_0001543-3 group （with transfection reagent and interference plasmid No. 3 targeting circ_0001543）.For the validation of the transfection efficiency of the CircRNA_0001543 overexpression plasmid， the experiment was divided into the following groups： blank group， OE-NC group （with transfection reagent）， and OE-circ_0001543 group （with transfection reagent and overexpression plasmid targeting circ_0001543）.To study the effects of CircRNA_0001543 interference/overexpression on cytokine and pathway indicators in each group， the experiment was divided into the following groups： si-NC group， si-CircRNA_0001543 group， OE-NC group， and OE-CircRNA_0001543 group. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of interleukin-1β （IL-1β）， IL-10， IL-37， and tumor necrosis factor-α （TNF-α）. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure the expression of CircRNA_0001543， IκBα， and NF-κB p65. ResultsAfter 48 hours， 30% Huangqin Qingre Chubi Capsules-containing serum significantly inhibited the proliferation of co-cultured PBMCs and FLSs， which was determined to be the optimal experimental drug-containing serum concentration. Compared with those in the normal group， the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α in the model group were significantly increased （P<0.01）， while the expressions of CircRNA_0001543 mRNA， IL-10， and IL-37 were significantly decreased （P<0.01）. Compared with those in the model group， the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α in the Huangqin Qingre Chubi Capsules-containing serum group were significantly decreased （P<0.05）， and the expressions of CircRNA_0001543 mRNA， IL-10， and IL-37 were significantly increased （P<0.05）， with the most prominent changes in the 30% drug-containing serum group （P<0.01）. Compared with that in the si-NC group， the expression of CircRNA_0001543 was significantly reduced in the si-CircRNA_0001543 group （P<0.01）. Compared with that in the OE-NC group， the expression of CircRNA_0001543 was significantly increased in the OE-CircRNA_0001543 group （P<0.01）， indicating that the si-CircRNA_0001543 and OE-CircRNA_0001543 plasmids were successfully transfected. Based on the optimal drug-containing serum of Huangqin Qingre Chubi Capsules， si-CircRNA_0001543 transfection led to significantly increased expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α and decreased the expressions of IL-10 and IL-37 （P<0.01）. In contrast， OE-CircRNA_0001543 transfection significantly decreased the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α （P<0.01） and increased the expressions of IL-10 and IL-37 （P<0.01）. ConclusionHuangqin Qingre Chubi capsules-containing serum can improve immune inflammation in AS by increasing the expression of CircRNA_0001543， regulating the NF-κB pathway， suppressing pro-inflammatory cytokines， and enhancing anti-inflammatory cytokine expression.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

Objective: To analyze the serotypes and drug resistance of Salmonella isolated from food-borne disease surveillance samples in Longwan District, Wenzhou City, Zhejiang Province, so as to provide evidence for the prevention and treatment of Salmonella infection. Methods: Salmonella strains isolated from feces or anal swabs of patients with foodborne diarrhea in Longwan District People's Hospital from 2018 to 2024 were collected. After re-identification, slide agglutination test was used to identify serotypes. The drug susceptibility test of live Salmonella strains was performed using the broth microdilution method, and the resistance patterns were analyzed. Results: A total of 2 293 samples were collected, and 186 strains of Salmonella were isolated, with a detection rate of 8.11%. The detection rate was higher from May to October. A total of 28 Salmonella serotypes were identified, with S. typhimurium (72 isolates, 38.71%), S. enteritidis (31 isolates, 16.67%), and S. London (30 isolates, 16.13%) being dominant. Among the 121 Salmonella live strains, 20 strains were susceptible to 14 antibacterial drugs. A total of 101 strains were resistant to antibacterial drugs, and the drug resistance rate was 1.65%-67.77%, with the drug resistance rate of ampicillin being the highest, and the drug resistance rate of imipenem was the lowest. S. typhimurium had the highest resistance rate to tetracycline (78.26%). S. enteritidis had the highest resistance rate to ampicillin (100.00%). S. London had the highest resistance rate to tetracycline (66.67%). Fifty-five types of drug resistance patterns were detected, showing a number of drug resistance of 1-10, of which 76 strains were multi-drug resistant, accounting for 75.25%. The predominant multidrug resistance patterns were ampicillin/sulbactam-cefazolin-ampicillin-nalidixic acid (10.53%), tetracycline-ampicillin-nalidixic acid (9.21%), and ampicillin/sulbactam-ampicillin-nalidixic acid (7.89%). Conclusions Salmonella strains isolated from foodborne diseases in Longwan District were mainly detected in summer and autumn. S. typhimurium, S. enteritidis, and S. London were the predominant serotypes. The drug resistance of Salmonella to different antibacterial drugs was different, and the drug resistance spectrum showed diversity.