ObjectiveTo investigate the therapeutic effect and mechanism of Xueshisanjia San against liver fibrosis by regulating PTEN-induced putative kinase （PINK1）/Parkin signaling pathway-mediated mitophagy. MethodsForty specific pathogen free （SPF）-grade male C57BL/6 mice were randomized into the control， model， silibinin （100 mg·kg^-1）， high-dose （15.16 g·kg^-1） Xueshisanjia San， and low-dose （7.58 g·kg^-1） Xueshisanjia San groups. The mouse model of liver fibrosis was constructed by intraperitoneal injection of 20% carbon tetrachloride solution. The treatment lasted for 6 weeks. Blood was collected from the abdominal aorta after intraperitoneal anesthesia， and the liver was separated. Liver pathology was examined by hematoxylin-eosin （HE） staining， Masson staining， and Sirius Red staining. Transmission electron microscopy （TEM） was employed to observe the mitochondrial morphology in the liver tissue. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， C-reactive protein （CRP）， total bilirubin （TBil）， transforming growth factor-β₁ （TGF-β₁）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） in the serum of mice were measured by enzyme-linked immunosorbent assay. Immunohistochemistry， immunofluorescence assay， and Western blot were employed to determine the protein levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and collagen Ⅰ， as well as mitophagy markers microtubule-associated protein 1 light chain 3 （LC3）， p62， Beclin-1， PINK1， Parkin， and translocase of outer mitochondrial membrane 20 （TOM20）. ResultsCompared with the control group， the model group exhibited elevated levels of ALT， AST， CRP， TBil， IL-6， TGF-β₁， and TNF-α in the serum （P<0.05）， pathological changes such destroyed structure of hepatic lobules， disarrangement of hepatic cells， and collagen accumulation， swollen， vacuolated， and fragment mitochondria， down-regulated expression of p62 and TOM20， and up-regulated expression of LC3， Beclin-1， PINK1， and Parkin （P<0.05）. Compared with the model group， all the treatment groups exhibited declined levels of ALT， AST， CRP， TBil， IL-6， TGF-β₁， and TNF-α in the serum （P<0.05）， alleviated pathological damage of liver tissue and mitochondrial damage， up-regulated expression of p62 and TOM20， and down-regulated expression of α-SMA， COL1A1， LC3， Beclin1， PINK1， and Parkin （P<0.05）. ConclusionXueshisanjia San may prevent excessive mitophagy and improve mitochondrial quality by inhibiting PINK1/Parkin signaling pathway， thereby alleviating liver fibrosis.

Objective: To investigate the prevalence and influencing factors of menopausal syndrome among postmenopausal women in Pan'an County, Zhejiang Province, so as to provide the basis for guiding the health management of postmenopausal women. Methods: From May 2023 to April 2024, the postmenopausal women aged 40 to 69 years in Pan'an County were selected using the random cluster sampling method. Demographic information, lifestyle and prevalence of gynecological diseases were collected through questionnaire surveys. The prevalence of menopausal syndrome was assessed by modified Kupperman Score Scale. Factors affecting menopausal syndrome were analyzed by a multivariable logistic regression model. Results: A total of 816 postmenopausal women were surveyed, with an mean age of (57.63±2.92) years and a mean natural menopause age of (49.85±2.13) years. There were 574 cases with menopausal syndrome, with a prevalence of 70.34%. Flashes and sweating, insomnia and irritability were common symptoms, accounting for 62.87%, 47.43% and 41.18%, respectively. Multivariable logistic regression analysis showed that monthly personal income of ≤5 000 yuan (<3 000 yuan, OR=3.124, 95%CI: 1.829-5.335; 3 000-5 000 yuan, OR=2.399, 95%CI: 1.370-4.201) and having gynecological diseases (OR=1.970, 95%CI: 1.292-3.004) were associated with a higher risk of menopausal syndrome, while average (OR=0.141, 95%CI: 0.072-0.276) or sufficient sleep quality (OR=0.095, 95%CI: 0.049-0.185) were associated with a lower risk of menopausal syndrome. Conclusion The prevalence of menopausal syndrome among postmenopausal women in Pan'an County is relatively high, and is mainly influenced by personal economic status, sleep quality and the presence of gynecological diseases.

OBJECTIVE To investigate the impact of vesicular stomatitis virus envelope glycopro-tein-G(VSV-G)modification on the mucosal immune efficacy of antigen-loaded engineered exosome vaccines.METHODS In vitro experiments:Dendritic cells(DCs)were divided into three groups:cell-control(treated with culture medium),receptor binding domain(RBD)(transfected with plasmid RBD),and RBD+VSV-G(co-transfected with plasmids RBD and VSV-G).Expression levels of RBD and VSV-G were assessed using Western blotting,flow cytometry,and immunofluorescence.Exosomes were extracted via ultracentrifugation,whose morphology,size distribution,and marker proteins were analyzed using transmission electron microscopy,nanoparticle tracking analysis,and Western blotting that confirmed the expressions of RBD and VSV-G in the exosomes.In vivo experiments:① Female BALB/c mice were divided into the control group Mock exosomes(Mock-Exo)(derived from the supernatant of cell-control),RBD decorated exosomes(RBD-Exo)(derived from the RBD cell supernatant),and RBD and VSV-G decorated exosomes(RBD+VSV-G-Exo)(derived from RBD+VSV-G cell supernatant).Follow-ing intranasal immunization with the respective vaccines,the nasal retention effects were evaluated using in vivo imaging.Flow cytometry was used to assess the ability to recruit immune cells to the nasal tissue.Serum RBD-specific immunoglobulin G(IgG)and mucosal immunoglobulin A(IgA)(bronchoal-veolar lavage fluid/nasal wash)were quantified at 7 and 21 d post-immunization by enzyme-linked immuno-sorbent assay.Body weight changes were monitored and key serum biochemical parameters along with histopathological damage to major organs were analyzed following immunization.② Female BALB/c mice were divided into the Mock-Exo group(intranasally inoculated with Mock-Exo),RBD+VSV-G-Exo group(intranasally inoculated with RBD+VSV-G-Exo),and RBD+VSV-G-Exo(im)group(intramus-cularly injected with RBD+VSV-G-Exo).RESULTS In vitro experiments:RBD and VSV-G were successfully expressed in cells,with positive rates of RBD+and VSV-G+cells at 64.4%and 31.2%,respectively.The extracted exosomes exhibited regular morphology and qualified purity,with a particle size of approximately 138 nm and successfully loaded RBD and VSV-G proteins.In vivo experiments:Compared to Mock-Exo and RBD-Exo,RBD+VSV-G-Exo prolonged nasal retention time to 96 h and markedly increased the numbers of CD49B+natural killer cells,CD11c+dendritic cells,and F4/80+macrophages in nasal tissues.RBD+VSV-G-Exo induced robust RBD-specific immune responses,with serum IgG titers,BALF IgA titers,and nasal wash IgA titers reaching 1∶5 215,1∶2 560,1∶1 114,respec-tively.In contrast,no RBD-specific IgA antibody titers were detected in the BALF and nasal wash of mice treated with RBD+VSV-G-Exo(im).Mice showed stable body weight gain during 30 d post-immu-nization.Major serum biochemical indices were within normal reference ranges,and no obvious patho-logical changes were observed in major organs or olfactory bulbs 7 d after immunization.CONCLU-SION VSV-G modification extends the retention time of engineered exosome vaccines in nasal tissues,enhance their ability to recruit immune cells,and induce a high-level antigen-specific respiratory mucosal immune response.

Objective:To analyze the predictive value of the prognostic nutritional index combined with inflammatory indicators for clinical outcomes in patients with ischemic stroke, providing a basis for targeted therapeutic interventions and nursing care for patients at potential risk of poor outcomes.Methods:This retrospective cohort study recruited 424 ischemic stroke patients admitted to the Stroke Center of the First Hospital of Jilin University from June 2021 to May 2024 by the convenience sampling method. Collect the general demographic data, routine laboratory examination results within 24 hours of admission, as well as the National Institutes of Health Stroke Scale (NIHSS) scores at admission and discharge of the patients. Based on 3-month functional outcomes, patients were divided into a favorable prognosis group and a poor prognosis group. Univariate analysis, least absolute shrinkage and selection operator regression, and binary Logistic regression were employed to screen predictive variables and develop a nomogram model. Internal validation was performed using the Bootstrap method. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve were drew to evaluate the predictive performance of the model.Results:The favorable prognosis group comprised 256 patients, including 57 females and 199 males, with an age of 61(54, 68) years. The poor prognosis group included 168 patients, with 55 females and 113 males, and an age of 66(58, 72) years. Binary Logistic regression identified age, sex, hyperlipidemia, NIHSS score at discharge, prognostic nutritional index, systemic inflammatory response index, and systemic immune-inflammation index as independent predictors of prognosis in ischemic stroke patients ( χ2 values were 4.52-56.18, all P<0.05). The prediction model demonstrated the area under the curve of ROC of 0.806 (95% CI 0.764-0.849), with an optimal cutoff value of 0.406, achieving specificity of 78% and sensitivity of 68%. The Hosmer-Lemeshow test yielded a non-significant P>0.05, and the calibration curve showed good agreement between predicted and observed outcomes, with a mean absolute error of 0.012. Decision curve analysis confirmed the clinical utility of the model across a wide range of threshold probabilities. Conclusions:The integrated prognostic model combining the prognostic nutritional index and inflammatory indicators demonstrated favorable discriminative ability, robust calibration, and substantial clinical utility. This risk stratification tool shows high applicability for predicting ischemic stroke outcomes, facilitating early identification of high-risk patients with poor prognosis and guiding personalized intervention strategies.

Objective:To summarize the clinical and genetic characteristics of 23 children with pathogenic ACAN gene variants, enhance the understanding of this disorder, and explore possible regulatory mechanisms. Methods:A retrospective case series summary.The clinical characteristics and genetic analysis results of 23 children with ACAN gene variants treated in the Department of Endocrinology, Genetics and Metabolism, Children′s Hospital of Soochow University from January 2016 and September 2024 were analyzed retrospectively.Transcriptome sequencing was performed on peripheral blood samples from 3 of affected children and 3 age-matched healthy children as controls.Differentially expressed genes (DEGs) in the peripheral blood transcriptome profiles were identified.Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to explore the potential signaling pathways involved. Results:Among the 23 cases, there were 13 males and 10 females, aged from 2 years and 8 months to 12 years old, with 11 cases presenting advanced bone age.Thirteen cases were treated with growth hormone (GH), including 6 cases who received concomitant gonadotropin-releasing hormone analogue therapy.The treatment duration ranged from 3 to 70 months, resulting in varying degrees of height improvement in all treated patients.Transcriptomic analysis identified 811 DEGs, with 516 up-regulated and 295 down-regulated.GO and KEGG enrichment analyses revealed that the heterozygous ACAN variants were significantly associated with FcγR-mediated phagocytosis, nuclear factor-κB signaling pathway, the intestinal immune network for IgA production, rheumatoid arthritis, and systemic lupus erythematosus signaling pathways. Conclusions:The predominant clinical manifestations of patients with ACAN gene variants are short stature and advanced bone age.Although GH provocation tests may indicate normal GH levels, GH therapy can be effective in improving height.Immune-related factors may play a role in the pathogenesis of this disorder.

Objective:To explore the dilemmas of caregivers in managing pulmonary rehabilitation exercises in children with post-infectious bronchiolitis obliterans, so as to provide guidance for the development of a pulmonary rehabilitation exercise program.Methods:This study utilized the descriptive qualitative research method. From August to December 2023, 22 primary caregivers of children with post-infectious bronchiolitis obliterans in the First Affiliated Hospital of Guangzhou Medical University were selected by purposive sampling method as study subjects for semi-structured interviews. The information was analyzed using the Colaizzi 7-step analysis.Results:A total of three themes and nine sub-themes were distilled, including information (concern for information on pulmonary rehabilitation exercise showing dynamic changes with the course of the disease, access to information on disease diagnosis and treatment and pulmonary rehabilitation exercise management through non-professional channels, biased perceptions of pulmonary rehabilitation exercise, and lack of a unified guide to information on pulmonary rehabilitation exercise) ; motivation (physiological and psychological barriers in the management and implementation of pulmonary rehabilitation exercises, lack of comprehensiveness and continuity of professional instruction in pulmonary rehabilitation exercises, and insufficient communication and collaborative support among family members) ; and behavioral skills (insufficient mastery of respiratory training methods with complex procedures, and lack of the ability to effectively plan a pulmonary rehabilitation exercise program) .Conclusions:Caregivers of children with post-infectious bronchiolitis obliterans face certain dilemmas in managing pulmonary rehabilitation exercises. It is necessary to improve caregivers' awareness of the benefits of pulmonary rehabilitation exercise, strengthen their perception of exercise benefits, and enhance their training in pulmonary rehabilitation exercise skills, pay attention to children's exercise preferences, and perfect the social support system for diseases to promote the implementation of pulmonary rehabilitation exercise in children.

BACKGROUND:Previous studies have found that Jiangu Formula can play a dual role in anti-osteoporosis therapy by inhibiting bone resorption and promoting bone formation,but its mechanism of action has not been elucidated.OBJECTIVE:To investigate the effect of Jiangu Formula on the coupling mechanism between bone resorption and bone formation at the cellular and molecular levels.METHODS:Serum containing Jiangu Formula was prepared and its toxicity to bone marrow derived macrophages was determined using MTT assay.The cell proliferation ability of MC3T3-E1 cells that treated Jiangu Formula medicated serum was measured by using cell counting kit-8 method.Tartrate resistant acid phosphatase staining was used to determine the bone resorption inhibition effect of serum containing Jiangu Formula on osteoclast differentiation.The Jiangu Fang conditional culture medium was prepared and the promoting effect of the conditional culture medium on bone formation of MC3T3-E1 was determined through alkaline phosphatase staining.The effect of serum containing Jiangu Formula on the mRNA levels of osteoclast associated sphingosine kinase 2,collagen triple helix repeat containing 1,and slit homolog 3 coupled genes,as well as the effect of conditioned culture medium on the mRNA levels of bone formation related secreted phosphoprotein 1,alkaline phosphatase,Sp7 transcription factor,and secreted protein acidic and rich in cysteine genes,were determined by RT-qPCR method.RESULTS AND CONCLUSION:(1)The MTT and cell counting kit-8 methods showed that serum containing Jiangu Formula had no significant cytotoxic effects at a concentration of<5%.(2)Tartrate resistant acid phosphatase staining results indicated that serum containing Jiangu Formula dose-dependently inhibited osteoclast differentiation at 2.5%,1.25%,and 0.63%concentrations.(3)The alkaline phosphatase staining results showed that the osteoclast conditioned medium of Jiangu Formula promoted osteoblast differentiation in a dose-dependent manner.(4)In addition,RT-qPCR results showed that serum containing 0.63%Jiangu Formula could increase the mRNA levels of osteoclast derived slit homolog 3 and sphingosine kinase 2 coupling factors,and the conditional culture medium could increase the mRNA expression levels of bone formation related secreted phosphoprotein 1,Sp7 transcription factor,and secreted protein acidic and rich in cysteine.To conclude,the serum containing Jiangu Formula can promote bone formation while inhibiting bone resorption,and its mechanism may be related to the mRNA expression of the coupling factors osteoclast derived slit homolog 3 and sphingosine kinase 2 that promote bone resorption and bone formation.

Objective:To explore the diagnostic value of transcranial magnetic stimulation (TMS), transsacral magnetic root stimulation combined with sacral reflexes, external anal sphincter electromyography and pudendal nerve somatosensory evoked potentials in the assessment of neurogenic lower urinary tract dysfunction (NLUTD).Methods:Twenty-one NLUTD patients (1 with a supra-pontine lesion, 5 with a spinal cord injury, 5 with a cauda equina injury, and 10 with pelvic floor disorders) were enrolled. Needle electromyography (EMG) was used to record TMS-induced and transsacral magnetic stimulation-induced motor evoked potentials (tc-MEPs and ts-MEPs, respectively) related to the external anal sphincter (EAS). The dorsal nerve of the penis or clitoris was stimulated electrically to record the latency of the sacral reflex related to the EAS. Central motor conduction time (CMCT) and the tc/ts-MEP latency ratio were calculated to distinguish central from peripheral lesions.Results:In the one patient with a supra-pontine lesion, although the tc-MEP and ts-MEP latencies were within normal limits, the CMCT was prolonged (28.2ms) and the tc/ts-MEP ratio was large (7.4). Among the five patients with a spinal cord injury, one exhibited prolonged tc-MEP latency (50.6ms) and CMCT (47.8ms), along with a large tc/ts-MEP ratio (18.1). In the five patients with cauda equina injury and the ten with NLUTD secondary to pelvic floor disorders, CMCT was within the normal range [averaging (22.9±4.9ms) and (24.2±3.5ms), respectively], but the ts-MEP latency was prolonged [(7.1±2.1ms) and (8.6±3.7ms), respectively], and the tc/ts-MEP ratio was small [(4.4±0.9) and (4.3±1.5), respectively]. The tc/ts-MEP ratio demonstrated the best rate of abnormality detection (93.8%), with an area under the curve of 0.99, indicating good sensitivity.Conclusions:The tc/ts-MEP ratio can be useful for distinguishing central and peripheral lesions. A markedly increased tc/ts-MEP ratio may suggest central nervous system injury, whereas a decreased ratio may indicate peripheral nervous system injury.

Objective:To explore the dilemmas of caregivers in managing pulmonary rehabilitation exercises in children with post-infectious bronchiolitis obliterans, so as to provide guidance for the development of a pulmonary rehabilitation exercise program.Methods:This study utilized the descriptive qualitative research method. From August to December 2023, 22 primary caregivers of children with post-infectious bronchiolitis obliterans in the First Affiliated Hospital of Guangzhou Medical University were selected by purposive sampling method as study subjects for semi-structured interviews. The information was analyzed using the Colaizzi 7-step analysis.Results:A total of three themes and nine sub-themes were distilled, including information (concern for information on pulmonary rehabilitation exercise showing dynamic changes with the course of the disease, access to information on disease diagnosis and treatment and pulmonary rehabilitation exercise management through non-professional channels, biased perceptions of pulmonary rehabilitation exercise, and lack of a unified guide to information on pulmonary rehabilitation exercise) ; motivation (physiological and psychological barriers in the management and implementation of pulmonary rehabilitation exercises, lack of comprehensiveness and continuity of professional instruction in pulmonary rehabilitation exercises, and insufficient communication and collaborative support among family members) ; and behavioral skills (insufficient mastery of respiratory training methods with complex procedures, and lack of the ability to effectively plan a pulmonary rehabilitation exercise program) .Conclusions:Caregivers of children with post-infectious bronchiolitis obliterans face certain dilemmas in managing pulmonary rehabilitation exercises. It is necessary to improve caregivers' awareness of the benefits of pulmonary rehabilitation exercise, strengthen their perception of exercise benefits, and enhance their training in pulmonary rehabilitation exercise skills, pay attention to children's exercise preferences, and perfect the social support system for diseases to promote the implementation of pulmonary rehabilitation exercise in children.

The anatomical structures of the perianal and perirectal regions are complex and prone to neoplastic and non-neoplastic lesions. Some non-neoplastic lesions may show morphological similarities with neoplastic lesions, potentially resulting in misdiagnosis and unnecessary treatment. This article focuses on the pathological diagnostic features of challenging non-neoplastic lesions in the anorectal region, including inflammatory cloacogenic polyp, solitary rectal ulcer syndrome, endometriosis of the intestinal mucosa and infectious proctitis.