摘要 目的 近年来多项研究提示瘦素可能在帕金森病（PD）患者神经元细胞中发挥保护作用，但相关结果尚不一致，因此本研究采用Meta分析方法系统评估瘦素在PD患者中的作用。方法 在PubMed、Embase、ISI Web of Science和中国国家知识基础设施（CNKI）数据库中系统性检索2020年3月底前的文献研究。为了评估总体效果，采用固定效应模型计算合并效应量、标准化均差（SMD）和95%CI。随后进行了亚组分析、敏感性分析和发表偏倚分析，以揭示纳入研究的稳定性和可信度。结果 本研究纳入了7项研究，包括167例帕金森病患者和141名健康对照者。本研究发现，帕金森病患者的血清瘦素水平显著低于健康对照者（SMD=-0.328，95%CI -0.560~-0.096，P=0.006）。亚组分析显示，白种人PD患者的血清瘦素水平较低（SMD=-0.301，95%CI -0.566~-0.036，P=0.026），而亚洲患者的血清瘦素水平差异无统计学意义（SMD=-0.414，95%CI -0.891~0.063，P=0.089）。敏感性分析显示总体效应量的稳定性。通过观察漏斗图，未发现明显的不对称，Begg检验也未发现显著的发表偏倚。结论 本Meta分析结果表明PD患者血清瘦素水平较健康人群降低，提示血清瘦素可能参与PD的病理过程，其具体机制尚待进一步研究阐明。 Abstract Objective Many studies in recent years have shown that leptin may exert a protective effect on neurons in patients with Parkinson disease（PD），but related research findings remain inconsistent. Therefore， this article systematically reviews the role of leptin in PD patients through a meta-analysis. Methods PubMed，Embase，ISI Web of Science， and CNKI were searched for related articles published up to March 2020. In order to assess the overall effect， the fixed effects model was used to calculate pooled effect size， standardized mean difference （SMD）， and 95% confidence interval（CI）. Subgroup analysis， sensitivity analysis， and publication bias analysis were performed to assess the stability and reliability of the studies included in the meta-analysis. Results A total of 7 studies were included in the meta-analysis according to strict inclusion criteria， involving 167 PD patients and 141 healthy controls. The results showed that the PD patients had a significantly lower serum level of leptin than the healthy controls （SMD=-0.328，95%CI -0.560 to -0.096， P=0.006）. The subgroup analysis showed that Caucasian PD patients had a relatively low serum level of leptin （SMD=-0.301， 95%CI -0.566 to -0.036，P=0.026）， while there was no significant difference in the serum level of leptin among Asian patients （SMD=-0.414， 95%CI -0.891 to 0.063， P=0.089）.The sensitivity analysis showed the stability of overall effect size. The funnel plots showed no significant asymmetry， and no obvious publication bias was observed by the Begg test. Conclusion This meta-analysis shows that PD patients have a lower serum level of leptin than the healthy population， suggesting that serum leptin might be involved in the pathological process of PD， and further studies are needed to clarify the specific mechanism.
Leptin ; Adipokines

ObjectiveTo construct an actor-network for integrating physical activity into rehabilitation services based on the World Health Organization Rehabilitation in Health Service System framework and actor-network theory (ANT). MethodsContent analysis was employed using the six building blocks of health service systems as the theoretical framework. Actors related to rehabilitation services were extracted and categorized into a rehabilitation actor pool, while a physical activity actor pool was formed based on four major physical activity scenarios. Actors from both pools were integrated, deduplicated and classified to form a final list of integrated actors. Using ANT, the construction process of the actor network integrating physical activity into rehabilitation was analyzed through the four stages of translation: problematization, interessment, enrollment and mobilization. ResultsA dynamic integration network was constructed, comprising human actors (patients, rehabilitation professionals, researchers, sports coaches, government departments, medical institutions, community organizations and industry media, etc.) and non-human actors (assistive devices, sports infrastructure, smart equipment, information systems, online exercise guidance systems, laws and regulations, strategic documents, and exercise prescriptions, etc.). The study identified maximizing rehabilitation outcomes as the mandatory passage point and elaborated on the critical role of government departments as focal actors in coordinating various stakeholders. ConclusionThe integration of physical activity into rehabilitation services is a dynamic network constructed by diverse actors through a process of translation. ANT provides an operational theoretical framework for cross-departmental governance of rehabilitation policies in China, promotes the spatial expansion of the rehabilitation field, and drives its transformation toward a networked and ecological system. The government needs to play a leading role in facilitating role reconstruction and synergy among heterogeneous actors in both the sports and rehabilitation sectors through mechanism design, to create a bidirectional empowerment mechanism that fosters mutual progress and ensures the sustainable development of integrated services.

Objective: To evaluate the effectiveness of school-family-community comprehensive intervention aimed at reducing sugar sweetened beverage(SSB) consumption among primary and secondary school students, so as to provide scientific basis for relevant departments to formulate campus sugar reduction measures for primary and secondary school students. Methods: In October 2023, a multi stage random cluster sampling method was used to select four primary schools (grade 4) and four junior high schools (grade 7) in Nanjing City, and they were randomly divided into the intervention group ( n =1 601) and the control group ( n = 1 433 ) (primary and secondary schools). The intervention group received a one year comprehensive intervention activity with the theme of “drinking less SSBs and enjoying a healthy life” for one consecutive year. The measures included the school conducting health education courses (once a month, 15 minutes each time), environmental support (posting promotional posters, changing them once a month), class bulletin board and interest projects (once a semester); interventions for families included conducting parent lectures (once per semester 30 min each time), new media (once a month) and hand in hand activities (once per semester); community carried out square promotion and create a supportive environment (post promotional posters and replace them once a month). The control group did not receive any intervention measures except regular health education classes. Self administered questionnaires were used to collect knowledge, attitudes, and intake of SSB at the baseline and after the intervention among primary and secondary school students. Results: After the intervention, the proportion of students in the intervention group with an SSB related knowledge awareness rate of 60% or above was 91.4%, which was higher than that of the control group (81.9%) ( χ 2=60.35, P < 0.01 ). The reporting rate of the behavior of choosing to drink beverages when thirsty in the intervention group was 25.4%, which was lower than that of the control group (33.3%); the reporting rates of informing parents about the hazards of sugar sweetened beverages and paying attention to nutrition labels were 62.0% and 78.0% respectively, both of which were higher than those of the control group (52.3%, 65.9%); the reporting rate of having sugar sweetened beverages at home frequently was 43.7% in the intervention group, which was lower than that of the control group (62.3%); the reporting rate of parents restricting the consumption of sugar sweetened beverages was 84.1%, which was higher than that of the control group (78.4%) ( χ 2= 22.66, 29.05, 54.40, 104.84, 16.24, all P <0.05). The reporting rate of students in the intervention group who consumed sugar sweetened beverages more than 4 times per week was 21.5%, which was lower than that of the control group (28.6%), and the difference was statistically significant ( χ 2=20.36, P <0.01). Conclusion The comprehensive intervention of school-family-community can effectively improve primary and secondary school students knowledge and attitudes regarding SSBs and reduce their consumption of these beverages.

ObjectiveTo investigate the potential mechanism of Yiqi Yangyin Huoxue Formula （益气养阴活血方， YYHF） in the treatment of membranous nephropathy （MN） based on the NOX4-mediated stromal cell-derived factor-1α（SDF-1α）/CXC chemokine receptor 4 （CXCR4） signaling pathway. MethodsA total of 42 male SD rats were randomly divided into blank group （n=6） and modeling group （n=36）. The modeling rats were given a single injection of sheep antirat Fx1A （6 ml/kg） serum into the tail vein to establish MN model. Thirty-six rats with successful modeling were further divided into model group （normal saline， 10 ml/kg）， benazepril group （10 mg·kg^-1·d^-1）， the medium-dose YYHF group （11.0 g·kg^-1·d^-1） and high-dose YYHF group （22.0 g·kg^-1·d^-1）， with 9 rats in each group. All groups received daily intragastric administration for 6 consecutive weeks. During the experimental period， the general condition of rats in each group was observed. After gavage administration finished， a fully automated biochemical analyzer was used to measure the 24-hour urine total protein （24 h-UTP） and serum biochemical parameters， including albumin （ALB）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， serum creatinine （SCr）， total cholesterol （TC）， and triglyceride （TG）. Hematoxylin-eosin （HE） staining and periodic acid-silver metheramine （PASM） staining were used to observe the histopathological changes of renal tissues in each group of rats. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were detected by ELISA. The protein expression levels of NOX4， SDF-1α， CXCR4， Nrf2， nuclear factor kappa B subunit p65 （NF-κB p65） and podocyte slit diaphragm protein nephrin in rat renal tissues were detected by Western Blotting. The mRNA expressions of NOX4， SDF-1α， CXCR4， Nrf2， NF-κB p65 and Nephrin in renal tissues were detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultsCompared to the blank group， rats in the model group exhibited typical features of MN， including lethargy， reduced activity， dull and coarse fur， marked edema， and massive proteinuria. Compared to the model group， these abnormal conditions were improved to varying degrees in all treatment groups. The high-dose YYHF group showed a level of improvement comparable to that of the benazepril group， with overall recovery superior to that of the medium-dose YYHF group. Compared to the blank group， the model group showed increased levels of 24 h-UTP， BUN， SCr， TC and TG， decreased level of ALB， increased levels of MDA and protein and mRNA expressions of NOX4， SDF-1α， CXCR4 and NF-κB p65 in renal tissue， along with decreased levels of SOD and protein and mRNA expressions of Nrf2， Nephrin （P＜0.01）， accompanied by severe renal pathological damage. Compared to the model group， the benazepril and the medium- and high-dose YYHF groups showed significant improvements in the above indicators （P＜0.01）， along with alleviation of renal pathological injury. The 24 h-UTP level in the high-dose YYHF group was lower than that in the medium-dose group （P＜0.01）， while no statistically significant difference was observed among the other treatment groups （P＞0.01）. ConclusionYYHF may alleviate oxidative stress and inflammatory responses by down-regulating the expression of NOX4 and inhibiting the SDF-1α/CXCR4-Nrf2 signaling pathway， thereby improving podocyte damage and protecting renal function.

ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

Objective To evaluate the diagnostic value of prostate health index(PHI)and prostate health index density(PHID)in identifying intermediate-to high-risk prostate cancer(PCa).Methods Clinical data of 160 treatment-na?ve patients with highly suspected PCa,who underwent initial prostate biopsy in our hospital during Jul.2022 and Feb.2024,were retrospectively analyzed.Data included age,body mass index(BMI),prostate volume(PV),total prostate-specific antigen(tPSA),free PSA(fPSA),[-2]proPSA(p2PSA),PHI and PHID.Biopsy-positive results were stratified according to the EAU D'Amico risk criteria.Receiver operating characteristic(ROC)curve and multivariate logistic regression analysis were employed to assess the diagnostic performance of PHI and PHID in predicting PCa and identifying intermediate-to high-risk PCa.Results There were statistically significant differences in tPSA,p2PSA,PHI and PHID between the negative and positive groups,as well as among the low-,medium-and high-risk groups(P＜0.01).Both PHI and PHID demonstrated good diagnostic performance in predicting PCa(AUC=0.820 8 and 0.875 7,respectively;all P＜0.001),and in identifying intermediate-to high-risk PCa(AUC=0.838 0 and 0.878 3,respectively;all P＜0.001).Compared to the baseline model,the incorporation of PHI and PHID individually into the multivariate model significantly improved the screening performance for PCa(AUC=0.910 and 0.898,respectively;all P＜0.001).Conclusion PHI and PHID exhibit high diagnostic efficacy in screening PCa,particularly in identifying intermediate-to high-risk disease.

Objective:To explore the association between oral health status, the lower respiratory tract microbiome, and the frequent acute exacerbation phenotype in chronic obstructive pulmonary disease (COPD).Methods:This cross-sectional study enrolled 39 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalized in the Department of Respiratory Medicine, Henan Provincial People′s Hospital between March 2021 and December 2022. Based on the number of hospitalization episodes for acute exacerbation in the past year, patients were divided into a frequent exacerbator group (≥2 times, n=28) and a non-frequent exacerbator group (<2 times, n=11). Bronchoalveolar lavage fluid (BALF) samples were collected from all subjects for metagenomic next-generation sequencing (mNGS). Oral health indicators and clinical data were also collected. Statistical analyses were performed using Spearman correlation analysis and multivariable Firth logistic regression analysis. Results:The frequent exacerbation group showed a significantly higher percentage of individuals with≥8 tooth loss compared to the non-frequent exacerbation group (96.4% vs 18.2%, P<0.001), a significantly younger age at first tooth loss in adulthood (53.96±7.30 years vs 62.10±5.80 years, P=0.003), and a significantly higher proportion of individuals who hardly brushed their teeth (50.00% vs 9.09%, P=0.038). The alpha-diversity indices of the lower respiratory tract microbiota were significantly lower in the frequent exacerbation group than in the non-frequent exacerbation group (all P<0.01). The relative abundances of Bacillota, Bacteroidota, Fusobacteriota, Streptococcus, Prevotella, Veillonella, Neisseria, Rothia, Prevotellamelaninogenica, Prevotellajejuni, Rothia mucilaginosa, Veillonella parvula, and Neisseria subflava were lower in the frequent exacerbation group (all P<0.05). In patients with AECOPD, the exacerbation frequency and the presence of ≥8 tooth loss were both negatively correlated with the Shannon index ( r=-0.854, P<0.001; r=-0.642, P<0.001, respectively). Further analysis revealed that Bacillota ( r=-0.862, P<0.001) and Streptococcus ( r=-0.814, P<0.001) were significantly negatively correlated with exacerbation frequency, while Pseudomonas was positively correlated with exacerbation frequency (all P<0.05). Bacillota ( r=0.369, P=0.021), Fusobacteriota ( r=0.368, P=0.021), and Veillonella ( r=0.379, P=0.017) were positively correlated with FEV 1% predicted. Multivariable Firth logistic regression analysis revealed that the first principal component of the microbial community ( OR=2.29, 95% CI: 1.20-11.07) and the loss of≥8 teeth ( OR=14.37, 95% CI: 1.42-482.51) were independent factors associated with frequent acute exacerbations. Conclusion:Frequent acute exacerbations of COPD are significant association with deteriorated oral health and dysbiosis of the lower respiratory tract microbiome, characterized by reduced alpha-diversity and depletion of commensal bacteria.

Objective:To examine the clinical features and genetic profiles of patients with thyroid peroxidase(TPO) gene mutations and provide diagnostic guidance for clinicians.Methods:A retrospective review of four patients with TPO mutations treated at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2014 to December 2023. Data on demographics, clinical manifestation, genotypes, treatment, and prognosis of these patients were analyzed.Results:Two males and two females, aged 13 to 27 years at diagnosis, presented with goiter as the initial symptom, with three cases menifesting during puberty. Laboratory findings showed mildly elevated or upper-limit-normal serum thyroid-stimulating hormone(TSH) levels, significantly increased free triiodothyronine/free thyroxine(FT 3/FT 4) ratios, and elevated thyroglobulin(TG) levels. Genetic testing revealed compound heterozygous pathogenic or likely pathogenic TPO mutations. Despite regular levothyroxine(L-T 4) therapy, goiter persisted. Three patients required thyroidectomy due to cosmetic or compressive symptoms, with pathology showing follicular hyperplasia. Conclusion:TPO mutations are characterized by adolescent-onset goiter, elevated FT 3/FT 4 ratios, and normal to high TSH. Genetic testing confirms the diagnosis. L-T 4 offers limited improvement, and surgery is often needed.

Objective To explore the potential clinical value of the ratio of glycated albumin to albumin(GA/ALB)in the occurrence of heart failure(HF)among patients with coronary atherosclerotic heart disease(CHD).Methods A total of 337 CHD patients admitted to the Department of Cardiology in Shanxi Provincial People's Hospital from July 2023 to June 2024 were selected in this study.CHD patients were divided into HF group and non-HF group based on whether they progressed to HF.The clinical data and laboratory parame-ters of the two groups were compared.Restricted cubic spline curve was used to analyze the relationship be-tween GA/ALB levels and the risk of HF in CHD patients.Receiver operating characteristic curve was applied to evaluate the diagnostic efficacy of GA/ALB,GA,platelet to lymphocyte ratio(PLR),and monocyte to lym-phocyte ratio(MLR)in CHD patients with the occurrence of HF.Logistic regression was used to explore the relationship between serum GA/ALB levels and the risk of CHD patients occurrence of HF,and to analyze the degree of influence and stability of subgroup variables on results.Results There were statistically significant differences in GA/ALB,GA,PLR,MLR,and other indicators between the HF group and the non-HF group in CHD patients(P＜0.05).A non-linear relationship was observed between GA/ALB levels and the risk of HF in CHD patients.When the value of GA/ALB multiplied by 10 was less than 5.751,the risk of HF in CHD pa-tients increased with the increase of GA/ALB levels(P＜0.001).GA/ALB was an effective predictor for HF occurrence in CHD patients.Multivariable Logistic regression model showed that GA/ALB was an independ-ent risk factor for CHD patients with occurrence of HF.Subgroup analysis also confirmed the stability of GA/ALB in predicting the occurrence of HF in CHD patients.Conclusion GA/ALB is an independent risk factor for the occurrence of HF in CHD patients,and monitoring GA/ALB levels provides predictive value for the oc-currence of HF in these patients.

Objective To analyze the medication rules of traditional Chinese medicine compound patents for the prevention and treatment of urinary tract infection(UTI)through data mining technology.Methods The patents of traditional Chinese medicine compounds for the prevention and treatment of UTI in patent announcement module of China National Intellectual Property Administration website as data sources.The statistical analysis platforms of Excel 2021,IBM SPSS Modeler 18.0 and IBM SPSS Statistics 27.0 were used for frequency of use,medicinal properties,association rule analysis,and systematic clustering analysis and finally visualized by Cytoscape 3.7.2,RStudio.Results Through screening,a total of 179 compound patents met the inclusion criteria,involving 466 kinds of Chinese materia medica,and the top 5 high-frequency drugs were Pugongying,Huangbai,Gancao,Jinyinhua,Bianxu.The medicinal properties are mainly cold and mild;The medicinal taste is characterized by sweetness,bitterness,and bitterness;The main meridians of drugs are liver,lung and kidney meridians.Common couplet medicines included Qumai-Bianxu,Gancao-Bianxu and the three herb drug combinations included Cheqianzi-Qumai-Bianxu,Gancao-Qumai-Bianxu.A total of 5 high-frequency combinations of traditional Chinese medicine were obtained by cluster analysis.Conclusion This study preliminarily reveals the compatibility and medication rules of traditional Chinese medicine in the treatment of UTI,which provides data support for the optimization of clinical syndrome differentiation and treatment system and the development of new prescriptions.