Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

Objective To evaluate the reliability,validity,and feasibility of the diagnostic scale for toxic pathogen syndrome in heart failure(HF),and to verify its reliability and effectiveness in clinical diagnosis.Methods A cross-sectional study was conducted.Patients with HF who visited four hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,from March 1st to September 30th,2024 were selected.General information of the patients,including gender,age,smoking history,drinking history,and comorbidities,was collected.Cronbach's α coefficient,split-half reliability,and test-retest reliability were used to evaluate the reliability of the scale.Surface validity,discriminant validity,and structural validity were used to assess the validity of the scale.Acceptance rate,completion rate,and completion time were used to evaluate the feasibility.Results A total of 600 patients with HF meeting the research criteria were included,including 290 males and 310 females,with a median(IQR)age of 66.50(58.00,70.00)years.Internal consistency reliability:the Cronbach's α coefficients of the total scale and the four dimensions were all greater than 0.6,indicating a good consistency among the items of the scale.The Spearman-Brown coefficients of the total scale and the four dimensions were all greater than 0.7,indicating good stability and homogeneity within the scale.External consistency reliability:the Kappa coefficients of the total scale and the four dimensions were all greater than 0.7,indicating good external consistency of the scale.Discriminant validity evaluation:patients were divided into the toxic pathogen syndrome group(n=180)and the non-toxic pathogen syndrome group(n=420).There were no statistically significant differences in gender,age,smoking history,drinking history,and comorbidities between the two groups(P>0.05).The scores of the two groups were evaluated using the diagnostic scale for the toxic pathogen syndrome in HF.The toxic pathogen syndrome group had higher scores in all four dimensions and the total scale than the non-toxic pathogen syndrome group(P<0.01),indicating good discriminant validity of the scale.Structural validity assessment:principal component analysis was used to extract 28 factors,and a total of 7 common factors were extracted,with a total variance contribution rate of 60.554%.The absolute values of the loadings of each item were basically greater than 0.5,and the commonalities of the corresponding dimensions ranged from 52.1%to 96.5%,indicating good structural validity of the scale.The acceptance rate of the scale in this evaluation was 100%,the completion rate was 100%,and the average completion time was between 6 and 8 minutes,indicating good feasibility of the scale.Conclusion The diagnostic scale for the toxic pathogen syndrome in HF has good reliability,validity,and feasibility.

Objective To evaluate the reliability,validity,and feasibility of the diagnostic scale for toxic pathogen syndrome in heart failure(HF),and to verify its reliability and effectiveness in clinical diagnosis.Methods A cross-sectional study was conducted.Patients with HF who visited four hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,from March 1st to September 30th,2024 were selected.General information of the patients,including gender,age,smoking history,drinking history,and comorbidities,was collected.Cronbach's α coefficient,split-half reliability,and test-retest reliability were used to evaluate the reliability of the scale.Surface validity,discriminant validity,and structural validity were used to assess the validity of the scale.Acceptance rate,completion rate,and completion time were used to evaluate the feasibility.Results A total of 600 patients with HF meeting the research criteria were included,including 290 males and 310 females,with a median(IQR)age of 66.50(58.00,70.00)years.Internal consistency reliability:the Cronbach's α coefficients of the total scale and the four dimensions were all greater than 0.6,indicating a good consistency among the items of the scale.The Spearman-Brown coefficients of the total scale and the four dimensions were all greater than 0.7,indicating good stability and homogeneity within the scale.External consistency reliability:the Kappa coefficients of the total scale and the four dimensions were all greater than 0.7,indicating good external consistency of the scale.Discriminant validity evaluation:patients were divided into the toxic pathogen syndrome group(n=180)and the non-toxic pathogen syndrome group(n=420).There were no statistically significant differences in gender,age,smoking history,drinking history,and comorbidities between the two groups(P>0.05).The scores of the two groups were evaluated using the diagnostic scale for the toxic pathogen syndrome in HF.The toxic pathogen syndrome group had higher scores in all four dimensions and the total scale than the non-toxic pathogen syndrome group(P<0.01),indicating good discriminant validity of the scale.Structural validity assessment:principal component analysis was used to extract 28 factors,and a total of 7 common factors were extracted,with a total variance contribution rate of 60.554%.The absolute values of the loadings of each item were basically greater than 0.5,and the commonalities of the corresponding dimensions ranged from 52.1%to 96.5%,indicating good structural validity of the scale.The acceptance rate of the scale in this evaluation was 100%,the completion rate was 100%,and the average completion time was between 6 and 8 minutes,indicating good feasibility of the scale.Conclusion The diagnostic scale for the toxic pathogen syndrome in HF has good reliability,validity,and feasibility.

Objective To investigate the effect and mechanism of endothelin-1(ET-1)on atrial fibrosis in Atrial fibrillation(AF)rats.Methods Fourteen adult male SD rats were randomly divided into normal control(NC)group and Atrial fibrillation(AF)group.The rat model of Atrial fibrillation was established by injecting 0.1 ml/100g CaCl2-Ach mixture into the tail vein once a day for one week.The control group was injected with the same dose of normal saline.An electrocardiogram of normal or atrial fibrillation was recorded on the first day and the eighth day in each group,and echocardiography was used to monitor atrial size and cardiac function.The fibrosis of atrial was observed using Masson and HE staining.The expression of endothelin-1(ET-1),collagen-I(Col-I),transforming growth factor-β(TGF-β)and the store operated calcium channel(SOCC)protein Orai1,stromal in-teraction molecule 1(STIM1)in atrial tissue were detected by Western blot.HL-1 cells were cultured and treated with gradient concentration of ET-1 for 24 hours.Western blot was used to observe changes in the expression of TGF-β,Orai1 and STIM1 proteins in ET-1/SOCC/TGF-β signaling pathway of HL-1 cells.Small interfering RNA(siRNA)transfection method was used to knock down the expression of Orai1 in HL-1 cells,then the cells were treated with appropriate concentrations of ET-1 for 24 hours,and the expression of TGF-β protein in HL-1 cells was detected by Western blot.Results Compared with the control group,echocardiography showed a significant in-crease in left atrial diameter(LAD)of the heart in atrial fibrillation rats(P<0.05).The HE and Masson staining results showed significant fibrosis in the myocardial tissue of AF group rats(P<0.05),and the Western blot re-sults indicated the expression of ET-1,Orai1,STIM1,TGF-β and COL-Ⅰ in the myocardial tissue of AF group significantly increased compared to the NC group(P<0.05).After ET-1 treatment of HL-1 cells,the protein ex-pression of Orai1,STIM1and TGF-β increased(P<0.05),while knocking down Orai1 in HL-1 cells,ET-1 treat-ment no longer caused the expression of TGF-β a significant upregulation.Conclusion AF caused by atrial fibril-lation results in a significant increase in ET-1 expression in atrial tissue,and ET-1/SOCC/TGF-β signal pathway promotes atrial fibrillation and fibrosis.

Objective To explore the effects of microRNA-342-3p/Mg2+Mn2+-dependent protein phosphatase 1E(miR-342-3p/PPM1E)on the proliferation,migration,and invasion of clear cell renal cell carcinoma(ccRCC)cells.Methods The gene chips GSE12105,GSE23085,GSE66271,and GSE66270 were searched,and the relationship between miR-342-3p,PPM1E,and the clinical malignant phenotypes of ccRCC was analyzed.ACHN and 769-P cells were transfected with miR-342-3p inhibitor.The effects of miR-342-3p on cell proliferation,migration,and invasion were examined.ACHN cell line with stable and high expression of miR-342-3p was constructed,and the tumorigenicity of the cell line in BALB/c nude mice was observed.The targeted relationship between miR-342-3p and PPM1E was verified by dual-luciferase reporter gene assay.The cells were transfected with miR-342-3p mimic and pcDNA-PPM1E plasmids to observe whether PPM1E could reverse the effects of miR-342-3p overexpression on the proliferation,migration,and invasion of the cells.Results The expression of miR-342-3p was upregulated in ccRCC,and there were significant differences among patients with tumors of different T stages and G stages and those with different prognoses(P<0.05).The overall survival in the miR-342-3p high-expression group was significantly shorter than that in the low-expression group(P<0.05).Compared with those in the miR-NC group,the miR-342-3p level was significantly downregulated in the inhibitor group,and the cell proliferation ability and the numbers of migrating and invading cells were also significantly decreased(P<0.05).Compared with the miR-NC group,miR-342-3p group had significantly increased volume and mass of tumor tissues and miR-342-3p level,but significantly decreased level of PPM1E mRNA(P<0.05).The expression of PPM1E was downregulated in ccRCC,and there were significant differences among patients with tumors of different M stages,N stages,and G stages,and different recurrence statuses(P<0.05).The miR-342-3p could inhibit the expression of PPM1E in a targeted way.Compared with the miR-NC group,the miR-342-3p group had significantly increased cell proliferation ability and increased numbers of migrating and invading cells(P<0.05).However,PPM1E could reverse the promotion effect of miR-342-3p mimic on ccRCC cells(P<0.05).Conclusion The miR-342-3p can inhibit PPM1E expression in a targeted way,and thus promotes the proliferation,migration,and invasion of ccRCC cells.

Objective:This study aims to explore the feasibility of ethical review and mutual recognition, focusing on the operational efficiency and review processes of the Ethics Committees in Tianjin′s third-level hospitals.Methods:A thorough online survey was conducted across tertiary hospitals in Tianjin, utilizing a detailed questionnaire. The survey primarily examined the operations and reviews of Ethics Committees from 2019 to 2022, evaluating the efficiency of ethical reviews, the effectiveness of clinical research administration, and the hospitals′ perspectives on mutual recognition of ethical reviews. From 29 collected responses, 28 were deemed suitable for in-depth statistical analysis.Results:In Tianjin′s 28 surveyed tertiary hospitals, 16 routinely hold ethics review meetings monthly. Nine hospitals have established pre-ethics review processes, and three have achieved mutual recognition of their ethical review outcomes. Additionally, five hospitals have integrated electronic information systems. From 2019 to 2021, there has been an increase in clinical trials and Investigator-Initiated Trials (IITs) under initial review, with a significant presence of multi-center clinical trials (90%) and multi-center IIT studies (75%). The timeframe for clinical research review opinions ranged from 18.84 to 20.69 days between 2019 and September 2022, while the duration for clinical research review approvals varied from 22.03 to 23.68 days. During the same period, clinical trial management efficiency spanned from 48.42 to 62.65 days, and IIT study management efficiency was between 25.54 to 28.17 days. Participants identified the main factors influencing management efficiency as stemming from research institutions and sponsors.The majority of hospitals expressed support for the advancement of mutual recognition of ethical reviews and the implementation of a unified submission checklist and template.Conclusions:The Ethics Committees in Tianjin′s third-level hospitals have progressively evolved towards standardization. There is a marked improvement in the efficiency of ethical reviews and overall management of clinical research, indicating a positive development towards more streamlined and effective ethical governance in clinical studies.

Objective:To explore the preoperative diagnostic value of endoscopic ultrasonography (EUS) for intraductal papillary mucinous neoplasms (IPMN).Methods:Data of 62 patients with IPMN confirmed by pathology who underwent EUS before surgery from 2008 to 2018 in Peking Union Medical College Hospital were analyzed. Characteristics that could distinguish low-grade dysplasia (LGD), high-grade dysplasia (HGD) and invasive carcinoma (IC) were explored. A scoring system based on EUS findings was established to determine the preoperative pathology of IPMN by using logistic model.Results:Of the 62 patients, 15 (24.2%) were diagnosed as having LGD, 20 (32.3%) HGD and 27 (43.5%) IC. Univariate analysis showed that the size of mural nodules and width of main pancreatic duct (MPD) were predictive factors for IPMN pathology. The possibility of higher pathological grading would increase 8% for every 1 mm increment in mural nodules. Multivariate analysis showed that only mural nodules≥5 mm ( OR=7.31, 95% CI : 2.49-21.40, P<0.001) was an independent risk factor to distinguish LGD, HGD and IC. Mural nodules≥5 mm, main pancreatic duct (MPD)≥10 mm and mural nodules <5 mm were assigned 2 points, 1 point and 1 point, respectively. The sensitivity, specificity, and area under receiver operator characteristic curve (AUC) of the EUS scoring system to distinguish benign and malignant IPMN were 0.830, 0.867, and 0.867, respectively. Conclusion:Preoperative EUS helps to distinguish LGD, HGD and IC. The size of mural nodules and the width of MPD are vital risk factors to distinguish benign and malignant IPMN.

Objective:To compare the health knowledge of newly admitted patients with recurrent hypertensive stroke around 10 years, and analyze the influencing factors of health knowledge of patients.Methods:From September 2008 to December 2009 and from September 2018 to December 2019, convenience sampling was used to select newly admitted patients with recurrent hypertensive stroke from 3 ClassⅢ Grade A hospitals in Guangzhou as the research objects, and the Stroke Knowledge Questionnaire (SKQ) was used for investigation. In the two stages around 10 years, 120 and 130 questionnaires were distributed, and 109 and 116 valid questionnaires were returned with the valid response rates of 90.83% and 89.23%, respectively.Results:The education level, per capita monthly income of the family, family history of stroke, diabetes mellitus and hyperlipidemia, and smoking of the patients before and after 10 years were statistically significant ( P<0.05) . After 10 years, SKQ total scores, dimension scores in exercise, medication, stroke risk factors, stroke auras, and stroke management of patients were higher than those of 10 years ago, and dimension scores low-salt diet and smoking were lower than 10 years ago, and the differences were statistically significant ( P<0.05) . Conclusions:The level of health knowledge of newly admitted patients with recurrent hypertensive stroke is higher than that of 10 years ago, but education on low-salt diet and smoking cessation knowledge should be further strengthened.

To evaluate the optimal administration frequency for interferon-α (IFN-α) and the effect of its combined use with inactive virus on chicken flocks, the prokaryotic expression plasmid pET-22b-ChIFN-α was constructed and transferred into Escherichia coli BL21(DE3) host bacteria to induce the expression of chicken IFN-α and to harvest recombinant proteins inclusion bodies. The expression of recombinant chicken IFN-α was confirmed by SDS-PAGE, and the results demonstrated that the chicken IFN-α (20 kDa) was highly expressed using the prokaryotic expression vector with a concentration of 0.2 mg/mL in the medium. Chicken IFN-α was diluted to 2.5×10⁴ U/fowls and administered to immunized specific-pathogen-free chickens orally in combination with inactivated H9N2 subtype influenza virus. Chicken that received chicken IFN-α were safe after three repeated immunizations (96 h). In addition, chicken IFN-α could induce higher levels of antiviral-related inducible genes in peripheral blood, spleen, and thymus of chicken flocks. The results of a challenge assay revealed that the lowest detoxification rates of chicken IFN-α ranged from three to five days, suggesting a higher capacity to resist H9N2 subtype avian influenza virus. The present study obtained the optimal immune frequency and immunization period for chicken IFN-α to provide theoretical support for the optimal clinical application of IFN-α.
Administration, Oral ; Animals ; Chickens ; Humans ; Influenza A Virus, H9N2 Subtype ; Interferon-alpha ; Virus Replication

The hospital spirit is not only the spiritual support and vital source for staff, but also the concentrat-ed expression of ideology and faith, value orientation, moral trait, psychology tendencies, culture stereotypes, the unified will and code of conduct for all kinds of personnel.The party organizations are the best helmsmen to culti-vate and carry forward the hospital spirit, which reveals distinctive and profound medical ethical principles and norms.In this paper, taking X hospital as an example, we describe the core function of the party committee′s lead-ership and results in the process of breeding, inheritance and innovation of hospital spirit and reflect ethically so as to provide good references for the current hospital spirit cultivation and promotion.