Objective:Abnormal immune system activation and inflammation are crucial in causing Parkinson's disease.However,we still don't fully understand how certain immune-related genes contribute to the disease's development and progression.This study aims to screen key immune-related gene in Parkinson's disease based on weighted gene co-expression network analysis(WGCNA)and machine learning. Methods:This study downloaded the gene chip data from the Gene Expression Omnibus(GEO)database,and used WGCNA to screen out important gene modules related to Parkinson's disease.Genes from important modules were exported and a Venn diagram of important Parkinson's disease-related genes and immune-related genes was drawn to screen out immune related genes of Parkinson's disease.Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze the the functions of immune-related genes and signaling pathways involved.Immune cell infiltration analysis was performed using the CIBERSORT package of R language.Using bioinformatics method and 3 machine learning methods[least absolute shrinkage and selection operator(LASSO)regression,random forest(RF),and support vector machine(SVM)],the immune-related genes of Parkinson's disease were further screened.A Venn diagram of differentially expressed genes screened using the 4 methods was drawn with the intersection gene being hub nodes(hub)gene.The downstream proteins of the Parkinson's disease hub gene was identified through the STRING database and a protein-protein interaction network diagram was drawn. Results:A total of 218 immune genes related to Parkinson's disease were identified,including 45 upregulated genes and 50 downregulated genes.Enrichment analysis showed that the 218 genes were mainly enriched in immune system response to foreign substances and viral infection pathways.The results of immune infiltration analysis showed that the infiltration percentages of CD4+ T cells,NK cells,CD8+ T cells,and B cells were higher in the samples of Parkinson's disease patients,while resting NK cells and resting CD4+ T cells were significantly infiltrated in the samples of Parkinson's disease patients.ANK1 was screened out as the hub gene.The analysis of the protein-protein interaction network showed that the ANK1 translated and expressed 11 proteins which mainly participated in functions such as signal transduction,iron homeostasis regulation,and immune system activation. Conclusion:This study identifies the Parkinson's disease immune-related key gene ANK1 via WGCNA and machine learning methods,suggesting its potential as a candidate therapeutic target for Parkinson's disease.

Objective:To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR.Methods:This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants′ near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye′s damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level.Results:A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β=0.136, P=0.003), near vision ( β=0.163, P<0.001), visual adaptation ( β=0.092, P=0.042), subjective vision ( β=0.120, P=0.009) and stereo vision ( β=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion:Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

Objective:To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR.Methods:This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants′ near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye′s damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level.Results:A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β=0.136, P=0.003), near vision ( β=0.163, P<0.001), visual adaptation ( β=0.092, P=0.042), subjective vision ( β=0.120, P=0.009) and stereo vision ( β=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion:Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

Objective:To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases,and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables,and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence.Methods:From the UK Biobank Database,315 896 participants and related variables were included.The feature selection was performed by categorical boosting(CatBoost)algorithm,and the participants were randomly divided into training set and test set in the ratio of 7∶3.A Bayesian network model was constructed based on the max-min hill-climbing(MMHC)algorithm.Results:The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8％.The top 10 variables selected by the CatBoost algorithm were age,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),the triglyceride-glucose(TyG)index,family history,apolipoprotein A/B ratio,high-density lipoprotein cholesterol(HDL-C),smoking status,and gender.The area under the receiver operating characteristic(ROC)curve(AUC)for the CatBoost training set model was 0.770,and the model accuracy was 0.764;the AUC of validation set model was 0.759 and the model accuracy was 0.763.The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81.The Bayesian network model analysis results indicated that age,gender,smoking status,family history,BMI,and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors.TyG index,HDL-C,LDL-C,and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio.Conclusion:Controlling BMI,apolipoprotein A/B ratio,and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases.The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

Objective:To discuss the clinical efficacy of recombinant human growth hormone(rhGH)in the treatment of the pediatric patients with growth hormone deficiency(GHD)and idiopathic short stature(ISS),and to clarify its clinical application value in the pediatric patients with short stature of different etiologies.Methods:The clinical data of 132 children with short stature who treated with rhGH from January 2018 to January 2023 were collected.They were divided into GHD group(n=70)and ISS group(n=62)based on different etiologies.The bone age,target height(TH),body mass index(BMI),height standard deviation score(HtSDS),changes in height standard deviation scores(ΔHtSDS)before treatment and 6 months after treatment,and growth velocity(GV)of the pediatric patients were calculated.Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were used to balance the confounding factors between the pediatric patients in two groups and the efficacy and safety of the pediatric patients in two groups were evaluated.Results:There were significant differences in whether children were full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).Compared with before treatment,the height and HtSDS of the pediatric patients in both GHD and ISS groups were significantly increased after treated for 6 months(P<0.05).Before matched by PSM,there were significant differences in full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).After matched by PSM,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);the standardized mean difference(SMD)differences of covariates except for region were<0.2.After weighted by IPTW,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);all SMD of covariates except for term birth status were<0.2.Before balancing covariates,after meatched by PSM matching,and after weighted by IPTW weighting compared with GHD group,the GV and ΔHtSDS of the pediatric patients in ISS group were slightly increased,but the difference was not significant(P>0.05).In terms of adverse reactions,2 cases(2.68%)of fasting hyperglycemia and 7 cases(10.00%)of hypothyroidism occurred in GHD group;3 cases(4.84%)of fasting hyperglycemia and 2 cases(3.23%)of hypothyroidism occurred in ISS group.Conclusion:rhGH can promote the height increase in the patients with GHD and ISS,and there is no significant difference in the height-increasing efficacy between GHD and ISS children.The incidence of adverse reactions is relatively low during treatment,indicating good overall safety.

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

Objective:To investigate the current status of health checkups and the management willingness of post-test abnormal values in residents of mega communities, and to explore the factors affecting the demand for health management of abnormal values after examination.Methods:A cross-sectional study. The residents of Huaguoyuan Community in Guiyang City were enrolled as the objects of this surveywith stratified systematic sampling method and questionnaire survey. The binary logistic regression was used to analyze the influencing factors of health management demand for abnormal values after examination.Results:There were 404 residents participating in this survey, and 182 cases were male (45.05%) and 222 cases were female (54.95%); the mean age was (39.64±15.03) years. There were 179 (44.31%) urban residents and 225 (55.69%) rural residents. There were 162 (40.10%) floating population and 242 (59.90%) non-floating population. Of the residents, 34.2% participated in the physical examination independently due to physical reasons. The age ( χ 2=16.227), household registration ( χ 2=16.117) and occupation ( χ 2=36.454) had statistically significant differences in residents′ participation in physical examination; the household registration ( χ 2=18.726, P<0.001) and occupation ( χ 2=18.094, P=0.034) had significant differences in the handling methods of abnormal values of physical examination. The age ( OR=7.00, P=0.032) and income ( OR=0.33, P=0.047) were the influencing factors of health management needs of abnormal values after health checkup. Conclusion:The awareness of active physical examination of residents in mega community is weak, and it is recommended to strengthen health education and health promotion; residents have a high willingness to the management of abnormal values after health checkup, it can be an important supplement to improve the service quality of physical examination related institutions.

Objective:To evaluate the effects of different doses of sivelestat sodium on perioperative acute lung injury (ALI) in the patients undergoing emergency surgery for acute Stanford type A aortic dissection (AAAD).Methods:A total of 120 patients of both sexes, aged 30-64 yr, with body mass index of 18.5-24.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ, scheduled for emergency AAAD surgery, were divided into 3 groups using a random number table method: low-dose sivelestat sodium group (SL group), medium-dose sivelestat sodium group (SM group)and high-dose sivelestat sodium group (SH group), with 40 patients in each group. Sivelestat sodium 4.8, 6.0 and 7.2 mg/kg were intravenously infused starting from 10 min before anesthesia until 24 h after surgery in SL, SM and SH groups, respectively. Blood samples from the radial artery were collected for blood gas analysis after anesthesia induction and before skin incision (T 1), immediately after the end of surgery (T 2), at 24 h after surgery (T 3), and 72 h after surgery (T 4), the alveolar-arterial oxygen tension difference (PA-aDO 2), oxygenation index (OI)and respiratory index (RI) were calculated. The duration of postoperative mechanical ventilation, length of stay in the intensive care unit (ICU) and length of postoperative hospital stay were recorded. Central venous blood samples were collected at T 1-T 4 to measure serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)and IL-8. Peripheral venous blood samples were collected on preoperative day 1 and postoperative days 1 and 3 to measure white blood cell (WBC) count, neutrophil (NEUT) count, neutrophil percentage (NEUT%), and C-reactive protein (CRP) concentration. The occurrence of postoperative pulmonary complications (PPCs)and 90-day all-cause mortality were recorded. Results:Compared with the baseline at T 1, PA-aDO 2 and RI were significantly increased, OI was decreased, and the serum concentrations of TNF-α, IL-6 and IL-8 were increased at T 2-T 4 in all the three groups ( P<0.05). WBC, NEUT, NEUT% and concentrations of CRP were significantly higher on postoperative days 1 and 3 than on 1 day before surgery in the three groups ( P<0.05). Compared with SL and SM groups, PA-aDO 2 and RI were significantly decreased, OI was increased, and the serum concentrations of TNF-α, IL-6 and IL-8 were decreased, the WBC count, NEUT count, NEUT% and concentrations of CRP were decreased, the incidence of postoperative hypercapnia, hypoxemia, emerging lung rales and bronchospasm was decreased, and the duration of postoperative mechanical ventilation and length of intensive care unit stay were shortened( P<0.05), and no significant change was found in the postoperative length of hospital stay and 90-day all-cause mortality rate in SH group ( P>0.05). Conclusions:Sivelestat sodium 7.2 mg/kg can significantly inhibit the inflammatory responses, alleviate perioperative ALI, and improve early prognosis in the patients undergoing AAAD surgery.

Objective:To explore the mechanism of Tanshinone ⅡA(TⅡA)in improving ischemia/reperfusion(I/R)injury of H9c2 cardiomyocytes by activating Sirtuin 1(SIRT1)-adenosine 5'-monophosphateactivated protein kinase(AMPK)pathway through miR-155-5p.Methods:H9c2 cells were cultured in vitro and I/R damage model was established.After modeling,H9c2 cells were randomly divided into model group,TⅡA group,TⅡA+miR-NC group,TⅡA+miR-155-5p mimics group,10 μmol/L TⅡA was added for intervention after transfection,and the H9c2 cells supplemented with DMSO were used as control group.qRT-PCR was used to detect expression level of miR-155-5p;MTT method was used to analyze cell proliferation ability;flow cytometry was used to evaluate cell apoptosis;ELISA was used to determine the levels of TNF-α,IL-4,IL-10,IL-17,lactate dehydrogenase(LDH),malo-ndialdehyde(MDA)and superoxide dismutase(SOD);Western blot was used to detect relative expressions of SIRT1,AMPK and p-AMPK proteins.Results:Compared with control group,expression of miR-155-5p in model group was increased,cell viability was decreased,apoptosis rate and expressions of TNF-α,IL-17,LDH and MDA were increased,while expressions of IL-4,IL-10,SOD,SIRT1 and p-AMPK were decreased(P<0.05);compared with model group,expression of miR-155-5p in TⅡA group was reduced,cell viability was increased,apoptosis rate and expressions of TNF-α,IL-17,LDH and MDA were decreased,while expressions of IL-4,IL-10,SOD,SIRT1 and p-AMPK were increased(P<0.05);compared with TⅡA group and TⅡA+miR-NC group,expression of miR-155-5p in TⅡA+miR-155-5p mimics group was increased,cell viability was decreased,apoptosis rate and expressions of TNF-α,IL-17,LDH and MDA were increased,while expressions of IL-4,IL-10,SOD,SIRT1 and p-AMPK were decreased(P<0.05).Conclusion:TⅡA can improve I/R injury of H9c2 cardiomyocytes by down-regulating miR-155-5p,and its mechanism may be related to the activation of SIRT1-AMPK pathway.

Retinopathy of prematurity (ROP) is a blinding eye disease characterized by abnormal proliferation of retinal blood vessels in children.Vascular endothelial growth factor (VEGF) can specifically stimulate retinal vascular endothelial cell proliferation and neovascularization.Retinal ischemia and hypoxia in preterm infants promote the compensatory increase of intraocular VEGF expression, and then induce the pathological growth of retinal vessels.The intravitreal injection of anti-VEGF drugs provides a new therapeutic way for ROP by inhibiting the biological activity of VEGF and delaying retinal neovascularization.However, the blood-retina barrier of children with ROP is likely to be destructed, which can cause the imbalanced homeostasis of the retinal microenvironment.The anti-VEGF drugs can cause irreversible damage to nerve cells through the blood-retina barrier and blood-brain barrier, which affects the development of the nervous system in children with ROP.At present, whether anti-VEGF drugs result in the abnormal development and functional changes of nervous system in premature infants remains unknown and attracts much attention.In this paper, the role of VEGF in the pathogenesis of ROP and neurodevelopment, as well as the effects of anti-VEGF drug intravitreal injections on the neurological development of children with ROP were reviewed to provide the clinical basis for the rational and safe application of anti-VEGF drugs.