Objective Differentially expressed genes in oral squamous cell carcinoma (OSCC) were subjected to bioinformatic and Mendelian randomization analyses to elucidate their prognostic significance in OSCC. Methods The TCGA database and dataset GSE138206 were used to screen the common differential genes of OSCC, and their relationship was analyzed by using Mendelian randomization. The prognostic value of differential genes was further analyzed by Cox risk regression. The biological function of genes with high prognostic value was further evaluated by single gene differential analysis. Results A total of 147 common differential genes were screened from the two databases. Results of two-sample Mendelian randomization showed that GREM2 was associated with the increased risk of OSCC. In addition, SH3BGRL2 was associated with a decreased risk of OSCC, and DKK1, CCL11, and HOXC6 were considered as independent prognostic markers of OSCC. The predicted results of DKK1 were consistent with the actual results. KEGG enrichment analysis indicated the potential involvement of DKK1 in arachidonic acid and linoleic acid metabolism. Furthermore, DKK1 showed positive correlations with Tgd and Th2 cells, while displaying negative associations with PDC, Cytotoxic cells, Mast cells, CD8 T cells, TFH cells, B cells, T cells, and Th17 cells. Conclusion GREM2 is associated with an increased risk of OSCC. DKK1 is highly expressed in OSCC and associated with poor prognosis, which may be involved in regulating the metabolism of arachidonic acid and linoleic acid and immune cell invasion in OSCC.

Objective: To investigate the current status and trends of depressive symptoms among middle school and college students in Hunan Province, and to explore the primary related factors of depressive symptoms, so as to provide a scientific basis for strengthening mental health among students. Methods: A total of 279 382 students in Hunan Province were selected through a stratified cluster random sampling method from 2021 to 2023. National Survey Questionnaire on Common Diseases and Health Influencing Factors among Students was adopted for the survey, and the Center for Epidemiological Studies Depression Scale was used to assess their depressive symptoms. The χ 2 test and trend χ 2 test were used to analyze depressive symptoms prevalence and trends, and multivariable Logistic regression was used to analyze the related factors of depressive symptoms. Results: The prevalence of depressive symptoms among students in Hunan Province from 2021 to 2023 were 19.66%, 20.17% and 21.47%, respectively, showing an upward trend ( χ 2 trend =9.07, P <0.01). In addition, the results of the multivariable Logistic regression analysis showed that students with healthy diet ( OR=0.43, 95%CI =0.40-0.45), adequate sleep ( OR=0.88, 95%CI =0.86-0.90), and acceptable screen time ( OR=0.61, 95%CI =0.60-0.62) had lower risks in depressive symptoms detection, while students with smoking ( OR= 1.95, 95%CI =1.88-2.02), secondhand smoke exposure ( OR=1.33, 95%CI =1.30-1.36) and Internet addiction ( OR= 4.19 , 95%CI =4.05-4.34) had higher risks in depressive symptoms detection, with differences in the degree of association among different genders, educational stages and urban rural groups ( OR=0.40-6.04, Z =-12.69-11.98) ( P <0.05). Conclusions There is an increasing trend of depressive symptoms among middle school and college students in Hunan Province from 2021 to 2023.Targeted depression prevention measures should be taken for students with different demographic characteristics to promote their mental health.

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 summarize the clinical features,diagnosis and treatment of multisystem inflammatory syndrome in children (MIS-C) after novel coronavirus infection(COVID-19),so as to improve the early recognition of MIS-C.Methods:The general information,clinical manifestations,treatment and length of hospital stay of fifteen children diagnosed with MIS-C and hospitalized in the Department of Cardiology,Children's Hospital,Capital Institute of Pediatrics from December 1，2022 to January 31，2023 were retrospectively analyzed.Fifteen children were divided into shock group( n=6) and non-shock group( n=9) according to the criteria of shock,and the differences in general conditions and laboratory examinations before treatment were compared between two groups. Results:The mean age of fifteen children were (3.28±2.48) years (ranging from 9 months to 7.9 years),with a male to female ratio of 4:1.The mean time interval from COVID-19 to the onset of MIS-C was (30.60±9.91) days.The novel coronavirus vaccination rate was 7%.Fever,enlarged lymph nodes,cracked lips and a strawberry tongue were present in all children,with just one exhibiting peeling of the hands and feet.Compared with the non-shock group,patients in the shock group were older,the level of platelet decreased significantly,the level of procalcitonin,interleukin-10,N-terminal pro-brain natriuretic peptide(NT-proBNP) and ferritin significantly increased,the left ventricular ejection fraction and left ventricular fractional shortening decreased significantly,and the Z score of left ventricular end-systolic diameter significantly increased,and there were significant differences between two groups ( P<0.05).All 15 patients were treated with human intravenous immunoglobulin,and five patients with severe myocarditis and shock accepted combined high-dose methylprednisolone pulse therapy over a period of five days,with the doses gradually tapering off afterwards.The mean hospital stay of all patients was (11.00±4.80) days,while the mean shock correction time of six patients was (5.14±2.12) days.After six months of follow-up,15 patients showed excellent prognosis with coronary lesions recovered and without any new complications. Conclusion:Generally,MIS-C tends to occur 3-6 weeks after COVID-19,with more boys than girls.Older ones are more likely to suffer from shock.Focusing on NT-proBNP and cardiac function indicators could identify shock early.High-dose methylprednisolone pulse therapy may be effective and benefit for prognosis improvement in children complicated with both shock and severe myocarditis.

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.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective To investigate the expression and clinical significance of microRNA-93-5p (miR-93-5p) in patients with type 2 diabetes mellitus (T2DM) complicated with coronary heart disease (CHD). Methods A total of 60 patients with T2DM (T2DM group), 57 patients with T2DM complicated with CHD (T2DM with CHD group), and 60 healthy individuals (control group) were enrolled in this study from August 2019 to May 2021. The general information, serum miR-93-5p, and interleukin-6 (IL-6) levels were compared among the T2DM with CHD group, control group and T2DM group; the relationships of serum miR-93-5p and IL-6 levels with low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), triglyceride (TG), glycated hemoglobin (HbA1c), and total cholesterol (TC) were analyzed in T2DM with CHD patients; the influencing factors of T2DM complicated with CHD were analyzed; the predictive value of serum miR-93-5p and IL-6 for T2DM complicated with CHD was evaluated. Results The levels of LDL-C, FINS, TG, FPG, TC, HbA1c, serum miR-93-5p, and IL-6 in the T2DM with CHD group and T2DM group were significantly higher than those in the control group, while the HDL-C level was significantly lower (P < 0.01); the levels of LDL-C, FINS, TG, FPG, TC, HbA1c, serum miR-93-5p, and IL-6 in the T2DM with CHD group were significantly higher than those in the T2DM group, while the HDL-C level was significantly lower (P < 0.01). The serum miR-93-5p and IL-6 levels in T2DM with CHD patients were positively correlated with LDL-C, FINS, HbA1c, TC and FPG (P < 0.01), and negatively correlated with HDL-C (P < 0.01); the expression level of miR-93-5p in serum was positively correlated with IL-6 (P < 0.05). LDL-C, FINS, FPG, HbA1c, TC, miR-93-5p, and IL-6 were the influencing factors of T2DM complicated with CHD (P < 0.05); the area under the curve (AUC) of serum miR-93-5p and IL-6 for predicting T2DM complicated with CHD was 0.888 and 0.898 respectively, with cut-off values of 2.59 and 77.98 ng/L respectively, sensitivity of 75.4% for both serum miR-93-5p and IL-6, and the specificity was 89.2% for miR-93-5p and 85.8% for IL-6; the AUC of the combined prediction of miR-93-5p and IL-6 for T2DM complicated with CHD was 0.939, with sensitivity and specificity of 91.2% and 83.3% respectively. Conclusion The serum miR-93-5p level is elevated in patients with T2DM complicated with CHD, and miR-93-5p together with IL-6 may participate in the process of T2DM complicated with CHD. The combined detection of IL-6 and miR-93-5p is expected to serve as an auxiliary method for prediction of T2DM complicated with CHD.

The cardiovascular diseases, which have the increasing incidence and high mortality rate, have brought a great impact on people′s lives and health.Being lipid inclusions with 30~150 nm in diameter, exosomes can be secreted by most cells in the body, and proteins, lipids, nucleic acids and other substances derived from those cells are wrapped inside.Exosomes play a variety of biological roles in the communication between cells, such as mediating immune response, inflammatory response, cell migration and differentiation.Research on exosomes has made significant progress, and the roles of exosomes in cardiovascular diseases have consequently attracted more and more attention in recent years.The communication of exosomes between cardiomyocytes and between heart and peripheral tissues has provided new strategies for the diagnosis and treatment of cardiovascular diseases.Application of exosomes in the diagnosis and treatment of cardiovascular diseases such as heart failure, viral myocarditis, Kawasaki disease and dilated cardiomyopathy is summarized in this review.

Objective:To evaluate the performance of the European Evidence-based Guidelines on Pancreatic Cystic Neoplasms (EEGPCN)(2018) and International Association of Pancreatology(IAP) Guideline(Version 2017) in predicting high grade dysplasia/invasive carcinoma-intraductal papillary mucinous neoplasm(HGD/INV-IPMN).Methods:A retrospective analysis of 363 patients,who underwent surgical resection in Changhai Hospital affiliated to Navy Medical University from January 2012 to December 2018 and were pathologically identified as (intraductal papillary mucinous neoplasm, IPMN),was performed. The patients,including 230 males and 133 females,aging (61.7±10.1) years(range:19 to 83 years). The proportion of HGD/INV-IPMN who met with the absolute indication(AI) of EEGPCN and high risk stigma(HRS) of IAP were compared. The binary Logistic regression analysis was used to find the independent risk factors of HGD/INV-IPMN.Eight combinations of risk factors derived from relative indication/worrisome feature or risk factors in this study,were made to evaluate the diagnostic efficacy. The area under curve(AUC) of receiver operating characteristics was used to evaluate the the cutoff value of risk factors(①CA19-9≥37 U/ml,②diameter of main pancreatic duct 5.0-9.9 mm,③enhancing mural nodule<5 mm,④(acute) pancreatiti,⑤ acyst diameter ≥40 mm,⑤ bcyst diameter ≥30 mm, ⑥thickened or enhancing cyst walls,⑦neutrophile granulocyte to lymphocyte ratio(NLR)≥2, ⑧cyst located in head, uncinate or neck,⑨carcinoembryonic antigen(CEA) ≥5 μg/L) number for predicting HGD/INV-IPMN.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value,true positive,true negative,false positive,false negative,positive likelihood ratio,negative likelihood ratio,Youden index and F1 score were calculated. Results:Ninety-two patients(49.5%) of 186 ones who met AI and 85 patients(48.3%) of 176 ones who met HRS were respectively confirmed as HGD/INV-IPMN. In those patients who were not met AI,tumor location,thickened/enhancing cyst wall,CA19-9 elevated,NLR≥2 and CEA elevated were significantly ( P<0.05) correlated with HGD/INV-IPMN. And tumor location(head/uncinate/neck vs. body/tail, OR=3.284,95% CI:1.268-8.503, P=0.014),thickened/enhancement cyst wall (with vs.without, OR=2.713,95% CI:1.177-6.252, P=0.019),CA19-9(≥37 U/L vs.<37 U/L, OR=5.086,95% CI:2.05-12.62, P<0.01) and NLR(≥2 vs.<2, OR=2.380,95% CI:1.043-5.434, P=0.039) were the independent risk factors of HGD/INV-IPMN. Patients with ≥4 risk factors of 9 in combination Ⅷ(①②③④⑤ b⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the moderate accuracy(71.0%),moderate sensitivity (62.0%) and moderate specificity (73.0%). Patients with ≥4 risk factors of 9 in Combination Ⅶ(①②③④⑤ a⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the highest specificity(83.0%) and patients with ≥3 risk factors of 8 in combination Ⅵ(①②③④⑤ b⑥⑧⑨) were diagnosed as HGD/INV-IPMN with the highest sensitivity(74.0%). The AUC for diagnosis of HGD/INV-IPMN in combination Ⅵ,Ⅶ and Ⅷ were 0.72,0.75 and 0.75,respectively. Older patients and younger patients could respectively refer to combination Ⅶ and combination Ⅵ to improve the management of IPMN. Conclusions:Patients who meet AI of EEGPCN should undertake resection, otherwise the method we explored is recommended. The method of improvement for diagnosis of HGD/INV-IPMN is relatively applicable and efficient for decision-making of surgery, especially for younger patients with decreasing of missed diagnosis and elder patients with decreasing of misdiagnosis.