BackgroundGraduate students frequently face life events， many of which may adversely affect their mental well-being. However， the interaction between life events and the development of depression， anxiety， and somatic symptoms remains unclear. ObjectiveTo explore the relationship between life events and the development of depressive， anxiety and somatic symptoms in graduate students， thereby informing prevention strategies for these conditions. MethodsA sample of 6 722 newly enrolled graduate students at a comprehensive university in Southwest China from September to November 2018 was selected. The assessment was conducted using the Adolescent Self-rating Life Events Checklist （ASLEC）， the 7-item Generalized Anxiety Disorder scale-7 item （GAD-7）， the Patient Health Questionnaire Depression Scale-9 item （PHQ-9）， and the Patient Health Questionnaire-15 （PHQ-15）. Network analysis was implemented by using the bootnet and qgraph packages in the R software （version 4.2.3）， with centrality indices calculated to identify core and bridge symptoms within the network. ResultsThe study encompassed a total of 6 171 graduate students， representing 91.80% of the target population. The prevalence rates of anxiety， depressive， and somatic symptoms among graduate students were 12.59% （777/6 171）， 16.63% （1 026/6 171）， and 27.66% （1 707/6 171）， respectively. Network analysis revealed that 'academic stress' was the core symptom with the highest strength and expected influence （both values=1.207）， while 'feeling down， depressed， or hopeless' was the bridge symptom with the highest bridge strength and bridge expected influence （both values=0.454）. There was no significant difference in global network strength and edge weight between women and men （P>0.05）. ConclusionAcademic stress， emerging as the core symptom， assumes a dominant position within the symptom network and exhibits strong interactions with other negative affective states. There was no gender difference in the network structure.

Background::Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension.Methods::The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60–80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes.Results::The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8–73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7–110.1 cm/s) in the standard treatment group ( P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s –1·year –1vs. 36.7 cm·s –1·year -1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70–80 years or with SBP <140 mmHg. Conclusion::Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension.Clinical trial registration::http://www.clinicaltrials.gov; No. NCT03015311.

Objective To screen and verify the genes that play key role in the occurrence and development of esophageal cancer by u-sing bioinformatics and real-time fluorescence quantitative PCR(qRT-PCR)methods to find new markers for diagnosis of esophageal cancer(ESCA).Methods Using the TCGA database and Wayne plot analysis,the cross genes between the differentially expressed genes of ESCA and the genes which have the most significant impacts on disease-free survival(DFS)rate in esophageal cancer patients were preliminarily identified.Following conducting protein-protein interaction(PPI)network analysis on the overlapping genes,GO and KEGG functional analysis was performed to screen the potential key genes as the diagnostic markers of esophageal cancer.qRT-PCR was used to quantitatively analyze the expression of mRNA of the key gene in peripheral blood.Statistical analysis was con-ducted based on the clinico-pathological characteristics of the patients to determine its potential value as a new diagnostic marker for e-sophageal cancer.Results After overlapping of differentially expressed genes of ESCA and disease-free survival genes in the TCGA database,39 upregulated genes and 20 downregulated genes were found to be differentially expressed,all of which affected disease-free survival rate.After conducting PPI network analysis,15 upregulated genes with core interactions were identified,and the downregulat-ed genes did not form any interaction network.Further enrichment analysis of these 15 core interacting genes through GO and KEGG,revealed that fibronectin 1(FN1)may be a potential biomarker for ESCA diagnosis.The qRT-PCR results showed that compared with the healthy control group,the mRNA expression level of FN1 in the peripheral blood of esophageal cancer patients was significantly ele-vated.After analyzing the clinical characteristics of patients,it was found that the patients with poor differentiation and high clinico-pathological staging had significantly increased peripheral blood FN1 mRNA levels.The model with FN1 mRNA expression levels can distinguish esophageal cancer patients from healthy individuals.Conclusion FN1 mRNA may be a potential non-invasive diagnostic biomarker for esophageal cancer.

Objective To analyze the relationship between the level of microRNA-29b in circulation and left ventricular hypertrophy in hypertensive patients.Methods A total of 240 subjects from Henan Province People's Hospital from June 2015 to June 2018 were included in the present study.Among them,160 were hospitalized patients,and were divided into two groups.Patients with simple hypertension and had no left ventricular hypertrophy (80 cases) were in the simple hypertension group (HBP-NLVH),and patients with hypertension combined with left ventricular hypertrophy (80 cases) were in the high blood pressure with left ventricular hypertrophy group (HBP-LVH).Normal control subjects (80 cases) were those with no hypertension and randomly selected from the medical center of Henan Province People's Hospital.Serum microRNA-29b expressions were detected by real time fluorescence quantitative PCR.The thickness of interventricular septum (IVSD) and left ventricular posterior wall thickness (LVPWD) were measured by echocardiography.Results Compared with the normal control group (1.95±0.79),the relative expression of microRNA-29b in the patients both in the HBP-NLVH group (2.67±0.92) and the HBP-LVH group (5.12 ± 1.23) was up-regulated,and the difference between normal control and patients was statistically significant (P＜0.05).In patients,the microRNA-29b level in the HBP-LVH group was significantly higher than that in the HBP-NLVH group (P＜0.05).The expression level of microRNA-29b was positively correlated with IVSD (r=0.71,P＜0.05) and LVPWD (r=0.74,P＜0.05),respectively.The sensitivity and specificity of serum microRNA-29b levels in the diagnosis of left ventricular hypertrophy in hypertension patients were 96.8％ and 91.3％,respectively.Conclusion Serum microRNA-29b level is elevated in hypertensive patients with left ventricular hypertrophy,and is positively correlated with left ventricular hypertrophy.The circulation microRNA-29b might be a useful biomarker with prognostic value in left ventricular hypertrophy in hypertension patients.

Objective To discuss the surgical strategy for children with complex congenital heart disease (CHD) and end-stage liver disease (ESLD).Methods We reported two eases of pediatric liver transplantation in patients with complex CHD and ESLD.Medical data including operation procedure,ICU management and outcomes were reviewed retrospectively.Also we reviewed the literature on the topic of clinical outcomes resulted from different surgery options.Results The first case was a seven-month-old male patient with biliary atresia and complex CHD (unroofed coronary sinus syndrome,persistent left superior vena cava,patent foramen ovale,and peripheral pulmonary stenosis).Liver transplantation was successfully performed without corrective heart surgery.The operation time was 6 h and 35 min.The patient suffered acute cardiac dysfunction and significant hypoxemia after extubation,then pneumonia developed,and eventually the patient died on post-operative day 12.The second case was a seven-month-old male patient with biliary atresia and complex CHD (ventricular septal defect,patent foramen ovale,patent ductus arteriosus,pulmonary stenosis).Liver transplantation was performed on the same day following total correction of cardiac defects by open-heart surgery.The operation time was 16 h and 15 min.The patient was extubated after 60 h ventilation,and was transferred to ward from ICU on post-operative day 6 with stable cardiopulmonary function.However,hepatic artery occlusion occurred on early postoperative stage,and consequently the patient received the second liver transplantation for ischemic biliary complication on post-operative day 40.The second liver transplantation procedure was uneventful.The liver graft recovered smoothly with stable hemodynamics.Conclusion Children with complex CHD undergoing liver transplantation are at an increased perioperative risk.The surgical strategy for each patient must be tailored individually according to specific cardiovascular status and limited hepatic reserve.

Objective To explore the effectiveness of octreotide therapeutic strategy to attenuate portal hyperperfusion resulted from small-for-size graft in infant liver transplantation.Methods A total of 22 infants received small-for-size liver graft (defined as GV/SLV＜0.5,and GV＜ 150 g) in our hospital from December 2013 to August 2016.Twelve cases (octreotide group) were treated with intravenous octreotide infusion (300 g daily for 24-96 h) to attenuate the portal hyperperfusion after transplantation,and the rest 10 cases given liver transplantation at the early stage did not receive the intervention of octreotide and served as control group.Results The initial portal vein flows (PVFs) in octreotide group and control group were (413.43 ± 76.24) (390.83 ± 107.89) ml/(min 100 g),and there was no significant difference between two groups (P＞0.05).The PVFs on postoperative day (POD) 3 and POD5 in octreotide group and control group were (334.90 ± 96.67) and (441.04 ± 117.41),and (322.20 ± 81.04) and (423.23 ± 100.81) mL/(min 100 g) respectively (P＜0.05 for all).However,there were no significant differences in serum AST and bilirubin levels at four time points (initial,POD3,POD5 and POD7) after transplantation between two groups (P＞0.05).The incidence of hepatic artery occlusion,and biliary complications in octreotide group and ontrol group was 33.33％ and 44.44％,and 33.33％ and 11.11％ respectively (P ＞ 0.05 for all).Conclusion Octreotide treatment attenuated portal hyperperfusion resulted from small-for-size graft in infant liver transplantation.However,the effects of octreotide therapy on graft biochemical tests,the hepatic artery and biliary complications were still unclear,and further investigation is needed.

Objective To explore the relationship between the levels of plasma coagulation factors (F) and acute myocardial infarction (AMI) in low age period (<60 years old) and their diagnostic value in diagnosing AMI in low age period.Methods One hundred and sixty inpatients with low age AMI in the cardiology department of the Heze Municipal Hospital were selected as the case group,and contemporaneous 160 cases of low age non-AMI served as the control group.F Ⅱ,FⅦ,FⅧ,fibrinogen (Fg) and von willebrand (vWF) were measured with enzyme-linked immunoabsorbent anti-sandwich assay.The relationship between coagulation factors and low age AMI was analyzed with univariate and multivariate analysis,and their value for diagnosing low age AMI was evaluated with diagnostic test and receiver operating characteristics (ROC) curve.Results The univariate analysis showed that FⅡ,FⅦ,FⅧ and Fg levels had significantly statistical difference between the case group and control group(P<0.05),and the vWF level had no statistically difference(P>0.05).The multivariate analysis indicated that the FⅡ level≥ 14.27 μg/L and FⅦ level ≥22.99 μg/L were the independent risk factors for low age AMI.The value of FⅡ for diagnosing low age AMI was lower,and the optimal cut off value of Fg for diagnosing low age AMI was 22.99 μg/L,its area under ROC curve was 0.709 with a moderate diagnostic value,and the sensitivity (91.88%) and negative predictive value (86.02%) were higher,the false negative rate (13.98%) was lower,and the accuracy (70.94%) was moderate.Conclusion The FⅡ level ≥14.27 μg/L and Fg level ≥22.99 μg/L are the independent risk factors for low age AMI,and detecting the Fg level could have hint significance in diagnosing low age AMI.

Objective To retrospectively analyze the clinical epidemiology features of adult idiopathic membranous nephropathy (IMN) in Zhongshan Hospital,and to investigate their therapeutic effect and its possible influence factors.Methods A total of 183 patients admitted to the Zhongshan Hospital of Fudan University and diagnosed as IMN by renal biopsy from January 2013 to December 2015 were involved.Their baseline information including demographics and pathologic was collected.Patients were followed up for at least 12 months.Serum albumin ＜ 30 g/L and 24 h urine protein ＞ 3.5g were defined as nephrotic syndrome (NS).IMN patients were divided into NS and non-NS groups and compared.Furthermore,the baseline data of remission and no remission patients were compared,and the correlations of their baseline data with conservative and immunosuppressive therapy were assessed by logistic regression analysis.Results (1) IMN accounted for 11.1％ of renal biopsy cases in our hospital,with an average age of 57 years and 59.6％ male patients.(2) Compared with patients without NS,IMN patients with NS were older,had a shorter time from the onset to receive renal biopsy,lower estimated glomerular filtration rate,and higher total cholesterol,low density lipoprotein cholesterol,triglyceride and serum creatinine (all P ＜ 0.05).(3) The effective rate of conservative treatment in IMN patients without NS was 65.7％,and the ineffective group had higher triglyceride compared with the effective group (P=0.019).(4) The effective rate of immunosuppressive therapy in IMN patients with NS was 81.2％,and low serum albumin was an independent risk factor for the poor efficacy of immunosuppressive therapy (OR=1.202,95％ CI 1.003-1.440,P=0.046).(5) The effective rate of conservative treatment in IMN patients with NS was 55.5％,and low serum albumin was an independent risk factor for the poor efficacy of conservative treatment (OR=1.629,95％CI 1.047-2.536,P=0.023).Conclusions The detection rate of IMN is increasing year by year,but the remission rate of conservative treatment is still not low in mild and moderate patients.For the patients without NS,high triglyceride may predict a poor effect of conservative treatment.Hypoproteinemia is a predictor of poor effect,no matter what a NS patient takes immunosuppressive therapy or conservative treatment.

BACKGROUNDAdoptive cell transfer (ACT) immunotherapy has been used clinically for years to treat malignancies. Improving the killing efficiency of effector cells, such as tumor-specific cytotoxic T lymphocytes (CTLs), is an important component for enhancing the clinical response of cancer immunotherapy. Hence, we explored a novel method for preparing cancer-specific CTLs using naive T lymphocytes.

METHODSC57BL/6 mice bearing B16 melanoma tumors were pretreated with cyclophosphamide (CTX) by peritoneal injection. The immunosuppressive influence of CTX on tumor regression and the tumor microenvironment was assessed. Naive T cells and T cell pools were isolated via negative selection using immunomagnetic beads. The proliferative potential and cytokine production of different T cell subpopulations were evaluated in vitro. Tumor-specific CTLs derived from naive T cells (naive CD4+ T cells: naive CD8+ T cells = 2:1) and pooled T cells were generated in vitro, respectively. B16 melanoma-bearing C57BL/6 mice were pretreated with CTX, followed by ACT immunotherapy using dendritic cell-induced CTLs. The homing abilities of the effector cells and interleukin-2 (IL-2), interferon-γ, granzyme B, and perforin mRNA levels in tumor tissues were evaluated, and the change in tumor volume was measured.

RESULTSMice receiving CTX peritoneal pretreatment injections did not display tumor regression compared with control mice. However, a significant downregulation of splenic Tregs and tumor growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) serum levels was observed (P < 0.05). Naive T cells showed a stronger proliferative capacity and elevated cytokine production than did pooled T cells (P < 0.05). In addition, effector cells generated from naive T cells displayed more potent antitumor activity in vivo than those derived from pooled T cells (P < 0.05).

CONCLUSIONEffector cells derived from the naive T cells possess a stronger proliferative potential, homing capacity, and enhanced cytokine production, which leads to a superior antitumor response.

Animals ; Cell Line, Tumor ; Cells, Cultured ; Female ; Flow Cytometry ; Immunotherapy, Adoptive ; methods ; Melanoma, Experimental ; therapy ; Mice, Inbred C57BL

Objective To compare the efficacy, tolerance and cost of interferon (IFN) α-2b and adefovir (ADV) in patients with chronic hepatitis B (CHB) for two years. Methods The treatmentnaive outpatients with CHB were treated with IFN α-2b or ADV according to intention to treat.Among 77 patients, 34 were treated with recombinant IFN α-2b 5 MU once every other day subcutaneously (IFN group), 43 were treated with ADV 10 mg/day orally (ADV group). The medications were stopped or the regimens were changed due to intolerant adverse reactions or without effects according to intention to treat. The patients were followed up for 24 months. The therapeutic effects, adverse reactions, compliance and cost of two initial treatments were compared. The data were analyzed by Fisher exact probability test. Results The complete virological response (HBV DNA＜500 copy/mL) rates after 12 months of therapy in IFN group and ADV group were 41.2% (14/34)and 67. 4 % (29/43), respectively, while the alanine aminotransferase (ALT) normalization rates were41.2% (14/34) and 93. 0% (40/43), respectively. The rates in ADV group were both significantly greater than those in IFN group (both P＜0.01). There were no statistically significant differences of HBeAg negative rate and HBeAg seroconversion rate between the two groups. In IFN group, the expulsion rate was 23. 5% (8/34), the therapy was discontinued in 8. 8% (3/34) of patients due to adverse reactions and the medication was changed in 47.1% (16/34) of patients. In ADV group, there were no adverse reactions associated with medication during 2-year therapy and patients were well tolerant, the expulsion rate was 7.0% (3/43) and the regimen in 9.3% (4/43) of patients was changed (P＜0.01). The comparison of therapeutic cost between the two groups showed that the cost of anti-viral therapy, management with adverse reactions and laboratory examinations in IFN group were all higher than those in ADV group. The average cost per person of two years was increased with RMB 4855 yuan in IFN group. Conclusion In HBeAg-positive CHB patients, ADV is cost-effective and suitable choice for initial antiviral treatment.