Objective To explore the significance of gene mutations of cystathionine ? synthase (CBS) 844ins68,methione synthase (MS) A2756G and methylene tetrahydrofolate reductase (MTHFR) C677T in patients with unexplained repeated spontaneous abortion(URSA). Methods The genotypes of CBS,MS and MTHFR in 50 patients and 56 healthy controls were determined by PCR-based assay and their restricted enzyme digested maps were analyzed. Results Allelic frequency of MTHFR 677C→T mutations in URSA patients was obviously higher than those in controls (24.0% vs 7.1%). The frequency of allelic mutations was elevated in the URSA group comparing with the control (26.0% vs 17.9%). No significant difference was shown in the frequency of CBS and MS mutations between the two groups. Conclusions The MTHFR 677 C→T mutation is associated with URSA. CBS and MS mutations might not be an independent risk factor for URSA.

Objective:To investigate the methylation status of N-myc downstream regulated gene-1(NDRG-1) gene in breast cancer and the effects of methylation enzyme inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) on growth and expression of NDRG-1 mRNA in human breast cancer cell line T47D.Methods:Sensitive methylation-specific (MSP)-PCR was used to detect the methylation status in the promoter regions of NDRG-1 gene in 47 samples of breast cancer and tumor adjacent tissues and 15 cases of benign breast disease. The change in expression of the tumor suppressor gene NDRG-1 mRNA in cultured T47D cells was detected by RT-PCR before and after 5-Aza-CdR treatment. Cell proliferation was observed by MTT assay.Results:Hypermethylation frequencies of NDRG-1 gene promoter were 46.8% in breast cancer tissues and 21.3% in tumor adjacent tissues. No hypermethylation of NDRG-1 gene was observed in the tissues of breast benign disease. The growth of T47D cells was suppressed obviously after 5-Aza-CdR treatment compared with the control group. RT-PCR showed that compared with the control group, NDRG-1 mRNA expression was increased at different concentrations in 5-Aza-CdR treatment group. Conclusion:The promoter methylation status of NDRG-1 gene was significantly related with the occurrence of breast carcinoma. 5-Aza-CdR could effectively reverse the methylation of NDRG-1 gene and recover its expression, thereby inhibiting the growth of tumor cells.

Primary mediastinal choriocarcinoma in male is not a very common disease,with nonspecific clinical manifestations.Gynecomastia and testicular atrophy are present in some cases.The levels of serum human chorionic gonadotropin are often significantly increased.Giant lump in the mediastinum and bilateral lungs multiple metastases can be seen on the computed tomography for lung.The diagnosis for it depends on pathological biopsy.Current treatment method is a comprehensive,consisting of chemotherapy,radiotherapy and surgery.This paper reported a case of primary mediastinal choriocarcinoma in male,who were diagnosed and treated in the Second Xiangya Hospital of Central South University.He was admitted for cough and hemoptysis,and finally diagnosed by biopsy.The prognosis is very poor.Therefore,it is important to take physical examination regularly because it can be detected and diagnosed early.

A 61-year-old woman with pulmonary alternariosis and aspergillosis was reported.The patient presented with recurrent hemoptysis and cough for 3 years.Alternaria was identified by fungal culture.Biopsy specimen showed pulmonary aspergillosis.The patient had been treated with voriconazole at 400 mg/d through intravenous guttae for 7 days,and then switched amphotericin B at 25 mg/d through intravenous guttae for 11 days.The patient was treated with voriconazole at 400 mg through oral when she was discharged from hospital.After the treatment,the clinical symptoms ofhemoptysis and cough were recovered,and the lung CT examinations showed normal.

Objective: To investigate the expressions of histone lysine-specific demethylase 1 (LSD1), O⁶-methylguanine DNA methyltransferase (MGMT) and cell proliferation-associated antigen Ki-67 in high-grade glioma and their influences on prognosis. Methods: Sixty-five cases of grade Ⅲ and Ⅳ glioma confirmed by pathology from January 2011 to June 2017 in the First Affiliated Hospital of Xinjiang Medical University were selected. Immunohistochemistry (SP method) was used to detect the expressions of LSD1, MGMT and Ki-67 in pathological specimens. The therapeutic effect was evaluated by long-term follow-up. The relationships between the three markers and pathological grade, progression-free survival (PFS) and overall survival (OS) were analyzed. Results: The overall positive rates of LSD1, MGMT and Ki-67 in the 65 high-grade glioma specimens were 70.8% (46/65), 60.0% (39/65) and 100.0% (65/65), respectively. There were no significant differences in the expressions of LSD1 and MGMT in grade Ⅲ and Ⅳ glioma (χ²=1.588, P=0.208, χ²=0.013, P=0.908). Ki-67 expression (+ ), (+ + ), (+ + + ) in grade Ⅳ glioma were observed in 18, 19 and 11 cases, respectively. Ki-67 expression (+ ), (+ + ) in grade Ⅲ glioma were observed in 11, 5 cases, and 1 case was (+ + + ), and the difference in expression intensity between the two groups was statistically significant (Z=-2.083, P=0.037). Log-rank test showed that the positive expressions of LSD1, MGMT and Ki-67 were negatively correlated with the PFS of patients with high-grade glioma (χ²=12.217, P=0.007; χ²=4.446, P=0.035; χ²=12.536, P=0.002), also were negatively correlated with OS (χ²=11.708, P=0.008; χ²=6.637, P=0.010; χ²=11.807, P=0.003). Grade Ⅳ patients were more likely to have relapse progression than grade Ⅲ patients (χ²=6.573, P=0.010), and OS was shorter (χ²=3.974, P=0.046). Cox proportional hazards model analysis showed that the expressions of LSD1 (HR=1.361, 95%CI: 1.094-1.694, P=0.006; HR=1.406, 95%CI: 1.117-1.771, P=0.004) and Ki-67 (HR=1.703, 95%CI: 1.175-2.468, P=0.005; HR=1.778, 95%CI: 1.209-2.616, P=0.003) were the independent prognostic risk factors for PFS and OS of patients with high-grade glioma. Correlation analysis results showed that the expression of MGMT was positively correlated with the expression of LSD1 (r=0.406, P=0.001). Conclusion LSD1, MGMT and Ki-67 have higher positive expression rates in high-grade glioma. MGMT is a prognostic factor for high-grade glioma, and LSD1 and Ki-67 can be used as independent predictors of prognosis for high-grade gliomas.

Objective:To investigate the predictive value of peritoneal protein clearance (Pcl) for cardiovascular events and cardiovascular mortality in peritoneal dialysis (PD) patients.Methods:Eligible PD patients were prospectively enrolled from January 2014 to April 2015 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University. All patients were followed up until death, withdrawing from PD, transferring to other centers, or the end of study period (October 1, 2018). The patients were divided into high Pcl group and low Pcl group by the median Pcl, and the differences of related indicators between the two groups were compared. A multiple linear regression model was used to analyze the influencing factors of Pcl. The Kaplan-Meier method and Log-rank test were used to compare the cumulative survival rates of patients between the two groups. A multivariate Cox regression model was used to estimate the risk of cardiovascular events and cardiovascular mortality in relation to Pcl in PD patients.Results:A total of 271 patients were enrolled, with 135 males (49.8%), age of (56.92±0.84) years old and a median PD duration of 38.77(19.00, 63.10) months. There were 70 patients (25.8%) comorbiding with diabetes and 81 patients (29.9%) with cardiovascular diseases (CVD). The median Pcl of this cohort was 67.93(52.31, 88.36) ml/d. Compared with the low Pcl group (Pcl<67.93 ml/d), the high Pcl group (Pcl≥67.93 ml/d) had older age, and greater proportion of CVD, body mass index (BMI), pulse pressure, brain natriuretic peptide, mass transfer area coefficient of creatinine (MTACcr), and lower serum albumin (all P<0.05). There was no significant difference in gender, dialysis duration, proportion of diabetes, proportion of angiotensin converting enzyme inhibitor and angiotensin receptor blocker, proportion of continuous ambulatory PD, high sensitivity C reactive protein, fluid removal including 24 h urine volume and 24 h ultrafiltration, and residual renal function between the two groups (all P>0.05). Multiple linear regression analysis showed that serum albumin ( β=-0.388, P<0.001), BMI ( β=0.189, P<0.001), and MTACcr ( β=0.247, P<0.001) were independently related to lg(Pcl). During the study period, 55 patients experienced one or more cardiovascular events and 39 patients had cardiovascular mortality. According to Kaplan-Meier analysis, cardiovascular mortality in the high Pcl group was higher than that of low Pcl group (Log-rank χ2=6.902, P=0.009). Multivariate Cox regression analysis showed that, high lg(Pcl) was an independent influencing factor of cardiovascular events in PD patients ( HR=7.654, 95% CI 1.676-34.945, P=0.009). Conclusions:Serum albumin, BMI and MTACcr are independently associated with Pcl, and Pcl is an independent predictor of cardiovascular events in PD patients.

Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P＜0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P＜0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P＜0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Mitochondrial morphology abnormalities and network damage did not recover(P＜0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.

BACKGROUND: There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. METHODS: The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. RESULTS: During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. CONCLUSIONS NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/complications* ; Prehypertension/diagnosis* ; Risk Factors ; Hypertension ; Incidence