Objective To study the clinical characteristics and gene mutation of hereditary spinocerebellar ataxia type 7 (SCA7). Methods The regions of SCA 7 gene containing CAG repeat were amplified by means of PCR and agarose gelelectrophoresis (AGE) technique in 26 patients and 37 normal family members from 5 families with autosomal dominant SCA. The abnormal allele fragments were sequenced by DNA sequencing machine. The correlation between clinical manifestations and CAG repeat size in SCA 7 gene product was analyzed. Results The patients carried 44-50 repeated CAG in the SCA7 allele of 2 SCA 7 gene families with main clinical manifestations as ataxia, hypopsia and retinal pigmental degeneration. About 10-30 repeated CAGs in the SCA7 allele were seen in other healthy members. Conclusion Expanded triplet repeats in SCA 7 gene contributes to the pathologic phenotype,and molecular genetic analysis is effective in the diagnosis and differentiation of SCA 7 gene.

OBJECTIVETo investigate whether or not NADPH oxidase (NOX) participates in leptin-induced reactive oxygen species (ROS) production in hepatic stellate cells (HSC) and to explore the possible mechanism.

METHODSHSC-T6 cells (rat hepatic stellate cells line) were divided into nine groups: Group1: leptin (100 ng/ml) treated; Group2-6: leptin treated together with inhibitors that block different ROS-producing systems: diphenylene-iodonium (DPI) (20 micromol/L), Rotenone (20 micromol/L), Metyrapone (250 micromol/L), Allopurinol (100 micromol/L) and Indomethacin(100 micromol/L); Group7: leptin treated together with Janus kinase (JAK) inhibitor AG490 50 micromol/L; Group8: normal control group (treated DMEM with 0.1% DMSO); Group9: negative control group (untreated). Intracellular ROS levels were measured with dichlorodihydrofluorescein diacetate (DCFH-DA) dye assay by Fluorescence microscope and/or flow cytometry. NOX activity was analyzed by using spectrophotometer to calculate the absorbance of NADPH. The mRNA levels of Rac1 and p22Phox were evaluated by RT-PCR.

RESULTS(1) Leptin increased significantly the ROS production as compared to normal control group (92.91+/-4.19 vs.27.56+/-6.27, P<0.01) in HSC-T6 cells. Both the NADPH oxidase inhibitor DPI and AG490 (50 micromol/L) blocked the ROS production, inhibitors of other ROS producing systems had no significant effect on ROS production induced by lepin (P is more than 0.05). (2) Leptin treated HSC-T6 cells for 1 hour up-regulated the NOX activity significantly compared with that in normal control group [(1.90+/-0.22) pmol.min(-1).mg(-1) vs. (0.76+/-0.06) pmol.min(-1).mg(-1), P<0.05]. Furthermore, the NOX activity increased after being treated with leptin for 12 hours and 24 hours than being treated for 1 hour. Leptin-induced up-regulation of NOX activity was inhibited by pretreatment with DPI or AG490. (3) The RT-PCR results indicated that mRNA expressions of Rac1 and p22Phox in HSC-T6 cells with 12 hours of leptin stimulation increased significantly as compared with normal control group (0.41+/-0.13 vs 0.14+/-0.08, 0.45+/-0.12 vs 0.20+/-0.08, all P<0.05), while the DPI and AG490 had no effect on the mRNA expressions of Rac1 and p22Phox.

CONCLUSIONNOX is the main cellular source of the reactive oxygen species (ROS) generated by HSCs in response to leptin stimulation. The mechanism is probably that leptin can directly activate NOX through JAK signal transduction and hence induce the expression of NOX subunit to promote the activity of NOX which generates considerable ROS in HSC.

Animals ; Cells, Cultured ; Hepatic Stellate Cells ; drug effects ; metabolism ; Leptin ; pharmacology ; NADPH Oxidases ; genetics ; metabolism ; Rats ; Reactive Oxygen Species ; metabolism

In recent years, more attention has been paid to the role of the glutamate transporter 1 (GLT-1, EAAT2) in major depressive disorder (MDD). However, experimental data on brain GLT-1 levels are, to some extent, inconsistent in human postmortem and animal studies. These discrepancies imply that the role of GLT-1 in the pathophysiology of MDD and the action of antidepressants remain obscure. This work was designed to study the impact of chronic unpredictable stress (CUS) for 2 sessions per day for 35 days and four weeks of fluoxetine (FLX) on depressive-like behaviors in rats, as well as the concomitant expression of the GLT-1 protein in the hippocampus. Behavioral changes were assessed by the sucrose preference and open field tests. GLT-1 levels were detected by immunohistchemistry and Western blot analysis. Our study demonstrated that the animals exposed to CUS showed depressive-like behaviors and exhibited a significant decrease in GLT-1 expression in the hippocampus. Chronic FLX treatment reversed the behavioral deficits and the CUS-induced decrease in GLT-1 levels. Taken together, our results support the reduction of GLT-1 in human postmortem studies in MDD and suggest that GLT-1 may be involved in the antidepressant activity of FLX. Our studies further support the notion that GLT-1 is an attractive candidate molecule associated with the fundamental processes of MDD and may be a potential, and novel pharmacological target for the treatment of MDD.
Animals ; Antidepressive Agents, Second-Generation ; pharmacology ; Behavior, Animal ; drug effects ; Brain ; metabolism ; pathology ; Chronic Disease ; Depressive Disorder, Major ; drug therapy ; metabolism ; pathology ; Excitatory Amino Acid Transporter 2 ; metabolism ; Fluoxetine ; pharmacology ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological ; drug therapy ; metabolism ; pathology

Objective To determine the effect of local mild hypothermia on patients with acute cerebral infarction and ascertain its optimal therapeutic window. Methods According to the time receiving treatment, 114 patients with acute cerebral infarction were divided into group A (≤6 h), group B (6-24 h) and group C (≥ 24 h). Then, each group was subdivided into 2 groups at random: treatment group (A1, B1, C1) and control group (A2, B2, C2). Patients in the control group were subjected to such conventional therapy as anti-platelet aggregation. Patients in the treatment group were treated with local mild hypothermia (33-35 ℃ body-core temperature) for 48 h besides conventional therapy. Clinical outcomes were assessed by the National institutes of health stroke scale (NIHSS) on admission and 7, 14,30 d after treatment. Furthermore, we detected the serum level of nitrogen monoxidum (NO) and superoxide dismutasc (SOD) on admission, and 7 and 14 d after treatment. Results Compared with the control group, treatment group enjoyed significantly decreased scores of NIHSS 7, 14 and 30 d after treatment and significantly decreased level of NO 7 and 14 d after treatment (P＜0.05), but obviously increased SOD vitality 7 and 14 d after treatment (P＜0.05). No significant differences in terms of NIHSS scores, level of NO and SOD vitality were noted between group C1 and group C2 at each time point (P＞0.05). Group Al and group B1 had obviously lower scores of NIHSS than group C1 on the 7th, 14th and 30th d of treatment, and had significantly lower level of NO and obviously increased SOD vitality as compared with group C1 on the 7th and 14th d of treatment (P＜ 0.05), and group A1 enjoyed its advantage.Conclusion Early local mild hypothermia therapy can improve neurological function in patients with acute cerebral infarction. The mild hypothermia induced within 6 h may be optimal therapeutic window;mild hypothermia induced at 6-24 h is less effective and that above 24 h is non-effective.

BACKGROUNDUnregulated commercial blood/plasma collection among farmers occurred between 1992 and 1995 in central China and caused the second major epidemic of human immunodeficiency virus type 1 (HIV-1) infection in China. It is important to characterize HIV-1-infected former blood donors and to study characteristics associated with disease progression for future clinical intervention and vaccine development.

METHODSA cross-sectional study was performed on HIV-1-infected former blood donors (FBDs) and age-matched HIV-seronegative local residents. Demographic, epidemiologic, clinical and key laboratory data were collected from all study participants. Both unadjusted and adjusted multivariate linear regressions were employed to analyze the association of the decrease of CD4(+) T-cell counts with other characteristics.

RESULTSTwo hundred and ninety-four HIV-1-infected FBDs and 59 age-matched HIV-seronegative local residents were enrolled in this study. The unregulated blood/plasma collection occurred more than a decade (10.8 - 12.8 years) ago, which caused the rapid spread of HIV-1 infection and the high prevalence of co-infection with hepatitis C virus (HCV, 89.5%); hepatitis B virus (HBV) co-infection was observed in only 11 HIV(+)participants (3.7%). Deterioration in both clinical manifestation and laboratory parameters and increase of viral loads were observed in parallel with the decrease of CD4(+) T-cell counts. The decrease of total lymphocyte counts (P < 0.001) and hemoglobin levels (P < 0.001) and the appearance of dermatosis (P = 0.03) were observed in parallel with the decrease of CD4(+) T-cell counts whereas viral loads (P < 0.001) and CD8(+) T-cell counts (P = 0.01) were inversely associated with CD4(+) T-cell counts.

CONCLUSIONSCo-infection with HCV but not HBV is highly prevalent among HIV-1-infected FBDs. CD4(+) T-cell counts is a reliable indicator for disease progression among FBDs. Total lymphocyte counts, hemoglobin level and appearance of dermatosis were positively associated with CD8(+) T-cell counts and viral loads were inversely associated with the decreased CD4(+) T-cell counts.

Adult ; Aged ; Blood Donors ; China ; epidemiology ; Cross-Sectional Studies ; Female ; HIV Infections ; complications ; epidemiology ; immunology ; HIV-1 ; Hepatitis C ; complications ; Humans ; Male ; Middle Aged

Objective:To investigate the level and prognostic significance of RNF87 in human hepatocellular carcinoma.Methods:Detected the expression of RNF87 in 98 HCC tissues by immunohistochemistry and Western Blot.According to the clinical data of the patients,we analyzed the relationship between RNF87 level and the prognosis of the HCC patients.Results:The level of RNF87 in HCC tissues is down-regulated,compared with the adjacent tissues.And the expression of RNF87 was significantly related to the prognosis of HCC patients.Besides,the lower level of RNF87 was also obviously related with microvascular invasion.Conclusions:The down-regulated level of RNF87 may be one of the risk factors of human hepatocellular carcinoma progression;RNF87 maybe one of potential tumor suppressors;the level of RNF87 can be used as an indicator to predict the prognosis of HCC patients.

BACKGROUNDThe liver is the most common site for colorectal cancer (CRC) metastases. Their removal is a critical and challenging aspect of CRC treatment. We investigated the prognosis and risk factors of patients with CRC and liver metastases (CRCLM) who underwent simultaneous resections for both lesions.

METHODSFrom January 2009 to August 2016, 102 patients with CRCLM received simultaneous resections of CRCLM at our hospital. We retrospectively analyzed their clinical data and analyzed their outcomes. Overall survival (OS) and disease-free survival (DFS) were examined by Kaplan-Meier and log-rank methods.

RESULTSMedian follow-up time was 22.7 months; no perioperative death or serious complications were observed. Median OS was 55.5 months; postoperative OS rates were 1-year: 93.8%, 3-year: 60.7%, and 5-year: 46.4%. Median DFS was 9.0 months; postoperative DFS rates were 1-year: 43.1%, 3-year: 23.0%, and 5-year 21.1%. Independent risk factors found in multivariate analysis included carcinoembryonic antigen ≥100 ng/ml, no adjuvant chemotherapy, tumor thrombus in liver metastases, and bilobar liver metastases for OS; age ≥60 years, no adjuvant chemotherapy, multiple metastases, and largest diameter ≥3 cm for DFS.

CONCLUSIONSSimultaneous surgical resection is a safe and effective treatment for patients with synchronous CRCLM. The main prognostic factors are pathological characteristics of liver metastases and whether standard adjuvant chemotherapy is performed.

Adult ; Aged ; Colorectal Neoplasms ; complications ; mortality ; surgery ; Disease-Free Survival ; Female ; Hepatectomy ; Humans ; Liver Neoplasms ; mortality ; secondary ; surgery ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Outcome

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; China ; Ischemia ; Aortic Aneurysm, Abdominal/surgery*

Objective: To evaluate the efficiency of left cardiac sympathetic denervation (LCSD) in inherited arrhythmia patients with adrenergic activity-induced malignant ventricular arrhythmia, and observe exercise-stress test features before and after LCSD. Methods: This retrospective observational study included catecholaminergic polymorphic ventricular tachycardia(CPVT) and long QT syndromes(LQTS) patients who underwent video-assisted LCSD at Beijing Tsinghua Changgung Hospital and Peking University People's Hospital from September 2006 to May 2020. The indications for LCSD surgery were intolerant or refractory to beta-blocker medication. Clinical and exercise-stress tests data of included patients were collected before and 1 month after LCSD. Heart rate, exercise tolerance, atrial and ventricular arrhythmia, QTc interval and predictors for sudden cardiac death were analyzed. Patents were regularly followed up at 1, 3, 6, and 12 months after LCSD and then once every year thereafter. Cardiac events and medication adjustment records were collected. Results: Five patients (2 CPVT, 1 LQT1, and 2 LQT2)were included in the study. All patients experienced syncope as first symptom at the median age of 12(10, 16)years, and underwent LCSD at the median age of 21(16, 26)years, Baseline heart rate was similar before and after LCSD ((65.6±6.5) beats/min vs. (68.0±11.1) beats/min, P=0.57); while maximum workload tended to be lower after LCSD ((12.1±2.8) metabolic equivalents (METS) before surgery vs. (10.5±2.4) METS after surgery, P=0.07). Incidence of atrial and ventricular arrhythmia were significantly reduced post LCSD, and the ventricular arrhythmia score was decreased after LCSD in CPVT patients (4 points before LCSD vs. 3 points after LCSD in case 1;5 points before LCSD vs. 3 points after LCSD in case 2). QTc interval was shortened significantly in three LQTs patients (QTc interval at baseline heart rate: (546.6±72.3) ms before surgery vs. (493±61.1) ms after LCSD, P=0.047; QTc interval at maximal exercise heart rate: (516.3±73.7) ms before surgery vs. (486.7±64.2)ms after LCSD, P=0.035). Additionally, sudden cardiac death risk indicator ΔHRR1 (heart rate decreasing value within the first 1 min during recovery phase) decreased from (51.5±21.1) beats/min before surgery to (32.0±13.9) beats/min after surgery (P=0.035). During a median follow-up of 1(1, 4) year, all five patients were on low dosage of propranolol (37.0±21.7) mg/d. Cardiac events free survival was achieved in four out of 5 patients (80%) after sympathectomy, while 1 case suffered from sudden cardiac death after emotional stress. Conclusion: LCSD surgery can be safely and effectively performed in most hereditary arrhythmia patients with adrenergic activity-induced life-threatening cardiac events. Exercise stress test results show that LCSD could reduce malignant arrhythmias and improve sudden cardiac death risk indicators without decreasing heart rate.

Objective To evaluate the efficiency of a recombinase-aided amplification (RAA) assay for the detection of Schistosoma japonicum infections in Oncomelania hupensis snails. Methods A group test was employed. Fifty Oncomelania snails were collected as a detection sample. The detection samples without infected snails were designated as negative specimens, while the detection samples that contained different numbers of infected snails were designated as positive specimens. A total of 10 negative specimens, 10 positive specimens containing 1 infected snail, 20 positive specimens containing 2 infected snails and 10 positive specimens containing 3 infected snails were assigned. Following random grouping, 40 specimens were subject to the florescent RAA assay using a blind method. The miradium shedding method served as a gold standard, and the sensitivity, specificity, Youden’s index and coincidence rate of the florescent RAA assay were estimated. In addition, 20 samples consisted of 5 negative specimens and 15 positive specimens with 1, 2 and 3 infected snails respectively were grouped randomly. The same specimens were detected using the crushing method and fluorescent RAA assay with the blind method in a paired-design manner. Then, the test results were compared and analyzed. Results Florescent RAA assay detected 29 positives in the 30 specimens containing different numbers of infected snails, with a sensitivity of 96.67%, and 8 negatives in the 10 detection specimens without infected snails, with a specificity of 80.00%, showing a Youden’s index of 0.77. The coincidence rate was 100% among 10 repeated assays for a detection specimen. In addition, there was no significant difference in the detection of infected snails between the florescent RAA assay and the crushing method (χ² = 0, P > 0.05), and the actual coincidence rates of the florescent RAA assay and crushing method were 95.00% (19/20) and 90.00% (18/20) with the real results, respectively. Conclusion Fluorescent RAA assay has a favorable efficiency for the detection of S. japonicum infections in Oncomelania snails, which shows a potential in screening of S. japonicum-infected Oncomelania snails.