Interfering with B7-H4 expression can inhibit proliferation of breast cancer cells by down-regulating E2F family related transcription factors / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨干扰B7-H4表达对乳腺癌细胞增殖、凋亡、周期以及相关下游分子表达的影响。方法：利用脂质体转染技术分别将特异性靶向B7-H4的siRNA（siB7-H4）及其阴性对照（siNC）转染至对数生长期的乳腺癌T47D和MCF-7细胞，分别命名为T47D-siB7-H4、T47D-siNC、MCF-7-siB7-H4和MCF-7-siNC组。用qPCR法和WB法验证siRNA干扰效果及其对细胞周期分子cyclin D1表达的影响，CCK-8法和FCM分别检测干扰B7-H4表达对T47D和MCF-7细胞增殖、周期和凋亡的影响，qPCR法检测B7-H4干扰对E2F家族相关转录因子表达的影响。结果：成功构建干扰B7-H4表达的乳腺癌T47D和MCF-7细胞。与T47D-siNC和MCF-7-siNC组相比，T47D-siB7-H4和MCF-7-siB7-H4组细胞中B7-H4 mRNA和蛋白表达水平均显著降低、细胞增殖能力显著降低（均P<0.01），并伴有G1/S期细胞周期阻滞以及cyclin D1表达下调（均P<0.01），但细胞凋亡率差异无统计学意义（均P>0.05）。与T47D-siNC相比，干扰B7-H4后T47D细胞中E2F1、E2F2、E2F7和E2F8 mRNA水平有不同程度的降低（均P<0.01）；与MCF-7-siNC相比，干扰B7-H4后MCF-7细胞中E2F1、E2F2、E2F3、E2F7和E2F8 mRNA水平均有不同程度的降低（P<0.05或P<0.01）。结论：干扰乳腺癌细胞B7-H4表达可下调cyclin D1和E2F家族相关转录因子的表达，导致细胞周期阻滞并抑制细胞增殖。

Implication of epigenetic factors in the pathogenesis of type 1 diabetes / 中华医学杂志(英文版)

Type 1 diabetes (T1D) is an autoimmune disease that resulted from the severe destruction of the insulin-producing β cells in the pancreases of individuals with a genetic predisposition. Genome-wide studies have identified HLA and other risk genes associated with T1D susceptibility in humans. However, evidence obtained from the incomplete concordance of diabetes incidence among monozygotic twins suggests that environmental factors also play critical roles in T1D pathogenesis. Epigenetics is a rapidly growing field that serves as a bridge to link T1D risk genes and environmental exposures, thereby modulating the expression of critical genes relevant to T1D development beyond the changes of DNA sequences. Indeed, there is compelling evidence that epigenetic changes induced by environmental insults are implicated in T1D pathogenesis. Herein, we sought to summarize the recent progress in terms of epigenetic mechanisms in T1D initiation and progression, and discuss their potential as biomarkers and therapeutic targets in the T1D setting.

Effect and Safety of Hydroxysafflor Yellow A for Injection in Patients with Acute Ischemic Stroke of Blood Stasis Syndrome: A Phase II, Multicenter, Randomized, Double-Blind, Multiple-Dose, Active-Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS).@*METHODS@#A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment.@*RESULTS@#Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P0.05).@*CONCLUSIONS@#HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608).

Logistic regression analysis on risk factors for surgical site infection after colorectal surgery / 中国感染控制杂志

Objective To explore risk factors for surgical site infection(SSI) in colorectal surgery,and provide evidence for formulating measures for preventing SSI.Methods Patients who underwent colorectal surgery in the department of gastrointestinal surgery of a hospital from June 2013 to June 2016 were surveyed retrospectively,the related risk factors for SSI were analyzed by unconditional logistic regression analysis.Results Among 397 patients who underwent colorectal surgery,67 (16.88％) had SSI.Logistic regression analysis showed that smoking,low albumin,seniority of surgeons less than 5 years,irrational use of antimicrobial agents during perioperative period,and high National Nosocomial Infection Surveillance (NNIS) score were independent risk factors for SSI after colorectal surgery (all P＜0.05).Conclusion There are multiple risk factors for SSI after colorectal surgery,it is necessary to pay attention to it and formulate preventive measures,so as to reduce the occurrence of SSI effectively.

Mibefradil reduces blood glucose concentration in db/db mice

OBJECTIVE: Numerous recent studies suggest that abnormal intracellular calcium concentration ([Ca2+]i) is a common defect in diabetic animal models and patients. Abnormal calcium handling is an important mechanism in the defective pancreatic β-cell function in type 2 diabetes. T-type Ca2+ channel antagonists lower blood glucose in type 2 diabetes, but the mechanism remains unknown. METHODS: We examined the effect of the Ca2+ channel antagonist mibefradil on blood glucose in male db/db mice and phenotypically normal heterozygous mice by intraperitoneal injection. RESULTS: Mibefradil (15 mg/kg, i.p., b.i.d.) caused a profound reduction of fasting blood glucose from 430.92±20.46 mg/dl to 285.20±5.74 mg/dl in three days. The hypoglycemic effect of mibefradil was reproduced by NNC 55-0396, a compound structurally similar to mibefradil but more selective for T-type Ca2+ channels, but not by the specific L-type Ca2+ channel blocker nicardipine. Mibefradil did not show such hypoglycemic effects in heterozygous animals. In addition, triglycerides, basal insulin and food intake were significantly decreased by mibefradil treatment in the db/db mice but not in the controls. Western blot analysis, immunohistochemistry and immunofluorescence staining showed a significantly increased expression of T-type Ca2+ channel α-subunits Cav3.1 and Cav3.2 in liver and brain tissues from db/db mice compared to those from heterozygous animals. CONCLUSIONS: Collectively, these results suggest that T-type Ca2+ channels are potential therapeutic targets for antidiabetic drugs. .

Identification of factors associated with YMDD mutation in patients with chronic hepatitis B receiving lamivudine treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To identify factors associated with YMDD mutation in patients with chronic hepatitis B before and after lamivudine treatment in Zunyi region.</p><p><b>METHODS</b>53 patients with chronic hepatitis B were enrolled in this study, HBV DNA,HBV markers, ALT, AST, TBil, albumin in the serum were examined at 0, 3, 6, 12, 18 and 24 months after lamivudine treatment. HBV genotype and YMDD mutation were determined by sequencing before lamivudine treatment. YMDD mutation was checked again if serum HBV DNA rebound to more than 1 x 10(4) copies/ml after the initial decrease.</p><p><b>RESULTS</b>HBV genotype in Zunyi region is constitute of B, C and B+C genotype. YMDD mutation occurred in 18 cases after lamivudine treatment, the rate of YMDD mutation was 15.1%, and 34.0% after 1 year and 2 years treatment. There are four types of mutation: rtL180M/M204V, rtL180M/M204I, rtM204I, rtL180M. rtM204V mutation in C gene was always accompanied by rtL180M mutation (100%). The rate of rtL180M/M204V mutation in genotype C group was significantly higher than that in genotype B group (77.8% to 25.0%), the same was true for the rtL180M/ M204I mutation (22.2% to 12.5%). There was no point mutation in genotype C group. The point mutation of rtM204I and rtL180M appeared only in genotype B group. Gender, nation, family history of hepatitis B and HBeAg were not associated with YMDD mutation (P more than 0.05), while the mutation rate was associated with the disease course and severity of disease. YMDD mutation did not occur in patients with low HBV DNA level (less than 10(5) copies/ml).</p><p><b>CONCLUSION</b>YMDD mutation after lamivudine therapy is associated with HBV genotype and P gene mutation type, and prolonged treatment increases the the mutation rate. In order to reduce the incidence of YMDD mutation, patients with shorter disease course, lower HBV DNA level, more serious liver damage should be treated with lamivudine.</p>

The Effect of Silk Fibroin-Alginic Acid Sponge Treatment as an Artificial Skin on Wound

PURPOSE: This study was designed to compare the wound healing effect of silk fibroin, alginate and fibroin/ alginate blend sponge with clinically used Nu gauze in a rat skin defect model. METHODS: Two full thickness excisions were made on the back of Sprague-Dawley rat. The excised wound was covered with either of the silk fibroin(SF), alginate (SA), or fibroin/alginate blend sponge(SF/SA). On the postoperative days of 3, 7, 10 and 14, the wound area was calculated by image analysis software. At the same time, a skin wound tissue was biopsied. RESULTS: Healing time 50% (HT(50)) of SF/SA sponge treated group was dramatically reduced as compared with that of control treatment. We also found that the HT50 of SF/SA sponge was significantly decreased as compared with either those of SF or SA treatment. Furthermore, SF/SA treatment significantly increased the size of epithelialization and collagen deposition as well as the number of PCNA positive cells on epidermal basement membrane as comapred with those of control treatment. CONCLUSION: Our results suggest that the wound healing effect of SF/SA blend sponge is the best among other treatments including SF and SA during the whole wound healing period.