Objective To evaluate clinical effect of Compound Fanshiliu Recipe(CFR) for the treatment of over-weighted type 2 diabetes mellitus(T2DM). Methods One hundred and twenty over-weighted T2DM patients were randomized into treatment group and control group, 60 cases in each group. Both groups were given oral use of Metformin Hydrochloride Enteric-Coated Tablets, and additionally the treatment group was treated with CFR orally. The treatment of both groups lasted for 12 continuous weeks. Before and after treatment, we detected the waist circumference (WC), body mass index (BMI), and the levels of fasting blood glucose(FBG), postprandial 2-hour blood glucose(P2hBG), glycosylated hemoglobin(HbA1c), total cholesterol(TC), triglyceride (TG), and free fatty acid (FFA). The therapeutic effect of the two groups was also evaluated after treatment. Results (1) The total effective rate for traditional Chinese medical symptoms was 95.00% in the treatment group, and was 70.00%in the control group, the difference being significant(P<0.01).(2) After treatment, WC and BMI were decreased in the treatment group(P<0.01 compared with those before treatment), but had no significant decrease in the control group(P>0.05). The decrease of WC and BMI of the treatment group was superior to that of the control group(P<0.05).(3) After treatment, levels of FBG, P2hBG, HbA1c, TC, TG, and FFA of both groups were significantly improved (P<0.05), and the improvement of the treatment group was superior to that of the control group(P<0.05).(4) Three patients of the treatment group suffered from slight gastric discomfort, and the discomfort was relieved without any special treatment. Other patients of the two groups had no adverse reaction. Conclusion Treatment of CFR combined with Metformin has been proved to be an effective and safe approach to decrease blood glucose and blood lipid levels, promote weight loss, and ameliorate traditional Chinese medical symptoms.

Objective:To analyze the arsenic exposure of industrial residents and its influencing factors, so as to provide scientific basis for protecting the health of industrial residents.Methods:In 2017, the samples of PM 2.5, drinking water and soil were collected by using cross-sectional survey and were tested for arsenic contents in Xigu District, Lanzhou City. The environmental arsenic exposure was analyzed by using Environmental Protection Agency of USA health risk assessment models. The levels of urinary arsenic and blood arsenic were measured in residents who included adults, children and teenagers. The internal exposure level of arsenic and its influencing factors were analyzed. The correlation between arsenic and internal and external exposure factors were also analyzed. The content of arsenic was expressed by geometric mean. Results:A total of 84 samples of PM 2.5 were collected, and the content of air arsenic was 7.53 ng/m 3. A total of 108 samples of drinking water were collected, and the content of water arsenic was 0.002 2 mg/L. A total of 40 samples of soil were collected, and the content of soil arsenic was 0.14 mg/kg. The total non-carcinogenic risk of environmental arsenic was 0.39, which was lower than the acceptable level of non-carcinogenic risk (1.00). The total carcinogenic risk of environmental arsenic was 6.59 × 10 -5. The total carcinogenic risk of arsenic was the highest through drinking water exposure and followed by the respiratory inhalation exposure, accounting for 78.60% [(5.18 × 10 -5)/(6.59 × 10 -5)] and 20.79% [(1.37 × 10 -5)/(6.59 × 10 -5)] of the total carcinogenic risk of environmental arsenic, respectively. There were 135 subjects, and 135 blood samples were collected. The content of blood arsenic was 0.92 μg/L. The level of blood arsenic of adults (1.05 μg/L) was higher than that of children and teenagers (0.75 μg/L, U = - 3.594, P < 0.05). One hundred and thirty-five urinary samples were collected, and the content of urinary arsenic was 14.17 μg/L. There was a positive correlation between urinary arsenic and blood arsenic ( r = 0.357, P < 0.05). Blood arsenic levels were positively correlated with the total carcinogenic risk and the risk of carcinogenesis through respiratory, oral and skin exposures ( r = 0.252, 0.244, 0.255, 0.255, P < 0.05). Conclusion:Arsenic in the environment of industrial areas has a potential carcinogenic risk to the residents, so the intake of arsenic in drinking water through oral exposure and respiratory inhalation exposure should be limited.

Objective:To study the effects of compound preparation of Fanshiliu on lipid metabolism and pancreatic pathological changes in type 2 diabetes mellitus(T2DM)rats with insulin resistance. Methods:After fed with high-calorie food for 8 weeks,the rats received intraperitoneal injection with low dose of streptozotocin(STZ)to induce T2DM animal model,and then the rats were randomly divided into the model group,metformin group,high and low dose group of compound preparation of Fanshiliu. The normal group was given ordinary feed. The rats were sacrified after intragastric administration for six weeks,and fasted for 12 hours after the last administration. The lipid and lipoprotein indices were detected,and pathological morphology of pancreatic tissue was observed. Results:Compared with those in the model group,TC,TG,LDL-C and FFA in each treatment group were reduced,and HDL-C was increased(P < 0. 05). Fanshiliu high dose group and metformin group had obvious hypoglycemic and lipid-lowering effects. The results of pathological morphology of pancreatic tissue under a light microscope showed that the damage was the most obvious in the model group. Compound preparation of Fanshiliu groups and metformin group showed damage in varying degrees. Conclusion:Fanshiliu preparation can effectively adjust blood lipid levels,enhance the insulin sensitivity and reduce damage in pancreas in T2DM rats.

Objective: To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth. Methods: HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student’s t-test was used to test means of two groups and chi-square test was used for multiple samples. Results: The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm³), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ² = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96). Conclusion AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.

Objective:Aldo-keto reductase family 1 member B10 (AKR1B10) pathogenesis, early diagnosis and prognosis are closely related with hepatoma. Therefore, this study explores the effect and mechanism of AKR1B10 on cell cycle in hepatoma cells.Methods:HepG2 cells were infected with lentivirus LV-AKR1B10-shRNA or treated with epalrestat, an AKR1B10 inhibitor. The expression level of AKR1B10 was detected by Western blot assay and real-time fluorescence quantitative PCR (RT-qPCR). Decreased AKR1B10 activity was detected by reduced coenzyme II (NADPH) absorbance at 340 nm. The low expression of AKR1B10 and the effect of different concentrations of epalrestat on cell proliferation and cell cycle were detected by CCK-8 method and flow cytometry. The protein expression levels of p-rb, cyclin D1, E1, p27 in HepG2 cells were detected by Western blot. The mean of the two samples was tested using independent sample t-test.Results:AKR1B10 expression level in hepatoma cells was significantly increased compared to normal liver cells, and the relative expression level of AKR1B10 protein in HepG2 cells was 6.71 ± 1.11 ( P = 0.012). Epalrestat was significantly inhibited with the enzymatic activity of AKR1B10 in a dose-dependent manner. AKR1B10 gene in HepG2 cells was effectively silenced. HepG2 cells treated with different concentrations of epalrestat (AKR1B10 inhibitor) for 24, 48 and 72 h had inhibited cell proliferation, promoted G0/G1 cell cycle arrest, reduced the expression of p-Rb, cyclin D1, and cyclin E1 and increased the expression of cyclin dependent kinase inhibitor p27 expression. Conclusion:AKR1B10 inhibitory expression and activity can promote G0/G1 cell cycle arrest in HepG2 cells through the p27 / p-Rb pathway.

Objective To assess and compare the incidence,clinical characteristics,treatment,and prognosis of acute heart failure patients from different grades hospitals in Beijing.Methods In this prospective internet prognosis registered study (Beijing AHF Registry),a total of 3 335 consecutive patients admitted to 14 emergency departments in Beijing from January 1st 2011 to September 23rd 2012 were enrolled.According to hospital grade,these patients were divided into two groups,349 patients were from secondary hospitals,and 2 956 patients were from tertiary hospitals.Results Among the 3 335 patients,the medium age was 71 (58,79) years,and male accounted for 53.16％.The most common underlying disease were coronary disease (43.27％),hypertension (17.73％),cardiomyopathy (16.07％) etc.The average treatment time in Emergency Department was 66.82 h.The emergency department mortality rate was 3.81％ (127 cases).The 30-day and 1-year cumulative all-cause mortality were 15.3％ and 32.27％,respectively.The 30-day and 1-year cumulative all-cause readmission were 15.64％ and 46.89％,respectively.Compared with patients in tertiary hospitals,patients in secondary hospitals had more onset acute heart failure patients (63.64％ vs.49.93％),shorter emergency department treatment time (12 h vs.41 h),lower discharge rate (3.43％ vs.37.45％) and emergency department mortality(1.58％ vs.4.09％).Compared with those in tertiary hospitals,1-year cumulative all-cause mortality (25.6％ vs.33.2％),cardiovascular disease mortality (20.2％ vs.26.0％),aggravated heart failure mortality (22.4％ vs.28.8％) were lower in secondary hospitals.Following propensity score matching,compared to tertiary hospitals,patients in secondary hospitals showed lower utilization rate of beta-blockers and ACEFARB (4.51％ vs.28.17％,1.41％ vs.9.58％),except the pironolactone.Conclusion Acute heart failure in emergency department is associated with a high mortality rate and readmission rate.There is still a big gap between guidelines recommend medication current treatments for acute heart failure.

Objective To establish an efficient method for isolating migrasomes from RAW264.7 macrophages and identifying these isolated migrasomes. Methods Scanning electron microscopy was used to observe the morphological characteristics of migrasomes produced by RAW264.7 cells. A 0.45 μm filter was employed for reverse filtration and elution to isolate the migrasomes. The morphological characteristics of the migrasomes were then observed using transmission electron microscopy. Western blot analysis was performed to determine the expression of characteristic markers of the migrasomes. The RNA carried by the migrasomes was analysed by using LabChip bioanalyzer. Results Scanning electron microscopy revealed that the migrasomes, with membranous structures, were attached to the tip or bifurcation of the retraction fiber formed in the tail of RAW264.7 cells. Transmission electron microscopy showed that the isolated migrasomes had a typical oval vesicle-like structure with wrinkled membrane surfaces. Western blot analysis confirmed the expression of the characteristic markers phosphatidylinositol glycan anchor biosynthesis class K (PIGK), epidermal growth factor domain-specific O-linked N-acetylglucosamine transferase (EOGT) and tetraspanin 4 (TSPAN4) in the migrasomes, while the EV (extracellular vesicle) markers tumor susceptibility gene 101 (TSG101) and Arabidopsis homolog of apoptosis-linked gene 2-interacting protein X (ALIX) were not detected. Furthermore, the isolated migrasomes were found to be rich in small RNA, which were approximately 25-200 nt in length. Conclusion A method for the extraction of well-structured and high quality migrasomes from macrophages is established.
Extracellular Vesicles ; Microscopy, Electron, Transmission ; RNA ; Macrophages