Objective To investigate the different distribution and expression of mammalian target of rapamycin complex (mTORC) in the kidney of diabetic nephropathy (DN) mice.Methods Fourteen eight-week-old male C57BL/6 mice were assigned to 2 groups: the control group ( n=7 ) and the streptozotocin ( STZ )-induced DN group ( n=7 ) . Blood and urinary variables including glucose , albumin, creatinine and albumin/creatinine ratio were assessed 2 weeks after STZ injection.Hematoxylin-eosin staining was performed for renal pathological analyses .The distributions of mTOR , phosph-ser2448-mTOR(p-mTOR), mTORC1(Raptor), mTORC2(Rictor) and phosph-ser240/244-S6K1 (p-S6K1) were determined by immunofluorescence.The expression levels of mTOR, p-mTOR, mTORC1(Raptor), mTORC2(Rictor), S6K1 and p-S6K1 were detected by Western blotting .Results Two weeks after STZ injection , the diabetic mice developed albuminuria (P<0.01) and renal hypertrophy (P<0.05).The immunofluorescence positive staining for mTOR , Raptor, and Rictor was distributed in the epithelial cells of proximal tubules , glomerular mesangium and capillary loops as well as the medullary collecting ducts of the control mouse kidney .These positive signals increased in the DN mouse kidney ( P<0.05).However, pS6K1 was not detected in the inner medulla of control mouse and p-mTOR was not found in the glomeruli of both control and DN mice .Conclusion mTORC is widely expessed in the mouse kidney and participates in the development of DN , whereas the 2448 serine phosphorylation of mTOR may be not implicated in the hyperglycemia mediated glomerular injury .

Objective: To explore the mechanism of congestive heart failure (CHF) by observing the effects of Tingli Shengmai Decoction on myocardial fibrosis and expression of TGF-?1 of rats with CHF. Methods: The CHF animal models were duplicated by the abdomen arteriarctia method, and 60 male wistar rats were randomly divided into the sham-operation group, the model group, the high-dose of Tingli Shengmai Decoction group, the low-dose of Tingli Shengmai Decoction group and the positive medicine (Xinbaowan) control group. After 4 weeks common fed, every group rats were given a certain dose of distilled water or medicine. After 8 weeks, hemodynamic parameters were detected, MASSON staining was used in the study of collagen type in left ventricular interstitial tissue, collagen volume fraction (CVF) were measured by image analysis, and expression of TGF-?1 in myocardium were evaluated by immunohistochemical staining. Results: Compared with the sham-operated group, CVF of model control group increased significantly (P

OBJECTIVE:To establish a method for determining the main contents and entrapment efficiency in the bruc-ine nanostructured lipid carrier(NLC). METHODS:HPLC was adopted to determine the main content,sephadex gel filtration meth-od was employed to separate free drug in brucine NLC to determine the entrapment efficiency. The column was Dikma C18 with the mobile phase of mobile phase A(methanol)-mobile phase B [water-acetic acid-triethylamine(230∶2.4∶0.3,V/V/V)](30∶70,V/V)at the flow rate of 1 ml/min,the detection wavelength was 265 nm,volume was 10 μl and temperature was 30 ℃. RESULTS:The linear range of brucine was 4.00-80.00μg/ml(r=0.999 9);RSDs of precision,stability and reproducibility tests were≤1.67%;av-erage recoveries of content determination and sephadex gel filtration method were respectively 99.66%(RSD=0.45%,n=9) and 99.75%(RSD=1.74%,n=9);and the average entrapment efficiency was 69.92%. CONCLUSIONS:The method is simple,re-producible and efficient,and can be used for the determination of main contents and entrapment efficiency in brucine NLC.

Objective To detect the expressions of osteopontin (OPN) and inerleukin-18 in patients with bullous pemphigoid (BP),and to analyze their relationship with clinical and laboratory indices.Methods Enzyme linked immunosorbent assay (ELISA) was performed to quantify the serum levels of osteopontin (OPN) and inerleukin (IL)-18 in 30 patients with BP and 30 health controls.Results The serum level of OPN was statistically higher in the patients than in the healthy controls ((8.29 ± 2.76) vs.(3.88 ± 1.41 ) ng/ml,P ＜ 0.01 ),and was positively correlated with the severity of BP (r =0.658,P ＜ 0.01 ) and with some laboratory indices in the patients.Increased serum IL-18 level was observed in patients complicated by cardiovascular diseases compared with those without cardiovascular diseases ((37.49 ± 6.43) vs.(31.10 ± 5.40) pg/ml,P ＜ 0.01).Moreover,the BP patients with diabetes,tumor,hepatic and renal impairment displayed an enhanced level of serum OPN and IL-18 than those without (all P ＜ 0.05).Conclusions OPN may be positively correlated with the severity of BP,while IL-18 may be involved in the development of complications of BP.

Objective To investigate the difference of apparent diffusion coefficients (ADCs) changes in three major salivary glands after gustatory stimulation using two different stimuli. Methods Thirty healthy volunteers were examined with a 1.5 T MR unit. A diffusion-weighted MR imaging (MR DWI) sequence was performed once at rest and continuously repeated 13 times after gustatory stimulation using a commercially available lemon juice and vitamin C tablets in the same volunteer by using self-controlled method. The subsequence of two stimuli was random. In addition, the salivary flow rates at rest and after stimulation were measured. Characteristics and differences in ADCs curves of three salivary glands before and after stimulation between two stimuli were analyzed. Comparison of maximum ADCs, maximum ADCs increase rates (IRs) and times to maximum ADCs(Tmax) between two stimuli was performed by using independent-samples t test. Correlation analysis between rest salivary flow rates and rest ADCs, the maximum salivary flow rates and ADCs after stimulation, the maximum salivary flow IRs and ADC IRs after stimulation were performed by using Pearson correlation test. Results In lemon juice stimulation group, the mean ADCs mostly showed a steady increase to peak values during the first DW MRI scan after stimulation in all glands, followed by a gradually decrease fluctuating slightly around the baseline values. In vitamin C stimulation group, the mean ADCs were significantly increased in all glands during the first DW MRI scan after stimulation, followed by a gradual upward trend till peak values. In lemon juice stimulation group, the mean Tmax of submandibular and sublingual glands[(184±122)s, (345±232)s, respectively] were significantly earlier than those[(454 ± 301)s, (528 ± 297)s, respectively] in vitamin C stimulation group (t=-3.517 and-2.548 respectively, P<0.01 for all). The mean maximum ADCs of three glands in lemon juice stimulation group[(1.05 ± 0.12) × 10-3 mm2/s, (1.22 ± 0.10) × 10-3 mm2/s and (1.26 ± 0.21) × 10-3 mm2/s, respectively] were all lower than those in vitamin C stimulation group[(1.13±0.13) ×10-3 mm2/s, (1.32±0.25) × 10-3 mm2/s and (1.57 ± 0.36) × 10-3 mm2/s, respectively], and the differences in parotid and sublingual glands between two groups were significant(t=-2.894 and-3.681 respectively, P<0.01 for all). The mean maximum ADC IRs of three glands in lemon juice stimulation group[(11.35±4.07)%, (8.81±5.40)%, (34.08±21.66)%, respectively] were significantly lower than those[(17.80 ± 12.72)%, (18.16 ± 18.93)%, (67.49 ± 46.04)% , respectively] in vitamin C stimulation group (t=-2.252,-2.330 and-3.432 respectively, P<0.05 for all) . In two groups, the mean maximum ADC IRs of parotid and submandibular gland were all significantly lower than sublingual gland (t=-5.994 and-6.443 respectively, P<0.01 for all). No correlation was observed between ADCs and salivary flow rates, ADC IRs and salivary flow rate IRs in two groups (P>0.05). Conclusion MR DWI with transient stimulation using lemon juice is more stable for evaluating the physiologic changes of salivary glands in vivo.

Summarize the application of SOAP in the medical field and find out its problems in the course of traditional Chinese medicine, to explore the significance and value of SOAP in teaching practice in TCM. Organize relevant literature and discuss the application of SOAP in the course of Chinese medicine. SOAP is widely used in various aspects of medicine, and there are still some problems in the course of TCM. The use of SOAP model for teaching and assessment has important practical significance and value in the course of Chinese medicine internal medicine practice, and SOAP emphasize the practice of the post competence oriented teaching, which is worth promoting.

Objective　To investigate the role and molecular mechanism of long intergenic non-coding RNA 1116 (LINC01116) in hippocampal astrocytes of acute ischemic stroke (AIS).Methods　The expressions of LINC01116 and miR-203 in serum of 131 AIS patients before and after thrombolysis were detected by real-time fluorescence quantitative PCR.The regulatory effect of LINC01116 on miR-203 was detected by dual-luciferase reporter gene and RNA-binding protein immunoprecipitation assay.Human hippocampal astrocytes (hHA) were applied to establish an oxygen-glucose deprivation/reoxygenation (OGD/R) model and were treated with LINC01116 interference and LINC01116 combined with miR-203 interference.The changes of cell proliferation,cell apoptosis,production of reactive oxygen species (ROS),activity of lactate dehydrogenase (LDH),and inflammatory factors were detected by CCK-8,TUNEL and Western blotting,ROS assay,LDH assay,and enzyme-linked immunosorbent assay,respectively.Results　The expressions of LINC01116 and miR-203 in serum after thrombolysis were higher and lower than those before thrombolysis,respectively,and the expressions of LINC01116 and miR-203 were negatively correlated (P<0.05).LINC01116 inhibited miR-203 expression by sponge of miR-203 (P<0.05).LINC01116 interference alleviated the OGD/R-induced injury of hHA cells,which manifested as elevated cell proliferation ability,decreased cell apoptosis rate,decreased protein expressions of cleaved caspase-3 and Bax but raised protein expression of Bcl-2,reduced ROS production,decreased LDH activity,and downregulated TNF-α,IL-1β and IL-6 concentrations but upregulated IL-4,IL-10 and IL-13 concentrations (P<0.05).miR-203 interference reversed the protective effect of LINC01116 interference on the OGD/R-induced injury of hHA cells (P<0.05).Conclusions　LINC01116 promotes the OGD/R-induced injury of hHA cells by targeting miR-203,suggesting that the LINC01116/miR-203 pathway might be a potential therapeutic target for AIS.

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Objective To explore the influence of lifestyle intervention on long-term diabetes in subjects with impaired glucose tolerance (IGT) returned to normal glucose tolerance (NGT) within 6 years.Methods A total of 577 subjects (aged 25-74 years old) with IGT in Daqing were enrolled and randomly assigned to control,and diet,exercise and diet plus exercise groups in a six-year intervention trial in 1986.Subjects who were non-diabetic at the end of the intervention were followed up for additional 14 years.Results Among all the subjects,41.38％ of them who had returned to NGT from IGT within 6 years maintained NGT status after 20 years,and had a lower incidence of diabetes than subjects maintained IGT status (46.55％ vs.75.25％).Of note,in the intervention group,the percentage of participants developed diabetes in the NGT subjects was significantly lower than that in the IGT group (43.71％ vs.76.25％) after 20 years.There was high long-term risk for diabetes in the IGT subjects after the adjustment of age,sex and baseline glucose (HR=1.81,95％CI 1.27-2.58,P=0.001),whereas in the non-intervention group,no significant difference could be viewed in long-term diabetic risk between subjects maintained IGT status and those returned to NGT (71.43％ vs.65.22％) after adjusting of the same confounders (HR=1.03,95％CI 0.45-2.35,P=0.94).Conclusions IGT subjects who had returned to NGT in early years had lower risk for future diabetes than those who remained IGT.However,this beneficial effect could only be viewed in the intervention group,but not in the non-intervention group.

Objective:To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes.Methods:A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality.Results:During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95 %CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status ( HR=1.97,95 %CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders ( HR=1.22, 95 %CI 1.08-1.39, P=0.002). Conclusions:Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.