Sacubitril/valsartan attenuates left ventricular remodeling and improve cardiac function by upregulating apelin/APJ pathway in rats with heart failure / 中华心血管病杂志

Objective: To investigate the effect and mechanism of sacubitril/valsartan on left ventricular remodeling and cardiac function in rats with heart failure. Methods: A total of 46 SPF-grade male Wistar rats weighed 300-350 g were acclimatized to the laboratory for 7 days. Rats were then divided into 4 groups: the heart failure group (n=12, intraperitoneal injection of adriamycin hydrochloride 2.5 mg/kg once a week for 6 consecutive weeks, establishing a model of heart failure); heart failure+sacubitril/valsartan group (treatment group, n=12, intragastric administration with sacubitril/valsartan 1 week before the first injection of adriamycin, at a dose of 60 mg·kg-1·d-1 for 7 weeks); heart failure+sacubitril/valsartan+APJ antagonist F13A group (F13A group, n=12, adriamycin and sacubitril/valsartan, intraperitoneal injection of 100 μg·kg-1·d-1 APJ antagonist F13A for 7 weeks) and control group (n=10, intraperitoneal injection of equal volume of normal saline). One week after the last injection of adriamycin or saline, transthoracic echocardiography was performed to detect the cardiac structure and function, and then the rats were executed, blood and left ventricular specimens were obtained for further analysis. Hematoxylin-eosin staining and Masson trichrome staining were performed to analyze the left ventricular pathological change and myocardial fibrosis. TUNEL staining was performed to detect cardiomyocyte apoptosis. mRNA expression of left ventricular myocardial apelin and APJ was detected by RT-qRCR. ELISA was performed to detect plasma apelin-12 concentration. The protein expression of left ventricular myocardial apelin and APJ was detected by Western blot. Results: Seven rats survived in the heart failure group, 10 in the treatment group, and 8 in the F13A group. Echocardiography showed that the left ventricular end-diastolic diameter (LVEDD) and the left ventricular end-systolic diameter (LVESD) were higher (both P<0.05), while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the heart failure group than in the control group (both P<0.05). Compared with the heart failure group, rats in the treatment group were featured with lower LVEDD and LVESD (both P<0.05), higher LVEF and LVFS (both P<0.05), these beneficial effects were reversed in rats assigned to F13A group (all P<0.05 vs. treatment group). The results of HE staining showed that the cardiomyocytes of rats in the control group were arranged neatly and densely structured, the cardiomyocytes in the heart failure group were arranged in disorder, distorted and the gap between cells was increased, the cardiomyocytes in the treatment group were slightly neat and dense, and cardiomyocytes in the F13A group were featured similarly as the heart failure group. Masson staining showed that there were small amount of collagen fibers in the left ventricular myocardial interstitium of the control group, while left ventricular myocardial fibrosis was significantly increased, and collagen volume fraction (CVF) was significantly higher in the heart failure group than that of the control group (P<0.05). Compared with the heart failure group, the left ventricular myocardial fibrosis and the CVF were reduced in the treatment group (both P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). TUNEL staining showed that the apoptosis index (AI) of cardiomyocytes in rats was higher in the heart failure group compared with the control group (P<0.05), which was reduced in the treatment group (P<0.05 vs. heart failure group), this effect again was reversed in the F13A group (P<0.05 vs. treatment group). The results of RT-qPCR and Western blot showed that the mRNA and protein levels of apelin and APJ in left ventricular myocardial tissue of rats were downregulated in heart failure group (all P<0.05) compared with the control group. Compared with the heart failure group, the mRNA and protein levels of apelin and APJ were upregulated in the treatment group (all P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). ELISA test showed that the plasma apelin concentration of rats was lower in the heart failure group compared with the control group (P<0.05); compared with the heart failure group, the plasma apelin concentration of rats was higher in the treatment group (P<0.05), this effect was reversed in the F13A group (P<0.05 vs. treatment group). Conclusion: Sacubitril/valsartan can partially reverse left ventricular remodeling and improve cardiac function in rats with heart failure through modulating Apelin/APJ pathways.

Establishment of an Iron-overloaded Mouse Model with Tuberculosis and Analysis of the Iron Metabolism Index / 中国医学科学院学报

Objective To establish a mouse model of exogenous iron overload combined with tuberculosis(TB). Methods C57BL/6N mice were divided into negative control, low-, medium-, and high-dose iron groups and received intraperitoneal injection of iron dextran at 0, 3.75, 7.50, and 15.00 mg/dose(3 times/week for 4 weeks), respectively.After 4 weeks, the organ morphology and body weight of the mice were evaluated.The content of serum iron, ferritin, transferrin, and transferrin receptor was determined by ELISA.Heart, liver, spleen, lung, kidney, and small intestine were analyzed for tissue iron content and iron deposition pathology.

Fructose and metabolic diseases: too much to be good / 中华医学杂志(英文版)

Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element-binding protein in regulating fructose metabolism.

Metabolic regulation in constructing microbial cell factories / 生物工程学报

The regulation of the expression of genes involved in metabolic pathways, termed as metabolic regulation, is vital to construct efficient microbial cell factories. With the continuous breakthroughs in synthetic biology, the mining and artificial design of high-quality regulatory elements have substantially improved our ability to modify and regulate cellular metabolic networks and its activities. The research on metabolic regulation has also evolved from the static regulation of single genes to the intelligent and precise dynamic regulation at the systems level. This review briefly summarizes the advances of metabolic regulation technologies in the past 30 years.

Contribution of depression to instrumental ability of daily living among the elderly with mild cognitive impairment / 预防医学

Objective To examine the independent effect of depression on activities of daily living of patients with mild cognitive impairment (MCI). Methods Data were obtained through the face-to-face interview. Totally 154 elderly patients that were screened from 552 old people by the Montreal Cognitive Assessment (MoCA) were diagnosed as MCI. They were investigated with the Geriatric Depression Scale, and instrumental ability of daily living (IADL) were measured by the Functional Activities Questionnaire. The effect of depression on IADL of patients with MCI was analyzed by logistic regression analysis. Results The prevalence of depressive symptoms among Chinese elders with MCI was 31.82％. The scores of Medical Outcomes Study Social Support Survey, and Functional Activity Questionnaire of depression group and non-depression group were significantly different (P<0.05) . Logistic regression analysis showed that scores of Functional Activity Questionnaire was positively associated with the scores of Memory Inventory for the Chinese (OR=1.36, 95％ CI: 1.15-1.61) and depression (OR=6.19, 95％ CI:2.07-18.55) . Conclusion The prevalence of depression in elderly patients with MCI was high. Depression would significantly reduce the IADL of the old patients with MCI. Medical workers should be aware of the extent and impact of depressive symptoms in MCI and take active measures in evaluating and treating the depressive symptoms.

Expression of microRNA-15b in endometrial carcinoma and its effect on proliferation of endometrial carcinoma cells / 新乡医学院学报

Objective To investigate the expression of microRNA-15b (miR-15b) in endometrial carcinoma and its effect on proliferation of endometrial carcinoma cells.Methods Eighty-seven cases of endometrial cancer tissues were selected as the research objects from patients with endometrial cancer undergoing endometrial cancer staging surgery in Xinxiang Central Hospital from February 2013 to February 2017.Another 45 cases of normal endometrial tissues from patients with uterine fibroids undergoing line hysterectomy were collected as the control.The expressions of miR-15b in endometrial carcinoma tissues and normal endometrial tissues were detected by real-time quantitative polymerase chain reaction(PCR) and relationship between the miR-15b expression and clinicopathological feature was analyzed.The HEC-1A cells were cultured and were randomly divided into miR-15b mimics group,control sequence group and blank control group.The expression of miR-15b in HEC-1A cells was detected by real-time quantitative PCR.Tetramethylazolazole blue (MTT) assay was used to detect the cell proliferation.Flow cytometry was used to detect the apoptotic rate and cell cycle.Results The relative expression levels of miR-15b in endometrial carcinoma tissues and normal endometrial tissues were 1.32 ±0.13 and 2.49 ±0.16,respectively.The relative expression level of miR-15b in endometrial carcinoma tissues was lower than that in the normal endometrial tissues (t =46.184,P ＜0.05).The relative expression level of miR-15b in endometrial carcinoma was correlated with International federation of gynecology and obstetrics staging,myometrial invasion and lymph node metastasis (P ＜ 0.05),but it was not correlated with age,histological type,differentiated degree,in filtrating lymph vessel and blood vessel or not.Compared with the blank control group and the control sequence group,the relative expression level of miR-15b in miR-15b mimics group was significantly increased (P ＜ 0.05),the cell proliferation abilities at cultured 24,48,72 and 96 h were decreased (P ＜ 0.05),while the apoptosis rate increased (P ＜0.05),the proportion of G0 + G1 phase was significantly increased,while the proportion of G2 + M phase was decreased (P ＜0.05).There was no significant difference in the relative expression level of miR-156,the cell proliferation ability at cultured 12,24,48,72,96 h,the apoptosis rate,the proportion of G0 + G1,S and G2 + M phase between the blank control group and the control sequence group(P ＜0.05).Conelusion miR-15b is low expression in endometrial carcinoma tissue.Up-regulation of miR-15b expression in endometrial carcinoma cells can inhibit cell proliferation,it may be related to block cell cycle to promote cell apoptosis.

Retrospective Study of Ph/BCR-ABLAcute Myelogenous Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical manifestation, features of laboratorial examination results and prognosis of patients with Ph/BCR-ABLacute myelogenous leukemia(AML).</p><p><b>METHODS</b>The clinical data of 5 AML patients with Ph/BCR-ABLadmitted in Department of Hematology of Chinese PLA general hospital from July 2007 to May 2015 were collected and their clinical characteristics, laboatorial examination results and long-term survival were analyzed.</p><p><b>RESULTS</b>The median age of 5 cases was 39 years old, and 2 cases with splenomegaly. All the cases were assayed for BCR-ABL fusion gene, and 2 of them were accompanied with other molecular abnormalities. In 4 cases, Ph chromosome was not found in one case, and one was with complex karyotype. 3 cases still are live till now and are treated by traditional chemotherapy combined with TKI, and consolidated by allo-HSCT. One case treated by traditional chemotherapy survived for 6 months. And one case treated by traditional chemotherapy combined with TKI survives till to now.</p><p><b>CONCLUSION</b>The survival time of Ph/BCR-ABLacute myelogenous leukemia is improved by the traditional chemotherapy combined with TKI and the consolidation with allo-HSCT.</p>

Expression of thyroid stimulating hormone β splice variant in thyroid of mouse with autoimmune thyroiditis / 中华地方病学杂志

Objective To investigate the expression of marrow-derived thyroid stimulating hormone β (TSHβ) splice variant in thyroid of mouse with autoimmune thyroiditis induced by thyroglobulin(Tg) immunization,and to analyze whether TSHβ splice variant participated in the pathological process of autoimmune thyroiditis.Methods Using random number table,forty-eight mice(24 females and 24 males) of 7 to 8 weeks old with body mass 20 to 25 g were randomly divided into 4 groups(12 females and 12 males in each group) based on body weight and gender.The control group:fed with deionized water; the Tg-treated group(TG):fed with deionized water,and immunized subcutaneously with 0.1 mg Tg at 8 weeks old,boost immunized twice at 11 and 15 weeks old,respectively; the high iodine-treated group (HI):fed with deionized water containing 0.05％ sodium iodide (NaI); the Tg combined with HI group (TG + HI):fed with deionized water containing 0.05％ NaI,and immunized the same way as the TG group did.Peripheral blood was collected after 8 weeks treatment,which was used for determination of total tetraiodothyronine (TT4),free tetraiothyronine (FT4),total triiodothyronine (TT3) and free triiodothyronine (FT3) with chemiluminescence immunoassay (CIA); thyroid glands were collected to examine the expression of TSHβ splice variant with SYBR Green fluorescent quantitative real-time PCR,and frozen sections were HE stained for observation of histopathological changes of thyroid cells under light microscopy.Results Under naked eyes,the thyroid gland enlarged significantly,and looked dark red in HI and TG + HI groups.Under an optical microscope,thyroid follicular epithelial cells presented cuboidal,with abundant cytoplasm,presented abundant glial in follicular cavity,without lymphocyte infiltration in the control group; in TG group,the thyroid follicular epithelial cells presented cuboidal,with some single scattered lymphocytes; in HI group,colloid volume expansion appeared in thyroid follicles,thyroid follicular epithelial cells presented low cuboidal or flat,with few single scattered lymphocytes; in TG + HI group,most colloid accumulative large follicles presented in thyroid,thyroid follicular epithelial cells presented flat,some destructive thyroid follicular structure and infiltrating lymphocytes appeared.The differences of FT3,TT4,FT4 and TSHβ splice variant between groups were statistically significant(F =4.00,12.54,31.92,214.29,all P ＜ 0.05).Compared to the control group,the serum TT3(nmol/L:0.92 ± 0.07 vs.1.30 ± 0.33,t =-2.24),TT4(nmol/L:1.30 ± 0.33 vs.95.60 ± 14.10,t =-3.02),FT4(pmoL/L:54.07 ± 3.67 vs.154.80 ± 0.01,t =-54.87) and the thyroids' TSHβ(× 10-3:4.11±0.32 vs.8.38 ± 0.22,t =-19.11) were higher in TG group(all P ＜ 0.05) ; the serum TT4(nmol/L:67.75 ± 11.91 vs.45.50± 3.85,t =3.55,P ＜ 0.05) was lower in HI group; the serum FT4(pmol/L:54.07 ± 3.67 vs.139.46 ± 30.00,t =-5.65) and the thyroids' TSHβ splice variant (× 10-3:4.11 ± 0.32 vs.5.33 ± 1.47,t =-5.95) were higher in TG + HI group (all P ＜ 0.05).Conclusions High iodine has aggravated thyroiditis of BALB/c mice induced by Tg immunization; the level of thyroid TSHβ in mice with autoimmune thyroiditis is higher; all of these results indicated that TSHβ is involved in the pathogenesis of autoimmune thyroiditis.

A new saikogenin from the roots of Bupleurum bicaule / 中国天然药物

AIM@#To study the chemical constituents from the roots of Buleurum bicaule Helm (Apiaceae).@*METHOD@#Silica gel, Sephadex LH-20, MPLC Rp-C18 column chromatography, and HPLC were used for isolation of compounds. The structures were elucidated on the basis of 1D- and 2D-NMR technology and HRESI-MS. Compounds were evaluated in vitro for their inhibitory ability against the proliferation of rat mesangial cells by the MTT method.@*RESULTS@#Twelve compounds were isolated, and their structures were identified on the basis of their spectroscopic and physico-chemical properties as 13, 28-epoxy-olean-11-en-3-one (1), saikogenin E (2), saikogenin G (3), 11α-methoxy-3β, 16β, 23, 28-tetrahydroxyolean-12-ene (4), saikogenin D (5), prosaikogenin F (6), prosaikogenin A (7), prosaikogenin G (8), prosaikogenin D (9), laccaic acid (10b), methyl gallate (11), and ethyl gallate (12). Compounds 1, 2, 7, 8, and 10 were observed to have inhibitory activity against mesangial cell proliferationin to different degrees.@*CONCLUSION@#Compound 1, 8, and 10 exhibit significant inhibitory effects on rat mesangial cell proliferation induced by Ang II.

Polyinosine-polycytidylic acid promotes excessive iodine intake induced thyroiditis in non-obese diabetic mice via Toll-like receptor 3 mediated inflammation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Excessive iodine intake and viral infection are recognized as both critical factors associated with autoimmune thyroid diseases. Toll-like receptors (TLRs) have been reported to play an important role in autoimmune and inflammatory disorders. In this study, we aimed to clarify the possible mechanism of TLR3 involved in polyinosine-polycytidylic acid (poly(I:C)) promoting excessive iodine intake induced thyroiditis in non-obese diabetic (NOD) mice.</p><p><b>METHODS</b>Both NOD and BALB/c mice were randomly assigned to four groups: control group (n = 5), high iodine intake (HI) group (n = 7), poly(I:C) group (n = 7) and combination of excessive iodine and poly(I:C) injection (HIP) group (n = 7). After 8 weeks, mice were weighed and blood samples were collected. All the mice were sacrificed before dissection of spleen and thyroid gland. Then, thyroid histology, thyroid secreted hormone, expression of CD3(+) cells and TLR3 as well as inflammatory mRNA level were evaluated.</p><p><b>RESULTS</b>Both NOD and BALB/c mice from HI and HIP group represented goiter and increasing thyroid relative weight. Thyroid histology evidence indicated that only HIP group of NOD mice showed severe thyroiditis with lymphocytes infiltration in majority of thyroid tissue, severe damage of follicles and general fibrosis. Immunofluorescence staining results displayed a large number of CD3(+) cells in HIP NOD mice. Real-time polymerase chain reaction (PCR) results suggested interferon (IFN)-α increased over 30 folds and IFN-γ expression was doubled compared with control group, but interleukin (IL)-4 remained unchanged in HIP group of NOD mice thyroid. Meanwhile, over one third decrease of blood total thyroxine (TT4) and increased thyroid-stimulating hormone (TSH) was observed in HIP group of NOD mice. Only HIP group of NOD mice represented significantly elevation of TLR3 expression.</p><p><b>CONCLUSION</b>Poly(I:C) enhanced excessive dietary iodine induced thyroiditis in NOD mice through increasing TLR3 mediated inflammation.</p>

Expression and clinical significance of Ki-67 in diffuse large B cell lymphoma / 中国实验血液学杂志

This study was aimed to evaluate the proliferation-associated antigen Ki-67 expression in diffuse large B cell lymphoma (DLBCL) and its clinical significance. The Ki-67 expression and its correlation with prognosis in 50 patients with DLBCL treated with rituximab plus CHOP (R-CHOP) between January 2008 and December 2010 were analyzed retrospectively. The results indicated that there was no significant relationship between Ki-67 expression and clinical features, including age, sex, staging, B symptoms, LDH level, IPI, extranodal site involvement, presence of bulky tumors (>10 cm in diameter), bone marrow involvement, GCG nor GCB type, or response to first line treatment. The median survival was 50 months and 15 months in low Ki-67 expression group (<85%) and in high Ki-67 expression group ( ≥ 85%) respectively. The overall survival (OS) and progress-free survival (PFS) in low Ki-67 expression group were obviously longer than that in high Ki-67 expression group (P = 0.001; P = 0.027). In univariate analysis, the clinical factors associated with OS included Ann Arbor staging and Ki-67 expression. The clinical factors associated with PFS included Ann Arbor staging. IPI and Ki-67 expression. In multivariate analysis. The Ki-67 expression level was an independent prognostic factor for OS (HR = 4.90; 95% CI, 1.456-16.511; P = 0.0103). It is concluded that Ki-67 expression level seems to be an effective marker for evaluation of DLBCL prognosis.

New hydrolysable tannin from Cibotium barometz / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents from Cibotium batometz.</p><p><b>METHOD</b>Column chromatograph and HPLC were used to isolate and purify the compound, and the structure was elucidated on the basis of MS and NMR spectroscopic methods.</p><p><b>RESULT</b>A new phenolic compound, 4-O-caffeoyl-D-glucopyranose, has been isolated from the rhizome of C. barometz. The structure of the new compound was elucidated on the basis of chemical and spectroscopic methods, including intensive 1D, 2D NMR and ESI-MS data analysis.</p><p><b>CONCLUSION</b>4-O-caffeoyl-D-glucopyranose was a new phenolic compound.</p>