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.

Effect of nuciferine on gut microbiota and inflammatory response in obese model mice / 中国中药杂志

The aim of this study was to elucidate the mechanism of nuciferine on alleviating obesity based on modulating gut microbiota, ameliorating chronic inflammation, and improving gut permeability. In this study, the obese model mice were induced by high-fat diet and then randomly divided into model group, and nuciferine group; some other mice of the same week age were fed with normal diet as normal group. In the modeling process, the mice were administered intragastrically(ig) for 12 weeks. In the course of both modeling and treatment, the body weight and food intake of mice in each group were measured weekly. After modeling and treatment, the Lee's index, weight percentage of inguinal subcutaneous fat, and the level of blood lipid in each group were measured. The pathological changes of adipocytes were observed by HE staining to evaluate the efficacy of nuciferine treatment in obese model mice. 16 S rRNA sequencing analysis was conducted to study the changes in diversity and abundance of gut microbiota after nuciferine treatment. Enzyme-linked immunosorbent assay(ELISA) and quantitative Real-time polymerase chain reaction(qPCR) were used to detect the levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and the expression of related genes in adipose tissue of mice in each group, so as to evaluate the effect of nuciferine on chronic inflammation of mice in obese model group. qPCR was used to detect the expression of occludin and tight junction protein 1(ZO-1)gene in colon tissure, so as to evaluate the effect of nuciferine on intestinal permeability of mice in obese group. Nuciferine decreased the body weight of obese mice, Lee's index, weight percentage of inguinal subcutaneous fat(P<0.05), and reduced the volume of adipocytes, decreased the level of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-C)(P<0.05) in serum, improved dysbacteriosis, increased the relative abundance of Alloprevotella, Turicibacter, and Lactobacillus, lowered the relative abundance of Helicobac-ter, decreased the expression of inflammatory cytokines IL-6, IL-1β, and TNF-α genes in adipose tissue(P<0.01), decreased the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in serum(P<0.05), and increased the expression of occludin and ZO-1 genes related to tight junction in colon tissue(P<0.01). Nuciferine could treat obesity through modulating gut microbiota, decreasing gut permeability and ameliorating inflammation.

Impact of follow-up information platform combined with health education on compliance behavior and cardiac function in patients with chronic heart failure / 中国实用护理杂志

Objective:To explore the effect of follow-up information platform combined with full-course health education on compliance and cardiac function in patients with chronic heart failure.Methods:A total of 150 patients with chronic heart failure treated in He′nan People′s Hospital between November 2018 and November 2019 were selected for study. Patients were divided into observation group and control group by random number table method, and each group had 75 cases. The control group received routine health education intervention, and the observation group implemented follow-up information platform combined with full-course health education intervention. The intervention time was 6 months, and then the compliance behavior, cardiac function and quality of life of the two groups of patients were compared.Results:The overall compliance rate of the observation group was significantly higher than that of the control group ( Z value was -5.634, P<0.01), and the total compliance rate of the observation group was 92.00% (69/75), which was significantly higher than 74.67% (56/75) of the control group ( χ2 value was 8.112, P<0.01). After the intervention, both the 6-minute walking test and the left ventricular ejection fraction in the observation group were (482.75±81.45) m, (48.34±6.10)%], which were significantly higher than (406.92±68.20) m, (39.61±5.73) % of the control group ( t values were 6.182, 9.034, P<0.01). After the intervention, the physical limitation, psychological mood, disease symptoms, and social relationship scores of the observation group patients were (11.00±1.58), (10.06±1.55), (6.06±1.29), and (5.09± 1.14) points, which were significantly lower than (17.15±1.90), (11.79±1.55), (9.52±1.23), and (8.09±1.02) points of the control group ( t values were 6.835-21.533, P<0.01). Conclusion:Compared with conventional health education, the whole course of health education combined with the follow-up information platform is beneficial to improve the compliance rate, quality of life and cardiac function of patients with chronic heart failure.

Extraction Technology Optimization of the Total Polysaccharides and Saponins from American Ginseng / 中国药师

Objective: To optimize the extraction method for American ginseng. Methods: Based on the contents of the total poly-saccharides and saponins in American ginseng, the ethanol concentration, extraction duration, solid-liquid ratio and extraction time were selected to determine the factors and levels by single-factor test. And then 3 factors further considered were the concentration of ethanol, solid-liquid ratio and extraction time. Results: The optimum extraction process was adding 12-fold amount of 40% ethanol, and extracting for 3 times. Conclusion: The optimized extraction process is simple, quick and stable, and can be used to extract the total polysaccharide and saponins from American gingeng.

Therapeutic Observation of Herb-partitioned Fire Therapy plus Medication for Stomachache Due to Cold- deficiency / 上海针灸杂志

Objective To observe the clinical efficacy of herb-partitioned fire therapy in treating stomachache due to cold-deficiency. Method Sixty patients with stomachache due to cold-deficiency were randomized into a treatment group and a control group, 30 cases each. The control group was intervened by Western and Chinese medications, based on which, the treatment group was given herb-partitioned fire therapy. The clinical efficacies of the two groups were observed, as well as the symptoms scores before and after the treatment. Result There was a significant difference in the clinical efficacy between the two groups (P<0.01). The symptoms scores dropped after the intervention in both groups, and the score in the treatment group was significantly lower than that in the control group (P<0.01). Conclusion Herb-partitioned fire therapy plus medication is effective in treating stomachache due to cold-deficiency, and it can produce a more significant efficacy than medication alone.

Wnt/Glycogen Synthase Kinase 3β/β-catenin Signaling Activation Mediated Sevoflurane Preconditioning-induced Cardioprotection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sevoflurane preconditioning (SP) has been shown to invoke potent myocardial protection in animal studies and clinical trials. However, the mechanisms underlying SP are complex and not yet well understood. We investigated the hypothesis that the cardioprotection afforded by SP is mediated via the Wnt/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway.</p><p><b>METHODS</b>Two models were established: a Langendorff perfused rat heart model and the H9C2 cell hypoxia/reoxygenation model. Both rats and H9C2 cells were randomly divided into 6 groups as follows: S group, ischemia-reperfusion (I/R) group, DMSO group, IWP group, SP group, and SP + IWP group. Hemodynamic parameters, lactate dehydrogenase (LDH) activity in coronary effluent and cell culture supernatant, and the infarct size were measured to evaluate myocardial ischemia-reperfusion injuries. To determine the activity of Wnt/GSK3β/β-catenin signaling pathway, the expressions of Wnt3a, phospho-GSK3β, and β-catenin were measured by Western blotting.</p><p><b>RESULTS</b>SP improved cardiac function recovery, reduced infarct size (18 ± 2% in the SP group compared with 35 ± 4% in the I/R group; P < 0.05), decreased LDH activity in coronary effluent, and culture supernatant. IWP-2, an inhibitor of Wnt, abolished the cardioprotection by SP. In addition, Western blotting analysis demonstrated that the expressions of Wnt3a, phospho-GSK3β, and β-catenin significantly (P < 0.05) increased in the I/R group, compared with the S group; and compared to I/R group, SP significantly (P < 0.05) increased Wnt3a, phospho-GSK3β, and β-catenin expressions. Pretreatment with IWP-2 significantly (P < 0.05) abolished SP-induced Wnt/GSK3β/β-catenin signaling activation.</p><p><b>CONCLUSIONS</b>The results showed for thefirst time that cardioprotection afforded by SP may be mediated partly via the Wnt/GSK3β/β-catenin signaling pathway.</p>

Treatment of Kangxian Pills to Chronic Liver Injury in Mice Induced with Carbon Tetrachloride / 中草药·英文版

Objective: Kangxian Pills, containing Angelicae Sinensis, Chuanxiong Rhizoma, radix paeoniae rubra, and 12 other kinds of Chinese materia medica, have the functions of softening and dispersing blood stasis. It has been used for liver injury and liver fibrosis. The current study was designed to evaluate the anti-hepatic injury activity and the mechanism of Kangxian Pills on a CCl4-induced animal model. Methods: To induce chronic liver injury, mice were treated with CCl4 twice a week for four weeks. Kangxian Pills (6 or 12 g/kg) and Compound Biejia Ruangan Tablet (0.901 g/kg) were ig given to mice once daily for four weeks after CCl4 was withdrawal. The anti-hepatic injury activities and mechanisms of Kangxian Pills were assessed by hepatic histology and by measuring the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), and total protein (TP) of serum as well as superoxide dismutase (SOD) and glycogen (Gn) of the liver. Results: Kangxian Pills significantly decreased the levels of liver index, ALT, and AST in mice liver injury models in treatment group. Moreover, Kangxian Pills and Compound Biejia Ruangan Tablet inhibited the CCl4-induced reduction of SOD and Gn levels in the liver. The histological study showed that Kangxian Pills could reduce cellular swelling and infiltration of inflammatory cells in liver injury. Conclusion: Kangxian Pills possess the potent abilities to alleviate chronic liver injury, suggesting that Kangxian Pills exert this effect by enhancing the anti-oxidant ability and metabolism of the liver.

Effects of electroacupuncture at "Yishu" (EX-B 3) on the relative hormones of HPA axis in rats with type-2 diabetes mellitus / 中国针灸

<p><b>OBJECTIVE</b>To observe the intervention effects of electroacupuncture at "Yishu" (EX-B 3) on rats with type-2 diabetes mellitus (T2DM), so as to provide experiment references for acupuncture to treat T2DM.</p><p><b>METHODS</b>Among seventy male Wistar clean-grade rats, 8 rats were randomly selected into a control group; the rest rats were made T2DM model. Fifty-two rats which were successfully made T2DM model, according to randomized block method, were divided into a model group (10 rats), a medication group (10 rats), an electroacupuncture at "Shenshu" (BL 23) group (11 rats), an electroacupuncture at "Pishu" (BL 20) group (10 rats) and an electroacupuncture at "Yishu" (EX-B 3) group (11 rats). Seven days after successful establishment of model, the rats in the model group were fixed in the self-made rat bag without receiving any treatment; the rats in the medication group, according to body mass (10 mL/kg), were treated with intragastric administration of glimepiride; the rats in all the electroacupuncture groups were treated with electroacupuncture at "Shenshu" (BL 23), "Pishu" (BL 20) and "Yishu" (EX-B 3), respectively. The continuous wave was selected with a frequency of 15 Hz and a current intensity of 4 to 6 mA. The treatment was given 20 min per treatment, once a day, 5 treatments per week for continuous 4 weeks. Before the establishment of model and continuous 4 weeks after the intervention, blood samples were collected from rats' caudal vein, and fasting blood glucose (FBG) was measured with FBG device each week. After the last intervention, the rats were killed and hypothalamus, pituitary and adrenal gland were collected. The colorimetric method was applied to measure the contents of triglyceride (TG), cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C); radioimmunoassay was used to test the contents of glycated serum protein (GSP), fasting insulin (FINS), corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortin (CORT).</p><p><b>RESULTS</b>Four weeks after the intervention, except that the rat's body mass in the normal group continued to increase, body mass in the model group, medication group and each electroacupuncture group were significantly reduced (P<0.01, P<0.05). Compared with the model group, the FBG in the electroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu" (EX-B 3) group were obviously reduced (P<0.05, P<0.01); FBG in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (both P<0.05). The contents of TG, HDL-C and LDL-C in the electroacupuncture at "Yishu" (EX-B 3) group were reduced (P<0.05, P<0.01), the content of TG was significantly lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (both P<0.05), the content of LDL-C was significantly lower than that in electroacupuncture at "Shenshu" (BL 23) group (P<0.05). Insulin sensitivity index (ISI) in the medication group, electroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu (EX-B 3)" group were evidently increased (P<0.05, P<0.01); ISI in the medication group was lower than that in the electroacupuncture at "Yishu" (EX-B 3) group (P<0.05). The content of CRH in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (P<0.05, P<0.01); the content of CORT in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Pishu" (BL 20) group (both P<0.05).</p><p><b>CONCLUSION</b>Electroacupuncture at "Yishu" (EX-B 3) could reduce the level of CORT to improve the insulin resistance in rats with T2DM, improve insulin sensitivity index, regulate blood lipid metabolism and relieve the hyperactivity of the HPA axis.</p>

Endoscopic pleomorphic adenoma of nasal septum resection assisted by low-temperature plasm radiofrequency: a case report / 临床耳鼻咽喉头颈外科杂志

We present an extremely rare case of pleomorphic adenoma of the nasal septum in a 24-year old woman who went to consultation because of right nasal neoplasm. The radiologic discoveries by computerized tomography showed a tumor in the right nasal septum. Incisional biopsy was done, with a histopathological report of pleomorphic adenoma. Later, nasal endoscopy was used to remove the neoplasm and histology revealed pleomorphic adenoma of the nasal septum.

Apigenin accelerates lipopolysaccharide induced apoptosis in mesenchymal stem cells through suppressing vitamin D receptor expression / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Transplantation of mensenchymal stem cells (MSCs) has been proposed as a promising way for tissue engineering. However, the application of MSCs for transplantation will undergo apoptosis due to the extremely harsh microenvironment such as excessive inflammation. Apigenin (API) has been reported to protect cells against inflammatory damage and cell death by exhibiting anti-inflammatory and anti-oxidative capacity. Here we investigated the modulatory effects of API in lipopolysaccharide (LPS)-mediated inflammation and apoptosis of MSCs, and further defined the underlying mechanism.</p><p><b>METHODS</b>Effects of different concentrations of API (0, 5, 10, 20, 40 and 80 µmol/L) for 24 hours, and LPS (0, 0.5 and 5.0 µg/ml) for 6 hours and 24 hours on MSCs viability were assayed by MTT. Based on this, MSCs were pretreated with different concentrations of API (0 - 40 µmol/L) at the indicated times (6, 12 and 24 hours) followed by exposure to 5 µg/ml LPS for 24 hours. MTT, phase-contrast microscopy, annexinV/propidium iodide (PI) double stain flow cytometry (FCM) and Hoechst staining were applied to explore the effects of API on MSCs induced by 5 µg/ml LPS for 24 hours. In addition, reverse-transcription polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression of pro-inflammatory factors including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), pro-apoptotic gene caspase-3, Bad, and anti-apoptotic gene Bcl-2. Moreover, AutoDock software was used to imitate the docking score of API and vitamin D receptor (VDR). In parallel, Western blotting and RT-PCR were used to investigate protein and mRNA expression of VDR.</p><p><b>RESULTS</b>MSCs stimulated with LPS 5 µg/ml for 24 hours was used as a model of apoptosis induced by over inflammatory stimulus. API (0 - 40 µmol/L) had non-toxic effect on MSCs; however, it could decrease mRNA expression of COX-2, iNOS and NF-κB at different time points in MSCs induced by LPS, except for API at the concentration of 5 µmol/L.</p><p><b>RESULTS</b>from phase-contrast microscopy, MTT, Hoechst staining and AnnexinV/PI double stain FCM demonstrated that with the increasing concentrations of API and extension of administrating time, significant morphological changes of MSCs occurred, viability of cells was strongly inhibited, and meanwhile, apoptosis of LPS-administrated MSCs was exacerbated, compared with LPS individual group. In addition, API promoted caspase-3, Bad mRNA expression and inhibited Bcl-2 mRNA expression in a time-dependent and concentration- dependent manner. Further study found that pro-apoptosis effect of API was related to suppress VDR expression.</p><p><b>CONCLUSIONS</b>API could inhibit the expression of inducible inflammatory factors, therefore exert the strong anti-inflammatory function. However, API could not protect MSC apoptosis induced by LPS but amplified the apoptosis. The apoptosis is related to Bad/Bcl-2 increasing and caspase-3 activation, which is mediated through suppressing VDR expression.</p>

Mindfulness-based relapse prevention for female incarcerated substance abusers with protracted withdrawal syndromes / 中华行为医学与脑科学杂志

Objective To evaluate effects of mindfulness-based relapse prevention treatment in female incarcerated substance abusers with protracted withdrawal syndromes.Methods 120 female incarcerated substance abusers were selected from compulsory rehabilitation/treatment center,they were randomly assigned by throwing coin to either treatment group or control group.All participants in treatment group got mindfulness-based relapse prevention treatment.At pre- and post-session assessment points,all participants completed the Five Factor Mindfulness Questionnaire and Opiate Protracted Abstinent Symptoms Scale.Two sample t -test and chi-square were used to examine the baselines,repeated measures ANOVA for assessing changes of mindfulness and protracted abstinent syndromes between and within groups.Results No differences between-group were found on mindfulness and protracted abstinent syndromes.Group x Time effects emerged for observe facet (F=27.87,P=0.000),describe facet(F=15.10,P=0.000) and total scores of mindfulness (F =12.05,P=0.001 ),the same as craving symptoms(F=7.53,P=0.007) and sleeping symptoms (F=4.40,P=0.038) of protracted abstinent symptoms.On sleep symptoms,participants in treatment group got(5.7 ±4.0) score before treatment points,got (3.5 ±3.1 )after treatment points.Participants in control group got (4.3 ± 3.6) at pre-session assessment,got (3.7 ± 3.5 ) at post-session assessment,participants in treatment group got better improvement in sleeping symptoms.Physical symptom score of protracted abstinent symptoms among treatment group participants showed a downward trend over time(F=14.89,P =0.000).Conclusion Mindfulness-based relapse prevention treatment can increase mindfulness scores,and improve physical and sleeping problems.Compulsory rehabilitation center is helpful for substance abusers.