Inhibition of Proprotein Convertase Subtilisin/Kexin Type 9: A Novel Mechanism of Berberine and 8-hydroxy Dihydroberberine against Hyperlipidemia

Objective:To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine(Hdber) for the treatment of hyperlipidemia in rats.Methods:A rat model of hyperlipidemia was established by feeding rats a high-fat diet for 4 weeks in 70 rats of 80 animals,and 10 rats were randomly selected as control group.The hyperlipidemic rats were then randomly divided into the following groups:a model group(MOD);a berberine group[BBR,156 mg/(kg·day)];Hdber groups,which were treated with different doses of Hdber[78,39 and 19.5 mg/(kg·day)];and a simvastatin group[SIM,4 mg/(kg·day)].The corresponding therapy was administered to the rats of each treatment via gastric tubes.Normal animals were used as a control group.The blood levels of various lipids,including total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,free fatty acid(FFA),apolipoprotein AⅠ(Apo-A Ⅰ) and apolipoprotein B(Apo-B) were examined.The protein expressions of low-density lipoprotein receptor(LDL-R),sterol regulatory element-binding protein 2(SREBP-2),3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR) and proprotein convertase subtilisin/kexin type 9(PCSK-9) in liver tissues were determined by Western blot analysis.Results:Compared with the control group of rats,the model group demonstrated a deteriorated blood lipid profile and exhibited increased expression levels of PCSK-9protein in their liver tissues(P0.01).In addition,the high-fat diet decreased the expression levels of LDL-R,SREBP-2and HMGCR proteins in murine liver tissues.However,the addition of berberine or Hdber reversed the blood lipid profile changes(P0.05 or P0.01),decreased the expression levels of PCSK-9 proteins(P0.01),and increased the expression levels of LDL-R proteins in the hyperlipidemic rats(P0.01).These compounds did not significantly influence the expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats.Conclusions:Hdber is effective in the treatment of hyperlipidemia in rats.The therapeutic mechanisms of Hdber may be associated with increasing the expression of LDL-R protein and decreasing the expression of PCSK-9 protein in liver tissues.     

Xuezhikang(血脂康) Reduced Renal Cell Apoptosis in Streptozocin-Induced Diabetic Rats through Regulation of Bcl-2 Family

Objective: To investigate the effect of Xuezhikang(血脂康, XZK) on renal cell apoptosis in diabetic rats and the possible mechanism. Methods: Sixty-six rats were randomly divided into 3 groups: the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK(1200 mg/kg body weight) everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours' urine was collected for urinary albumin excretion(UAE) measurement. Periodic acid-Schiff(PAS) and Masson's trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by Td T-mediated d UTP nick end labeling(TUNEL) staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C(Cyt C) and caspase-9 concentration were detected by Western blot. Results: Compared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months(P0.05 or P0.01). Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson's trichromestained collagen to different extent. Conclusions: Renal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.     

Antioxidant Mechanism of Xiaojin Pill(小金丸) for Treatment of Peyronie's Disease in Rats Based on Matrix Metalloproteinases

Objective: To evaluate the effects of Xiaojin Pill(小金丸) in the treatment of Peyronie's disease(PD) in a rat model. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups with 6 in each: sham operation, PD model, vehicle control and Xiaojin Pill groups. The rats in the sham operation group received penile tunica albsginea(TA) injection with 50 μL vehicle, while the rats in the other 3 groups received 50 μL penile TA injection of 50 μg transforming growth factor(TGF)-β1. Forty-two days after the injection, rats in the vehicle control and Xiaojin Pill groups received 0.5 mL water and Xiaojin Pill solution(107 mg/kg of body weight), respectively by gavage for 28 days, while those in the sham operation and PD model groups did not receive any intervention. After intervention, the expressions of matrix metalloproteinase 2/9(MMP2/9), nitric oxidesynthase(NOS), superoxide dismutase(SOD) and malondialdehyde(MDA) were measured. Results: Rats in the PD model and vehicle control groups presented obvious fibrosis in corpus cavernosum(CC) and demonstrated a significantly increased expressions of MMP2 and MMP9 in the CC compared with the sham operation group(all P0.01). In contrast, the expressions of MMP2 and MMP9 in the Xiaojin Pill group were significantly down-regulated(both P0.01). In addition, the levels of NOS and MDA in CC were significantly increased while the activity of SOD was decreased in the PD model and vehicle control groups compared with the sham operation group(al P0.01). After Xiaojin Pil treatment, the levels of MDA, NOS and SOD appeared to be corrected(al P0.01). Conclusions: Xiaojin Pill could reduce fibrosis in the CC by decreasing the expressions of MMPs, NOS and MDA, and by increasing the activity of SOD. Therefore, Xiaojin Pill might be a therapeutic option for PD.     

Role of DOR-β-arrestinl-Bcl2 Signal Transduction Pathway and Intervention Effects of Oxymatrine in Ulcerative Colitis

This study was aimed to investigate the role of the delta-opioid receptor （DOR）-β-arrestinl-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis （UC） and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into nor- mal group, model group, oxymatrine-treated group and mesalazine-treated group （n=10 each） at ran- dom. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/（kg·day）] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/（kg·day）] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expres- sion levels of DOR, β-arrestinl and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction （RT-PCR）, respectively. It was found that the expression levels of DOR, [3-arrestinl and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups （P〈0.05）. They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group （P〈0.05）. No statistically significant difference was noted in these indices between mesalazine- and oxyma- trine-treated groups （P〉0.05）. This study indicated that the DOR-β-arrestinl-Bcl-2 signal transduc- tion pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the de- velopment of UC by regulating the DOR-β-arrestin 1-Bcl-2 signal transduction pathway.     

Clinical Experience in Treatment of Alzheimer's Disease with Jiannao Yizhi Formula (健脑益智方) and Routine Western Medicine

Objective: To investigate the long-term therapeutic effects of the Chinese medicine Jiannao Yizhi Formula(健脑益智方, JYF) in the treatment of Alzheimer's disease(AD). Methods: Sixty mild-to-moderate AD participants were recruited and randomly allocated to the treatment(30 with JYF) and the control groups(30 with donepezil) for 6 months with the random numbers. The primary outcomes were scores of Alzheimer's Disease Rating Scale-Cognitive(ADAS-Cog) and Chinese Medicine Symptom Scale(CM-SS). The secondary outcomes were scores of Mini Mental State Examination(MMSE), Montreal Cognitive Assessment(MoCA), and Activities of Daily Living(ADL). Safety assessments were conducted at baseline and the 6 th month of treatment. Serum levels of acetylcholine(Ach), amyloid-β protein 42(Aβ_(42)), and the microtubule-associated protein tau(Tau) were also determined by enzyme-liked immunosorbent assay. Results: Fifty-one participants were included in the final analyses(JYF n=27; donepezil n=24). Compared with baseline, both JYF and donepezil increased the MoCA and MMSE scores and decreased the ADAS-Cog and CM-SS scores(P0.05 or P0.01). Both drugs increased the serum levels of Ach and decreased the serum levels of Aβ_(42) and Tau(all P0.05). There was no significant difference in these variables between the two groups, which showed that JYF was not inferior to donepezil. No obviously significant changes were observed in the ADL. No severe adverse events were observed in both groups. Conclusion: The effect and safety of JYF for the treatment of AD were not inferior to those of donepezil.     

Effects of Xuezhikang Capsule(血脂康胶囊) on Blood Lipids,Platelet Activation and Coagulation-Fibrinolysis Activity in Patients with Hyperlipidemia

Objective: To investigate the effects of Xuezhikang capsule (XZK, 血脂康胶囊) on blood lipids level, platelet activation and coagulation-fibrinolysis activity in patients with hyerlipidemia. Methods:Seventy-six patients of hyperlipidemia were randomly divided into two groups, the XZK group (n = 38) treated with XZK 600mg, taken two times per day and the Simvastatin (SIM) group (n = 38) treated with SIM 20mg per day, with the treatment lasting 8 weeks for both groups. Levels of fasting serum lipids, including total cholesterol (TC), triglyceride (TG), high and low density l ipoprotein cholesterol (HDL-C and LDL-C),plasma GMP-140, fibrinogen (FIB), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAl-) and prothrombin time (PT) were all measured before and 8 weeks after treatment. Data were compared before and after treatment and also compared with those measured in 20 healthy subjects of control. Results: Before treantment the levels of TC, TG and LDL-C were obviously higher and HDL-C level was significantly lower in hyperlipidemia patients than those in healthy subjects ( P＜0.05 or P＜0.01). After 4-8 weeks of XZK treatment, the levels of TC, TG, LDL-C and FIB and activities of GMP-140 and PAl-1 were obviously lowered (P＜0.05 or P＜0.01). But in the SIM group there was no obvious change in FIB (P＞0.05), instead it showed obvious increase of HDL-C and decrease of TC and LDL-C after treatment ( P＜0.05 or P＜0.01). Conclusion: XZK could inhibit platelet activity and improve coagulation-fibrinolysis function, besides its lipids lowering effect.     

Increased serum and ascitic fluid levels of soluble tumor necrosis factor-p55 in hepatocellular carcinoma patients

Objective: To explore the levels of serum and ascitic fluid soluble tumor necrosis factor receptor-p55 (sTNFR-p55) and understand their clinical implication in primary hepatocellular carcinoma (HCC) patients. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to examine the levels of sTNFR-p55 in the serum and ascitic fluid in 25 HCC patients and 25 patients with liver cirrhosis (LC). The test was also performed on the serum of 30 healthy subjects who served as control group. To assess the clinical effects of increased serum concentrations of sTNFR-p55, four parameters were analyzed by logistic regression. Results: Serum and ascitic fluid levels of sTNFR-p55 in HCC patients were significantly higher than those in LC patients and controls (P=0. 001). No significant difference was found between serum sTNFR-p55 levels in the latter 2 groups (P = 0. 19), and positive correlation between serum levels of sTNFR-p55 and that in ascitic fluid was noted in the 2 patient groups (r=1. 000, P<0. 001). Level     

Effect of the Recipe of Zhishi Xiaopi Pill and its Ingredients on Gastric Emptying Rate and Plasma Motilin Level in Rats

To investigate the influence of the recipe of Zhishi Xiaopi Pill （ZSXPP） and its ingredients on gastric emptying and plasma motilin （MOT） level in rats. After the rats were douched by different herbs, cisapride or normal saline in different groups for 4 weeks, The gastric emptying rate and plasma MOT levels were measured respectively. The gastric emptying rate and plasma motilin levels were both increased significantly by using the total recipe of ZSXPP and some parts of the recipe. ZSXPP can increase the gastric emptying rate and plasma motilin levels in rats. The herbs can remove food and qi stagnancy and relieve flatulence; Zhishi, Houpu and Maiya were the main effective ingredients in this recipe.     

Effect of Quercetin on Atherosclerosis Based on Expressions of ABCA1, LXR-α and PCSK9 in ApoE-/- Mice

Objective: To investigate the effect of quercetin on ATP binding cassette transporter A1(ABCA1), liver X receptor(LXR), and proprotein convertase subtilisin/kexin type 9(PCSK9) expressions in apo E-knockout(Apo E~(-/-) ) mice. Methods: The high-fat diet-induced atherosclerosis(AS) in Apo E~(-/-) mice was established. Thirtysix mice were divided into 3 groups using random number table method: model group(n=12), quercetin group(n=12), and atorvastatin group(n=12), with C57 BL/6 J mice of the same strain and age as the control group(n=12). Quercetin group and atorvastatin group were administrated with quercetin and atorvastatin by oral gavage, with doses of 12.5 and 4 mg/(kg·d), respectively. Animals in the control and model groups were given an equal volume of distilled water by oral gavage once per day for a total of 12 weeks. Western blot and immunohistochemical methods were employed to determine the aortic ABCA1, LXR-α and PCSK9 protein expression. Enzyme linked immunosorbent assay method was used to detect the expression of serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-C), low density lipoproteincholesterol(LDL-C), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and IL-10, combined with tissue pathological examination. Results: Apo E~(-/-) mice fed with a high-fat diet had notable atherosclerosis lesions, with reduced ABCA1, LXR-α and IL-10 levels(all P0.01), elevated PCSK9, TNF-α and IL-6 expression, and increased TC and LDL-C contents(all P0.01). After quercetin intervention, the areas of AS plaques and the expressions of PCSK9, TNF-α and IL-6 were significantly reduced(all P0.01), while the expressions of ABCA1 and LXR-α were increased significantly(all P0.01). Conclusion: Quercetin effectively interfered with AS development by regulating the expressions of ABCA1, LXR-α and PCSK9 in Apo E~(-/-) mice.     

Effects of Hedan Tablet(荷丹片)on Lipid Profile,Proprotein Convertase Subtilisin/Kexin Type 9 and High-Density Lipoprotein Subfractions in Patients with Hyperlipidemia:A Primary Study

Objective: To investigate the effects of Hedan Tablet(荷丹片) on serum lipid profile, proprotein convertase subtilisin/kexin type 9(PSCK9) and high-density lipoprotein(HDL) subfractions in patients with hyperlipidemia. Methods: Thirty-seven patients with hyperlipidemia were randomized to treatment with Hedan Tablet 4.38 g/day as Hedan group(18 cases) or placebo(19 cases) as control group for 8 weeks. The lipid profile, PCSK9 and HDL subfractions were determined at day 0 and week 8 in both groups respectively. Results: Hedan treatment for 8 weeks mildly decreased serum low-density lipoprotein cholesterol(LDL-C) levels, while no changes were found in total cholesterol(TC), triglycerides(TG) and PCSK9 concentrations. Furthermore, Hedan treatment increased the concentration of large high-density lipoprotein cholesterol(HDL-C) and the percentage of large HDL subfraction, while decreased the concentration of small HDL-C and the percentage of small HDL subfraction without changing serum HDL-C levels in patients with hyperlipidemia. Conclusion: Hedan treatment of 4.38 g per day for 8 weeks could confer a favorable effects on serum LDL-C concentration as well as HDL subfractions.     

Huoxue Anxin Recipe(活血安心方)Promotes Myocardium Angiogenesis of Acute Myocardial Infarction Rats by Up-Regulating miR-210 and Vascular Endothelial Growth Factor

Objective: To investigate the microR NAs(miR NAs) expression profile of acute myocardial infarction(AMI) rats and the regulating effects of Huoxue Anxin Recipe(活血安心方, HAR) on angiogenesis-related miR NAs and genes. Methods: Forty-five Wistar rats were randomly assigned to 3 groups according to a random number table: sham, AMI, and AMI+HAR groups(15 in each group). AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI+HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miR NAs expression profile was detected by quantitative realtime polymerase chain reaction(qR T-PCR). The mR NA and protein expressions of vascular endothelial growth factor(VEGF), and a target gene of miR-210 was further detected by qR T-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining. Results: Compared with the sham group, ejection fraction(EF) and fractional shortening(FS) values were decreased significantly in the AMI group(P0.01), while the infarction area and the interstitial collagen deposition were increased obviously. As for the AMI+HAR group, EF and FS values were increased significantly(P0.05 vs. AMI group), and the infarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miR NAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miR NAs in the AMI+HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI+HAR group. The relative mR NA and protein expressions of VEGF were decreased significantly in the AMI group(P0.05 vs. sham group), and increased significantly in the AMI+HAR group(P0.01 vs. AMI group). CD31 expression area and optical intensity were decreased significantly in the AMI group(P0.05 vs. sham group), and increased significantly in the AMI+HAR group(P0.01 vs. AMI group). Conclusions: HAR could reduce the infarction area, alleviate the interstitial fibrosis and improve the cardiac function of AMI rats. Those effects could be related to promoting myocardium angiogenesis of HAR by up-regulating miR-210 and VEGF.     

Possible Role of Mast Cells and Neuropeptides in the Recovery Process of Dextran Sulfate Sodium-induced Colitis in Rats

Objective To clarify the role of mast cells and neuropeptides substance P(SP),somatostatin(SS),and vasoactive intestinal peptide(VIP) in dextran sulfate sodium(DSS)-induced colitis in rats.Methods Experimental colitis was induced in Sprague-Dawley rats(180-200 g,n=20) by oral ingestion of 4%(w/v) DSS in drinking water for 7 days.Control rats(n=5) drank water and were sacrificed on day 0.Mast cell number,histamine levels in whole blood and tissue,tissue levels of SP,SS and,VIP in the distal colon of the rats were measured on day 8,day 13,and day 18 of experimentation.Results Oral administration of 4% DSS solution for 7 days resulted in surface epithelial loss and crypt loss in the distal colon.Mast cell count increased on day 8(1.75±1.09/mm vs.0.38±0.24/mm,P<0.05) and day 13(1.55±1.01/mm vs.0.38±0.24/mm,P<0.05) after DSS treatment.Whole blood histamine levels were increased on day 8(266.93±35.62 ng/mL vs.76.87±32.28 ng/mL,P<0.01) and gradually decreased by day 13 and day 18 after DSS treatment.Histamine levels in the distal colon were decreased on day 8(1.77±0.65 ng/mg vs.3.06±0.87 ng/mg,P<0.05) and recovered to control levels by day 13 after DSS treatment.SP level in the distal colon gradually increased and were raised significantly by day 13(8777.14±3056.14 pg/mL vs.4739.66±3299.81 pg/mL,P<0.05) after DSS treatment.SS and VIP levels in the distal colon were not changed.Conclusions Mast cell degranulation followed by histamine release may play an important role in the pathogenesis of colitis induced by DSS.SP may be a significant substance in the progression of inflammation and the recovery process of DSS-induced colitis.     

Effects of simulated microgravity on antioxidant system in testis of adult rats

Objective： To study the effects of simulated microgravity induced by tail-suspension on histological structures and antioxidant system in testis of adult rats. Methods： Forty Spraque-Dawley adult male rats were randomly divided into four groups, two experimental groups and two synchronic control groups. Rats in the two experimental groups were tail-suspended for 14 d and 28 d respectively, then serum hormone, testicular morphology and biochemical changes were evaluated. Results： Compared with the synchronic controls, serum testosterone （T） levels and testicular superoxide dismutase （SOD） significantly decreased（P 〈 0.05）, while testicular malondialdehyde（MDA） significantly increased （P 〈 0.05） in tail-suspended rats. The changes were more prominent in the 28 d tail-suspended rats. In addition, hematoxylin and eosin （HE） staining showed that seminiferous tubules atrophied, spermatogenic cells decreased, and seminiferous epithelial cells disintegrated and shed, abnormal multinucleated giant cells appeared and the lumina were azoospermic in tail-suspended rats. ConcIusion： Simulated microgravity induced by tailsuspension has a harmful effect on male reproduction of adult rats by decreasing the ability of testicular antioxidant defense.     

Clinical study of electro-acupuncture treatment with different intensities for functional constipation patients

Functional constipation （FC） is a common functional bowel disorder disease that affects life quality of a large number of people. This study aimed to explore the impact of different intensities of electro-acupuncture （EA） treatment for FC patients. Totally, 111 patients with FC meeting the Rome III criteria were randomly assigned to different intensities of EA groups （low and high intensity of EA groups） and medicine-controlled （MC） group. In EA groups, patients were treated with EA at quchi （Llll） and shangjuxu （ST37） bilaterally for 4 weeks, 5 times/week in the first 2 weeks, and 3 times/week in the last 2 weeks. In MC group, 5 mg mosapride citrate was administered orally 3 times/day for 4 weeks. Spontaneous bowel movement frequency each day was recorded using a consti- pation diary. Self-rating anxiety scale （SAS） and self-rating depression scale （SDS） were used to assess the patients＇ psychological state. Cortisol （CORT）, substance P （SP）, and vasoactive intestinal polypep- tide （VIP） were evaluated at baseline and at the end of 4 weeks after treatment. As compared with the baseline, there was statistically significant increase in stool frequency every week （P〈0.01）, but there was no statistically significant difference among the three groups. As compared with the baseline, after 4 weeks of EA therapy, the scores of SDS and serum levels of CORT were decreased significantly in low intensity of EA group （P〈0.01）, and the serum levels of SP and VIP were increased significantly （P〈0.05）; the scores of SAS and SDS and serum levels of CORT were decreased significantly in high intensity of EA group （P〈0.05）, and the serum levels of SP and VIP were increased significantly （P〈0.05）; the serum levels of CORT and VIP were increased significantly in MC group （P〈0.05）. As compared with MC group, after 4 weeks of treatment, the serum levels of SP were signifcicantly in- creased in low intensity of EA group （P〈0.01）. Low and high intensi     

Preliminary Comparative Study on the Effect of Different Chinese Drugs for Strengthening Pi(脾)in Antagonizing Diet Induced Obesity

<正>Objective:To observe the difference in fatty degree,glucose-lipid disorder and adipose-hormones between diet induced obesity(DIO) rats and diet induced obesity resistance(DIO-R) rats,and to explore the effect and acting mechanism of Chinese drugs for strengthening Pi(脾,CD-SP) and those for both strengthening Pi and dissolving phlegm(CD-SPDP) in inhibiting obesity.Methods:Excepting eight rats allocated in the blank control group,the other 54 rats were fed with high-lipid forage for 12 weeks to establish models of obesity. Finally,30 DIO rats and 8 DIO-R rats(shown by their body weight) were obtained.The DIO rats were divided into three groups,which were given gastric perfusion,respectively,with normal saline(Group A),CD-SP(Group B),and CD-SPDP(Group C).Fourteen weeks later,the animals' body weight(BW),length(BL),blood levels of fasting insulin(Fln),fasting glucose(FBG),triglyceride(TG),cholesterol(TC),leptin(LP),neuropeptide Y(NPY), C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),adiponectin(AN),and resistin(RS) were measured; insulin resistance index(IRI) was calculated,and the degree of obesity and lipid content in abdominal cavity of rats were estimated.Moreover,the levels of LP,CRP,TNF-α,AN and RS in homogenate of rats' adipose tissues(ATH) were determined.Results:After 12 weeks of high-lipid diet,the BW of DIO rats was higher than that of normal or DIO-R rats.After a 14-week continuous high-lipid diet feeding,in DIO rats,BW,lipid coefficient (LC),and IRI were significantly increased(P0.01);serum levels of TNF-α,LP and AN were lower,NPY was higher,while the ATH levels of LP and AN were lower and TNF-αwas higher in DIO rats than in DIO-R rats (P0.05 or P0.01);blood levels of FBG and lipids in DIO rats showed an increasing trend but was statistically insignificant(P0.05);no significant difference was found in serum levels of CRP and RS due to the overly high data dispersion.Comparisons of the 3 DIO groups showed that BW,body weight index(BWI),LC and IRI were significantly lowered after treatment(P0.01) in Group C,while these indexes were not significantly different between Group A and B;the serum levels of TNF-α,LP,and AN increased,NPY decreased in Group B and C, ATH levels of LP and AN increased,and TNF-αdecreased in the two groups;but NPY,LP,and AN in blood and ATH were higher in Group C than those in Group B(P0.05 or P0.01).Conclusion:CD-SPDP could inhibit DIO and IR,showing that the effect is better than that of CD-SP,and its mechanism is related to promotion of LP and AN secretion and elevation of serum NPY.     

Is the use of cardiopulmonary bypass for isolated coronary artery bypass an independent predictor of mortality and morbidity in patients with severe left ventricular dysfunction?

Background Patients presenting with severe left ventricular dysfunction （SLVD） undergoing conventional coronary artery bypass grafting （CCABG） are at an increased risk of perioperative mortality and morbidity. The aim of this study was to assess the risk factors responsible for mortality and morbidity among patients with SLVD by comparing CCABG and oft-pump coronary artery bypass surgery （OPCAB）.
Methods We retrospectively evaluated 186 consecutive patients with SLVD who underwent coronary artery bypass grafting （CABG）, including 102 by CCABG and 84 by OPCAB. Registry database, medical notes, and charts were studied for preoperative and postoperative data of the patients. Different variables and risk factors （preoperative, intraoperative, and postoperative） were evaluated and compared. The morbidity and mortality outcomes were compared in the two groups. The follow-up results and quality of life were assessed after surgery.
Results The two groups had similar percentage of patients with preoperative high-risk profiles and no significant differences were found between groups in baseline variables such as age or comorbidities. There was a significant difference in the number of grafts used between the two groups. CCABG patients received （3.6±0.5） grafts per patient, while OPCAB patients had （2.7±0.6） grafts （P 〈0.05）. Completeness of revascularization was also significantly different between the two groups （CCABG 91.1% vs OPCAB 73.8%, P 〈0.05）. The hospital mortality was similar in the two groups （4.8% in OPCAB vs 5.9% in CCABG）. The risk-adjusted mortality, according to the calculated propensity score, did not reach statistical significance in the two groups. In this study, OPCAB seemed to have a beneficial effect on reducing reoperation for bleeding, blood transfusion requirement, and the length of stay at ICU. But the incidence of perioperative myocardial infarction was more common in the off-pump group （P 〈0.05）. The degree of improvement in angina and qual     

Effect of Acupuncture on Ovary Morphology and Function in DHEA-Induced Polycystic Ovary Syndrome Model Rats

Objective To investigate the effects of acupuncture on ovary morphology and function in dehydroepiandrosterone(DHEA)-induced polycystic ovary syndrome(PCOS)model rats.Methods A total of 40 adult female Wistar rats were randomly allocated to 4 groups by a random number table,including control,model,metformin and acupuncture groups,10 rats in each group.PCOS rat model was developed by injecting with DHEA(6 mg/100 g body weight)in 0.2 mL of oil subcutaneously.Electrical stimulation(2 Hz,3 mA)was applied to Guanyuan(CV 4),Zigong(EX-CA1)and Qihai(CV 6)acupoints for 30 min daily in the acupuncture group,and metformin(200 mg/kg)was given to rats in the metformin group,both once per day for 21 consecutive days,and rats in the normal group was fed with normal saline and fed regularly.After 21 days of administration,the rat blood samples were collected for detecting the reproductive hormonal levels[luteinizing hormone(LH),follicle stimulating hormone(FSH),estradiol(E2),progesterone(P),testosterone(T)]and inflammatory factors(visfatin,IL-6)analysis.Ovary tissue was used for histopathological analysis.Results Compared with the model group,rats in the acupuncture and metformin groups were significantly lower in weight gain,FSH,LH and T levels,and E2 and P levels significantly increased(alll P<0.05).Meanwhile,LH and FSH levels were significantly decreased,and P,T and E2 levels significantly increased in the acupuncture group,compared with the metformin group(P<0.05).Compared with the model group,IL-6 and visfatin levels were significantly decreased in the acupuncture and metformin groups(P<0.05).There were no significant differences in IL-6 and visfatin levels between the acupuncture and metformin groups(P>0.05).Ovarian diameter in the acupuncture and metformin groups were smaller than the model group(P<0.05).However,there were no significant differences in ovarian diameters between the acupuncture and metformin groups(P>0.05).Conclusion Acupuncture might improve ovary morphology and its function in DHEA-induced PCOS model rats.     

Protective Effects of Hu-Lu-Ba-Wan (葫芦巴丸) against Oxidative Stress in Testis of Diabetic Rats through PKCα /NAPDH Oxidase Signaling Pathway

Objective: To explore the protective effect and the underlying mechanism of Hu-Lu-Ba-Wan (葫芦巴丸, HLBW) on the testis of diabetic rats. Methods: Twenty-four male Wistar rats (160–180 g) were randomly divided into 3 groups according to a random number table, including a control group (n=8), diabetic group (n=8), and HLBW group (n=8). Diabetic rat model was established by high-fat-diet administration and single intravenous injection of streptozotocin (26 mg/kg). Then HLBW granule was administrated for 12 weeks. Fasting blood glucose and insulin levels as well as serum total testosterone level and testicular testosterone content were examined. Oxidative stress markers in both serum and testis were tested. Meanwhile, testicular morphology was observed under hematoxylin and eosin (HE) and the ultrastructure of Leydig cell was observed by electron microscope. The superoxide anion level was detected by DHE, and TUNEL-positive cells of testis was evaluated by TUNEL assay. The gene and protein expression of protein kinase C (PKCα ), phosphorylated PKCα (P-PKCα ) and P47phox in testicular tissues were determined by quantitative RT-PCR analysis and Western bolt analysis. Results: Compared with the diabetic group, HLBW treatment significantly reduced the fasting glucose levels and increased the levels of fasting insulin and testosterone in serum (P<0.01). HLBW administration also reduced the levels of reactive oxygen species (ROS) in plasma and alleviated the damage of oxidative stress in the testis of diabetic rats. Additionally, HLBW down-regulated the protein and mRNA levels of PKCα , P-PKCα and P47phox in testicular tissues. Conclusion: HLBW may attenuate the oxidative stress in the testis of diabetic rats via PKCα /NAPDH oxidase signaling pathway.