Objective:To explore the effects of coenzyme Q10(CoQ10) on high-fat diet-induced obesity, lipid disorders, and bile acid metabolism in mice.Methods:Eight-week-old C57BL/6J mice were randomly divided into control group(regular chow), high-fat diet group(45% high-fat chow), and CoQ10 intervention group(45% high-fat chow+ 100 mg·kg -1·d -1CoQ10) based on their body weights according to the randomized block design. The body weight and food intake of mice in each group were collected. The levels of serum total cholesterol, triglyceride, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase were detected. The contents of 17 bile acids in serum, liver, and colon contents of mice were detected by ultra-performance liquid chromatography-tandem mass(UPLC-MS/MS). The protein expressions of cholesterol 12α-hydroxylase(CYP8B1) and oxysterol 7α-hydroxylase(CYP7B1) in liver were detected by Western blotting. Results:CoQ10 significantly reduced body weight and ameliorated lipid metabolism disorders in mice fed a high-fat diet. Compared with the control group, serum total bile acid levels were reduced in the high-fat diet group( P<0.05); CoQ10 intervention elevated serum and colonic total bile acid levels( P=0.021, P=0.014) and increased liver, colon, and serum deoxycholic acid and ursodeoxycholic acid levels( P<0.05) in the mice compared with the high-fat diet group. Both colonic and serum deoxycholic acid levels in the CoQ10 intervention group were negatively correlated with body weights( P=0.024, P=0.019), and colonic deoxycholic acid and total cholesterol levels were also negatively correlated( P=0.006). CoQ10 increased the expression of CYP8B1 and CYP7B1 proteins in the liver of mice. Conclusion:CoQ10 can modulate bile acid metabolism in high-fat diet-fed mice and alleviate their obesity and lipid metabolism disorders.

Objective To establish a rapid detection method for zika virus based on direct amplification re-al-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-PCR)technique.Methods A direct amplification RT-PCR technique for the rapid detection of zika virus in 5 samples(whole blood,serum,saliva,throat swab and urine)was established by using a special function DNA polymerase and a preferred PCR enhancer.Results The detection limits of the 5 samples were 103 PFU/mL in serum,102 PFU/mL in urine,throat swab,and saliva,and 104 PFU/mL in whole blood.The coefficient of goodness-fit of stand-ard curves was above 0.98,and the amplification efficiency was 90％-110％.Zika virus nucleic acid was suc-cessfully amplified,but non-zika virus nucleic acid was not amplified.Based on the repeatable detection of sam-ples from urine,whole blood,and saliva,the variation coefficient of 6 repeated Ct values at 106 PFU/mL and 102 PFU/mL concentrations were all＜5％.The zika virus detection method established by the direct amplifi-cation RT-PCR technique was consistent with the detection results of conventional RT-PCR technique.Only two serum samples were detected in eight zika virus samples,and the remaining 62 non-zika virus samples and 12 negative samples were not amplified.Conclusion A rapid detection method for zika virus based on direct ampli-fication RT-PCR technique is successfully established.The method is simple,rapid,sensitive and specific.

Objective To investigate the correlation of the 1896 and 1899 mutations of hepatitis B virus (HBV)with the conversion of e antigen in serum and the progression of the disease. Methods 238 serum samples from the patients with HBsAg positive for over six months and HBV-DNA copy number > 5.0 × 102 IU/mL were collected,and the sequence analysis was used to analyze the nucleotide sequences of the 1896 and 1899 sites in the pre-C region of HBV. At the same time,the relevant clinical data and the expressions of HBeAg were collected,followed by Spearman correlation analysis and chi square test with SPSS 20.0. Results Both 1896 and 1899 sites in the pre-C region of HBV were mutated,and the base G was A,which was closely related to the expression of e antigen(P<0.05). Both G1896A and G1899A promoted the e antigen serological conversion ,and the e antigen serological conversion of G1899A was higher than that of G1896A. G1899A was associated with HBV related disease progression (correlation coefficient 0.280,P < 0.05),especially with the incurrence of HCC. Conclusions G1896A and G1899A in the pre-C region of HBV can promote the serological conversion of e antigen.

OBJECTIVE:To investigate the effect of clinical pharmacist intervention on prophylactic application of antibiotics in cardiothoracic surgery. METHODS:Medical records of patients underwent cardiothoracic surgery were collected from our hospi-tal during Mar. to Apr. in 2014 (before intervention) and during Jun. to Jul. in 2014 (after intervention). Those were divided into pre-intervention group(n=115)and post-intervention group(n=119). The prophylactic application effect of antibiotics was com-pared before and after intervention. RESULTS:After intervention,the rates of prophylactic application were decreased significantly from 96.5% to 72.3%;the rationality rate of antibiotics selection was improved significantly from 27.9% to 94.2%;The course of prophylactic medication decreased significantly from(5.4±2.8)days to(2.3±1.8)days;the difference had statistical significance before and after intervention(P<0.01). The postoperative infection rate was decreased from 13.0% to 5.9%,the difference had no statistical significance(P=0.074). The average hospitalization time,average drug costs,and average hospitalization expenses were decreased significantly,the difference had statistical significance(P<0.05 or P<0.01). CONCLUSIONS:Clinical pharmacist inter-vention to prophylactic application of antibiotics in cardiothoracic surgery can control the infection effective and guarantee reason-able and safe use of drugs during perioperative period.

The protective effects of diallyl trisulfide on liver were examined in rats with sepsis. Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-six male Wistar rats were randomly divided into sham-operated group (group S, n=8), sepsis model group (group C, n=24), diallyl trisulfide (DATS)-treated group (group D, n=24). Animals in groups C and D were further divided into three subgroups according to different observation time points, with 8 rats in each subgroup· Rats in group D and C were intravenously injected with normal saline or DATS respectively at a dose of 20 mg/kg after the establishment of sepsis model. Eight rats in groups C and D were sacrificed at 3, 6 and 24 h post-CLP and their livers were harvested for detection of interleukin (IL)-1 receptor associated kinase-4 (IRAK-4), nuclear factor-κB (NF-κB), c-fos, c-jun, malondialdehydethhe (MDA) and superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α) and for pathological examination. The results showed that the levels of serum IRAK-4, NF-κB and TNF-α in hepatic tissues were higher in group C than group S (control group) (P<0.05). After DATS treatment, the levels of IRAK-4 and NF-κB in the hepatic tissues and serum TNF-α in group D were lower than those in group C (P<0.05). The levels of c-fos and c-jun and MDA in the hepatic tissues were higher in group C than in group S (P<0.05). After DATS treatment, the levels of c-fos and c-jun and MDA in the hepatic tissues were significantly lower in group D than in group C (P<0.05). When compared with group S group, concentration of SOD in the hepatic tissues in group C was significantly lower (P<0.05). After DATS treatment, the concentration of SOD in the hepatic tissues was higher in group D than in group C (P<0.05). These findings suggested that treatment with DATS could ameliorate sepsis-induced liver injury in rats. The protective effect might be related to its ability to inhibit the signal pathway of IRAK-4 and NF-κB, thereby decreasing the production of oxygen free radicals and down-regulating the expression of c-fos and c-jun.
Allyl Compounds ; pharmacology ; Animals ; Disease Models, Animal ; Liver ; drug effects ; metabolism ; pathology ; Male ; Rats ; Rats, Wistar ; Sepsis ; complications ; Sulfides ; pharmacology

ObjectiveTo explore heart rate variability (HRV),cardiac troponin Ⅰ (cTnI),left ventricular ejection fraction (LVEF) and electrocardiogram (ECG) in order to clarify the function of cardiac autonomic nerve system and the incidence of potential myocardium injury in patients with severe brain injury.MethodsClinical data of 65 patients with severe brain injury admitted between June 2006 and June 2010 were reviewed.For the sake of comparison,patients were divided by different groupings as per different biomarkers or outcomes such as Glasgow coma scale (GCS) 6 - 8 group and GCS 3 - 5 group; cTnl ＞ 0.5 group,0.04 ＜ cTnl ＜ 0.5 group and CTnl ＜ 0.04 group; and survival group and death group.Another 30 healthy subjects were enrolled as control group.Heart rate variability (HRV) was analyzed with both timedomain and frequency domain methods based on data from 24-hour Holter monitoring.The level of serum cardiac troponin Ⅰ was detected. The left ventricular ejection fraction was measured by beside color ultrasonogram.The different relationships between HRV and GCS as well as prognosis,between cTnI and GCS as well as fatality,between cTnI and ECG,and between EF and GCS were analyzed.The computer statistical software SPSS version 13.0 was used for statistical analysis of data.ResultsAll of the 65 patents with severe brain injury were subjected to decrease in HRV.The patients of GCS 6 - 8 group and GCS 3 - 5 group showed significantly lowered HRV in comparison with control group ( P ＜ 0.05 ).The death group showed more obvious decrease in HRV than the survival group ( P ＜ 0.05 ).Fifty-one of the 65 patients had myocardial injury evidenced by increase in cardiac troponin Ⅰ.The patients of cTnl ＞0.5 group and 0.04 ＜cTnI ＜ 0.5 group showed significantly higher fatality compared with cTnI ＜ 0.04 group ( P ＜ 0.05 ).Compared with the GCS 6 ～ 8 group,more patients in the GCS 3 -5 group had abnormal serum CTnl level and lower EF.ConclusionsThere are cardiac autonomic nerve system disorders and different degrees of myocardial injury in patients with severe brain injury,and early intervention is essential to decrease the fatality of severe brain injury.

The protective effects of diallyl trisulfide on liver were examined in rats with sepsis. Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-six male Wistar rats were randomly divided into sham-operated group (group S, n=8), sepsis model group (group C, n=24), diallyl trisulfide (DATS)-treated group (group D, n=24). Animals in groups C and D were further divided into three subgroups according to different observation time points, with 8 rats in each subgroup· Rats in group D and C were intravenously injected with normal saline or DATS respectively at a dose of 20 mg/kg after the establishment of sepsis model. Eight rats in groups C and D were sacrificed at 3, 6 and 24 h post-CLP and their livers were harvested for detection of interleukin (IL)-1 receptor associated kinase-4 (IRAK-4), nuclear factor-κB (NF-κB), c-fos, c-jun, malondialdehydethhe (MDA) and superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α) and for pathological examination. The results showed that the levels of serum IRAK-4, NF-κB and TNF-α in hepatic tissues were higher in group C than group S (control group) (P<0.05). After DATS treatment, the levels of IRAK-4 and NF-κB in the hepatic tissues and serum TNF-α in group D were lower than those in group C (P<0.05). The levels of c-fos and c-jun and MDA in the hepatic tissues were higher in group C than in group S (P<0.05). After DATS treatment, the levels of c-fos and c-jun and MDA in the hepatic tissues were significantly lower in group D than in group C (P<0.05). When compared with group S group, concentration of SOD in the hepatic tissues in group C was significantly lower (P<0.05). After DATS treatment, the concentration of SOD in the hepatic tissues was higher in group D than in group C (P<0.05). These findings suggested that treatment with DATS could ameliorate sepsis-induced liver injury in rats. The protective effect might be related to its ability to inhibit the signal pathway of IRAK-4 and NF-κB, thereby decreasing the production of oxygen free radicals and down-regulating the expression of c-fos and c-jun.

To explore the protective effect of sodium tanshinone Ⅱ A sulfonate (STS) on microcirculatory disturbance of small intestine in rats with sepsis,and the possible mechanism,a rat model of sepsis was induced by cecal ligation and puncture (CLP).Rats were randomly divided into 3 groups:sham operated group (S),sepsis group (CLP) and STS treatment group (STS).STS (1 mg/kg) was slowly injected through the right external jugular vein after CLP.The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed.The levels of tumor necrosis factor-α(TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay (ELISA).The expression of intercellular adhesion molecule-1 (ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot,that of nuclear factor κB (NF-κB) and tissue factor (TF) by using Western blot,and the levels of NF-κB mRNA expression by using RT-PCR respectively.The microcirculatory disturbance of the intestine was aggravated after CLP.The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group.The expression levels of NF-κB p65,ICAM-1,TF and TNF-α were upregulaed after CLP (P＜0.01).STS post-treatment could ameliorate the microcirculatory disturbance,attenuate the injury of the intestinal tissues induced by CLP,and decrease the levels of NF-κB,ICAM-1,TF and TNF-α (P＜0.01).It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis,and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality.

To explore the protective effect of sodium tanshinone IIA sulfonate (STS) on microcirculatory disturbance of small intestine in rats with sepsis, and the possible mechanism, a rat model of sepsis was induced by cecal ligation and puncture (CLP). Rats were randomly divided into 3 groups: sham operated group (S), sepsis group (CLP) and STS treatment group (STS). STS (1 mg/kg) was slowly injected through the right external jugular vein after CLP. The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed. The levels of tumor necrosis factor-α (TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay (ELISA). The expression of intercellular adhesion molecule-1 (ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot, that of nuclear factor κB (NF-κB) and tissue factor (TF) by using Western blot, and the levels of NF-κB mRNA expression by using RT-PCR respectively. The microcirculatory disturbance of the intestine was aggravated after CLP. The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group. The expression levels of NF-κB p65, ICAM-1, TF and TNF-α were upregulaed after CLP (P<0.01). STS post-treatment could ameliorate the microcirculatory disturbance, attenuate the injury of the intestinal tissues induced by CLP, and decrease the levels of NF-κB, ICAM-1, TF and TNF-α (P<0.01). It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis, and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality.

Objective To investigate the effect of preptin on proliferation and differentiation of human osteoblasts. Methods After human osteoblasts were incubated with 10-10, 10-9, 10-8 , 10-7 mol/L preptin for 24 h,the proliferation of osteoblasts was determined by[3H]thymidine incorporation and alkaline phosphatase (ALP)activity was assayed by spectrophotometric measurement. The phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase ( MAPK), extracellular signal-regulated kinase (ERK) 1/2 were assayed by Western blot. ERK inhibitor PD98059, p38MAPK inhibitor SB203580, and JNK inhibitor SP600125were used for investigating the signal pathway of preptin-stimulated osteoblast proliferation and differentiation.Results Preptin dose-dependently increased human proliferation of osteoblasts and ALP activity with the maximum effect at the concentration of l0-9 mol/L (both P<0.01 ). Preptin stimulated ERK phosphorylation in human osteoblasts, but not p38 MAPK and JNK phosphorylation. PD98059 blocked preptin-sitmulated human osteoblasts proliferation and ALP activity (both P<0.05 ), while SB203580 and SP600125 had no effect. Conclusions Preptin promotes the proliferation and differentiation of human osteoblasts through ERK pathway.