Effect of low expression of sodium taurocholate cotransporting polypeptide on antiviral response in chronic hepatitis B patients with active inflammation / 中华传染病杂志

Objective:To investigate the relationship between the down-regulation expression of sodium taurocholate cotransporting polypeptide (NTCP) in proliferating hepatocytes and the response to antiviral therapy of chronic hepatitis B (CHB) patients.Methods:Sixty-eight hepatitis B e antigen (HBeAg)-positive CHB patients admitted to the Fifth Medical Center of PLA General Hospital from January 2011 to March 2015 were included. Basic information and laboratory data were collected. Based on the baseline (before antiviral treatment) inflammatory activity (G), the patients were divided into ≤G2 group and >G2 group. Twelve liver puncture tissue samples were selected from each group for NTCP and Ki67 immunofluorescence staining.The proportion of Ki67-positive cells was calculated, and the staining of NTCP was scored. Five pairs of tissue specimens of patients who had hepatitis B virus (HBV) infection were diagnosed with focal nodular hyperplasia (FNH) and underwent nodular resection surgery from March 2014 to March 2017 were collected.Immunohistochemical staining was used to detect the expressions of Ki67, NTCP and hepatitis B surface antigen (HBsAg) in each tissue specimen, and the proportion of staining positive cells or the staining intensity was calculated. Statistical analysis was performed by Mann-Whitney U test, chi-square test or Spearman correlation analysis. Results:The proportion of Ki67-positive cells (6.75%(6.20%, 8.16%))in five liver FNH tissues with HBV infection was significantly higher than that in adjacent non-FNH tissues (0.75%(0.66%, 1.20%)), while the immunohistochemical scores of NTCP and HBsAg (3.00 (1.00, 3.00) and 2.00 (1.00, 2.00), respectively) were both significantly lower than those in adjacent non-FNH tissues (8.00 (8.00, 9.00) and 8.00 (6.00, 8.00), respectively), the differences were all statistically significant ( Z=-2.611, -2.424 and -2.635, respectively, P=0.009, 0.015 and 0.008, respectively). There were 37 patients in >G2 group, and 31 patients in ≤G2 group. After six months of antiviral treatment, CHB patients with persistent inflammation in >G2 group obtained a better virological response, with serum HBV DNA and HBeAg showing a greater decline ((0.71±0.14) lg IU/mL and (0.92±0.13) lg IU/mL, respectively) than those in ≤G2 group ((0.54±0.30) lg IU/mL and (0.49±0.65) lg IU/mL, respectively) ( Z=-3.048 and -2.666, respectively, P=0.002 and 0.008, respectively). The proportion of Ki67-positive cells in the specimens of >G2 group (4.34%(1.84%, 8.77%)) was significantly higher than that of ≤G2 group (0.34%(0, 0.80%)) ( Z=-3.640, P<0.01), and the immunohistochemical staining score of NTCP (1.00 (0, 3.25)) was significantly lower than that of ≤G2 group (6.00 (4.00, 8.00)) ( Z=-3.012, P=0.003). Spearman correlation analysis showed that the NTCP immunohistochemical score was negatively correlated with the proportion of Ki67-positive cells ( r=-0.512, P=0.01). Conclusions:CHB patients with persistent inflammationare often accompanied by more active hepatocyte proliferation and low membrane NTCP expression, which is not conducive to HBV reinfection. It may facilitate these patients to obtain better virological response.

Cultivation of self-learning ability and critical thinking ability of nursing students under mobile teaching mode / 中华医学教育探索杂志

Objective:To explore the effect of self-learning ability and critical thinking ability in nursing students under mobile teaching mode based on portable classroom platform.Method:s Two classes of batch 2015 from nursing college were randomly selected and divided into control group ( n=58) and experimental group ( n=61). The control group adopted conventional teaching mode, while the experimental group used the same mode in addition to mobile teaching mode based on portable classroom platform. Self-learning ability questionnaire and critical thinking ability scale in Chinese were used to evaluate the teaching effect, and t test was performed to analyze the data using SPSS 19.0. Result:s After intervention, scores of different items and the total scores in the self-learning ability scale in the experimental group were higher than those in the control group, with statistical significance ( P<0.05); scores of different items and the total scores in the critical thinking ability questionnaire in the experimental group were higher than those in the control group, with statistical significance ( P<0.05). Conclusion:Mobile teaching mode based on portable classroom platform can improve the self-learning ability and critical thinking ability of nursing students.

Effects of Icariin on Partial Vasoactive Substances in Monocrotaline-induced Pulmonary Arterial Hypertension Rat Model / 医药导报

Objective To investigate the effects of icariin (ICA) on partial vasoactive substances in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model.Methods Sixty male SD rats were randomly divided into five groups:normal control group,model control group,ICA low-,middle-and high-dose (20,40,80 mg · kg-1 · d-1) group,12 rats in each group.Except for normal control group,the rats were injected with MCT (50 mg · kg-1 · d-1) to establish PAH model.After 1 week MCT-injection,ICA was given by intragastric administration for 3 weeks according to different groups.Mean pulmonary artery pressure (mPAP) was recorded through catheter connected with Power Lab system.Except for normal control group,the right ventricular hypertrophy index (RVHI) was calculated using formula:right ventricle weight/the weight of left ventricle with septum× 100％.The morphology of lung artery was assessed by HE staining.Concentration of angiotensin Ⅱ (Ang Ⅱ),endothelin (ET),prostaglandine F2α(PGF2α),thromboxane A2(TXA2) and prostacyclin (PGI2) in serum was measured by ELISA kit assay.The protein levels of angiotensin converting enzyme (ACE),cyclooxygenase-2 (COX-2) and thromboxane A2 synthetase (TXAS) were analyzed by Western blotting,expression of ACE,COX-2 and TXAS mRNA was measured by real time RT-PCR.Results Compared with the normal control group,mPAP [(48.5±5.2) mmHg] and RVHI (33.3±3.8)％in model control group were significantly increased (P ＜ 0.05),the morphology revealed there was obvious artery remodeling at distal artery,the contents of Ang Ⅱ,PGFA2,TXA2 in serum were elevated,and ACE,COX-2 and TXAS gene expression was up-regulated in rats treated with MCT.ICA (40,80 mg · kg-1 · d-1) treatment significantly attenuated mPAP,RVHI and pulmonary artery remodeling (P ＜ 0.05),and decreased the contents of serum Ang Ⅱ,ET,PGF2β,TXA2,and PGI2,and inhibited the gene expression of ACE,COX-2 and TXAS.Conclusion ICA decreases the contents of AngⅡ,ET,PGI2,PGF2α and TXA2 in the serum of MCT-induced PAH rats,which may be one of the mechanisms underlying ICA inhibiting PAH.

Study on Improvement Effect and Mechanism of Icariin on Renal Lesion in Rats with Spontaneous Hyper-tension / 中国药房

OBJECTIVE:To observe the effect of pathological lesion of renal tissue in rats with spontaneous hypertension (SHR),and study its mechanisms based on nuclear factorκB(NF-κB)signaling pathway. METHODS:21 SHR were randomly di-vided into model group and ICA low-dose,high-dose groups(20,40 mg/kg,denoted by ICA-L,ICA-H groups);other 7 homolo-gous Kyoto rats (WKY) were regarded as control group. All rats were intragastrically administrated,twice a day,for 11 weeks, rats in control group and model group received equal volume of double distilled water,ig. Pathological changes in renal tissue in each group were observed;Western blot method was used to detect protein expressions of p-NF-κB-p65,IκB and TNF-α in renal tissue. RESULTS:Compared with control group,model group showed disorder renal structure,narrow and irregular glomerular cysts;the protein expression of IκB was significantly down-regulated,protein expressions of p-NF-κB-p65 and TNF-α were signifi-cantly up-regulated(P0.05). CONCLUSIONS:ICA plays a role in improving renal pathological lesion in SHR,and the mechanism may be related to inhibiting NF-κB signaling pathway.

Anti-apoptotic effect of Icariin on renal tubular epithelial cell in SHR / 中国药理学通报

Aims To observe the effect of Icariin( Ica) on apoptosis of renal tubular epithelial cell in spontane-ously hypertensive rats( SHR) , and to explore its pos-sible mechanism. Methods 21 male SHR of 14 weeks were randomly divided into model groups, the Ica low and high dose groups (20 or 40 mg·kg-1 ,ig, bid, to 26 weeks ) , 14 week-old male homologous Kyoto rats ( WKY ) as control group, and the number of each group was 7 . WKY group and model group were ad-ministered by gavage with the same volume of double distilled water. The pathological changes were observed by using the HE staining and the apoptosis was detec-ted by TUNEL method in renal tubular epithelial cell, respectively. The mRNA levels of Bok, Bax, Bcl-2 were detected by the real time RT-PCR and the protein expressions of Bcl-2 , Bax and Active caspase-3 were detected by Western blot method in the renal tissue. Results Compared with WKY, renal capsule was nar-row and irregular, and glomerular mesangial matrix was increased with the cell arrangement disorder and the capillary dilation and congestion. Several glomeruli shrank and renal tubular epithelial cell was edema with luminal stenosis in model group. The apoptosis of renal tubular epithelial cell was evident and the mRNA levels of Bok and Bax, as well as the protein expressions of Bax and Active caspase-3 were significantly up-regula-ted in model group, while the mRNA Level and protein expression of Bcl-2 significantly down-regulated ( P <0. 05 or P<0. 01). Compared with model group, renal glomerular capsule widened, proliferation of glomerular mesangial matrix was reduced, and cell arrangement disorder and capillary dilation and renal tubular lumen stenosis were improved in Ica group. Renal tubular ep-ithelial cell apoptosis was decreased evidently, and the mRNA level of Bax, Bok and protein expression of Bax were significantly down-regulated in Ica group, and the mRNA level and protein expression of Bcl-2 in Ica-H group were significantly up-regulated while the protein expression of Active caspase-3 significantly down-regu-lated( P <0. 05 or P <0. 01 ) . Conclusion Ica can inhibit the apoptosis of renal tubular epithelial cell in spontaneously hypertensive rats and its mechanism may be related to the down-regulation of Bok, Bax, and Active caspase-3 , accompanied with the up-regulation of Bcl-2 .

Osthole could attenuate right ventricle remodeling in monocrotaline-treated rats by up-regulating PPARαand PPARγ / 中国药理学通报

Aim To explore the effect of Osthole (Ost)on the right ventricle remodeling in monocrot-alinetreated rats and the possible mechanism.Meth-ods ♂ SD rats were randomly divided into normal control group,model group,low dose of Ost treatment group (10 mg·kg -1 )and high dose of Ost treatment group (20 mg·kg -1 ).All rats were given a single dose of MCT 50 mg·kg -1 subcutaneously to establish the right ventricle remodeling except normal control group.Then the rats in Ost treatment group were ga-vaged once daily.After 28 days of administration,the right ventricle(RV)and left ventricle plus septum(LV+SEP)were weighed separately.RV hypertrophy in-dex (RVHI)were measured by the relative weight rati-o of RV to LV +SEP.The morphological changes of right ventricle were executed by HE staining.The pro-tein expression of PPARαand PPARγwere detected by Western blot.Results Compared with the control group,RVHI was increased obviously (P <0.05 ), myocardial hypertrophy and structure disorders were observed in model group.The protein expression of PPARαand PPARγwere down-regulated significantly in model group (P <0.05).Compared with the model group,the value of RVHI (P <0.05),myocardial hy-pertrophy,structure disorders were improved signifi-cantly in Ost treatment group.The protein expression of PPARαand PPARγwere up-regulated in Ost treat-ment group (P <0.05).Conclusion Ost can attenu-ate the right ventricle remodeling induced by MCT in rats,which may be related to up-regulating the expres-sion of PPARαand PPARγ.

Icariin attenuates left ventricular remodeling in SHR by up-regulating PPARαand PPARγ / 中国药理学通报

Aim To investigate the effect of Icariin ( Ica) on remodeling of left ventricular in SHR and ex-plore the mechanism. Methods Twenty-one male SHR aged 14 weekswere randomly divided into model group(n=7), low-dose of Ica-treated group(20 mg· kg-1 . bid, n =7 ) , high-dose of Ica-treated group ( 40 mg·kg-1. bid,n=7), and WKY as control group(n=7 ) . Low- and high-dose of Ica-treated groups were given Ica from the age of 14 weeks to 26 weeks. The other rats in the model group and control group were given the same amount of double distilled water. Then, the content of hydroxyproline ( Hyp) was measured by ELISA. The morphological changes of the left ventricu-lar were observed by Masson staining. The mRNA and the protein expression of PPARα and PPARγ were ex-amined by real time RT-PCR and Western blot tech-nique respectively. Results Compared with the nor-mal control group, interstitium fibrosis and myofibrilla were lined up in disorder; the content of Hyp was in-creased and the mRNA and protein expression of PPARα and PPARγ were down-regulated in model group(P<0. 01). Compared with the model group,the myocardial cells were arranged less disorderly and the myocardial fibrosis was reduced; the content of Hyp was decreased in low-and high-dose of Ica-treated groups(P<0. 01 or P<0. 05);the mRNA and protein expression of PPARα and PPARγwere up-regulated in low- and high-dose of Ica-treated groups ( P <0. 01 or P<0. 05 ) . Conclusion Ica may attenuate left ven-tricular remodeling in SHR by up-regulating PPARαand PPARγ.

Icariin attenuates renal interstitial fibrosis by reducing aldosterone in SHR / 中国药理学通报

Aim To investigate the effect of icariin ( ICA) on renal interstitial fibrosis in SHR and explore its mechanism. Methods Fourteen male SHR of 13-week-old were randomly divided into model group( n=7 ) and ICA group ( n=7 ) , and WKY as control group (n=7). One week after adaptive breeding,the rats in the ICA group were given ICA 40 mg·kg-1,ig,bid to 26-week-old. The other rats in the model group and control group were given the same amount of normal sa-line. Then, the morphological changes of the kidney were observed by HE and Masson staining,respective-ly. The contents of plasma aldosterone andⅢcollagen were measured by double antibody sandwich method. The mRNA expressions of TGF-β1 , Smad2 , CTGF and FN were examined by real time RT-PCR. Results Compared with the normal control group, the kidney structures of model group were disordered,the mesang-ial matrix and the tubular interstitial fibrosis were in-creased. The contents of plasma aldosterone and Ⅲcollagen were increased in model group ( P <0. 01 ) . And the mRNA expressions of TGF-β1 , Smad2 , CTGF and FN in kidney tissues were up-regulated in model group( P <0. 01 or P <0. 05 ) . Compared with the model group,the kidney structures were improved and the contents of plasma aldosterone and Ⅲ collagen were reduced, as well as the mRNA expressions of TGF-β1,Smad2,CTGF and FN in kidney tissues were down-regulated(P<0. 01 or P<0. 05)in ICA group. Conclusion ICA may have anti-renal interstitial fi-brosis effect on SHR,and the mechanism might be re-lated to the reduced plasma aldosterone levels and the down-regulated expression of TGF-β1 and Smad2 .

The exploration of learning and memory in pharmacology teaching / 中华医学教育探索杂志

Pharmacology is the bridge of preclinical and clinical medicine,as well as medical science and pharmaceutical sciences.Guiding students to grasp some memory method will make for inspiring student's thinking and increasing their interest in pharmacology teaching.And it will also help to improve the effect of pharmacology teaching.

Discussion on promoting the clinical pharmachology teaching effect / 中华医学教育探索杂志

This article aims to promote the teaching quality in clinical pharmachology. The methods are as follows: First, understanding the difference between the clinical pharmachology and pharmachology; Second, improving the teachers’ teaching level, especially increasing the clinical experiences in using drug; Third, developing the teachers’ spirits of occupation; Last, cultivating the ability of self-teaching of students.

Distrubution and excretion of protopine in rats by RP-HPLC method / 中国药理学通报

AIM To study the distrubution and excretion of protopine in rats. METHODS Reversed phase high performance liquid chromatographic method (RP HPLC) was developed for determining the level of protopine in rats. The analytical column were packed with 5 ?m C 18 . The mobile phase was a mixture of methanol, water and 10% acetic acid (80∶20∶2), in which the pH was modulated to 5 6 with 15% ammonia. Protopine biological samples were isolated well, in which two extraction with ether under basical condition and an extraction with 0 02 mol?L -1 sulfuric acid were performed, respectively. The content of protopine in the biological sample was measured by an UV detector at 285 nm. The distrubution and excetion of protopine have been investigated in rats after intravenous administration 10 mg?kg -1 . RESULTS Protopine distrubuted in many tissues after iv a dose of 10 mg?kg -1 . The higher level of protopine was found in lung, kidney, spleen and brain, and the highest was observed in lung at 5, 15 minutes after administration. However the top level tissue was testicle at 3 h, which may be due to small blood circulation. The excretion of the parent compound in urine was 36 87% of dose, but the excretion of the parent compound in feces and bile was less than 1% of dose. Plasma protein binding was less than 5%. CONCLUSION The distrubution of protopine is extensive and the parent compoud was mainly excreted by urine and plasma protein binding was low.