1.Efficacy of glucocorticoids in treatment of severe hepatitis : a Meta-analysis
Chinese Journal of Clinical Infectious Diseases 2012;5(5):264-269
Objective To evaluate the clinical efficiency of glucocorticoids in treatment of severe hepatitis.Methods A systematic review on the efficacy of glucocorticoids in treatment of severe hepatitis was conducted.Relevant literatures were searched in PubMed (1966-2011),EMCC (1995-2011),Springer,CNKI,Wanfang Database and CBM.The retrieved literatures were screened according to the predefined inclusion and exclusion criteria.RevMan 5.0 statistical software was used for Meta-analysis.The mortality was evaluated by relative risk (RR),while the total bilirubin (TBil),ALT and prothrombin activity (PTA) were evaluated by weighted mean difference (WMD) and 95% confidential interval (CI).The publication bias and sensitivity about the data were measured by forest plot and funnel plot.Results Twenty-three papers involving a total of 1457 patients were included in the study.Compared to control group,the mortality in glucocorticoids-treated group was lower (RR =0.39,95% CI:0.32-0.47,Z =9.75,P<0.01); and the TBil (WMD=-88.03,95%CI:-112.80-63.26,Z=6.97,P<0.01),ALT (WMD=-25.04,95%CI:-42.23-7.84,Z=2.85,P<0.01) and PTA levels (WMD=21.56,95% CI:6.52-36.60,Z=2.81,P <0.01) in glucocorticoids-treated group were improved.Conclusion Glucocorticoids can effectively improve TBil,ALT and PTA levels,and reduce the mortality of patients with severe hepatitis.
2.Various dosage forms of nimodipine:application and research advances
Cuicui LIN ; Zihua XIA ; Fan YANG
Journal of International Pharmaceutical Research 2017;44(6):518-521
Nimodipine is the second generation of dihydropyridine Ca2+ antagonist. The scope of its clinical application has been expanded because of the excellent curative effects on cerebrovascular diseases. Nimodipine is commonly available on the market as oral or injection preparation,which has to be given several times per day. It may induce peripheral cholinergia side effects and has low bioavailability. Therefore,it is necessary to develop novel drug formulation with optimized delivery system. In the present review, an attempt is made to discuss the current progress of nimodipine in pharmaceutics,including the difference of market situation,safety and efficacy of different dosage forms. Meanwhile,the main research directions of new dosage forms are summarized,which can pro-vide reference for developing more efficient and convenient nimodipine preparations.
3.Hepatitis B virus inhibits the immune function of natural killer cells
Cuicui SHI ; Gangde ZHAO ; Hui WANG ; Jiangao FAN ; Guangming LI ; Qing XIE
Chinese Journal of Infectious Diseases 2011;29(11):648-652
Objective To investigate the effect of hepatitis B virus (HBV) on the immune function of natural killer (NK) cells.Methods Healthy human peripheral blood-derived NK cells were cultured alone,or co-cultured with plasmacytoid dendritic cell (pDC) (NK∶ pDC=5∶1) for 48 h with or without HepG 2.2.15-derived HBV.Cell activation was assessed by flow cytometry.The specific enzyme linked immunosorbent assay (ELISA) and intracellular cytokine staining (ICS) were used to determine the cytokine production,the cytotoxic effect of NK cells on the carboxyfluorescein diacetate succinimidyl ester (CFSE)-labelled K562 target cells as well as the granzyme and perforin levels in NK cells.Paired results were analysed using Wilcoxon signed rank test.Results HBV did not affect interleukin (IL)-12/IL-18 and IL-18/interferon α (IFNα)-induced interferon γ (IFNγ) production by NK cells when NK cells were cultured alone (both P>0.05).However,HBV significantly inhibited pDC-induced IFNγ production by NK cells (146.1 pg/mL),while CpG enhanced pDC-induced IFNγ production by NK cells significantly (1135.4 pg/mL,P=0.0005).HBV did not affect pDC-induced NK cell activation and cytotoxicity to K562 target cells as well as intracellular granzyme and perforin levels.ConclusionHBV does not activate but inhibits pDC-induced NK cell function,which may contribute to the persistence of HBV infection.
4.Protective effect of necrostain-1 on oxygen-glucose deprivation induced caspase-independent cell death in primary cortical neurons
Hongbin FAN ; Cuicui ZHANG ; Weiwei CHEN ; Yanbo CHENG ; Xiagshun XU ; Deqin GENG
Chinese Journal of Behavioral Medicine and Brain Science 2011;20(12):1088-1091
Objective To explore whether hypoxia-inducible factor-1α( HIF-1α )is involved in oxygenglucose deprivation (OGD)induced caspase-independent cell death in primary cortical neurons and whether their expression is infected by necrostatin-1 ( Nec-1 ).Methods ( 1 ) Primary cerebrocortical neurons were cultured for 14 days.Pretred z-VAD.Fmk (z-VAD)and Nec-1 with 0.1,1,5,10,25 and 50 μ mol/L before the neurons were exposed to OGD for 2 hours and reoxygenated for 12 hours,then cell viability was determined by measure LDH level.(2)Pretred z-VAD before the neurons were exposed to OGD for 2 hours,then reoxygenated for 0,2,6,12,24and 48 hours.Then western blot analysis protein level of HIF-1 α ;rt-PCR check its RNA level.(3)Pretred z-VAD and Nec-1 with 25μ mol/L before the neurons were exposed to OGD for 2 hours and reoxygenated for 12 hours.Then western blot analysis protein level of HIF-1 α; rt-PCR check its RNA level.Result ( 1 ) When cells were pretread Nec-1 with 5 μ mol/L(6.97 ± 0.06),the level of LDH was lower than cells untreated( 14.23 ± 0.08 ) (P< 0.05);At 25 μmol/L( 2.21 ± 0.05),the level of LDH was essentially the same as that of the control( 1.03 ±0.03 ) (P>0.05).(2)The protein level of HIF-1 αwas different from normal (0.24 ±0.01 ) when exposed to OGD for 2 hours and reoxygenated for 2 hours (0.57 ± 0.09) and was highest after cells were exposed to OGD for 2 hours and reoxygenated for 12 hours(0.91 ± 0.08 ) (P< 0.05 ).The RNA level of HIF-1 α when cells were exposed to OGD was not deferent from normal (P > 0.05 ).( 3 ) When cells were pretread with Nec-1 (0.32 ± 0.04 ),the protein level of HIF-1α were lower than untreated(0.83 ±0.03) (P<0.05),but the RNA level of HIF-1α had no deference(P > 0.05).Conclusion HIF-1α was involved in cell' s caspase-independent cell death;Nec-1 can protect neurons through inhibiting the expression of HIF-1α.
5.Change of peripheral blood cortisol concentration in patients with hepatitis B virus-related acute-on-chronic liver failure
Cuicui FAN ; Caiyan ZHAO ; Yadong WANG ; Li ZHANG ; Jianmin HUANG ; Weijie WU
Chinese Journal of Infectious Diseases 2013;(6):353-357
Objective To study the profile of peripheral blood cortisol concentration in patients with hepatitis B virus (HBV)-related acute on chronic liver failure (ACLF) and its association with disease severity and predictive value on prognosis.Methods Forty-five patients with HBV-related ACLF,including 15 patients in early-stage,15 in medium stage and 15 in end-stage; and 15 patients with severe chronic hepatitis B (CHB) were also enrolled.Peripheral blood cortisol concentration was tested by chemiluminesence immunoassay.SPSS version 18.0 was used to compare peripheral blood cortisol concentration among different groups and analyze its correlation with prothrombin activity (PTA),total bilirubin (TBil),albumin (Alb),alanine aminotransferase (ALT),aspartate aminotransferase (AST),HBV DNA,international normalized ratio (INR) and model for end-stage liver disease (MELD) scores.The independent risk factors of prognosis in patients with HBV-related ACLF were determined by performing Logistic regression analysis.Results The concentrations of peripheral blood cortisol in severe CHB group,early stage ACLF group,medium stage ACLF group and end-stage ACLF group were (595.6±114.0),(496.0±87.2),(303.9±81.1),and (183.8±71.8) nmol/L,respectively.A decreasing trend was observed and the differences among groups were statistically significant (F =63.93,P < 0.01).Peripheral blood cortisol concentration were significantly different among subgroups of patients with MELD<30,followed by 30-40 and >40(F 9.01,P<0.01).Peripheral blood cortisol concentration in patients with ACLF was positively correlated with PTA level (r=0.83,P<0.01),and inversely correlated with TBil (r =-0.34,P<0.05),MELDscore (r =-0.60,P<0.01),AST/ALT (r =-0.35,P<0.05),and INR (r=-0.59,P<0.01).Association with Alb,ALT,AST and HBV DNA was not observed.According to multivariate Logistic regression analysis,MELD score,cortisol level,Alb and total cholesterol were independent risk factors of prognosis for patients with ACLF.Serum cortisol concentration in survival group of HBV-related ACLF was higher than that in death group,while the death group exhibited a gradually decreasing trend.Conclusions The peripheral blood cortisol concentration decreases in patients with HBV-related ACLF,which is related to the degree of liver dysfunction,disease severity and prognosis of patients.Moreover,the lower level of cortisol concentration indicates poor short-term prognosis in patients with HBV related ACLF.
6.Effect of dexmedetomidine on hippocampal neuron apoptosis and the brain-derived neurotrophic factor/tyrosine kinase receptor B signaling pathway in epileptic rats
Journal of Apoplexy and Nervous Diseases 2023;40(9):813-818
Objective To investigate the effect of dexmedetomidine on hippocampal neuron apoptosis and the brainderived neurotrophic factor(BDNF)/tyrosine kinase receptor B(TrκB) signaling pathway in epileptic rats. Methods A rat model of epilepsy was established by intraperitoneal injection of lithium chloride,atropine sulfate,and pilocarpine hydrochloride. After successful modeling,36 rats were randomly divided into model group,dexmedetomidine(50 μg/kg) group,and dexmedetomidine(50 μg/kg)+LM22B-10(a BDNF/TrκB pathway activator,5 mg/kg) group,with 12 rats in each group,and another 12 rats were selected as control group. After modeling ended,the rats in each group were given corresponding drug intervention once a day for 1 week. At 24 hours after the end of administration,seizure frequency and duration were recorded for each group;TUNEL staining was used to observe hippocampal neuron apoptosis;immunofluorescent staining was used to observe βtubulin Ⅲ(Tuj1)positive cells in brain tissue of the hippocampal CA1 region;ELISA was used to measure the levels of tumor necrosis factorα(TNFα) and interleukin6(IL6) in brain tissue of the hippocampal CA1 region;Western blot was used to measure the protein expression levels of BDNF,TrκB,Bcell lymphoma2 associated X protein(Bax),and B cell lymphoma2(Bcl2) in brain tissue of the hippocampal CA1 region. Results Compared with the control group,the model group had significant increases in seizure frequency and duration,the number of apoptotic hippocampal neurons,the levels of TNFα and IL6 in the hippocampal CA1 region,and the protein expression levels of BDNF,TrκB,and Bax in the hippocampal CA1 region(P<0.05) and significant reductions in the number of Tuj1positive cells and the protein expression level of Bcl-2 in the hippocampal CA1 region(P<0.05). Compared with the model group,the dexmedetomidine group had significant reductions in seizure frequency and duration,the number of apoptotic hippocampal neurons,the levels of TNF-α and IL6 in the hippocampal CA1 region,and the protein expression levels of BDNF,TrκB,and Bax in the hippocampal CA1 region(P<0.05) and significant increases in the number of Tuj1positive cells and the protein expression level of Bcl2 in the hippocampal CA1 region(P<0.05). LM22B10 could partially reverse the role of dexmedetomidine in improving various indicators of epileptic rats(P<0.05). Conclusion Dexmedetomidine can reduce seizure in epileptic rats,inhibit the apoptosis of hippocampal neurons,and alleviate inflammatory response in rats,possibly by inhibiting the activation of the BDNF/TkB signal pathway.
7.Echocardiographic evaluation of left ventricular diastolic function in patients with diastolic heart failure and comparative study of real‐time cardiac catheterization
Fen ZHANG ; Yi LIANG ; Liangjie XU ; Cuicui ZHOU ; Tingpan FAN ; Inxin X CHEN ; Weidong LI ; Wei YUAN ; Yang ZHAO ; Jingping SUN ; Jinchuan YAN
Chinese Journal of Ultrasonography 2019;28(3):218-223
Objective To evaluate the left ventricular diastolic function of patients with normal left ventricular ejection fraction ( LVEF) by echocardiography and real‐time cardiac catheter measurement ,and improve the accuracy and reliability of echocardiographic diagnosis . Methods One hundred and twenty patients with know n or suspected coronary artery disease w ho underwent coronary angiography and left ventricular catheterization were prospectively selected from July 2017 to January 2018 in the Affiliated Hospital of Jiangsu University . According to the left ventricular end diastolic pressure ( LVEDP) real‐time measurement ,the patients were divided into groups of LVEDP ≤15 mm Hg ( 43 cases ) and LVEDP > 15 mm Hg ( 77 cases) . General data were compared and the difference of echocardiographic parameters between the two groups were analyzed ,and the ROC curve of each echocardiographic parameter for diagnosing LVEDP was draw n . Results T he parameters including flow propagation velocity ( VP) ,the ratio of filling fraction of E and A ( E/A) ,early diastolic filling deceleration time ( DT ) ,the duration of mitral A ( A‐dur ,) mitral annulus velocity at the septal side ( e′sep) ,systolic pulmonary venous flow velocity ( PVs) ,diastolic pulmonary venous flow velocity ( PVd ) and PVs/PVd were used to the diagnosis of the increasing of LVEDP ,however their accuracies were low ( AUC between 0 .5~0 .7) . T he parameters including left atrial volume index ( LAVI ) , tricuspid regurgitation ( T Rmax ) ,mitral annulus velocity in lateral wall of left ventricle ( e′lat ) ,average e′,E/e′sep ,E/e′lat ,average E/e′,velocity of pulmonary vein atrial reversal ( PVa) ,pulmonary vein atrial reversal duration ( Pva‐dur) ,the difference between the duration of pulmonary venous A wave and mitral A wave( PvaD‐AD) were also used to the diagnosis of the increasing of LVEDP , but their accuracies were still poor ( AUC between 0 .7~0 .9 ) . According to the real‐time left ventricular pressure measurement and different parameters of echocardiography ,the multivariate regression equation :LVEDP= 0 .292 LAVI + 0 .35 PVa + 0 .04 T Rmax + 0 .075 ( PvaD‐AD ) -0 .109 PVs -6 .773 was put forward as a correction standard ,the accuracy of the diagnosis of LVEDP was significantly improved ( AUC =0 .922) . Conclusions T he assessment of left ventricular diastolic function needs to be performed comprehensively with multiple parameters . T he multiple regression equation can accurately evaluate left ventricular diastolic function in patients with normal LVEF .
8.Apoptosis-inducing activity of synthetic hydrocarbon-stapled peptides in H358 cancer cells expressing KRAS
Cuicui LI ; Ni ZHAO ; Luyan AN ; Zhen DAI ; Xiaoyi CHEN ; Fan YANG ; Qidong YOU ; Bin DI ; Chi HU ; Lili XU
Acta Pharmaceutica Sinica B 2021;11(9):2670-2684
Lung cancers are the leading cause of cancer deaths worldwide and pose a grave threat to human life and health. Non-small cell lung cancer (NSCLC) is the most frequent malignancy occupying 80% of all lung cancer subtypes. Except for other mutations (