1.The development of anti-HIV-1 drugs.
Acta Pharmaceutica Sinica 2010;45(2):165-76
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS). After over 26 years of efforts, there is still not a therapeutic cure or an effective vaccine against HIV/AIDS. The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART). Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients, the huge burden of ART in developing countries, together with the increasing incidence of drug resistant viruses among treated people, calls for continuous efforts for the development of anti-HIV-1 drugs. Currently, four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including: reverse transcriptase inhibitors (RTIs) (e.g. nucleoside reverse transcriptase inhibitors, NRTIs; and non-nucleoside reverse transcriptase inhibitors, NNRTIs), protease inhibitors (PIs), integrase inhibitors and entry inhibitors (e.g. fusion inhibitors and CCR5 antagonists). Here, we intend to provide updated information of currently available antiretroviral drugs for ART to promote the development of novel anti-HIV-1 drugs.
2.Dynamin-related protein 1-mediated mitochondrial fission and cerebral ischemia
Zhiwei LU ; Xinyong ZHU ; En XU
International Journal of Cerebrovascular Diseases 2015;23(4):306-310
Dynamin-related protein 1 (Drpl) is a major protein for regulating mitochondrial fission.Its activity is associated with the post-translational modification,mainly including phosphorylation,ubiquitination,sumoylation,and S-nitrosylation.During the cerebral ischemia,Drpl is activated and translocates from the cytoplasm to the mitochondrial outer membrane,mediates mitochondrial fission and eliminates damaged mitochondria.Drpl plays the important roles in the pathological processes of ischemic neuronal apoptosis,necrotic apoptosis,and mitophagy.Excessive mitochondria fission or accumulation of damaged mitochondria will aggravate neuronal injury.
3.A clinical analysis of 9 cases of pulmonary alveolar proteinosis with secondary infection
Hui HUANG ; Zhiwei LU ; Zuojun XU
Chinese Journal of Internal Medicine 2011;50(3):216-220
Objective To describe the clinical characteristics of 9 cases of idiopathic pulmonary alveolar proteinosis (iPAP) with secondary infections. Method The clinical and radiological data of 9 patients with iPAP and secondary infections admitted into Peking Union Medical College Hospital from 1 st January 1990 to 1st January 2010 were retrospectively analyzed. Results In that period, there were 97 patients of iPAP were admitted in our hospital. There were 9 patients of iPAP with secondary infections,aged (46.4±14.6)y. There were 5 males and 4 females. Among them, 6 patients were misdiagnosed as interstitial pneumonia and corticosteroids were given to them. When the infection appeared, corticosteroids were still given to 3 patients, and the other 3 patients had stopped corticosteroids for 3 to 15 and a half months. Five patients had accepted mono-lung or whole lung lavage before 1,2, 9, 14,24 months. The clinical manifestations were fever(8 cases) ,cough(9 cases) , expectoration(8 cases) ,hemoptysis(2 cases),chest pain(1 case) and moist rales(1 case). Glass-ground opacities (9 cases) and cavitations(4 case)were the main manifestations of chest radiology. Pleural effusions(1 case) was not common. The locations of infection was limited in chest:9 cases had pulmonary infection and one case was associated with pleurisy.The infectious pathogens were the acid-fast tubercle bacillus (4 cases), fungus (3 cases, candida albicans,penicillium and aspergillus fumigatus for each one) and norcardia (2 cases, one case was associated with cytomegalovirus infection). Follow-up: 6 patients were cured, 1 patient was improved and 2 patients were died. Conclusions For patients with iPAP, especially when they had been receiving corticosteroids, if they had fever and/or recently exaggerated dyspnea, especially whose chest radiology showed nodules and cavitations, the clinicians should be aware of infections diseases for them. Further specific microbiological studies and sufficient therapy should be obtained as quickly as possible.
4.Multiple-factor analysis of acute exacerbation of chronic obstructive pulmonary diseases short-tern origbisus.
Zhiwei LU ; Wei WANG ; Renhe XU ;
Chinese Journal of Practical Internal Medicine 2006;0(S2):-
Objective To guide the treatment of acute exacerbation of chronic obstructive puhnonary diseases (AECO- PD) through studing the principally related factors of AECOPD.Methods 190 AECOPD patients were investigated through retrospective study.First,we studied the thirty-two possible factors with single-factor analysis,then procee- ded to perform multiple-factor analysis with Logistic regression among the factors which P value was below 0.2 in single -factor analysis,and analyzed the principally related factors with two-factor correlation.Results According to Mul- tiple-factor analysis with Logistic regression analysis,there were eight factors that showed significance,which were us- age of respiratory excitant,LBC,usage of antioxidant,heart failure,Cr,selection of antibiotics respectively,WBC and Hb.Correlative analysis of the principally related factors showed no correlation between WBC and LBC.Conclusion The principally related factors of AECOPD prognosis were their recited in results.
5.The comparison of different methods for treating aerobic vaginitis and clinical effect of mixed infection
Li DONG ; Zhiwei SHOU ; Mengqi LU ; Xiaohong YAO ; Huaping HUANG
Chinese Journal of Primary Medicine and Pharmacy 2016;23(10):1493-1496
Objective To compare the different methods for treating aerobic vaginitis and mixed clinical effects of infection.Methods A randomized controlled method was used,298 cases of aerobic vaginitis and mixed infections were randomly divided into control group(149 cases):the use of combination anti -infective therapy,the treatment group(149 cases):the use of combination anti -infective at the same treatment plus lactobacillus vaginal medication.And the therapeutic effect was evaluated.Results The difference of the clinical efficacy of aerobic vagi-nitis treatment of mixed infections was not statistically significant (total effective rate of 95.3% in the treatment group,92.6% in the control group).With the time of treatment extended,the effective rate increased,the use of com-bination anti -infective therapy at the same time plus lactobacillus vaginal administration group of aerobic bacteria vaginosis and recurrence rate was significantly reduced in patients with mixed infection (recurrence rate was 6.0% in the treatment group and 12.8% was in the control group,χ2 =3.941 3,P <0.05).Conclusion The combination of anti -infective therapy at the same time plus lactobacillus vaginal drug treatment aerobic mixed infections and vagini-tis has slightly higher effective rate than the use of combination anti -infective treatment,the former relapse rate was significantly reduced.
6.Quantitative assessment of iron load in myocardial overload rabbit model: preliminary study of MRI T2* map
Lu HUANG ; Rui HAN ; Zhiwei LI ; Sishu YUAN ; Liming XIA
Chinese Journal of Radiology 2014;48(3):236-240
Objective To preliminarily investigate the feasibility of MRI-T2* map in evaluating myocardial iron load of myocardial iron overload rabbit models.Methods Eleven rabbits were included in this study and divided into two groups,myocardial iron overload group (n =10) and the control group (n =1).Iron dextrin (dose of 50 mg/kg) was injected in muscles of thigh once a week,totally 12 weeks.Serum iron test and MRI examination were performed before iron injection,and 1 week to 12 weeks after iron injection.MRI scan protocol included short axial T2* map of the left ventricle and cross-section T2* map of the liver.T2* and R2* of the heart and the liver were measured.One rabbit was killed after MRI examination at pre-iron injection,1 week to 8 weeks,11 weeks and 12 weeks after iron injection,respectively.Heart and liver were avulsed to undergo in vitro MRI scan and then paraffin embedded for pathological slices.MRI scan protocol and measurements of the heart and the liver samples were the same to that of in vivo ones.Pearson correlation was used to calculate the relationships between the parameters.Results Myocardial T2* [(32.5 ± 8.3 ms)] and R2* values [(38.4 ± 7.9) Hz] had significant correlation with injecting iron content(1 033.2 ± 673.4 mg),the Pearson coefficients were-0.799 (P =0.001) and 0.770 (P =0.002),respectively.Myocardial T2 had no significant correlation with liver T2* values (r =0.556,P =0.070).T2* values of heart and liver in vivo [(32.5 ± 8.3) ms and (8.8 ± 5.4) ms],respectively had strong correlation with those in vitro [(19.4 ± 6.5) ms and (9.8 ± 5.0) ms],respectively (r =0.757,P =0.007 and r=0.861,P=0.001).T2* and R2* values of the heart and the liver in vivo and in vitro had no significant correlations with serum iron (P > 0.05).On Prussian blue staining slices,blue particles of myocardium,sinus hepaticus and hepatocyte increased with injecting iron content.Conclusions It is feasible for MRI-T2* map to evaluate the myocardial iron load noninvasively.It may provide reliable information for detecting myocardial iron overload in patients with iron overload at an early stage.
7.Anticancer function of Shp2 in lung adenocarcinoma A549 cells and rela-ted molecular mechanisms
Zhiwei LU ; Yusheng CHENG ; Chunyang ZHAO ; Hanli WANG
Chinese Journal of Pathophysiology 2016;32(9):1589-1593
AIM: To explore the anticancer function of Shp2 in lung adenocarcinoma A549 cells and the related molecular mechanisms.METHODS: The viability and proliferation of A549 cells treated with Shp2 specific inhibi-tor Phps-1 or cisplatin (DDP) were measured by CCK-8 assay and EdU assay.Annexin V-FITC/PI double staining was ap-plied to detect apoptotic rate of A549 cells with different interventions.The protein levels of caspase-3-17p, Bcl-2, Bax, p-STAT3 /STAT3 and p-ERK/ERK were determined by Western blot.RESULTS: Compared with control group, Phps-1 at the concentration of 20 μmol/L significantly increased the viability of A549 cells after 24 h of treatment ( P <0.05). Meanwhile, the proliferation rate of A549 cells in Phps-1 20 μmol/L group was significant increased compared with control group (P <0.05).The apoptotic rate of A549 cells in DDP treatment group decreased from 13.01% ±2.62% to 3.67%±0.93% after adding Phps-1 (P <0.05).Phps-1 down-regulated the protein levels of caspase-3-17p, Bax and p-ERK, but up-regulated p-STAT3.CONCLUSION: Shp2 is a tumor suppressor in A549 cells, which may be associated with the activation of STAT3 signal pathway.
8.Bioinformatic analysis of antibody repertoire development in response to influenza vaccination
Lu ZHANG ; Qingchen ZHANG ; Tianyi QIU ; Zhiwei CAO ; Kailin TANG
Chinese Journal of Microbiology and Immunology 2017;37(2):133-139
Objective To analyze the immunogenomic characteristics of antibody repertoire in re-sponse to influenza vaccine in order to provide a theoretical basis for further development of antibody. Meth-ods Based on a time-series immunoglobulin heavy chain ( IGH) repertoire sequencing dataset, we analyzed the immunogenomic characteristics of antibody repertoire in response to trivalent influenza vaccine ( TIV ) from three aspects which included the features in complementarity-determining region 3 ( CDR3 ) , antibody mutation and VDJ usage. Results The frequency of antibody mutation increased significantly upon vaccina-tion. Analysis of the CDR3 region indicated that polar and aromatic amino acids had a higher preference. The length of CDR3 region in naive B cells followed a normal distribution, while specific CDR3 sequences with 15 to 18 amino acids in length occupied a dominant position after vaccination. In addition, the VDJ us-age altered obviously and IGHV3-7-derived antibody had a significant response to the vaccine. Response in-tensity reached the peak on day 7 and gradually weakened over time. Conclusion Antibody repertoire evolves dynamically to express specific antibody upon vaccination and the characteristics of immune responses at sequence level could be used to evaluate their effectiveness.
9.SolitaireAB stent-assisted endovascular embolization of intracranial wide-necked aneurysms:a clinical ;follow-up study
Zhiwei HUANG ; Xuedong LI ; Jun QING ; Jianwu LU ; Heqing HUANG
Journal of Interventional Radiology 2015;(4):282-286
Objective To investigate the mid-term effect of SolitaireAB stent-assisted interventional embolization with spring coils for the treatment of intracranial wide-necked aneurysms. Methods During the period from May 2009 to April 2013, a total of 49 patients with intracranial wide-necked aneurysm (49 aneurysms in total) received SolitaireAB stent-assisted interventional embolization treatment at authors’ hospital. In 41 patients, a total of 41 aneurysms were detected, of which ruptured aneurysm with bleeding was confirmed in 26 and un-ruptured aneurysm in 15. These 41 patients were followed up for 12-48 months. Based on modified Rankin scoring and DSA, CTA or MRA manifestations, the clinical results were evaluated. Results After the embolization treatment, re-bleeding of the aneurysm occurred in 2 cases, cerebral infarction in 3 cases, occlusion of the parent artery in one case and death in one case; the occurrence rate of complications was 14.2%. DSA, MRA or CTA performed at 12 months after the embolization treatment, showed that 32 aneurysms (78.0%) were completely obstructed, which was obviously higher than that observed on DSA performed immediately after the embolization procedure (21 aneurysms, 42.9%), the difference was statistically significant (P=0.02);residue of aneurismal neck was seen in 7 cases (17.1%) and partial occlusion in 2 cases (4.9%), which were much better than those observed on DSA that was performed immediately after the embolization procedure. Twenty-four aneurysms (58.5%) remained stable, showing no any change, and recurrence of aneurysm was observed in 4 cases (9.7%). At the last follow-up exam, the modified Rankin scoring showed that 0 point was seen in 18 cases (43.9%), one point in 10 cases (24.4%), 2 points in 5 cases (12.2%), 3 points in 4 cases (9.8%), 4 points in 2 cases (4.85%) and 5 points in 2 cases (4.85%). The self-care rate for daily activities was 80.5%, the prognosis was good. Conclusion For the treatment of intracranial wide-necked aneurysms, SolitaireAB stent-assisted interventional embolization with spring coils is safe and effective. This technique can improve the embolization rate and reduce the procedure-related complications.
10.Nuss procedure for recurrent and acquired pectus excavatum after open thoracic surgery
Yanan LU ; Jinfen LIU ; Zhiwei XU ; Zhaokang SU ; Wenxiang DING
Chinese Journal of Thoracic and Cardiovascular Surgery 2011;27(11):651-653
Objective To summarize the experiences with minimally invasive pectus repair (Nuss procedure) for recurrent and acquired pectus excavatum after open thoracic surgery.Methods From Jun 2004 to Sep 2011,eighteen patients with recurrent or acquired pectus excavatum underwent Nuss procedure,including 12 males and 6 females The age ranged from 3.1to 14.8 years with mean age of (8.8 ±4.0) years.The body weight was 11 to 55kg with mean weight of (30.2 ±14.8 ) kg.Ten cases were recurrent pectus excavatum with previously failed open surgery repair,eight were acquired pectus excavatum after other open thoracic surgery.Sixteen cases had symmetrical and 2 had asymmetrical pectus excavatum.Haller' s index was 5.4 ± 3.4.The operation was performed with thoracoscopic assistance.Results All patients had successful operation with one bar insertion in each patient,one stabilizer was put on right side in seventeen and double stabilizers were put in one case.Therapeutic results evaluation was excellent in 16 cases and good in 2.Percentage of excellent and good was the same with that in our primary Nuss procedure ( P > 0.05 ).Chest drainage duration was 1 to 4 days.One case had bar displacement revision 5 months later.Heart perforation occurred in one on whom a sternotomy and perforation repair were immediately performed.The echocardiography exam shows normal cardiac function after operation,and no nerve system complications were detected.One developed pneumothorax on operative day and one had pleural effusion three days later,both were treated by chest tube drainage.Twelve patients' bars were removed after 24 - 45 months of stagnation period.Anatomic results at bar removal were 10 excellent and 2 good,there were no recurrent cases.Conclusion Nuss procedure is an effective method and has good results on recurrent and acquired pectus excavatum.Safety of patients and complications minimization is always the first to be considered.