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.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.
3.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.
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.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.
6.Morphological patterns and surgical treatment of pulmonary vein stenosis after total anomalous pulmonary venous connection repair
Zhongqun ZHU ; Haibo ZHANG ; Zhiwei XU ; Zhaohui LU ; Jinfen LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2012;28(9):522-525
Objective Postoperative pulmonary vein stenosis(PPVS) is a severe complication after total anomalous pulmonary venous connection (TAPVC) repair,and represents a significant surgical challenge with a high recurrence rate and poor prognosis.This study was performed to analysis the morphological patterns of pulmonary vein stenosis after TAPVC,and to demonstrate the relationships between the pathological patterns with their clinical manifestations,pathogenesis,surgical options and their prognosis.Methods Between March,2004 to September,2011,11 consecutive patients with PPVS underwent reoperations.Supracardiac type in 5 cases,intracardiac type in 3 cases,mixed type in 1 case,single ventricle associated with supracardiac type in 1 case and infracardiac type in 1 cases.The age was 23 days to 28 months,body weight at the first operation was 5-19 kg,the median weight (10.7 ± 5.1) kg.The age at reoperation was 4 months to 6 years,the interval between the first and second operation was 82 days to 5 years.Morphological patterns of PPVS was classified into 4 types based on the preoperative imaging examinations and surgical findings:(1) anastomic stenosis (type Ⅰ),(2) ostial stenosis of individual pulmonary vein (type Ⅱ),(3) segemental stenosis of individual pulmonary vein (type Ⅲ),(4) complete occulsion of individual pulmonary vein (type Ⅳ).One or more pathological patterns may exit in one patient,and may involved one or more individual pulmonary veins.Fibrous resection in 1 case,patch augmentation in 3 cases,individual pulmonary endarterectomy in 7 cases and sutureless technique in 5 cases.Cardiopulmonary bypass with moderate hypothermia were used in 8 cases,with deep hypothermia and circulatory arrest in 3 cases.Results Type Ⅰ in 2 cases,type Ⅱ in 2 cases,type Ⅰ and type Ⅱ in 1 cases,type Ⅰ,type Ⅱ and type Ⅲ in 1 case,type Ⅱ and Ⅲ in 2 cases,type Ⅱ and Ⅳ in 1 case and type Ⅳ in 2 cases were found in our series.There was no early mortality,I case with residual anastomic obstruction and 2 cases with individual pulmonary vein obstruction.One patient died 17 monthes after reoperation,and the intermediate mortality was 10%.Reoperation was done in 1 case for recurrent pulmonary vein obstruction.Two patients need ViagTa or Bosentan for long time.The others did well during follow-up.Conclusion PPVS is a kind of progressive disease.The morphological patterns of PPVS are related to their clinical presentations and its pathogenesis,and are very important to make surgical decisions and pridict the patient's prognosis.
7.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.
8.Neuoprotective effect of gradient perfusion-rewarming after deep hypothermia crculatory arrest
Zhaohui LU ; Wei WANG ; Zhiwei XU ; Deming ZHU
Chinese Journal of Thoracic and Cardiovascular Surgery 2012;28(1):38-41
ObjectiveTo evaluate the neuroprotective effect of gradient perfusion-rewarming after deep hypothermia circulatory arrest (DHCA) in piglets.Methods12 Shanghai piglets (3-4 weeks old) were randomly divided into two groups of A (experiment group) and B (control group),average weight (9.78 ±0.93)kg.Animal CPB model is completed with microinvasive technique.DHCA duration is 90 min in two groups.During the rewarming period,group A was rewarmed with gradient perfusion strategy,maintain the temperature for 15 min every 5 ℃ elevation of the core temperature.Group B was rewarmed according normal consistent rewarming strategy.PH-stat management is adopt in both groups.Blood gas analysis,rectal temperature,heart rate,ECG,blood flow rate of carotid artery,glumatic acid/aspartate level of jugular vein and protein NFB of brain tissue are monitored during and/or after the cardiopulmonary bypass (CPB).ResultsDuration of rewarming in group A is (67.3 ± 7.8) min,and (41.8 ± 3.6)min in group B (P < 0.05).Sample collected at the beginning of CPB,15 min of rewarming,30 min of rewarming and 45 min of rewarming show that there is no difference between the blood flow rate at 15 min of rewarming; difference are shown at the 30 min and 45 min of rewarming (P < 0.5 ).High performance liquid chromatography ( HPLC ) analysis show the obvious difference of glumatic acid level of jugular vein at 30 min of rewarming and 45 min of rewarming ( P < 0.5),this kind of difference of aspartate can only be seen at the 45 min of rewarming.Histologic evaluation shows gradient rewarming has a better effect on preservation of CA1 area neuron in hippocampus,however,Immunohistochemistry doesn't find the same effect.ConclusionControlled gradient perfusion-rewarming strategy can improve the neuroprotective effect during DHCA,keeping the balance of the blood flow,cerebral local temperature and brain metabolism might be the mechanism.
9.Aortoplasty with pulmonary autograft patch for coarctation of the aorta combined with hypoplastic aortic arch in infant
Yanan LU ; Jinfen LIU ; Zhiwei XU ; Zhaokang SU ; Wenxiang DING
Chinese Journal of Thoracic and Cardiovascular Surgery 2011;27(4):193-196
ObjectiveTo discuss the operative techniques and results of coarctation resection plus aortoplasty with pulmonary autograft patch for coarctation of the aorta combined with hypoplastic aortic arch in infant.MethodsBetween May 2007 and Dec 2009,14 cases including 9 males and 5 females with caorctation of the aorta and hypoplastic aortic arch underwent coarctation resection plus aortoplasty with pulmonary autograft patch in our hospital.The age ranged from 23 days to 17 months,with a median of 4.33 months.The mean body weight was (6.14 ±2.36) kg.All patients were diagnosed as aortic coarctation combined with VSD and hypoplastic aortic arch.The surgery was performed under deep hypothermia cardiopulmonary bypass with selective cerebral perfusion in 8 cases and circulation arrest in 6 cases.Fresh pulmonary autograft patch harvested from the main pulmonary artery was used for aortoplasty.The associated VSD was repaired in the same stage.ResultsAll patients survived except one died from circulatory failure during the perioperative period.Low cardiac output syndrome occurred in another case who was cured afterwards by correspondent treatments.No residual obstruction was detected by echocar-diography after the operation.Follow-up was carried out in 13 cases from 4 months to 3 years.Echocardiographic examination showed that the pressure gradient across the aortic arch was less than 16 mm Hg in all cases.The blood velocity at the descending aortic arch was not significantly changed during the follow-up period as compared with that of the immediate after operation.Computed tomography showed that the morphology of aortic arch was normal.The left bronchus compression was relieved obviously or totally disappeared in patients who suffered from left bronchus stenosis before operation,and no aortic aneurysm were detected in these patients.ConclusionConclusion Coarctation resection plus aortoplasty with pulmonary autograft patch is the optimal surgical method for treating coarctation of the aorta combined with hypoplastic aortic arch in infant.
10.A modification of surgical procedure for infracardiac total anomalous pulmonary venous connection
Zhiwei XU ; Shunmin WANG ; Zhaohui LU ; Zhaokang SU ; Wenxiang DING
Chinese Journal of Thoracic and Cardiovascular Surgery 2011;27(3):155-157
Objective Infracardiac total anomalous pulmonary venous connection, a rare congenital cardiac defect, is associated with high mortality. A modification was designed for the procedure to reduce the post-operative obstruction in the pulmonary venous. Methods From September 2005 to December 2007, seven patients with infracardiac total anomalous pulmonary venous connection were treated with repair surgery through right side approach. The patients' age at operation was (70.57 ±44.67) days , the weight was (4.07 ±0.87) kg. Three patients had pulmonary venous obstruction, and 2 with small PFO. A modified right - side approach for repairing this defect was used. Results No death occurred after the operation. The postoperative complications included low cardiac output in 5 patients (71.43%), pulmonary hypertension crisis in 3patients ( 42.86% ) , mechanical ventilation for more than 7 days, which happened in 2 patients (28.58%) and pulmonary infection. All of the patients received follow-up. No residual shunt and pulmonary venous return obstruction were identified on echocardiogram(with a velocity from 1.2 m/s to 1.47 m/s). The heart function of patients was within the normal range(EF 0.70 -0.79, FS 0.32 -0.44). Conclusion The modified surgical procedure for the correction of infracardiac total anomalous pulmonary venous connection by right side approach was associated with favorite clinical outcomes, The post-operative outcomes depended on the size of anastomosis between the common vein and left atrium and the patency of the pulmonary venous return. Adequate size of anastomosis and maintenance of the spatial structures in adjacent regions were helpful in decreasing the adverse effect of postoperative obstruction.