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.

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.

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.

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.

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.

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.

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.

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.

Objective To observe the effects of differentiation of mature islet cells of mice on marrowmesenchymal stem cells (mMSCs). To provide transplant source for islet cell transplantation in the treatment of diabetes. Methods The culture, isolation and passage of mMSCs was performed by using patch wall, cell shape was observed by confocal microscope, and flow cytometry analysis was used to determine their biological characteristics. The type Ⅳ collagenase was injected into common bile duct to digest the pancreas, and then gradient centrifugation was used to isolate islet cells. The transwell co-culture system was used for third generation of mMSCs and isolated islet cells, then inversion microscope was used to observe the cell growth and morphological changes, immunochemistry methods was applied to detect the expression of insulin in mMSCs, and insulin release test was performed to determine the secretion of insulin. The control group consisted of cultured mMSCs alone. Results The cells from mouse bone marrow were found to be in long spindle shape with large volume after 48 hours in culture. One week later the cells grew in the form of colony with serial subcultivation. The cell surface molecules including Sca-l, CD29, CD44, CD105 were positive with high level of expression;while the cell surface molecules including CD34, CD45 were negative, all of these results confirmed that the ceils were mMSCs. After 7 days of coculture with mice islet cells, part of mMSCs cells were positively stained by insulin immunohistochemisty, the insulin secretion was (16.83±0. 15)μIU/ml.Conclusions After cocultured with islet cells, mMSCs isolated from mouse bone marrow could differentiate into islet like cells. These cells may be used in the islet cells transplantation in the treatment of diabetes, which provided a solution to the problems of donor-shortage and immunologic rejection.

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.