HIV-1 integrase enzyme is a 32kDa protein encoded by HIV pol gene. It is responsible for integration of viral cDNA into host chromosomal DNA, which is indispensable for HIV replication.Since there was no functional equivalent for this enzyme in human cells, inhibition of integrase will bring little side effect to human body. Thus HIV integrase has become an attractive and rational target for therapy of AIDS after reverse transcriptase and protease.The Recent research on HIV-1integrase structure,inhibitors and new therapeutic method target at HIV integrase was reviewed.

Objective To investigate the prognostic value of interim and post-therapy 18F-FDG PET-CT in patients with peripheral T-cell lymphoma.Methods A retrospective analysis was conducted on data from 44 patients with newly diagnosed peripheral T-cell lymphoma who underwent interim (after 3 cycles of chemotherapy,27 cases) or posttherapy PET-CT (after the completion of first-line therapy,35 cases).Interim and posttherapy PET-CT status (positive vs negative) was visually interpreted according to criteria of the International Harmonization Project,and PET-CT status was assessed for its ability to predict progression-free survival (PFS) and overall survival (OS).Results Interim 18F-FDG PET-CT results were positive in 16 cases and negative in 11 cases.The median PFS and OS in the patients with positive results were 8 months and 14 months,respectively,while those in patients with negative results were 30 months and 39 months,respectively.The 2-year PFS and 3-year OS rates in patients with positive results at interim PET-CT were 18.8 ％ (3/16) and 12.5 ％ (2/16),respectively,while those in patients with negative results were 90.0 ％ (10/11) and 63.6 ％ (7/11),respectively (x2 =13.092,P =0.000; x2 =7.386,P =0.007,respectively).Posttherapy 18F-FDG PET-CT results were positive in 14 cases and negative in 21 cases.The median PFS and OS in patients with positive results were 10 months and 22 months,respectively,while those in patients with negative results were 26 months and 38 months,respectively.The 2-year PFS and 3-year OS rates in patients with positive results at posttherapy PET-CT were 7.1％ (1/14) and 14.3 ％ (2/14),respectively,while those in patients with negative results were 76.2 ％ (16/21) and 57.1％ (12/21),respectively (x2 =15.574,P =0.000;x2 =6.245,P =0.012,respectively).Conclusion Both interim PET-CT status and posttherapy PET-CT status have significant value in monitoring response to therapy and predicting prognosis for patients with peripheral T-cell lymphoma.

OBJECTIVETo clone and produce ribosome inactivating protein MAP30 from the seeds of Momordica charantia L(bitter melon), and to evaluate the biological activity of the recombinant protein.

METHODSThe DNA sequence encoding MAP30 was cloned from the fresh seeds of Momordica charantia by PCR, the target DNA fragments were sequenced after T-A cloning. The expression plasmid was constructed by inserting the MAP30 fragment into vector pET30a. MAP30 was expressed in E.coli by addition of IPTG into final concentration of 1.0 mmol/L. The recombinant MAP30 was identified by SDS-PAGE, and the biological activity of MAP30 protein was evaluated by using MTT assay in cancer cells and normal cells following fluid-phase endocytosis.

RESULTThe nucleotide and amino acid sequences of the cloned MAP30 were identical with those of reported MAP30. The solubility of recombinant protein was analyzed by SDS-PAGE, and the MAP30 was mainly produced in soluble form. The recombinant MAP30 showed a greater cytotoxicity to cancer cells than that to normal cells.

CONCLUSIONThe gene of MAP30 has been successfully cloned.The recombinant MAP30 protein expressed by E.coli is bioactive.

Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Gene Expression ; Genetic Vectors ; Momordica charantia ; chemistry ; Recombinant Proteins ; biosynthesis ; genetics ; metabolism ; Ribosome Inactivating Proteins, Type 2 ; biosynthesis ; genetics ; metabolism ; Seeds ; chemistry ; Transformation, Bacterial

Human epidermal growth factor receptor 2 (HER2) belongs to the transmembrane glycoprotein receptor family. Overexpression of HER2 could directly lead to tumorigenesis and metastasis. This phenomenon could be observed in the breast cancer, ovarian cancer, gastric cancer, lung cancer and prostate cancer. Compared with the conventional chemotherapy, the targeted treatment of antibody is more specific and has lower side effects. This review describes the current status of monotherapy and combination therapies of anti-HER2 antibodies, trastuzumab and pertuzumab, with chemotherapeutic drugs. The development trends of new formats of anti-HER2 antibody drugs such as bispecific antibody, immunotoxin are also discussed.
Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Drug Delivery Systems ; Humans ; Immunoconjugates ; therapeutic use ; Immunotoxins ; therapeutic use ; Neoplasms ; metabolism ; therapy ; Receptor, ErbB-2 ; antagonists & inhibitors ; metabolism ; Trastuzumab

Monoclonal antibody-targeted therapy has been a hot spot in current clinical cancer treatment. As current antibody drugs have large molecule sizes leading to poor tissue penetration, and high dosage in clinical application leading to high cost, to overcome the problems, the development of new antibody drugs with miniaturization and high potency has become a new trend. In recent years, the conjugates of monoclonal antibodies and cytotoxins, called antibody-drug conjugates (ADCs), have entered the arsenal of anti-cancer drugs, becoming a new format of antibody drugs and attracting extensive attentions. The ADC molecule usually consists of antibody, linker and effector molecule. According to different effector molecules, ADCs can be divided into three categories as chemo-conjugates, immunotoxins and radio-conjugates. When ADC molecules are internalized into cancer cells, cytotoxins will be released by chemical, enzyme degradation or by action of lysosomal proteases, then kill targeted cells by inhibiting protein synthesis, depolymerizing microtubules or breaking double-strand DNA. Recently, two ADC drugs have been approved by the US FDA and more ADC drug candidates are in clinical phase II or III trials which show significantly clinical effects and attracting much attention and competition of pharmaceutical enterprises. In this review, antibody conjugates in the past and present will be summarized and the future development trends and challenges of this type of antibody drugs will be discussed.
Antigens, CD ; metabolism ; Hematologic Neoplasms ; metabolism ; therapy ; Humans ; Immunoconjugates ; chemistry ; therapeutic use ; Immunotherapy ; methods ; Immunotoxins ; chemistry ; therapeutic use ; Radioimmunotherapy ; methods

OBJECTIVESTo study the revascularization techniques in the treatment of intracranial complex aneurysms and occlusive reasons of bypass vessel.

METHODSThe 20 complex intracranial aneurysms who underwent saphenous bypass treatment from November 2006 to November 2008 were retrospectively analyzed and the occlusive reasons were studied. Of the 20 patients, 12 were female and 8 were male, mean age was 54.5 years (ranged 27 - 65 years). The distribution of the lesions included 13 cavernous sinus aneurysms, 4 para-clinoid aneurysms, 2 supraclinoid aneurysms, and 1 basilar trunk aneurysm. Four aneurysms were giant (diameter > 25 mm), 12 aneurysms were large (15 - 25 mm), and 4 aneurysms were medium (10 - 15 mm) size.

RESULTSOne saphenous vein was occluded intraoperatively and one saphenous vein was occluded postoperatively. At discharge, 18 out of the 20 patients had Glasgow Outcome Scale (GOS) score of 4 or 5, 2 patients had score of 3, and 1 patient had score of 1. At 6 months follow up, 18 of 19 survivors had GOS score of 4 or 5 and 1 patient had score of 3.

CONCLUSIONSExtracranial-intracranial revascularization technique is a safe and effective method in the treatment of complex aneurysms. Mechanical and hemodynamic factors are two leading reasons for occlusion of bypass vessels. Long-term bypass vessels patent rate still needs further observation.

Adult ; Aged ; Cerebral Revascularization ; methods ; Female ; Follow-Up Studies ; Graft Occlusion, Vascular ; etiology ; prevention & control ; Humans ; Intracranial Aneurysm ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Saphenous Vein ; surgery ; Treatment Outcome

Objective To study the clinical manifestations, radiological features, andpostoperative outcomes of patients with subependymal giant cell astrocytoma (SEGA). Methods Aretrospective analysis of the clinical presentations, imaging examinations, pathological features,treatments and follow-up results was conducted in 6 SEGA cases treated in our department from 2000 to2007. Results The most common clinical maifestations of SEGA included increased intracranialpressure and impaired visual acuity. CT scan of the tumors displayed isodensity or slightly increaseddensity with well defined border. Calcification was seen in some of the tumors. On T1-weighted magneticresonance images, the tumor masses presented with isointense or mixed signals, while on T2-weightedimages, the tumors exhibited isointense or hyperintense signals. The solid part of the tumor showedheterogeneous enhancement in contrast-enhanced imaging. No operative death occurred in these casesafter total removal of the tumors through a transcallosal approach (4 cases) or a frontal transcorticalapproach (2 cases). No postoperative tumor recurrence was found in the follow-up for 10 months to 8years. Conclusion The diagnosis of SGCA should be considered for the presence of tuberous sclerosisin the subependymal lesion adjacent to the foramen of Monro in cases presenting hydrocephalus orprogressive tumor growth. Surgical resection of the tumor should be performed as early as possible.SGCA is a benign tumor with good prognosis after a total resection. Regular follow-up examinationshould be undertaken to monitor the subependymal nodules for prevention of tumor recurrence.

OBJECTIVETo clinically study the antiviral effects of lamivudine and entecavir on patients with early-to-mid stage Hepatitis B related acute on chronic liver failure (HBV-ACLF). METHODS; A prospective, randomized, open and parallel controlled clinical trial was designed to observe the antiviral effects of nucleoside analogues on patients with early-to-mid stage HBV-ACLF. Three groups were set for controlled study, i. e. basic treatment group, lamivudine plus basic treatment group and entecavir plus basic treatment group.

RESULTSOne month after treatment, the improvement rates of lamivudine group and entecavir group were 58.85% and 59.15% respectively, significantly higher than that of basic treatment group which was 34.84% (Chi(2) = 9.8323, P = 0.043). By the end of six months, the cumulative survival rates of patients with the antiviral treatments, i.e., lamivudine, entecavir, were 65.8%, 60.1%, significantly higher than that (42%) without the antiviral treatment (P = 0.045, P = 0.04 respectively). The cumulative survival rate in patients with a MELD score < 30 was higher than that with a MELD score over 30 (Chi(2) = 3.920, P = 0.048). For the patients with pretreatment HBV DNA > or = 10(7), the cumulative survival rate in patients with entecavir treatments group was higher than that of patients in basic treatment group (Chi(2) = 5. 014 P= 0.025). According to the Ordinal Regression analysis, antiviral therapy by using either lamivudine or entecavia could significantly increase the improvement rate of patients with early-to-mid stage HBV-ACLF. But severe complications, including hepatorenal syndrome, electrolyte imbalance and hepatic encephalopathy, medical history of liver cirrhosis, and pretreatment HBV DNA > or = 10(7) had significant impacts on prognosis of this group patients.

CONCLUSIONSAntiviral therapy by using either lamivudine or entecavia could significantly increase the survival rate of patients with early-to-mid stage HBV-ACLF.

Anti-HIV Agents ; adverse effects ; therapeutic use ; Disease Susceptibility ; End Stage Liver Disease ; chemically induced ; Guanine ; adverse effects ; analogs & derivatives ; therapeutic use ; Humans ; Lamivudine ; adverse effects ; therapeutic use ; Prognosis

BACKGROUNDAcute-on-chronic hepatitis B liver failure (ACLF-HBV) is a clinically severe disease associated with major life-threatening complications including hepatic encephalopathy and hepatorenal syndrome. The aim of this study was to evaluate the short-term prognostic predictability of the model for end-stage liver disease (MELD), MELD-based indices, and their dynamic changes in patients with ACLF-HBV, and to establish a new model for predicting the prognosis of ACLF-HBV.

METHODSA total of 172 patients with ACLF-HBV who stayed in the hospital for more than 2 weeks were retrospectively recruited. The predictive accuracy of MELD, MELD-based indices, and their dynamic change (D) were compared using the area under the receiver operating characteristic curve method. The associations between mortality and patient characteristics were studied by univariate and multivariate analyses.

RESULTSThe 3-month mortality was 43.6%. The largest concordance (c) statistic predicting 3-month mortality was the MELD score at the end of 2 weeks of admission (0.8), followed by the MELD: sodium ratio (MESO) (0.796) and integrated MELD (iMELD) (0.758) scores, DMELD (0.752), DMESO (0.729), and MELD plus sodium (MELD-Na) (0.728) scores. In multivariate Logistic regression analysis, the independent factors predicting prognosis were hepatic encephalopathy (OR = 3.466), serum creatinine, international normalized ratio (INR), and total bilirubin at the end of 2 weeks of admission (OR = 10.302, 6.063, 5.208, respectively), and cholinesterase on admission (OR = 0.255). This regression model had a greater prognostic value (c = 0.85, 95%CI 0.791 - 0.909) compared to the MELD score at the end of 2 weeks of admission (Z = 4.9851, P = 0.0256).

CONCLUSIONSMELD score at the end of 2 weeks of admission is a useful predictor for 3-month mortality in ACLF-HBV patients. Hepatic encephalopathy, serum creatinine, international normalized ratio, and total bilirubin at the end of 2 weeks of admission and cholinesterase on admission are independent predictors of 3-month mortality.

Adult ; Female ; Hepatitis B, Chronic ; pathology ; physiopathology ; Humans ; Liver Failure ; pathology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Models, Theoretical

OBJECTIVETo investigate the prevalence and epidemiologic characteristics of seronegative spondyloarthritis (SpAs) in Chinese army force in different areas.

METHODS4-phase survey was conducted in 21 750 Chinese army, including: face-to-face interviews with standardized COPCORD questionnaires (Phase I screening); further examination on the suspected cases; identification of inflammatory joint and spinal diseases (Phase II); identification of SpAs (AS and uSpA) by more than two experienced specialists in rheumatology; further examination with X-rays and laboratory detection of HLA-B27 (Phase III); and data analysis (Phase IV).

RESULTSAmong 21 750 army men, 21 cases of RA, 106 cases of SpAs were identified, with prevalence rates of 0.966 per thousand, 4.87 per thousand respectively. In 106 cases of SpAs, there were 46 cases of ankylosing spondylitis (AS), 52 cases of undifferentiated SpAs (uSpAs) with the prevalence rates of 2.11 per thousand and 2.39 per thousand respectively. Few cases of reactive arthritis (ReA) and Reiter's syndrome (RS) were identified (6 and 1 cases respectively). The prevalence of AS, uSpAs were higher in navy than that in the ground force or the air force. Soldiers in cold and damp areas had higher prevalence rates than that in the plain and drought areas.

CONCLUSIONThe prevalence of SpA (especially AS and uSpA) in Chinese army force was similar to that in the civilians. SpA (AS and uSpA) was more prevalent seen in the Navy. The incidence of SpA (AS and uSpA) was influenced by environmental factors such as coldness and dampness.

Adult ; China ; epidemiology ; Humans ; Lumbar Vertebrae ; Male ; Military Personnel ; Prevalence ; Sacrum ; Spondylarthritis ; epidemiology ; etiology