HIV-1 integrase (IN) is an essential enzyme for retroviral replication. There is no analogue for this enzyme in human cells so that inhibition of IN will not bring strong effect on human body. Thus, HIV-1 IN has become a rational target for therapy of AIDS. This review provides a comprehensive report of alpha, gamma-diketo IN inhibitors discovered in recent years. Compilation of such data will prove to be beneficial in developing QSAR, pharmacophore hypothesis generation and validation, virtual screening and synthesis of compounds with higher activity.
Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; HIV Integrase ; chemistry ; physiology ; HIV Integrase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; HIV-1 ; drug effects ; Humans ; Keto Acids ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Quantitative Structure-Activity Relationship

OBJECTIVETo evaluate the results of total knee arthroplasty (TKA) in patients with posttraumatic degenerative arthritis due to a previous fracture around the knee.

METHODSWe analyzed the results of 15 TKAs, performed from 1997 to 2003, in 15 patients with post-traumatic degenerative arthritis due to a previous fracture around knee. There were 3 women and 12 men with an average age of 58 years (range, 31-76 years). The time from fracture to arthroplasty averaged 8.2 years (range, 2-27 years). Internal fixation had previously been performed in 8 patients resulting in retained hardware. At the time of arthroplasty a femoral fracture malunion was present in two knees. Lateral retinacular release (4 knees), extensor mechanism realignment (1 knee) or medial collateral ligament reconstruction (1 knee) were needed at the time of arthroplasty.

RESULTSFollow-up averaged 35 months (range, 12-73 months). No patient was lost for follow-up. According to the Knee Society Score scale, the mean preoperative knee score was 37 (range, 10-70) and functional score was 41 (range, 0-60). They were improved significantly to a mean of 84 (range, 10-100) and 76 (range, 20-100) points, respectively at the latest follow-up. The mean knee arc of motion were improved from 84 degree preoperation to 94 degree at the latest follow-up. Postoperative manipulation under anesthesia for poor motion was carried out in 4 knees. No knee had aseptic loosening that required subsequent revision. Two knees developed superficial infection and were treated with debridement. It subsequently recovered with the retention of components.

CONCLUSIONSSignificant improvement in function and relief of pain has been achieved in patients with previous fractures undergoing subsequent TKA. However, this procedure is technically demanding and patients are at increased risk for restricted motion and need more care following TKA. This study suggests that the outcome of TKA may be improved further by making special efforts to restore limb alignment, to ensure correct component positioning, and to manage soft tissue balance.

Adult ; Aged ; Arthroplasty, Replacement, Knee ; adverse effects ; Female ; Humans ; Knee Injuries ; complications ; Male ; Middle Aged ; Osteoarthritis ; surgery

OBJECTIVETo evaluate the clinical and radiographic results of extensively porous-coated femoral stem in revision of total hip arthroplasty (THA).

METHODSFrom January 1999 to December 2003, fifteen hips of fifteen cases received revision of THA with extensively porous-coated femoral stem. There were six males and nine females. The average age was 66 years (ranging 58-82 years). The reason for the revision was aseptic loosening in 10 cases, septic loosening in 2, femoral shaft fracture around loose implant in 2, and femoral revision for malposition of the femoral component in 1. All the patients were clinically evaluated using Harris hip score and radiographically evaluated both preoperatively and postoperatively at regular follow-up intervals.

RESULTSNo patients were lost for follow-up. The average length of follow-up was 2.3 years (range, 1-5 years). The average preoperative Harris hip score was 42 points, which was improved to 89 points at latest follow-up. The latest follow-up showed that bone in-growth occurred in fourteen stems and solid fibrous fixation in one. Complications consisted of femoral shaft fracture in two cases (1 undisplaced distal femur fracture and 1 cortical perforation at the tip of the prosthesis), and postoperative dislocation in one. There was no mechanical failure of the stem in this study.

CONCLUSIONSSatisfactory results of short-term clinical and radiographic follow-up have been achieved in using extensively porous-coated femoral stem for revision of THA. It should be noticed that the straight, 203 mm stem should be used with caution in short people.

OBJECTIVETo analyze and study types, infections routes and causes of global pathogenic microorganisms laboratory-acquired infections cases reported in the literatures from 2000 to 2009 and to discuss prevention and control strategies.

METHODS(1) Pathological observation of hepatic specimens: hepatic tissue pathogenic microorganisms laboratory-acquired infections. Methods PubMed, Embase, Biosis and Webs of Science covering SCIE, SSCI, CPCI-S and CPCI-SSH are chosen as data sources, "laboratory-acquired (associated) infections" are searched as the key words to search laboratory-acquired infections literature published from 2000 to 2009, from which information and data are accessed to be collected, analyzed and researched.

RESULTSThere are 19 species of pathogenic microorganisms causing laboratory-acquired infections in the last 10 years, including 15 species of bacteria, accounting for 78.9%; 4 species of virus, accounting for 21.1%. There are 83 cases reported, of which there are 60 bacterial cases, accounting for 72.3%; and 23 virus cases, accounting for 27.7%. Ingestion and inhalation are main routes of infections, respectively accounting for 32.5% and 31.3%, which are mainly due to accidents, accounting for 47.0%.

CONCLUSIONIn recent years, pathogenic microbiology laboratory-acquired infections continue to occur, and it is mainly due to accidental infections, which expose laboratory workers' low sense of safety and deficient operation methods. Laboratory staff should strengthen their senses of safety and comply with safe operation procedures, which are still the key to prevent laboratory-acquired infections.

Bacterial Infections ; microbiology ; prevention & control ; Humans ; Laboratory Infection ; microbiology ; prevention & control ; virology ; Occupational Exposure ; adverse effects ; Virus Diseases ; prevention & control ; virology

OBJECTIVETo investigate the effect of polysaccharide nucleic acid of BCG (BCG-PSN) injection on immune and pulmonary function in asthmatic children complicated with allergic rhinitis.

METHODSThirty-seven cases were separated at random into two groups, the BCG-PSN group (17 cases) was treated with BCG-PSN plus inhaled glucocortisteriods, and the control group (20 cases) was treated with inhaled glucocortisteriods only. The children in both groups were followed up for 6 months to record their lung function, allergic rhinitis scores, frequency of asthmatic attacks and respiratory infection. The levels of interleukin (IL)-4, interferon-gamma (IFN-g) and plasma total IgE were detected by using double antibody sandwich ELISA at the beginning and the end of treatment.

RESULTSIn comparison with the control group, after treatment, the levels of IFN-g and the ratio of IFN-g/IL4 in the BCG-PSN group significantly increased, whereas the level of IL-4 and the plasma total IgE significantly decreased (P less than 0.05), while those of the control group had no significant change. The lung function of both groups had significant improvement (p less than 0.05). The frequencies of asthmatic attacks in BCG-PSN and control groups were 0.81 +/- 0.20 vs. 1.72 +/- 0.80, and the difference was statistically significant. The frequencies of respiratory tract infection in BCG-PSN and control groups were 1.15 +/- 0.55 vs. 3.21 +/- 0.73, the difference was significant.

CONCLUSIONBCG-PSN may be able to correct the imbalance of Th1/Th2 and improve the lung function of children with asthma complicated with allergic rhinitis, which suggest that the immune adjusting treatment should be emphasized besides anti-inflammation therapy.

Adjuvants, Immunologic ; chemistry ; therapeutic use ; Adolescent ; Asthma ; blood ; complications ; drug therapy ; BCG Vaccine ; chemistry ; therapeutic use ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; methods ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Male ; Nucleic Acids ; chemistry ; Polysaccharides, Bacterial ; chemistry ; Rhinitis, Allergic, Perennial ; blood ; complications ; drug therapy ; Treatment Outcome

OBJECTIVETo investigate the effects of leukotriene receptor antagonist on the levels of Th1 and Th2 cytokines and the serum cysteinyl leukotrenes (CysLTs) in infants and young children with respiratory syncytial virus (RSV) pneumonia.

METHODSThirty-seven infants and young children with RSV pneumonia were divided into two groups after discharge. The cases in group 1 (n=24) were treated with a leukotriene receptor antagonist, Singulair 4 mg once daily for 12 weeks; the cases in group 2 (n=13) were treated with budesonide aerosol 200 ug once or twice daily for 12 weeks. The serum CysLTs, IFN-gamma and IL-4 were detected with enzyme_linked immunosorbent assays (ELISA) for all the 37 cases, and 10 healthy infants of the same age served as controls.

RESULTSThe serum CysLTs level in the cases with RSV pneumonia was significantly higher than that in controls (P<0.05). There was an imbalance in expression of Th1 and Th2 cytokines (IFN-gamma and IL-4 ) in these cases. Both Singulair and budesonide aerosol could correct the imbalance of Th1 and Th2 cytokines. The serum CysLTs level declined after treatment with Singulair in 24 cases, but no significant change occurred after treatment with budesonide aerosol in the remaining 13 cases.

CONCLUSIONSThe serum CysLTs level in children with RSV pneumonia was higher than that in healthy children, and there was an imbalance of Th1 and Th2 cytokines in these infants, which was similar to those with asthma. Leukotriene receptor antagonist may be effective in preventing children with RSV pneumonia from evolving into asthma.

Child, Preschool ; Cytokines ; blood ; Female ; Humans ; Infant ; Leukotriene Antagonists ; administration & dosage ; pharmacology ; Male ; Pneumonia, Viral ; drug therapy ; immunology ; virology ; Respiratory Syncytial Virus Infections ; drug therapy ; immunology ; virology ; Respiratory Syncytial Viruses ; drug effects ; immunology ; Th1 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology

OBJECTIVETo explore the effects of Angiotensin (ANG)-(1-7) on postangioplasty fibrotic remodeling and the involvement of TGF-beta/Smad signaling pathway in this process.

METHODSThirty two healthy New Zealand white rabbits were randomly divided into 4 groups: sham group, control group, ANG-(1-7) group and ANG-(1-7) + A-779 group. Rabbits underwent angioplasty in the abdominal aorta or sham surgery. Subsequently, an osmotic minipump was implanted for saline, ANG-(1-7) (576 microg x kg(-1) x d(-1)) or ANG-(1-7) + A-779 (576 microg x kg(-1) x d(-1)) delivery. Before and after 4 weeks treatment, the levels of ANG II in plasma were measured by ELISA. At week 4, angiography and histomorphometric analysis were performed, mRNA levels of collagen I and III were assayed by RT-PCR and protein levels of TGF-beta1 and Smad2 in local vessel were assayed by Western blot.

RESULTSFollowing 4 weeks treatment, ANG-(1-7) and ANG-(1-7) + A-779 group displayed a significant elevation in lumen diameter [(4.11 +/- 0.10) mm and (3.34 +/- 0.11) mm vs. (2.88 +/- 0.08) mm, P < 0.05, respectively] and reduction in neointimal thickness [(208 +/- 17) microm and (407 +/- 25) microm vs. (448 +/- 15) microm, P < 0.05, respectively], neointimal area [(0.27 +/- 0.09) mm2 and (0.38 +/- 0.01) mm2 vs. (0.41 +/- 0.02) mm2, P < 0.05, respectively] and restenosis rate [(28.1 +/- 2.7)% and (36.8 +/- 2.2)% vs. (40.1 +/- 2.7)%, P < 0.05, respectively] compared with control group. Collagen I, III mRNA and TGF-beta1, Smad2 protein levels were significantly elevated in control group, ANG-(1-7) group and ANG-(1-7) +A-779 group compared to sham group (P < 0.01 or P < 0.05) and reduced in ANG-(1-7) group compared to control group (all P < 0.05). Co-treatment with A-779 reversed the inhibitory action of ANG-(1-7). Plasma levels of ANG II postangioplasty were similar in control and ANG-(1-7) group and both were significantly higher than preoperation levels.

CONCLUSIONANG-(1-7) attenuates postangioplasty collagen synthesis in rabbits possibly through down-regulating the expression of TGF-beta1 and inhibiting the activation of Smad2 pathway.

Angiotensin I ; pharmacology ; Animals ; Aorta, Abdominal ; drug effects ; metabolism ; pathology ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Fibrosis ; metabolism ; Muscle, Smooth, Vascular ; metabolism ; Peptide Fragments ; pharmacology ; Rabbits ; Signal Transduction ; Smad2 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo investigate changes of T lymphocytes subsets in children with infectious mononucleosis (IM) and the effects of different interventions.

METHODSForty-eight children with IM were enrolled, 28 cases were assigned to the group treated with intravenous immunoglobulin (IVIG) 400 mg/(kg x d) for 5 continuous days or IVIG 1 g/(kg x d) for 2 continuous days, the remaining 20 cases were treated with ganciclovir (GCV) 5-10 mg/(kg x d) for 5 consecutive days. All these children were given general supportive therapies. Twenty healthy children from healthcare clinic serviced as control group.

RESULTSCD4 (%), CD8 (%) and the CD4/CD8 ratio in healthy control group were (34.12 +/- 3.53)%, (26.22 +/- 4.43)% and (1.41 +/- 0.3), in IVIG group were (24.2 +/- 4.3)%, (36.4 +/- 6.8)% and (0.72 +/- 0.12), and in GCV group were (23.7 +/- 5.1)%, (37.3 +/- 7.8)% and (0.67 +/- 0.13), respectively. CD4 (%), CD8 (%) and the ratio CD4/CD8 in the control group were significantly different from those in both groups with IM (P < 0.05). Compared with pre-treatment levels, the 28 cases treated with IVIG had significant improvement, the CD4 (%) increased, CD8 (%) decreased and the ratio of CD4/CD8 increased after treatment (P < 0.05). However, 20 cases in GCV treatment group made less changes (P > 0.05) . Meanwhile, the clinical symptoms and signs in the IVIG group were improved faster than that in the GCV group (P < 0.05). The rate of remission in IVIG group was 88.7% vs. 59.2% of GCV group (P < 0.05); the hospital days in IVIG group were (9.2 +/- 4.3) days vs. (13.8 +/- 5.1) days in the GCV (P < 0.05).

CONCLUSIONIt is indicated that the subsets of T lymphocytes in peripheral blood are obviously abnormal in children with IM caused by EBV infection in acute phase. IVIG can regulate the immunological derangements of T lymphocytes subsets, on which anti-viral therapy alone may have little impact.

CD4-CD8 Ratio ; Child ; Child, Preschool ; Female ; Ganciclovir ; administration & dosage ; Humans ; Immunoglobulins ; administration & dosage ; Infant ; Infectious Mononucleosis ; drug therapy ; immunology ; Male ; T-Lymphocyte Subsets ; drug effects ; immunology

OBJECTIVETo assess the value of immunoregulants in improving the prognosis of infants with wheezing.

METHODSForty-three infants with wheezing with given oxygen support, injection or inhalation of glucocorticosteroids or bronchodilatator to relieve the symptoms. Of these infants, 24 received immunoregulant treatment with bronchovaxom at the daily dose of 3.5 mg for 10 days every a month for a treatment course of 3 months. The other 19 infants were managed with budesonide aerosol at 200 microg once or twice daily for 3 months (basic treatment group). All the infants were followed up for 1 year to record the number of wheezing episode and infections. Ten healthy infants were also included in this study as the control group.

RESULTSIn infants with bronchovaxom treatment, 25% reported more than 3 wheezing episodes within the 1-year follow-up, a rate significantly lower than that in the control group (63.2%, Chi(2)=6.344, P<0.05). The episodes of respiratory infection were similar between bronchovaxom group and the healthy control group (t=0.72, P>0.05), but significantly higher in the basic treatment group than in bronchovaxom and the healthy control group (t=3.11 and 3.92, respectively. P<0.05).

CONCLUSIONSBronchovaxom can effectively reduce the recurrence of wheezing and respiratory infections in the infants with wheezing attack to reduce the risks of asthma development.

Asthma ; diagnosis ; drug therapy ; prevention & control ; Bacteria ; Cell Extracts ; administration & dosage ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Immunologic Factors ; therapeutic use ; Infant ; Male ; Prognosis ; Respiratory Sounds ; drug effects

·AIM: To evaluate the effects of foldable capsular vitreous body (FCVB) implantation on the treatment of severe ocular trauma and late silicone oil-dependent eyes due to severe ocular trauma and recurrent retinal detachment. · METHODS: We retrospectively reviewed the four patients (four eyes) with FCVB implantation at our hospital since November 2017. Out of these 4 patients,2 were males and 2 were females, with an average age of 31.5 years and an average intraocular pressure (IOP) of 5.6mmHg pre-operatively. Among those 4 eyes,3 eyes underwent silicone oil tamponade due to severe ocular trauma and the other one was recurrent retinal detachment in silicone oil - filled eye. Standard pars plana vitrectomy (PPV) was performed, and the FCVB was triple folded and implanted in the vitreous cavity of four eyes. The retinal was assessed, as well as visual acuity,IOP, FCVB condition before and after treatment, and applied therapy. ·RESULTS: All of those 4 eyes underwent successfully implantation of FCVB, which remained its proper position. During 1-3mo follow-up, the mean visual acuity was no different compared with pre - operative values.