Research progress in the structural modification of ketolides / 药学学报

Macrolide antibiotics have been widely utilized in the treatment of bacterial infections due to their strengths, low toxicity, and high efficacy. Because of the widespread application of macrolide drugs, the emergence of antibacterial resistance against antibiotics has become prominent. Ketolides, as the third generation macrolides, display improvement in activities against macrolide-resistant pathogens with broad antibacterial spectrum. Due to hepatotoxicity, the use of telithromycin has been limited. It is urgent to identify the novel sources of ketolides. So the structural modification of ketolides become the main research field of macrolide. This review introduces the recent progress in the structural modification of ketolide, with the purpose of providing support to development of new ketolide antibiotics.

Safety of stent-assisted coiling versus coiling-only in treatment of acute ruptured intracranial wide-necked aneurysms: A comparitive study / 第二军医大学学报

Objective To compare the peri-procedural complications and mortality between stent-assisted coiling versus coiling-only in the treatment for acute ruptured intracranial wide-necked aneurysms. Methods We retrospectively collected the clinical data of patients with acute ruptured intracranial wide-necked aneurysms who underwent stent-assisted coiling (stent group, n＝133) or coiling-only (coiling-only group, n＝289) between Jan. 2012 and Dec. 2014 in Changhai Hospital of Second Military Medical University. After 1∶1 propensity score matching, 104 cases were matched in each group. Baseline characteristics, peri-procedural complication incidences and mortality were compared between the two groups. Results The baseline characteristics (gender, age, location, relationship with parent vessel, maximum diameter, Hunt-Hess grade and Fisher grade of the aneurysms) were similar in the two groups (all P0.05). The hemorrhagic and thromboembolic complication incidences and mortality in the stent and coiling-only groups were 6.7% (7/104), 3.8% (4/104) and 1.9% (2/104), and 1.9% (4/104), 1.9% (4/104) and 1.0% (1/104), respectively, and the differences were not statistically significant (χ2＝1.858, 0.172, 0.000; P＝0.173, 0.679, 1.000). Conclusion The stent-assisted coiling and coiling-only are both safe and feasible for acute ruptured intracranial wide-necked aneurysms. Stents do not increase the risk of peri-procedural complication.

Immune mechanism and clinical significance of macrophage to medullary hematopoietic injury of immune-related hematocytopenia patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Immune-related hematocytopenia (IRH) is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage (Mφ) in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Mφ in hematopoietic cell injury.</p><p><b>METHODS</b>ELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-γ levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase (POX), nonspecific esterase (NSE), hemosiderin granules, and HLA-DR activity of Mφ in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Mφ membrane FcγIIreceptor (FcγIIR), mannitose receptor (MR), IFN-γ, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC) hematopoietic cell islands (HI) in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Mφ bloodthirsty phenomenon; if necessary, association of Cyclosporine A (CsA) should be used and chalybeate should be supplemented.</p><p><b>RESULTS</b>In the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-γ were increased. After treatment, the cytokine levels gradually became normal. The activated Mφ in the marrow highly expressed NSE and POX, and Mφ swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Mφ expressed HLA-DR, MR, ICAM-1, IFN-γ, and IL-12. For patients with humoral immunity activation and bacterial infection, Mφ weakly expressed IL-17A but highly expressed FcγIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count (WBC) significantly reduced, Mφ weakly expressed FcγIIR, secretory highly expressed IL-17A, and the phenomena that Mφ adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Mφ occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve.</p><p><b>CONCLUSIONS</b>Mφ is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Mφ, upregulate the impression of immune molecule and receptors, form ADCC HI, aggravate hematopoietic injury, and accelerate the destruction on hematopoietic cell.</p>

Distribution of chromium in whole blood and urine among general population in China between year 2009 and 2010 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the chromium (Cr) levels in blood and urine among general population in China between 2009 and 2010, and thereby to analyze its prevalent features.</p><p><b>METHODS</b>From year 2009 to 2010, a total of 11 983 subjects of general population aged between 6 and 60 year-old were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and 11 983 blood samples and 11 853 urine samples were also collected. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to test the Cr level both in blood and urine; and the Cr distribution in blood and urine among groups of population in different ages, genders and districts, were then analyzed.</p><p><b>RESULTS</b>Among general population in China, the geometric mean (GM) of Cr concentration in blood was 1.19 µg/L, with median at 1.74 µg /L and 95% percentile at 5.59 µg/L. The Cr concentration in blood among males and females were separately 1.18 µg/L and 1.20 µg/L(P > 0.05); while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 1.00, 1.22, 1.01, 1.40, 1.27 and 1.30 µg/L (P < 0.01), respectively; and the figures in populations from eastern, central and western China were 1.00, 1.70 and 1.98 µg/L (P < 0.01), respectively. Among general population, the GM of Cr concentration in urine was 0.53 µg/L, with median was lower than 0.42 µg/L and 95% percentile at 3.53 µg/L. The Cr concentration in urine among males and females were separately 0.52 µg/L and 0.53 µg/L (P > 0.05);while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 0.56, 0.60, 0.52, 0.50, 0.52 and 0.46 µg/L (P < 0.01), respectively;and the figures in populations from eastern, central and western China were 0.58, < 0.42 and 0.60 µg/L (P < 0.01), respectively.</p><p><b>CONCLUSION</b>The study reported the Cr levels in blood and urine among general population in China, and thereby provided basic data evidence for the following Cr biological monitoring studies in near future.</p>

Incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men in Beijing / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men (MSM) in Beijing.</p><p><b>METHODS</b>A total of 550 MSM were recruited on the basis of community and followed up after 6 and 12 months in Beijing. Each subject was investigated by only one investigator at one time to collect information on demographics and behaviors. Blood samples were collected to test HIV and syphilis seroconversion. ELISA was used for screening test, west blotting (WB) and Particle agglutination were used for confirmatory test.</p><p><b>RESULTS</b>A total of 550 MSM investigated, among which 4.5% (25/550) were HIV-positive and 29.3% (161/550) were syphilis-positive. For 525 HIV-negative MSM, 87.0% (457/525) retained during the 12-month investigation. Seroincidence for HIV and syphilis were 3.37/100 person-years (95%CI = 1.66 - 5.08) and 9.32/100 person-years (95%CI = 5.87 - 12.77) respectively. HIV seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 7.11/100 and 0.76/100 person-years respectively. Multivariate Cox regression analysis revealed that rectal douching after homosexual anal intercourse in the past 3 months (HR = 9.23, 95%CI = 2.08 - 40.88) was significantly associated with HIV seroconversion. Syphilis seroconversions for those who met male sex partners in parks, public washrooms or bathhouses in the past 3 months were 41.77/100 and 7.97/100 person-years respectively. Syphilis seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 16.17/100 and 4.92/100 person-years respectively. In the past 3 months, meeting male sex partners in parks, public washrooms or bathhouses (HR = 4.67, 95%CI = 1.77 - 12.34) and performing rectal douching after homosexual anal intercourse (HR = 3.09, 95%CI = 1.40 - 6.83) were significantly associated with syphilis seroconversion.</p><p><b>CONCLUSION</b>The seroconversions of HIV and syphilis during the follow-up visits in this MSM cohort study in Beijing were very serious, and that the associated factors for seroconversions were rectal douching after homosexual anal intercourse and meeting male sex partners in parks, public washrooms or bathhouses.</p>

Study on the relationship between behavioral factors,psychological status and HIV infection among men who have sex with men in Beijing / 中华流行病学杂志

Objective To study the prevalence and risk factors of human immunodeficiency virus (HIV) among men who have sex with men (MSM) in Beijing. Methods A sample of 550 MSM was recruited between March and June in 2008 in Beijing. Interviewer-administered interviews were conducted to collect information on demographics and behaviors. Blood samples were collected to test for HIV,syphilis,HBsAg and HCV infections. Chi-square test and logistic regression model were used to identify risk factors associated with HIV infection. Results Of the 550 eligible MSM surveyed,HIV prevalence appeared to be 4.5% (25/550). Data from multivariate logistic regression analysis demonstrated that factors as reporting unprotected anal intercourse with causal male sexual partners in the last month (X~2=11.381,P=0.001),rectal douching after homosexual anal intercourse in the past three months (X~2=5.326,P=0.021),feeling sad in the last month (X~2=8.809,P=0.003) were significantly associated with HIV infection. Conclusion Health education on safer sex behavior and mental health care should be taken to hinder the speed of HIV transmission among MSM.

RT-PCR identification and genetic characterizations of VP1 region of human enterovirus 71 isolated in Beijing in 2008 / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the genetic characterizations of VP1 region of Human enterovirus 71 (HEV71) isolated from clinical specimens of hand, foot and mouth disease (HFMD) patients in Beijing in 2008.</p><p><b>METHODS</b>285 clinical samples were collected from HFMD patients in hospitals and day-care centers in Chaoyang district. They were performed by reverse transcription-polymerase chain reaction (RT-PCR) specific for HEV71. 10 HEV71 isolates were selected for entire VP1 coding gene amplification and sequencing.</p><p><b>RESULTS</b>129 samples were RT-PCR positive, the positive rate is 45.26%. The homology of the nucleotide and the amino acid of the 10 strains were 94.6%-99.6% and 95.9%-100%. The phylogenetic tree revealed that 10 Beijing strains clustered within the C4a evolution branch of C4 subgenotype.</p><p><b>CONCLUSIONS</b>RT-PCR played an important role in identifying HFMD outbreak in Beijing in 2008. The HEV71 strains were all belong to C4a evolution branch of C4 subgenotype with several transmission chains, and it showed that C4 subgenotype HEV71 spread in mainland China widely after 1998. The molecular epidemiology surveillance and the research of genetic characterizations of HEV71 should be strengthened in mainland China.</p>

Detection of recent HIV-1 infections among men who have sex with men in Beijing during 2005 - 2006 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Men who have sex with men (MSM) have become one of the most risky populations for HIV infection in China. Though several cross-sectional sero-prevalence studies have been conducted, the annual HIV incidence remains unknown in this population.</p><p><b>METHODS</b>We applied IgG-capture BED-enzyme immunoassay (BED-CEIA) to define the recent HIV-1 infections among MSM in Beijing in the years 2005 and 2006 and the annual HIV incidence was estimated.</p><p><b>RESULTS</b>Overall, 1067 MSM samples were collected, including 526 samples in the year 2005 and 541 in 2006. In 2005, of 17 HIV seropositive samples, 7 were identified as recent HIV-1 infections and the estimated HIV infection incidence was 2.9% per year (95% CI, 0.8% - 5.0%). In 2006, of 26 HIV seropositive samples, 9 were identified as recent HIV-1 infections and the estimated annual incidence was 3.6% (95% CI, 1.3% - 5.9%), which was 0.7% higher than that in 2005. Individuals engaging in male group sexual intercourse (5.17% vs 0.87%, P = 0.019) and having receptive anal sexual intercourse more than five times (2.79% vs 0.33%, P = 0.047) in the past 6 months significantly increase the risk of being infected by HIV-1.</p><p><b>CONCLUSIONS</b>A high level of annual HIV-1 infection incidence was observed among MSM in Beijing for the consecutive years 2005 and 2006 with a continuous increasing trend. The rising incidence and related high risk behavior among MSM alarmed the health authorities and calls for more effective intervention strategies among this population.</p>

HIV-specific T cell immunity across the entire HIV genome in Chinese men who have sex with men / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Man who has sex with man (MSM) is one of the high risk groups for spreading HIV/AIDS. It was reported that the most prevalent human immunodeficiency virus type 1 (HIV-1) strain among MSM is subtype B; however, T cell immunity remains unknown across the HIV-1 B genome in this population.</p><p><b>METHODS</b>Using Elispot assay with synthetic peptides spanning the sequence of HIV-1 consensus B, HIV-1-specific cytotoxic T-cell lymphocyte responses were quantified among 3 treated and 19 untreated HIV-1 infected MSM from Beijing, China. Cross-sectional association between viral loads and cellular immune responses were analyzed.</p><p><b>RESULTS</b>Peptide pools corresponding to each HIV-1 protein were used for Env, Gag, Pol, Nef, Tat/Rev, Vpr/Vpu and Vif. The results showed that the magnitude of T cell responses in the 3 treated HIV(+) MSM group [median, 770 spot forming cells (SFCs) per 10(6) peripheral blood mononuclear cells (PBMCs)] might be significantly lower than that in the 19 untreated HIV(+) MSM group (median, 6175 SFCs per 10(6) PBMCs). Nef, Gag and Pol are the most frequently targeted HIV-1 antigens; and 16 subjects (73%) were identified with vigorous T cell immunity against each of these three proteins. The overall magnitude of T cell immunity closely related to its breadth (r = 0.72, P < 0.05) and was inversely but weakly associated with viral loads (r = -0.15). Further analysis showed that both Gag (r = -0.24) and Pol specific T cells (r = -0.12) contributed to this inverse association whereas Nef specific T cells showed no association with viral loads.</p><p><b>CONCLUSIONS</b>The magnitude of HIV-1 specific T cells is inversely but weakly associated with viral loads among MSM; HIV-specific T cell responses against conservative sequences (Gag and Pol) are the main contributors to this association among Chinese HIV(+) MSM. These findings have important implications for vaccine design.</p>