Mutation of drug resistant gene in HIV/AIDS patients with antiretroviral therapy in Shandong province in 2011 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate drug resistance status in patients with highly active antiretroviral therapy (HAART) in Shandong province.</p><p><b>METHODS</b>A total of 758 patients were separated from the anticoagulatory whole blood during May and October in 2011. The entire protease gene and part of the reverse transcriptase gene were amplified by RT-PCR and nest-PCR in the samples with viral load larger than 1000 copies/ml, then sequenced the gene fragments. Mutation of drug resistant gene and drug susceptibility was analyzed by the online tool HIV db program developed by Stanford University.</p><p><b>RESULTS</b>The rate of virologic failure in patients was 9.1% (69/758). A total of 53 gene sequences that acquired were used for genotypic resistance analysis. A total of 23 patients were indicated drug resistance with the total of 3.1% (23/742). Drug resistance rates of nucleotide reverse transcriptase inhibitor (NRTI) and non-NRTI(NNRTI) were 2.4% (18/742) and 3.0% (22/742), respectively, and the primary mutation types of drug resistance were M184V and Y181C for NRTI and NNRTI, with no resistance to protease inhibitor (PI). In the 23 patients indicated drug resistance, 78.3% (18/23) were NRTI resistance, 95.7% (22/23) were NNRTI resistance and 73.9% (17/23) dual NRTI and NNRTI resistance.</p><p><b>CONCLUSION</b>The presence of drug resistant gene in HIV strains among AIDS patients with HAART in Shandong province was at low level, but mutation diversity was found in drug resistant gene.</p>

The prevalence and evolution of HIV drug-resistant strains in people who live with HIV/AIDS during HIV antiretroviral therapy in Shandong province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To understand the prevalence and evolution of HIV drug-resistant strains in people who live with HIV/AIDS (PLWHA) during HIV antiretroviral therapy in Shandong province.</p><p><b>METHODS</b>Viral load testing was performed by using fluorescence real-time quantitative PCR (NucliSens EasyQ system) on 324 patients who were under HIV antiretroviral therapy (ART) over 1 year in Shandong province. HIV resistance testing was conducted on the samples with more than 1000 copies/ml by using genotypic resistance testing method established in our lab. We tested the samples from drug-resistant patients before and after treatment to analyze the evolution of HIV resistant strains.</p><p><b>RESULTS</b>The resistance rate for the patients under HIV ART over 1 year was 6.2% (20/324). The rate of drug-resistant mutation, but not resistant to ART was 0.6% (5/324). Nucleoside reverse transcriptase inhibitor (NRTIs) and non-NRTIs (NNRTIs) accounted for 93.1% (94/101) and protein inhibitors (PIs) accounted only 6.9% (7/101) of all mutations. M184V (48.0%, 12/25) and Y181C (32.0%, 8/25) were the most frequent mutations among 25 samples. Our research showed 20.0% (2/10) patients were resistant to primary ART and 1 patient was detected drug resistance in 6 months after ART treatment. HIV evolved from wild type to drug resistant virus, from low level to high level drug resistance, and from resistance to few to multiple drugs. In addition, interactions between mutations may influence the sensitivity of patients to other drug treatment.</p><p><b>CONCLUSION</b>The prevalence of HIV drug-resistant strains in Shandong province is still at a low level, but its evolution is complex.</p>

Relationship between MnSOD polymorphisms and susceptibility of chronic poisoning exposed to manganism occupationally / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the relationship between polymorphisms of MnSOD and the susceptibility of chronic poisoning exposed to manganism occupationally.</p><p><b>METHODS</b>In a study of case-control, genotypes were determined by PCR-RFLP in 164 patients with chronic occupational mangamism poisoning and 328 controls with age- and sex-matched for MnSOD 9Ala-Val.</p><p><b>RESULTS</b>There was a significant difference in the frequency of MnSOD 9Ala-Val at V locus mutant allele between cases and controls (χ(2) = 15.225, P < 0.01, 95%CI = 1.43 ∼ 3.00). Individuals with the genotype VV had a 1.30 of risk increase of occupational chronic manganism poisoning compared with the the genotype AV or AA (OR = 2.30, 95%CI = 1.52 ∼ 3.49, P < 0.05).</p><p><b>CONCLUSION</b>The MnSOD polymorphisms may be related with the susceptibility to chronic occupational manganism poisoning, the risk of chronic occupational manganism poisoning increases in carriers with genotype VV at MnSOD 9Ala-Val locus.</p>

Effectiveness of intravenous immunoglobulin therapy in treating unexplained recurrent spontaneous abortion and its effect on the level of serum soluble human leucocyte antigen G / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effectiveness of intravenous immunoglobulin (IVIG) in treating patients with unexplained recurrent spontaneous abortion (URSA) and the effect of IVIG on the level of soluble human leucocyte antigen G (sHLA-G).</p><p><b>METHODS</b>This prospective trial conducted at PUMC Hospital between 2004 and 2008 included 60 women with URSA. The patients were allocated into IVIG group (30 cases) and control group (30 cases). IVIG was intravenously used before conception at a dose of 0.2g/kg; once pregnancy was confirmed,IVIG was continued every 4 weeks till the 20th gestational week. Traditional Chinese medicine or/and progesterone were used in control group. The outcome of pregnancy was evaluated by live birth rate and effective rate(defined as the embryo living 4 week longer than previous pregnancy). Serum samples were collected randomly before pregnancy and in the 6th-8th gestational week from IVIG group (15 samples),control group (15 samples),and healthy women (20 samples). The levels of sHLA-G,interferon γ (IFN-γ), interleukin-2 (IL-2), and interleukin-10 (IL-10) were determined by enzyme-linked immunosorbant assay (ELISA).</p><p><b>RESULTS</b>The pregnancy rate was 93.3% in IVIG group. The live birth rate and effective rate were 85.7% (24/28) and 92.9% (26/28) in IVIG group,which were significantly higher than those in control group [56.7% (17/30) (P=0.021) and 63.3% (19/30) (P=0.011)]. Emesis occurred in one woman (3.3%) in IVIG group had during IVIG infusion but was relieved by lowering the speed of infusion. The mean sHLA-G level was (61.37∓35.57) U/ml in control group and (62.70∓37.24) U/ml in IVIG group (P>0.05); both of them were significantly lower than that of healthy women (88.49∓25.37) U/ml (Pü0.05). After pregnancy was achieved, the levels of sHLA-G and IL-10 were (34.19∓14.21) U/ml and (11.71∓2.75) pg/ml, respectively in the IVIG group, which were significantly higher than those in control group [(23.71∓12.83) U/ml and (8.71∓3.01) pg/ml, respectively] (P=0.008).</p><p><b>CONCLUSIONS</b>Low-dose IVIG before and after pregnancy is a safe and effective in treating URSA. IVIG improves the development of fetus by up-regulating sHLA-G and IL-10 levels.</p>

Comparison of the effect of positive and negative oral contrast agents on delineation and 18F-FDG uptake of gastrointestinal tract / 中华核医学杂志

Objective To compare the different effects of 1% diatrizoate meglumine,2.5% mannitol and water as oral contrasts in PET/CT scan in gastrointestinal tract delineation and 18F-fluorodeoxyglucose (FDG) uptake. Methods Sixty-one patients referred for PET/CT scan without gastrointestinal diseases were divided into three groups randomly ( random number method). One liter of 1% diatrizoate meglumine,2.5% mannitol,or water was orally taken by groups 1 (25 cases),2 (20 cases) and 3 ( 16 cases),respectively before scan. The scan was performed with GE Discovery LS PET/CT scanner in two-dimensional (2D) mode 50 min after 18F-FDG (5.55 MBq/kg) injection. Patients with abdominal lesions were excluded from this study. The degree of gastrointestinal filling and 18F-FDG uptake was evaluated by 3 nuclear medicine physicians using visual analysis according to a 4-grade classification method:none,mild,moderate,and high. Statistically analysis was performed by Kruskal-Wallis,Mann-Whitney and paired t tests.Results Both the differences of serum glucose and insulin levels were not significant before and after contrast taken in group 2. Group 2 had better gastrointestinal filling than that of group 1 and also better than group 3 except in rectum. The stomach,jejunum,ascending,and transverse colon were better filled in group 1 than in group 3. The degree of 18F-FDG uptake of group 3 was significantly higher than that of group 2 in stomach,jejunum and ileum (z= -3. 192,-3.290,-3.290,all P＜0.05),and was also significantly higher than that of group 1 (z = - 3. 603,P ＜ 0.05) in jejunum. The degree of 18 F-FDG uptake of group 3 was significantly lower than that of group 1 in ascending colon (z = - 2. 706,P ＜ 0. 05 ) and was significantly lower than that of group 1 and 2 in transverse and descending colon (z= - 3. 503,- 2.403,- 4.225,-4. 027,all P ＜0.05),and was also significantly lower than that of group 2 in rectum (z = -4. 128,P ＜0. 01 ). The maximum CT values in stomach,jejunum,ileum and ascending colon in group 1 were ( 132 ±23),(191 ±31),(313 ±47) and (374±53) HU,respectively,whose difference was significant (t = -7.088--1.781,all P ＜0. 01 ). Conclusion Oral iso-osmotic mannitol intake has better gastrointestinal filling and less physiological 18F-FDG uptake compared to diatrizoate meglumine and water.

Predictors and clinical significance of the positive cone margin in cervical intraepithelial neoplasia III patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Conization is being widely accepted for diagnosis and treatment of cervical intraepithelial neoplasia (CIN). There is controversy as to which factors are most predictive of a positive cone margin and the clinical significance of it. We conducted this study to identify the predictive factors and to evaluate the clinical significance of a positive cone margin in CIN III patients.</p><p><b>METHODS</b>A retrospective review was conducted of 207 patients who had undergone conization due to CIN III from January 2003 to December 2005 at Peking Union Medical College Hospital. Of these, 67 had a subsequent hysterectomy. Univariate and multivariate analysis were utilized to define the predictive factors for a positive cone margin, and to compare the pathologic results of conization with subsequent hysterectomy.</p><p><b>RESULTS</b>One hundred and fifty-one (72.9%) were margin free of CIN I or worse, 37 (17.9%) had CIN lesions close to the margin and 19 (9.2%) had margin involvement. A total of 56 cases (27.1%) had positive cone margins (defined as the presence of CIN at or close to the edge of a cone specimen). Univariate analysis showed that the parity, cytological grade, multi-quadrants of CIN III by punch biopsy, gland involvement, as well as the depth of conization were significant factors correlated with a positive cone margin (P < 0.05). However the age, gravidity, grade of dysplasia in punch biopsy, as well as the cone methods were not significantly correlated (P > 0.05). Multivariate analysis revealed that the cytological grade (OR = 1.92), depth of conization (OR = 2.03), parity (OR = 3.02) and multi-quadrants of CIN III (OR = 4.60) were significant predictors with increased risk for positive margin. The frequency of residual CIN I or worse in hysterectomy specimens was found to be 55.6% (20/36) in patients who were margin free, 71.4% (15/21) in patients with CIN occurring close to margin, and 80.0% (8/10) in patients with margin involvement. The frequency of residual CIN III or worse was found to be 13.9% (5/36), 23.8% (5/21) and 50.0% (5/10) respectively in different groups.</p><p><b>CONCLUSIONS</b>Cytological grade, depth of conization, parity and multi-quadrants of CIN III in punch biopsy were significant factors with increased risk in predicting a positive cone margin. Margin status of conization did not mean the presence or absence of CIN, but rather the varied frequency of residual CIN in specimens of subsequent hysterectomy. In view of this fact, it is suggested that the margin status of conization be a valuable surrogate marker for clinical management of CIN III.</p>

Risk factors in the living environment of early spontaneous abortion pregnant women / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the relationship between early spontaneous abortion and living environment, and explore the risk factors of spontaneous abortion.</p><p><b>METHODS</b>We conducted analysis based on the interview of 200 spontaneous abortion cases and the matched control (age +/- 2 years) by using multifactor Logistic regression analysis.</p><p><b>RESULTS</b>The proportions of watching TV > or =10 hours/week, operating computer > or =45 hours/week, using copycat, microwave oven and mobile phone, electromagnetism equipment near the dwell or work place, e. g. switch room < or =50 m and launching tower < or =500 m in the cases are significantly higher than those in the controls in single factor analysis (all P < 0.05). After adjusted the effect of other risk factors by multifactor analysis, using microwave oven and mobile phone, contacting abnormal smell of fitment material > or =3 months, having emotional stress during the first term of pregnancy and spontaneous abortion history were significantly associated with risk of spontaneous abortion. The odds ratios of these risk factors were 2.23 and 4.63, respectively.</p><p><b>CONCLUSION</b>Using microwave oven and mobile phone, contacting abnormal smell of fitment material > or =3 months, having emotional stress during the first term of pregnancy, and spontaneous abortion history are risk factors of early spontaneous abortion.</p>

Compliance and efficacy of standard antenatal care model / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the compliance of standard antenatal care (ANC) model with 12-13 visits currently used in Beijing region, and to assess the efficacy of this model in reducing adverse maternal and perinatal complication.</p><p><b>METHODS</b>The clinical data of 544 women who delivered at Peking Union Medical College Hospital (West Section) from January 1, 1999 to December 31, 2002 were retrospectively reviewed and analyzed. Three areas were addressed in this paper: compliance of pregnant women with standard ANC model; association of maternal and perinatal complication with different number of ANC visits; effectiveness of screening for risk factors at the first ANC visit.</p><p><b>RESULTS</b>A median of 8 ANC visits was made in 544 cases, of whom 22 cases (4.0%) never had ANC visit before delivery. The women were divided into three groups according to the status of residence and education levels: temporary residents in Beijing city (group A), permanent residents with middle or low education level (group B), and permanent residents with high education level (group C). The average number of ANC visits in group A was 4.55 +/- 3.1, which was much lower than in group B (8.71 +/- 2.2) and in group C (9.56 +/- 2.1) (P < 0.001). The mean duration of gestation at the first ANC visit in group A was (25.44 +/- 8.8) weeks much longer than (15.58 +/- 5.8) weeks in group B and (14.24 +/- 3.2) weeks in group C (P < 0.001). Among 544 cases, 93 (17.1%) had ANC visit for 0-3 times, 299 (55.0%) for 4-9 times and 152 (27.9%) for > or = 10 times. There was no statistical difference among varied number of ANC visits when the results were pooled for pregnancy induced hypertension, gestational diabetes mellitus, vaginal bleeding at the second and third trimesters, postpartum hemorrhage, fetal macrosomia, premature rupture of membrane, and fetal distress (P > 0.05). An increase in the number of ANC visits was associated with the decreased rates of fetal growth restriction (P < 0.05) and premature delivery (P < 0.05), whereas it was paralleled with increased rates of anemia and cesarean section (P < 0.001). It was found that 35.6% of women who developed maternal and perinatal complications would be identified through screening for risk factors at the first ANC visit.</p><p><b>CONCLUSIONS</b>Standard ANC model is currently not well complied. It has limited efficacy in reducing most maternal and perinatal complications. A more practical and effective ANC model for low educated women and temporary residents needs to be explored.</p>

The structure and virus-like particle vaccine of the HIV-1 capsid protein / 生物工程学报

The HIV-1 capsid protein (CA) plays an essential role in viral core assembly and maturation. Proteolytic cleavage at the MA-CA junction of the retroviral gag polyprotein refolds the amino-terminal end of capsid into a beta-helix structure that is stabilized by a salt bridge between the protein's processed amino-terminus and a conserved acidic residue. The refolded capsid aminoterminus then creates a new CA-CA interface, allowing assembly of the mature capsid core. Recently, researches focus on assembly of CA in vitro and development of CA vaccine. CA vaccine will provide widely immune protection because CA is comparatively conserved. Experiments demonstrate that fusing as few as four matrix residues onto the amino-terminus of capsid redirects protein assembly from cylinder to spheres in vitro. Evaluation of immunogenicity showed that immunization with virus-like particles induced both cellular and neutralizing antibody responses. Furthermore, mucosal administration of virus-like particles effectively induced both mucosal and systemic immune responses. These results indicate that virus-like particles consisting of HIV structural proteins are an attractive vaccine platform for eliciting anti-viral immune responses, especially neutralizing antibody responses. The production of antigens for vaccines in plants indicates that plant-based transgenic expression represents a viable means of producing CA vaccine for the development of HIV vaccine and for use in HIV diagnostic procedures and it has the potential as a safe and cost-effective alternative to traditional production systems.

Study of symptoms in terminally ill patients with ovarian carcinoma / 中华妇产科杂志

Objective To investigate symptom characteristics and their their prevalence in terminally ill patients with ovarian carcinoma.Methods A retrospective study was carried out based on clinical data of 98 terminally ill patients with ovarian carcinoma who died in our hospital during January 1995 to December 2004.Fifteen most common symptoms were analyzed with a focus on the followings:symptom incidence,survival time after symptom occurrence,regularity of symptom cluster,and common causes of death.Fifteen symptoms were:pain,cachexia,pleural effusion and ascites,dyspnea,fever,intestinal obstruction,renal failure,bone marrow depression,lung infection,hemorrhage,deep venous thrombosis (DVT),intestinal or pancreatic fistula,mycotic infection,jaundice and emergency conditions.Results (1)The most prevalent symptom was pleural effusion and ascites(63%),followed by pain(60%), cachexia(59%),dyspnea(52%)and intestinal obstruction(49 %).(2)The symptom which lasted longest survival time was mycotic infection(77 days),followed by intestinal or pancreatic fistula(75 days), intestinal obstruction(67 days),pain(60 days)and eachexia(60 days).Symptoms such as bone marrow depression,renal failure,dyspnea and emergency conditions were comparatively critical associated with shorter survival times(14,13,12,7 days,respectively).(3)Terminal symptoms occurred typically in clusters,with 4.9?1.5 symptoms per case.Of 98 cases,84 cases(86%)had 4 or more symptoms,with the median survival time of 63 days from the last day of anti-cancer therapy,and a slow death process.The remaining 14 cases(14%)with 3 or fewer symptoms survived only 25 days,of which 10 cases(71%)died of emergency diseases.The survival time for two groups was significantly different(P