Childhood Abuse Experiences and the COMT and MTHFR Genetic Variants Associated With Male Sexual Orientation in the Han Chinese Populations: A Case-Control Study.

BACKGROUND: Although it is widely acknowledged that genetic and environmental factors are involved in the development of male homosexuality, the causes are not fully understood. AIM: To explore the association and interaction of childhood abuse experiences and genetic variants of the catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR) genes with the development of male homosexuality. METHODS: A case-control study of 537 exclusively homosexual men and 583 exclusively heterosexual men was conducted, with data collected from March 2013 to August 2015. Data were analyzed using χ2 tests and logistic regression models. OUTCOMES: Sociodemographic characteristics, childhood abuse experiences, and polymorphisms of COMT at rs4680, rs4818, and rs6267 and MTHFR at rs1801133. RESULTS: More frequent occurrence of physical (adjusted odds ratio [aOR] = 1.78), emotional (aOR = 2.07), and sexual (aOR = 2.53) abuse during childhood was significantly associated with the development of male homosexuality. The polymorphisms of MTHFR at rs1801133 and COMT at rs4818 also were significantly associated with the development of male homosexuality in the homozygote comparisons (T/T vs C/C at rs1801133, aOR = 1.68; G/G vs C/C at rs4818, aOR = 1.75). In addition, significant interaction effects between childhood abuse experiences and the COMT and MTHFR genetic variants on the development of male homosexuality were found. CLINICAL TRANSLATION: This is the first time that an association of childhood abuse, COMT and MTHFR genetic variants, and their interactions with development of male homosexuality was exhaustively explored, which could help provide new insight into the etiology of male homosexuality. STRENGTHS AND LIMITATIONS: Because homosexual men are a relatively obscure population, it was impossible to select the study participants by random sampling, which could lead to selection bias. In addition, because this was a case-control study, recall bias was inevitable, and we could not verify causality. CONCLUSIONS: Childhood abuse and the COMT and MTHFR genetic variants could be positively associated with the development of homosexuality. However, it remains unknown how these factors jointly play a role in the development of homosexuality, and more studies in different ethnic populations and with a larger sample and a prospective design are required to confirm our findings. Qin J-B, Zhao G-L, Wang F, et al. Childhood Abuse Experiences and the COMT and MTHFR Genetic Variants Associated With Male Sexual Orientation in the Han Chinese Populations: A Case-Control Study. J Sex Med 2018;15:29-42.

In vitro percutaneous penetration studies of Jinhuang Gel based on principal component analysis / 中草药

Objective: To comprehensively evaluate the in vitro percutaneous penetration and provide the experimental basis of in vitro kinetics for new drug development of Jinhuang Gel. Methods: The skin penetration of Jinhuang Gel was investigated through in vitro excised rat skin using the improved Franz diffusion cell. HPLC fingerprint of receptive solution and skin retention was established and analyzed using principal component analysis (PCA). The common peaks of HPLC fingerprint between Jinhuang Gel and Jinhuang Ointment were selected and each area was calculated to obtain the PCA biplot. Paeoniflorin as a representative of common peaks was used to investigate the in vitro permeation kinetics. Results: The results showed that the PCA biplot based on common peaks areas displayed that the global in vitro transdermal absorption effects of Jinhuang Gel were significantly better than those of Jinhuang Ointment. The in vitro transdermal absorption of paeoniflorin followed zero kinetics, and the cumulative permeation amount, permeation rate, and skin retention of paeoniflorin from Jinhuang Gel were superior to those from Jinhuang Ointment. Conclusion: Jinhuang Gel could improve the overall effects of in vitro percutaneous absorption. PCA is an effective means for investigating in vitro percutaneous absorption experiments of Chinese materia medica for transdermal administration.

A preliminary validation of the Brief COPE instrument for assessing coping strategies among people living with HIV in China.

BACKGROUND: The Brief COPE instrument has been utilized to conduct research on various populations, including people living with HIV (PLWH). However, the questionnaire constructs when applied to PLWH have not been subjected to thorough factor validation. METHODS: A total of 258 PLWH were recruited from two provinces of China. They answered questions involving the scales of three instruments: the Brief COPE, the Perceived Social Support Scale, and the Perceived Discrimination Scale for PLWH. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were conducted. RESULTS: The CFA found a poor goodness of fit to the data. The subsequent EFA identified six preliminary factors, forming subscales with Cronbach's alphas, which ranged from 0.61 to 0.80. Significant correlation coefficients between the subscales and measures of perceived social support and perceived discrimination were reported, giving preliminary support to the validity of the new empirical factor structure. CONCLUSION: This study showed that the original factor structure of the Brief COPE instrument, when applied to PLWH in China, did not fit the data. Thus, the Brief COPE should be applied to various populations and cultures with caution. The new factor structure established by the EFA is only preliminary and requires further validation.

[Molecular characteristics of Neisseria gonorrhoeae isolates with decreased susceptibilities to ceftriaxone in Shenzhen from 2009 to 2011].

OBJECTIVE: To investigate the genotype and characteristics of Neisseria gonorrhoeae (N.gonorrhoeae) isolates with reduced susceptibility to ceftriaxone in Shenzhen from 2009 to 2011. METHODS: A total of 296 N.gonorrhoeae isolates were collected in Shenzhen from 2009 to 2011.ceftriaxone strains (minimum inhibitory concentration between 0.06 and 0.50 µg/ml) were determined by agar dilution method.Logistic regression was used to analyze the associated factors of ceftriaxone N.gonorrhoeae infection.Neighbor-joining (NJ) phylogenetic tree analysis and N.gonorrhoeae multi antigen sequence typing (NG-MAST) were performed on all ceftriaxone isolates and susceptible control isolates randomly selected in accordance with the principle of 1: 1 sampling. RESULTS: No isolates displayed resistance to ceftriaxone, whereas 53(17.9%) showed reduced susceptibility to ceftriaxone among 296 isolates.Only antibiotic use in recent two months was associated with ceftriaxone isolates infection (OR = 3.080, 95%CI: 1.376-6.894) . Among the ceftriaxone isolates, 48 different ST were identified including 5 STs (ST1768, ST3927, ST641, ST7076 and ST7078) containing 2 isolates and 43 single STs. There were 26 STs previously reported from HongKong in China.Low sensitive strains clustering was not observed by NJ phylogenetic tree. CONCLUSION: The proportion of ceftriaxone strains among the 296 N.gonorrhoeae isolates collected from 2009 to 2011 in Shenzhen is high. The STs of ceftriaxone strains may have unique epidemic features in Shenzhen.

[Primary drug resistance of HIV-1 infected men who have sex with men in Shenzhen, China].

OBJECTIVE: To evaluate the status of drug resistance among treat-naive HIV-1 infected men who have sex with men (MSM) in Shenzhen during the period of 2008 - 2010. METHODS: Plasma samples of 227 treatment-naive HIV-1 infected MSM were collected in Shenzhen. HIV-1 pol genes (RT and PR) were amplified by nested-polymerase chain reaction (PCR) from RNA. Phylogenetic and drug resistance analyses were performed on the nucleotide sequence data. RESULTS: A total of 164 pol gene sequences were amplified. The prevalence of primary genotypic drug resistance was 14.6%. The overall prevalence of drug-resistant mutations was 22.6%, corresponding to 8.54% for protease inhibitors (PI) minor drug resistance mutation, 1.22% for nucleotide reverse transcriptase inhibitors (NRTI) drug resistance mutation and 13.41% for non-nucleotide reverse transcriptase inhibitors (NNRTI) drug resistance mutation. The prevalence of drug-resistant mutations was 30.88% for CRF01_AE strain and 19.23% for B strain. CONCLUSION: The prevalence of drug resistance is relatively moderate in the treat-naive HIV-1 infected MSM in Shenzhen. The prevalence of drug-resistant HIV-1 among MSM in Shenzhen should raise a high alert.

[Study on the molecular-epidemiological characteristics of HIV-1 in Shenzhen, 1992-2008].

OBJECTIVE: To investigate the epidemiological characteristics of HIV-1 subtype in Shenzhen from 1992 to 2008. METHODS: 489 HIV-1 positive plasma samples were collected from 1992 to 2008 in Shenzhen. HIV-1 env genes were amplified by nested-PCR from RNA. Phylogenetic analysis was performed on data regarding the nucleotide sequence. RESULTS: A total of 464 sequences were amplified and genotyped. Data from this study revealed that CRF01_AE was a predominant HIV-1 subtype in Shenzhen (64.4%, 299/464), followed by subtypes CRF_BC (17.5%, 81/464), B' (14.7%, 68/464) and B (2.4%, 11/464). Subtype C (0.4%, 2/464), A1 (0.2%, 1/464), CRF02_AG (0.2%, 1/464) and CRF06_cpx (0.2%, 1/464) were also prevalent in Shenzhen. CRF01_AE and CRF_BC were predominant among heterosexuals, homosexuals and injection drug users, while B' was predominant among blood donors. Results from phylogenetic tree analysis showed that some of the HIV-1 clusters had been defined in CRF01_AE strains at different time or groups with different transmission routes. Cross-infections were also seen. CONCLUSION: CRF01_AE was the predominant HIV-1 subtype in Shenzhen while CRF_BC, B, B', C, A1, CRF02_AG and a small amount of CRF06_cpx or recombinant subtypes were prevalent in this city. Different subtypes showed great variation in the process of epidemics.

Molecular epidemiology of genital Chlamydia trachomatis infection in Shenzhen, China.

OBJECTIVE: To investigate molecular epidemiology of Chlamydia trachomatis infection among patients recruited from different clinic settings in Shenzhen, China. METHODS: A total of 2534 patients from the sexually transmitted disease (STD) clinics, obstetrics and gynaecology (OBGYN) clinics and genitourinary medicine (GUM) clinics in 34 hospitals participated in the study. The C trachomatis infection was determined using COBAS Amplicor system. DNA extracted in C trachomatis-positive samples was amplified using a nested PCR based on ompA gene and then genotyped using a microsphere suspension array. RESULTS: The overall prevalence of genital C trachomatis infection was 17.7%. The prevalence in patients at STD or GUM clinics was significantly higher than that in patients at OBGYN clinics. Being male (adjusted OR (AOR) 2.5, 95% CI 1.8 to 3.4), having no consistent use of a condom with casual partners in the past 3 months (AOR 1.7, 95% CI 1.1 to 2.8) and having any STD symptoms (AOR 3.3, 95% CI 2.0 to 5.4) were independently associated with C trachomatis infection. Eight genotypes were identified. The most prevalent genotypes were F (22.3%), E (22.0%) and D/Da (12.7%). Other genotypes were G/Ga (8.0%), J (7.3%), K (2.7%), H (2.7%) and I/Ia (0.4%). Eighty-two samples (18.3%) were infected with multiple genotypes. Genotype D/Da among patients from GUM clinics was more common than those from STD or OBGYN clinics. Infections with genotypes G and F were statistically associated with abnormal vaginal discharge (p=0.001) and being married (p=0.014), respectively. Infection with multiple genotypes was more common among patients with a higher income (p=0.011). CONCLUSION: A substantial prevalence of genital C trachomatis infection in Shenzhen suggests the importance of detection and treatment of the infection in high-risk groups.

[Epidemic trend and evolution of HIV-1 CRF01_AE strains isolated from 1992 through 2008 in Shenzhen district].

OBJECTIVE: To study the prevalent status of CRF01_AE strains of recombinant HIV-1 in Shenzhen and their source of infection in order to predict the epidemic trend and evolution. METHODS: A total of 489 samples of HIV-1 positive plasma were collected from 1992 to 2008 in Shenzhen. HIV-1 Env genes were amplified by nested-PCR from RNA. Subtype analysis were performed on the nucleotide sequence data. CRF01_AE sequences were analyzed by phylogenetic methods and characterized by calculating the genetic distance. RESULTS: A total of 300 CRF01_AE strain sequences were amplified, accounting for 64.5% of all genotyped samples of all the 465 samples. The CRF01_AE strains of recombinant in 1992 - 1999, 2000 - 2005 and 2006 - 2008 accounted for 56.8% (21/37), 68.4% (78/114) and 64.0% (201/314) of genotyped samples, respectively. And in these three periods of times, 52.4% (11/21), 43.6% (34/78) and 45.8% (92/201) were heterosexually acquired adults; 4.8% (1/21), 0.0% (0/78) and 22.4% (45/201) were homosexually acquired adults; 19.0% (4/21), 51.3% (40/78), 30.8% (62/210) were intravenous drug users, respectively.Phylogenetic tree analysis revealed that HIV samples from different period of time showed distinct aggregation in time and transmission as well as cross infection. The gene divergence rate of CRF01_AE strains in the three different periods of time were (8.783 ± 4.717)%, (11.054 ± 7.141)%, and (13.218 ± 4.080)%, respectively. CONCLUSION: CRF01_AE is the major epidemic strains in Shenzhen, which is transmitted through heterosexual contact, MSM and intravenous drug users. The gene variation increased gradually as time goes by.

[Molecular epidemiological survey on HIV-1 among the injecting drug users population in Shenzhen].

OBJECTIVE: To study the prevalent status of human immunodeficiency virus-1 (HIV-1) subtypes in IDU (injecting drug users) population in Shenzhen and to study their source of infection in order to predict the epidemic trend and evolution. METHODS: 166 HIV-1 positive plasma from the IDUs was collected from 1996 to 2008. HIV-1 env genes were amplified by nested-PCR from RNA. The C2-V3 regions (450 bp) of HIV-1 env were sequenced for analyses. Phylogenetic analyses were performed on the nucleotide sequence data. RESULTS: Among 166 samples, there were 6 HIV-1 strains including CRF01_AE, CRF08_BC, CRF07_BC 3 circulating recombinant forms (CRFs) and B', C, A1 3 subtypes. Data from the genotype analyses showed that 65.06% (108/166) were CRF01_AE, 19.88% (33/166) were CRF07_BC, 6.02% (10/166) were CRF08_BC, 7.23% (9/166) were subtype B', 0.60% (1/166) were subtype C and 1.20% (2/166) were subtype A1. Phylogenetic tree analysis showed that some of HIV-1 clusters defined in CRF01_AE, CRF07_BC and subtype B' in different time groups. Significant increase of gene distance in CRF01_AE and CRF07_BC strains in the three different periods. CONCLUSION: CRF01_AE and CRF07_BC were the major epidemic CRF strains among the IDU population in Shenzhen while the subtype B', C, A1 and CRF08_BC were also circulating in IDU population in this region. The variation of all different subtypes was increasing through these years.

[Analysis of the tandem-repeat polymorphisms in DC-SIGNR alleles among drug users population with or without HIV/HCV infection].

OBJECTIVE: To study the distribution of DC-SIGN/DC-SIGNR alleles among drug user (DUs) populations with or without HIV/HCV infection in Shenzhen, and to evaluate the role of these alleles in the construction of genetic resistance to HIV or HCV and screen out the anti-HIV/HCV gene in Shenzhen. METHODS: All 500 DU blood samples were collected from Shenzhen Detoxification Center, including 313 from injected drug users (IDUs). All samples were screened for HIV and HCV antibody by means of ELISA. The genomic DNA were extracted and amplified by PCR. The neck domain repeat regions of DC-SIGN/DC-SIGNR were sequenced directly from the PCR products to confirm the amplification for some samples and all positive PCR products were analyzed by agarose gel electrophoresis. RESULTS: Of 500 samples, 97 were found HIV positive, all of which were IDUs and HCV positive. The total positive rate of HCV among all HIV negative DU was 57.57% (232/403), and it was 63.89% (138/216) among IDUs; in comparing to the 50.26% (94/187) of DUs with other manners there showed significant difference (chi(2) = 7.61, P = 0.0058). Among HIV + DUs, there was a higher proportion of patient with the DC-SIGNR 5/6 and 5/8 (Fisher's exact, P = 0.043 and P = 0.034) with statistical significance; there was no statistically significant difference between HCV + and HCV-DUs and no significant difference between IDUs and other DUs for the DC-SIGNR polymorphism. CONCLUSION: The results might indicate that DC-SIGN/DC-SIGNR polymorphism might not influence the susceptibility to HCV. Genotype 5/6 might probably have a relation with HIV infection, but still need further investigation for the low frequency.

[Human immunodeficiency virus type 1 strains epidemic in Shenzhen].

OBJECTIVE: To study the epidemic status of human immunodeficiency virus type 1 (HIV-1) subtypes in Shenzhen and to study their transmission source and routes. METHODS: HIV-1 env and gag genes were amplified by nested PCR from uncultured peripheral blood mononuclear cells (PBMCs) obtained from 122 HIV-1 carriers confirmed in Shenzhen. The C2-V3 region (about 450 bp) of HIV-1 env and P17/ P24 region were sequenced. RESULTS: Among 122 samples, 6 HIV-1 strains including 3 circulating recombinant forms (CRFs) of CRF01_AE, CRF08_BC, CRF07_BC and 3 subtypes of B', B, C were found in Shenzhen, and the percentages were 45.1% (55/122) for CRF01_AE, 31.1% (38/122) for CRF08_BC, 6.6% (8/122) for CRF07_BC, 14.8% (18/122) for B' subtype, 1.6% (2/122) for B subtype, and 0.8% (1/122) for C subtype. The intragroup genetic distances were (4.455 +/- 1.478)%, (2.997 +/- 1.345)%, (4.380 +/- 2.024)%, (5.186 +/- 2.487)%, and (4.869 +/- 2.638)%, respectively. In comparison with the sequence of respective international strains 01AE. TH. 90. CM240, 97CNGX-9F, CN. 97. C54A, B. US. 83. JRFL, and RLA2, the genetic distances were (5. 228 +/- 0.823)%, (3.634 +/- 1.073)%, (4.233 +/- 1.119)%, (4.950 +/- 2.564)%, and (5.795 +/- 2.198)%, respectively. The major subtypes found in injection drug users (IDUs) were CRF07_BC, CRF08_BC, and CRF01_AE strains. CRF01_AE and B' strains were epidemic mainly in sexual workers. CONCLUSION: There are 3 HIV-1 subtypes (B', B, C) and 3 CRFs (CRF01_AE, CRF08_BC, CRF07_BC) epidemics in Shenzhen. The predominant subtypes varies among different transmission routes. While CRF01_AE is predominant among sexual workers, CRF08_BC and CRF01_AE are major subtypes among IDU population.