Objective To investigate the effects of alcohol on hepatitis C virus( HCV) replication and type I interferon signaling pathway in human hepatocytes .Methods Primary hepatocytes were treated with different concentrations of alcohol , and then infected with HCV .The infected cells were collected to measure the level of HCV RNA .The alcohol-treated hepatocytes were also collected to detect the expression of HCV Core, IFN-α, IFN-β, IRF-7, suppressor of cytokine signaling SOCS-2 and SOCS-3 at mRNA and protein levels by real-time quantitative PCR and ELISA or Western blot , respectively .Results Alcohol treatment enhanced HCV infection and replication in primary hepatocytes at concentrations higher than 10 mmol/L in a dose-dependent manner (P<0.05).Treatment with 40 mmol/L of alcohol significantly reduced the expression of IFN-α, IFN-βand IRF-7 at mRNA and protein levels , and increased the expression of SOCS-2 and SOCS-3 at mRNA and protein levels .Conclusion Alcohol treatment could damage the host in-nate immunity in human hepatocytes and promote HCV replication by reducing the expression of type Ⅰinter-feron ( IFN-αand IFN-β) and IRF-7 and increasing the expression of negative regulators including SOCS-2 and SOCS-3.These results demonstrated that the impairment of innate immunity in liver of alcohol abusers might contribute to the enhancement of HCV infection and result in poor therapeutic effect of IFN -α.

Objective To study the phylogenetic evolution and genetic variations of gag gene among the prevalent human immunodeficiency virus (HIV )‐1 strains in Guangxi Zhuang Autonomous Region . Methods Plasma samples of 158 HIV‐1 infected patients in Guangxi area were collected during October 2011 to March 2012 .The gag gene fragments of HIV‐1 were amplified by reverse transcription/nested‐polymerase chain reaction and then sequenced .MEGA 5 .03 was utilized to construct phylogenetic tree and to calculate the genetic distances and selection pressures (globle ω) of gag gene and its coding regions . The comparisons between two groups were tested by Student′s t test ,and the comparisons of multiple groups were tested by one‐way ANOVA .Results A total of 140 amplification products of gag gene were obtained from 158 samples .Four subtypes of HIV‐1 were found ,including CRF01_AE (80 ,57 .1% ) , CRF08_BC (46 ,32 .9% ) ,CRF07_BC (10 ,7 .1% ) ,and subtype B (B′) (4 ,2 .9% ) .The genetic distances of gag gene of the above subtypes were 0 .036 ± 0 .001 ,0 .031 ± 0 .002 ,0 .043 ± 0 .003 and 0 .102 ± 0 .006 ,respectively ,with statistical significance (F=220 .62 ,P<0 .01) .The p17 and p24 coding regions suffered negative selection pressure (globleω<1) .Neither the globle ω in p17 region nor that in p24 region had significant differences among different subtypes (F=0 .761 ,P=0 .469 and F=0 .037 ,P=0 .964 , respectively ) . Conclusion CRF01_AE is the major subtypes of HIV‐1 in Guangxi Zhuang Autonomous Region .The coding regions of gag gene are relatively conserved during evolution .Changes of HIV‐1 prevalence ,however ,may affect the genetic variation of gag gene ,which should be continuously monitored .

Objective To investigate the HIV-1 drug resistance in Guangxi during 2009 to 2012 and to analyze the correlations between drug resistance and HIV-1 subtypes.Methods Patients with human immunodeficiency virus infection or acquired immune deficiency syndrome ( HIV/AIDS) were randomly re-cruited from different areas in Guangxi.HIV-1 RNA was extracted from blood samples of the subjects and converted into complementary DNA ( cDNA) by using reverse transcription.The pol gene was amplified and sequenced.Subtyping analysis was performed by using the online analysis tool of Genotyping in combination with the MEGA 5.03 software.The HIV resistance mutations were determined and scored with the use of Stanford HIV Drug Resistance Database.Results A total of 196 pol gene sequences were obtained from 103 antiretroviral therapy (ART)-treated subjects (52.55%) and 93 ART-na?ve subjects (47.45%).The 196 pol gene sequences were classified into four subtypes including CRF01_AE, CRF08_BC, CRF07_BC and B, accounting for 48.47%, 44.90%, 6.12%and 0.51%, respectively.The HIV drug resistance rates in sub-jects with and without ART were 10.68% and 7.53%, respectively.Among the 196 subjects, 14 cases showed low level of drug resistance, 3 cases showed moderate level of drug resistance and 4 cases showed high level of resistance.Only one case was resistant to both nucleoside reverse transcriptase inhibitors ( NR-TIs) and non-nucleoside reverse transcriptase inhibitors ( NNRTIs) .The resistance rates of the 196 cases to protease inhibitor (PIs), NRTIs, NNRTIs, and integrase inhibitors (INs) were 6.63%, 3.06%, 11.22%and 8.67%, respectively.The frequencies of PIs-related mutations in subtypes CRF01_AE, CRF07_BC and CRF08_BC were 6.32%, 41.67% and 2.27%, respectively.Most of the PI-related A71V/T mutations were identified in strains belonging to subtype CRF07_BC, accounting for 75% of all A71V/T mutations found in the 196 strains.The NNRTI-related E138A mutations only appeared in strains belonging to subtype CRF08_BC.Conclusion The drug resistance rate among patients with HIV-1/AIDS in Guangxi was higher than the average level in China.The drug resistance rates varied with the subtypes of HIV-1 strains.

OBJECTIVETo investigate the distribution and proportion of subtypes of pol gene in HIV-1 epidemic strains in Guangxi Autonomous Region.

METHODS152 HIV-1 patients were enrolled from 11 cities in Guangxi Autonomous Region from 2010 to 2012 by convenient sampling. Inclusion criterias were listed as the fdlowing: HIV-1 infection was confirmed by Western blot, HIV-1 viral load >1 000 copies/ml, > 18 year-old, and without any serious illnesses. 5 ml of peripheral blood samples were obtained from each patient. The viral RNA was isolated from plasma and used for amplification of full-length pol gene by nested RT-PCR. The amplified products were sequenced. After editing and modification, all sequences were characterized for preliminary subtyping by genotyping and confirmed with phylogenetic tree constructed by MEGA 5.03 software. The recombinant identification of 2 unknown recombinant strains was determined by RIP and jpHMM at GOBICS.

RESULTSAmong 152 patients, 137 full-length pol genes were successfully amplified and 127 HIV-1 subtypes were identified. The distribution and proportion of subtypes was summarized as the following 71 cases of CRF01_AE, accounting for 55.9% (71/127), 38 CRF08_BC, 29.9% (38/127), 13 CRF07_BC, 10.2% (13/127), and 3 B (B'), 2.4% (3/127), 2 unknown recombinant strains, 1.6% (2/127). In 11 cites of Guangxi Autonomous Region, subtype CRF01_AE was the dominant strain. Among heterosexual transmitted patients and drug abusers, the proportions of subtype CRF01_AE were 67.4% (58/86) and 34.1% (14/41), respectively. There was a significance different in the distribution of CRF01_AE in different routes of transmission (χ(2)=15.07, P<0.001). In age 21- 35, age 36- 60 and age>60 groups, the proportions of CRF01_AE was 43.6% (17/39), 57.6% (38/66), 77.3% (17/22), and CRF08_BC was 43.6% (17/39), 28.8% (19/66), 9.1% (2/22), respectively, the difference in proportions was significant(χ(2)=8.48, P= 0.014). The patterns of two unknown recombinant strains were found to be CRF01_AE/B (B') and CRF01_AE/C/B(B'), respectively.

CONCLUSIONCRF01_AE was the dominant HIV-1 subtype in Guangxi Autonomous Region from 2010 to 2012, with heterosexual transmission as its main spreading route. The two unknown recombinant strains in Guangxi Autonomous Region were reconstructed by subtype CRF01_AE and CRF_BC.

Blotting, Western ; China ; epidemiology ; Cities ; Drug Users ; Genes, pol ; Genotype ; HIV Infections ; epidemiology ; transmission ; virology ; HIV-1 ; genetics ; Humans ; Phylogeny ; Polymerase Chain Reaction ; RNA, Viral ; blood ; pol Gene Products, Human Immunodeficiency Virus ; genetics

Objective To explore the risk factors for orchidism and the curative efficacy of intensive corticosteroids therapy for the testicular adrenal rest tumors ( TART ) in the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency ( 21OHD) during childhood and pubescent periods. Methods A total 12 cases (27 case-times) with TART were adopted in intensive corticosteroids therapy, 7 cases (7case-times) as control group without intensive therapy. Retrospective analysis following parameters:( 1) The testicular volume and the echogenic characteristics of TART by B-mode ultrasound. ( 2 ) Serum levels of FSH, LH, testosterone, 17-hydroxyprogesterone, androstendion, and inhibin-B were measured. ( 3 ) Orchidism was defined by one of following events:serum level of inhibin-B≤3rd％ for norm, and/or serum level of testosterone<1. 47 ng/ml for the individual which is already in TannerⅣstage. ( 4) The relationship between regression of TART and intensive therapy project. Results The prevalence of TART in 21-OHD was 28.18％during 2-18 years old, and the youngest age with TART was 2. 48 year of old. The regression rate of TART by intensive therapy was higher than that of the control significantly, 20/30 and 1/11(tumor-times) respectively(P=0.004). When the dose of dexamethasone≥30％ of total doses of corticosteroids, the regression rate of TART was higher than those less than 30％ ones, or adopted hydrocortisone alone, were both respectively 16/20 and 4/10(P=0.045). The risk factors for orchidism related to early diagnosis:The TARTs stages in diagnosis (≥stages III;P=0.003) , the tumor in size, hyperechogenicity in B ultrasound of the tumors ( P = 0. 003 ) . Inhibin-B is the earliest displayed biochemical warker for orchidism. Conclusions The TART could regress when got early diagnosis and adopted intensive corticosteroids therapy on time. Delayed diagnosis was the main risk factor for orchidism. For early diagnosis of TART, we suggest to conduct the scrotal ultrasound regularly started from 2 years of age.

Objective: To summarize the experience in diagnosis and treatment of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism and bilateral gonadoblastoma (Gb) secreting human chorionic gonadotrophin(HCG). Methods: A female patient aged 5 years and 3 months was admitted to the hospital with a complaint of "enlarged breasts for 27 months, and elevated blood β-HCG for 8 months". The clinical data were summarized, and related literature up to March 2022 with the key words"Turner syndrome" "Gonadoblastoma" "Y chromosome" "human chorionic gonadotropin" "precocious" in PubMed, CNKI and Wanfang databases were reviewed. Results: The girl went to the local hospital for 2-month breast development at age of 3 years, and was found with a heart murmur diagnosed with "pulmonary venous malformation and atrial septal defect (secondary foramen type)". Surgical correction was performed. She experienced the progressive breast development, rapid linear growth and markedly advanced skeletal age, which cannot be explained by partial activation in the hypothalamic-pituitary-gonadal axis determined at the age of 3 years and 7 months in local hospital. Then whole-exome sequencing revealed chromosome number abnormality 45, X, which was confirmed by Karyotyping. At the age of 4 years and 6 months, serum β-HCG was found to be elevated (24.9 U/L) with no lesion found at the local hospital. On physical examination, she was found with breast development, pubic hair development and clitoromegaly with elevated serum testosterone (1.96 μg/L) and β-HCG (32.3 U/L). Sex determining region Y(SRY) gene was negative in peripheral blood sample. Thoracic and abdominal CT, head and pelvic magnetic resonance imaging were normal. Exploratory laparotomy confirmed the presence of a left adnexal tumor and a right fibrous streak gonad. During surgery, simultaneous samples of bilateral gonadal and peripheral venous blood were obtained and serum β-HCG, estradiol and testosteron concentrations was higher to lower from left gonadal venous blood, right gonadal venous blood, to peripheral venous blood. Bilateral gonadectomy was performed. Histopathology revealed bilateral gonadoblastomas. SRY was positive in bilateral gonadal tissues. After surgery, serum E₂, testerone and β-HCG returned to normal. So far 4 cases of HCG-secreting gonadoblastoma had been reported worldwide. The phenotypes of the 4 cases were all female, with virilization or amenorrhea, and the preoperative peripheral blood β-HCG concentrations were 74.4, 5.0, 40 456.0, and 42.4 U/L, respectively. Conclusions: There is a high risk of Gb in TS with Y chromosome components. Gb is infrequently presented with breast development, and Gb associated with HCG secretion is rare. Karyotyping should be performed in a phenotypic female with masculinization, and virilization in TS indicates the presence of Y chromosome material with concurrent androgen secreting tumors.
Humans ; Female ; Child, Preschool ; Gonadoblastoma/surgery* ; Turner Syndrome/complications* ; Virilism ; Chorionic Gonadotropin ; Ovarian Neoplasms