Role of 5-HT degradation in acute liver injury induced by carbon tetrachloride.

5-hydroxytryptamine (5-HT) is involved in the pathological processes of several liver diseases. Acute liver injury underlies the development of many liver diseases, but the mechanism remains unclear. We aimed to investigate the role of 5-HT in carbon tetrachloride (CCl4)-induced acute liver injury. Acute liver injury was induced with CCl4 (10 mg/kg) in mice pretreated with the 5-HT2A receptor antagonist sarpogrelate hydrochloride (SH) and the 5-HT synthesis inhibitor carbidopa (CDP). LO2 cells were treated with CCl4, 5-HT or 2,5-dimethoxy-4-idopametamine and pretreated with SH, CDP or the monoamine oxidase A (MAO-A) inhibitor clorgyline. Hematoxylin-eosin staining, immunohistochemistry, Real-time quantitative PCR, western blotting, fluorescent probe and biochemical markers were used to evaluate liver compromise. 5-HT2A receptor, 5-HT synthetase and MAO-A were expressed in hepatocytes; their gene and protein expression were upregulated by CCl4, which led to the degradation of mitochondrial 5-HT and overproduction of reactive oxygen species (ROS). Hepatic injury may be aggravated by ROS, which induce oxidative stress and the phosphorylation of p38 mitogen-activated protein kinase, Jun N-terminal kinase, extracellular regulated protein kinase, signal transducer and activator of transcription 3 and nuclear factor kappa-B. 5-HT2A receptor may contribute to acute liver injury by modulating 5-HT synthase and MAO-A expression. The synergistic action of SH and CDP treatment may inhibit CCl4-induced acute liver injury in a dose-dependent manner. Hence, CCl4-induced acute liver injury is due to an increase in mitochondrial ROS production caused by increased 5-HT degradation and probably involves increases in 5-HT2A receptor expression and 5-HT synthesis.

High-risk behaviour and HIV infection risk among non-local men who have sex with men with less than a single year's residence in urban centres: a multicentre cross-sectional study from China.

OBJECTIVES: Traditionally, subjects' migration status has usually been defined on the basis of their registered residency status. We attempted to redefine migration based on the duration of residency in their cities of migration and to explore more precisely the impact of migration on HIV infection risk in men who have sex with men (MSM). METHODS: A multisite cross-sectional study was conducted during 2012-2013 in seven Chinese cities. Questionnaire surveys were conducted and blood was drawn to test for antibodies to HIV, syphilis and herpes simplex virus-2 (HSV-2). MSM who were unregistered local residents and had resided in their cities of migration for ≤1 or >1 year were defined as migrant MSM, or transitional MSM, respectively. RESULTS: Compared with transitional MSM and local MSM, migrant MSM had poorer HIV knowledge and higher rates of high-risk behaviour, including earlier sexual debut, multiple sexual partners, participation in commercial sex and recreational drug use. Multivariate logistic regression analysis showed that HIV prevalence among migrant MSM was higher than local MSM (p<0.05). This relationship, however, did not hold for transitional MSM and local MSM (p>0.05). Male sex work, recreational drug use, syphilis infection and HSV-2 infection were independently associated with HIV infection among migrant MSM. CONCLUSIONS: Non-local MSM with shorter residence were at greater risk of HIV acquisition. More focus should be placed on HIV behavioural interventions targeting non-local MSM with temporary residence.

Treatment-seeking behaviour and barriers to service access for sexually transmitted diseases among men who have sex with men in China: a multicentre cross-sectional survey.

BACKGROUND: Delayed or inappropriate treatment for sexually transmitted diseases (STDs) increases the risk of HIV acquisition and may cause other harmful outcomes. However, studies on STD treatment-seeking behaviour and correlated factors in men who have sex with men (MSM) are scarce. This information is crucial for the promotion of STD treatment-seeking behaviour and reduction of HIV transmission among Chinese MSM. METHODS: During 2012-2013, a multicentre cross-sectional study was conducted in 7 Chinese cities. Participants completed an interview-questionnaire and gave venous blood samples, which were then tested for antibodies to HIV, syphilis, and herpes simplex virus-2 (HSV-2). MSM who tested positive for syphilis/HSV-2 or had obvious STD-related symptoms within the last 12 months were defined as suspected STD-infected MSM. RESULTS: Of the 4 496 eligible MSM who completed this survey, 24.4% (1 096/4 496) were categorized as suspected STD-infected MSM. 35.7% (391/1 096) of these MSM with suspected STD infections sought STD treatment in clinics within the last 12 months. Among MSM who did not attend STD clinics for treatment, the prevalence of syphilis and HSV-2 was significantly higher; the HIV prevalence and incidence within this subpopulation reached as high as 14.5% and 12.2/100 person-years, respectively. Multivariate logistic regression analysis indicated that having 7-12 years of education (vs. ≤6 years; aOR, 2.5; 95%CI, 1.0-6.1), ≥13 years of education (vs. ≤6 years: aOR, 2.8; 95%CI, 1.2-7.0), monthly income >500 USD (vs. ≤500 USD: aOR, 1.5; 95%CI, 1.1-2.1), obvious STD-related symptoms within last 12 months (aOR, 5.3; 95%CI, 3.7-7.5), being HIV infected (aOR, 1.7; 95%CI, 1.1-2.6), currently syphilis infected (aOR, 0.6; 95%CI, 0.4-0.9) and HSV-2 infected (aOR, 0.6; 95%CI, 0.5-0.9) were independent correlates with seeking STD treatment in clinics among Chinese MSM. CONCLUSIONS: The high prevalence of STD infection coupled with a low proportion of individuals who exhibit appropriate treatment-seeking behaviour create a high risk of a growing HIV epidemic among Chinese MSM. Models that prioritize better screening for and education about STDs should be urgently implemented, especially among low-income MSM.

Commercial sex and risk of HIV, syphilis, and herpes simplex virus-2 among men who have sex with men in six Chinese cities.

BACKGROUND: Men who have sex with men (MSM) are at high risk of HIV and sexually transmitted infections (STIs) in China and globally. Engaging in commercial sex put them at even greater risk. This study estimated the prevalence of HIV/STIs among three subgroups of MSM: MSM who sold sex (MSM-selling), MSM who bought sex (MSM-buying), and non-commercial MSM (NC-MSM) and evaluated the relationship between commercial sex and HIV/STIs. METHODS: We conducted a cross-sectional survey among MSM in six Chinese cities (Shenyang, Ji'nan, Changsha, Zhengzhou, Nanjing, and Kunming) from 2012 to 2013. Data on socio-demographics and sexual behaviors were collected. Serological tests were conducted to detect HIV, syphilis, and human simplex virus type 2 (HSV-2). RESULTS: Of 3717 MSM, 6.8% were engaged in commercial sex. The overall prevalence of HIV, syphilis and HSV-2 infections was 11.1, 8.8 and 12.1%, respectively. MSM-selling had higher prevalence of HIV (13.4%), syphilis (12.1%) and HSV-2 (17.9%) than NC-MSM (10.9, 8.7 and 11.9% for HIV, syphilis and HSV-2, respectively), though the differences are not statistically significant. Among MSM-selling, HIV prevalence was significantly higher for those who found sex partners via Internet than those did not (19.4% vs. 8.1%, P = 0.04). Compared to NC-MSM, MSM-selling were more likely to use recreation drugs (59.3% vs. 26.3%), have unprotected anal intercourse (77.9% vs. 61.7%), and have ≥10 male sex partners (46.2% vs. 6.2%) in the past 6 months (each P < 0.05). CONCLUSIONS: All three subgroups of MSM in six large Chinese cities have high prevalence of HIV/STIs. Those who sell sex only have a particularly high risk of acquiring and transmitting disease, and therefore, they should be considered as a priority group in HIV/STIs surveillance and intervention programs.

High HIV incidence epidemic among men who have sex with men in china: results from a multi-site cross-sectional study.

BACKGROUND: Recent upsurge of new HIV infections among men who have sex with men (MSM) is a major concern in China. Paucity of national-level information regarding the burden and predictors of this progressive epidemic of new infections called for a multi-centric, timely and comprehensive investigation. METHODS: Mixed methods were used to recruit MSM from seven cities in China between 2012 and 2013. Recent and established HIV infections were estimated by Western Blot and BED HIV-1 capture enzyme immunoassay. Syphilis and herpes simplex virus-2 (HSV-2) were also tested. RESULTS: A total of 4496 eligible MSM were recruited. The majority was aged ≤35 years (77.5 %), migrants (60.3 %), never married (69.8 %), and played receptive role in anal sex (70.5 %). The HIV prevalence was 9.9 %, and 41.9 % were recently infected, with sensitivity/specificity adjusted HIV incidence of 8.9 (95 % CI: 7.6-10.2)/100 Person-Years. The prevalence of history HSV-2 and syphilis were 12.5 % and 8.5 %, respectively. Recent HIV infection was associated with having multiple male partners (aOR = 1.4, 95 % CI 1.1-1.9), recreational drug use (aOR = 2.2, 95 % CI 1.6-3.0), anal bleeding (aOR = 2.1, 95 % CI 1.4-3.0), syphilis infection (aOR = 2.8, 95 % CI 1.9-4.3) and history HSV-2 infection (aOR = 2.3, 95 % CI 1.5-3.3). CONCLUSION: High rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among MSM in China. Targeted interventions to address high-risk MSM including those having multiple partners, history of recreational drug use and syphilis or HSV-2 infection seemed to be the need of the hour.

Recreational drug use and risks of HIV and sexually transmitted infections among Chinese men who have sex with men: Mediation through multiple sexual partnerships.

BACKGROUND: Recreational drug use (RDU) may result in sexual disinhibition and higher risk for HIV and other sexually transmitted infections (STIs) among men who have sex with men (MSM) in China. We assessed whether RDU was associated with HIV, syphilis, and herpes simplex virus type 2 (HSV-2) within the context of multiple sexual partnerships and unprotected sex. METHODS: We conducted a cross-sectional study among sexually-active MSM in six Chinese cities (Kunming, Jinan, Changsha, Zhengzhou, Nanjing, and Shanghai) in 2012-2013. We interviewed participants regarding RDU and sexual activity and drew blood for HIV, syphilis, and HSV-2. We fit multiple logistic regression models to assess associations of drug use and HIV, syphilis and HSV-2 infections, controlling for number of sexual partners and unprotected sex. RESULTS: Of 3830 participants, 28% reported ever using ≥1 of these drugs in the past 6 months: popper (alkyl nitrites), ecstasy, ice (methamphetamine), amphetamine, tramadol, and ketamine. In the past six months, 62% of MSM reported ≥2 sexual partners and 76% did not use condoms at last sexual encounter. HIV, syphilis and HSV-2 prevalences were 9.2%, 12.2%, and 10.3%, respectively.RDU was associated with HIV infection (aOR = 1.67; 95% CI, 1.31-2.13). Men with RDU were more likely to report multiple sexual partners (OR = 1.69; 95% CI, 1.44-1.98) and unprotected sex (aOR = 1.25; 95% CI, 1.05-1.49). The RDU-HIV association persisted (aOR = 1.58; 95% CI = 1.23-2.02) after adjusting for numbers of partners. CONCLUSIONS: RDU was associated with multiple sexual partnerships, unprotected sex, and HIV among Chinese MSM. It is plausible that RDU is a driver of increased sexual/HIV risk and/or may be an associated behavior with sexually risky lifestyles. Community engagement is needed.

[Relationship between MnSOD polymorphisms and susceptibility of chronic poisoning exposed to manganism occupationally].

OBJECTIVE: To study the relationship between polymorphisms of MnSOD and the susceptibility of chronic poisoning exposed to manganism occupationally. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[The prevalence and evolution of HIV drug-resistant strains in people who live with HIV/AIDS during HIV antiretroviral therapy in Shandong province].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The prevalence of HIV drug-resistant strains in Shandong province is still at a low level, but its evolution is complex.

[Survival analysis of 530 HIV infected former unsafe commercial blood and plasma donors].

OBJECTIVE: To investigate HIV survival time and it's influencing factors among former commercial blood and plasma donors engaged in unsafe blood donation practices in China. METHODS: HIV/AIDS cases from 8 counties (districts) in 4 provinces confirmed prior to January 24, 2006 related with former commercial blood and plasma donors were selected and data regarding infection, AIDS progression, death, and influencing factors were retrospectively collected. RESULTS: In 530 cases of HIV infection, 334 (63.0%) cases had developed AIDS, 168 (50.3%) had received antiretroviral therapy (ART), and 152 (29.0%) had died. For the 530 cases, there was an average (10.1 +/- 1.8) years of observation from time of infection. Among 166 AIDS patients not receiving ART, average survival was 9.1 years (95% CI: 9.1 - 9.4), with an 8 year survival rate of 52.0%. Among 168 AIDS patients receiving ART, average survival was 12.1 years (95% CI: 11.9 - 12.3), with a 12-year survival rate of 80.0%. In 3 years of ART, average survival was longer in the treatment group as compared to the no treatment group with a hazard ratio for death of 12.2. Univariate analysis showed a significant difference (P < 0.05) in AIDS patient average survival based on gender, age, location, ART status, and baseline CD(4)(+) T cells count. Results from multivariate COX-regression showed that highly active ant iretroriral therapy (HAART) was the strongest protective factor for prolonging AIDS patients' survival (HR = 13.3, P = 0.00). CONCLUSION: Although there are many factors influencing AIDS patients survival, intervention with HAART is the principle measure to prolong survival and decrease the risk of death.

[Study on the incidence and spatiotemporal dynamic variation of hemorrhagic fever with renal syndrome in Shandong province].

OBJECTIVE: To study the incidence and spatiotemporal dynamic variation of hemorrhagic fever with renal syndrome (HFRS) in Shandong province. METHODS: According to surveillance data on HFRS epidemics and host animals, a 'contour area multifractal model' was estimated on the HFRS' incidence and multi-analysis model was applied to study spatiotemporal dynamic variation. RESULTS: The process could be classified into 5 periods: 1st period (1974-1981) when HFRS was in completely natural focal state in Shandong, and the nature of focus was typical Apodemus type. 2nd period (1982-1986) indicated the process of expanding and merging of the Apodemus type focus in the southeastern part of Linyi district and the Rattus type focus was in the southern part of Jining city. 3rd period (1987-1990) indicated that through the expanding and merging of the two epidemic focuses,one mixed focus dominated by the Apodemus type had been formed in the hilly area of the southern and middle part of Shandong while another one dominated by the Rattus type in the Yellow River valley of the northwestern part of Shandong. 4th period (1991-1993) showed that the process of the spatial pattern of the mixed focus dominated by the Rattus type in Shandong. 5th period (1994-2004) referred to the spatial pattern of the mixed focus dominated by the Rattus became stabilized. CONCLUSION: Evolution of the characteristics of HFRS focus in Shandong province experienced the following three processes: the simple Apodemus type and the simple Rattus type were seen separately to the mixed foci with the Apodemus type dominant and the Rattus dominant type coexisted and merged to the stable state of the mixed focus with Rattus as the dominant one.

A novel transdermal patch incorporating isosorbide dinitrate with bisoprolol: in vitro and in vivo characterization.

The combination therapy of nitrate and selective beta-adrenoceptor antagonist has shown benefits for treatment of hypertension and heart disease than either drug alone. The objectives of the present study were to define effects on the anti-hypertension activity and pharmacokinetics of a novel transdermal patch incorporating isosorbide dinitrate (ISDN) with bisoprolol (BP). The 3:2 ratio of ISDN to BP (mg/mg) in the transdermal patches exhibited better anti-hypertension effect synergistically with a similar inhibiting heart rates effect to that of BP alone in renovascular hypertensive rats, and was therefore selected as a final formulation. The in vitro transdermal penetration of both ISDN and BP from the patches displayed a zero-order process, and the penetration rate constants were 7.4 microg/(cm(2)h) for ISDN, and 5.9 microg/(cm(2)h) for BP, respectively. After transdermal administration at single dose or multiple doses, the synergistic anti-hypertension effect was confirmed in spontaneously hypertensive rats also. The effect of each patch lasts for 3 days, and increased with the total dose of two drugs (2mg/cm(2), ISDN:BP=3:2, mg/mg), showing a dose dependant manner. After transdermal administration to rabbits, the absolute bioavailabilities were 33.6% for ISDN, and 31.3% for BP, respectively. The maximal concentrations (C(max)) of both drugs were significantly reduced while the areas under the plasma concentration-time curve (AUC), and mean residence times (MRT) were evidently increased and extended, respectively. As a patient-friendly, convenient, and multi-day dosing therapeutic system, the transdermal patches incorporating ISDN and BP could be promising for prevention and treatment of hypertension.

[Study on the effect of treatment and the status of drug resistance among HIV/AIDS patients treated with highly active antiretroviral therapy in Shandong province].

OBJECTIVE: To understand the effect of highly active antiretroviral therapy (HAART) on AIDS patients, and to explore the prevalence and the impact of HIV-1 drug resistance in Shandong province. METHODS: 2 cross-sectional studies were carried on in 2004 and 2005, to collect data on clinical symptoms and compliance of the AIDS patients with HAART through questionnaire. Informed-consent principle was followed to test on immunological, viral and laboratory index of them. HIV-1 drug genotype resistance by sequencing the gene of HIV-POL after RT-PCR was performed and analyzed. RESULTS: 31 AIDS cases with and. 27 AIDS cases without HAART, were studied. 83.3% and 64.5% of the AIDS patients with HAART showed that the CD4+ T cell count was rising to over 350/microl, in the first study (2004) and in the second (2005) study respectively but still 45.8% and 45.2% of AIDS patients under HAART in the 2 years showed a decreasing HIV load under the detected limit. However, these findings were showing remarkable difference when compared with the AIDS without HAART. 7 drug resistance gene sites were found in AIDS patients with HAART and in AIDS patients without HAART. The rate on high degree drug resistance mutation and total drug resistance rate of mutation of the former were higher remarkably than those of the latter. CONCLUSION: Most of the AIDS patients with HAART met the purpose of rebuilding immunity and control of HIV,as well as alleviation of symptoms. Although the drug resistance stain appeared in Shandong,but had little effect on HAART. AIDS; Drug resistance; Highly active antiretroviral therapy

[The epidemiological study on human immunodeficiency virus infection among paid blood donors living in Shandong provincial China Comprehensive Response Project Areas].

OBJECTIVE: To understand the current epidemic situation and high risk factors of human immunodeficiency virus (HIV) infection among paid blood donors living in Shandong provincial China Comprehensive Response (CARES) Project Areas. METHODS: All residents between 20 to 60 years old were selected from one or several counties in August 2003. RESULTS: There were 19 HIV(+) infections among 661 subjects interviewed. HIV prevalence rate among paid blood donors was higher (3.98%) than that of others (0.48%) while HIV prevalence rate was higher in plasma donors (7.24%) than that in both plasma and full blood donors (2.90%). There was no infections identified in full blood donors. Donors who donated blood during 1994 - 1995 had a higher prevalence rate (7.07%) than those who started donation after 1995 and those began donation before 1993 (0.99%). The rate of condom use was lower among paid blood donors (13.72%) than that of others. There was a lower rate of voluntary HIV testing among paid blood donors than that of others. CONCLUSION: The main high risk population of HIV infection were paid donors in CARES Project Areas, whose risk factor was plasma donation and were infected mainly before 1995. Both the rate of condom use and HIV testing were all very low, indicating that they knew little on HIV/AIDS and paid less attention to self-proctection. It is necessary to enhance HIV/AIDS health education and behavior intervention on paid blood donors.

[Study on the molecular epidemiology of people infected with human immunodeficiency virus-1 in Shandong province].

OBJECTIVE: To study the distribution of human immunodeficiency virus-1 (HIV-1) strains subtypes in Shandong province and to study their source in order to predict the epidemic trend. METHODS: Epidemiological investigation was made and 93 DNA fragments of HIV-1 env, gag, tat gene were amplified by nested polymerase chain reaction from people infected with HIV-1, in 2002 - 2003. Their C2-V3, P17/P24, 1st exon of tat and adjacent region were sequenced. RESULTS: Sequence analysis showed that there were 7 HIV-1 strains or circulating recombinant forms (CRFs), B' (n = 71), CRF01-AE (n = 9), CRF07-BC (n = 3), CRF08-BC (n = 3), B (n = 2), C (n = 2), CRF02-AG (n = 2). B' strains was the predominant which, covered 10 cities and 4 kinds of population including blood donors, blood receivers, spouses of the infected people and clients of the sex workers. CRF07-BC, CRF08-BC strains were identified in 5 cities, mainly from injecting drug users. CRF01-AE and other strains were found distributed in developed cities, among sex workers. CONCLUSION: There were many kinds of subtypes and CRFs of HIV and their genomes which generated obvious variation in Shandong province, suggesting that they might facilitate the spread of the disease in Shandong province.

[Molecular analysis of hantavirus isolated from Shandong province].

OBJECTIVE: To compare the molecular characteristics of hantaviruses isolated from Shandong province by using PCR typing and nucleotide sequencing. METHODS: Total cellular RNA was extracted from hantaviruses infected Vero E6 cells, viral cDNA was amplified by polymerase chain reaction. PCR products of partial M Segments of 4 strains of hantaviruses were sequenced. Cross neutralization tests were performed. RESULTS: Four strains of hantavirus isolated from Rottus in Shandong province were SEO like viruses. The homology between Shandong isolates and other SEO like viruses was high at both amino acid and nucleotide levels. The homology among those 4 strains of hantaviruses was 98%. CONCLUSIONS: The SEO like hantaviruses were more conserved than other hantaviruses. The homology of SEO like hantaviruses isolated from Shandong province was as high as 98% at nucleotides level, though they were isolated at more than 10-year intervals.