Risk and Protective Factors for the Mental Wellbeing of Deployed Healthcare Workers During the COVID-19 Pandemic in China: A Qualitative Study.

Background: Though many literatures documented burnout and occupational hazard among healthcare workers and frontliners during pandemic, not many adopted a systemic approach to look at the resilience among this population. Another under-studied population was the large numbers of global healthcare workers who have been deployed to tackle the crisis of COVID-19 pandemic in the less resourceful regions. We investigated both the mental wellbeing risk and protective factors of a deployed healthcare workers (DHWs) team in Wuhan, the epicenter of the virus outbreak during 2020. Method: A consensual qualitative research approach was adopted with 25 DHWs from H province through semi-structured interviews after 3 months of deployment period. Results: Inductive-Deductive thematic coding with self-reflexivity revealed multi-layered risk and protective factors for DHWs at the COVID-19 frontline. Intensive working schedule and high-risk environment, compounded by unfamiliar work setting and colleagues; local culture adaptation; isolation from usual social circle, strained the DHWs. Meanwhile, reciprocal relationships and "familial relatedness" with patients and colleagues; organizational support to the DHWs and their immediate families back home, formed crucial wellbeing resources in sustaining the DHWs. The dynamic and dialectical relationships between risk and protective factors embedded in multiple layers of relational contexts could be mapped into a socio-ecological framework. Conclusion: Our multidisciplinary study highlights the unique social connectedness between patient-DHWs; within DHWs team; between deploying hospital and DHWs; and between DHWs and the local partners. We recommend five organizational strategies as mental health promotion and capacity building for DHWs to build a resilient network and prevent burnout at the disaster frontline.

A national survey of HIV knowledge, sexual practices and attitude towards homosexuality for HIV elimination among young people in China.

Background Elimination of HIV is a public health priority in China, but there has been reports of an upsurge in HIV among young people. A nationwide cross-sectional survey was conducted to assess the awareness of HIV knowledge, attitudes towards homosexuality and practice of sexual behaviours among Chinese aged 15-24 years. METHODS: The face-to-face survey was conducted from June to August 2017, collecting data on sociodemographic characteristics, HIV-related knowledge, attitudes towards homosexuality and practice of sexual behaviours among Chinese senior high school and university students. A generalised linear model (GLM) was used to assess the different levels of HIV knowledge between groups, and identify the key contributors to HIV knowledge scores. RESULTS: The survey was completed by 73.6% (1355/1840) of the students approached. The overall level of HIV-related knowledge was low (58.9%, 10.6/18); 48.0% (650/1355) supported same-sex marriage; and 6.9% (93/1355) self-identified as homosexual or bisexual. The major factors associated with higher scores [mean ± standard deviation (s.d.)] in HIV knowledge among students included: having received school-based HIV education (11.47 ± 3.51 vs 9.02 ± 4.14, P < 0.05); support for same-sex marriage (11.69 ± 3.33 vs 9.49 ± 4.29, P < 0.05) and older age (11.61 ± 2.78 vs 9.87 ± 4.17, P < 0.05). Compared with females, males were significantly more likely (all P < 0.05) to report masturbation (60.7% vs 7.6%), pornography experiences (77.4% vs 35.3%), sexual encounters (24.6% vs 12.3%), casual sex (37.0% vs 18.1%) and sex under the influence of alcohol (29.5% vs 12.8%). CONCLUSIONS: There is is still much room for improvement in terms of HIV/AIDS prevention and health education for Chinese young people, and more comprehensive and diverse models of education for HIV prevention are urgently needed.

Design and Development of Smoking Cessation Apps Based on Smokers' and Providers' Perspectives in China: Survey Study.

BACKGROUND: Although there are more than 60 smartphone apps for smoking cessation in China, many of them do not include the content and features that health care professionals and smokers prefer-which may make them impractical, unengaging, and ineffective. Therefore, we investigated both health care providers' and smokers' preferences for features of future smoking cessation apps. OBJECTIVE: This study aimed to investigate Chinese health care providers' and smokers' desired features of a smoking cessation app, with the goal of providing design recommendations for app designers and researchers. METHODS: Both Chinese smokers who own smartphones (n=357) and Chinese health care providers (n=224) responded to a survey collecting data on their sociodemographic characteristics and opinions on the importance of 20 smoking cessation app design features studied in previous US research. RESULTS: Chinese health care providers expressed strong support of smoking cessation apps on a number of attitude indicators (range 153/224, 68.3% to 204/224, 91.1%). They rated nearly all (18/20) features as very or extremely important (range 52.2%-83.4%) and rated nearly all features (17/20) as more important than the smokers did. More than 60% of smokers rated the following 4 features as very or extremely important: allow sharing the process of smoking cessation with family members and friends (216/319, 67.7%), helping smokers track their progress (such as the amount of smoking per day; 213/319, 66.8%), helping with the side effects of medications and nicotine withdrawal symptoms (201/319, 63.0%), and adapting to ongoing needs and interests of smokers (194/319, 60.8%). Contrary to a similar study of US smokers and health care providers, Chinese smokers and providers rated reputation and ability to communicate with family members and friends as important features, whereas Chinese smokers rated privacy and security as less important. CONCLUSIONS: The design of future smoking cessation and health behavior change apps should consider perspectives of both providers and smokers as well as the role of culture.

Long non-coding RNA THRIL predicts increased acute respiratory distress syndrome risk and positively correlates with disease severity, inflammation, and mortality in sepsis patients.

BACKGROUND: This present study aimed to investigate the correlation of long non-coding RNA THRIL (lnc-THRIL) with acute respiratory distress syndrome (ARDS) risk, disease severity, inflammation, and mortality in sepsis patients. METHODS: A total of 109 sepsis patients admitted to intensive care units were consecutively recruited, and their blood samples were collected. After admission, patients were supervised and screened daily to identify the occurrence of ARDS. Clinical characteristics, routine laboratory testing, and disease severity were recorded, and all enrolled patients were followed up until death in the hospital or discharge for mortality records. Lnc-THRIL was detected by quantitative polymerase chain reaction, and inflammatory cytokine levels were measured by human enzyme-linked immunoassay. RESULTS: A total of 32 (29.4%) sepsis patients occurred ARDS and 77 (71.6%) did not. Lnc-THRIL was upregulated in ARDS group compared with non-ARDS group, and it had good value in distinguishing ARDS from non-ARDS in sepsis patients (AUC: 0.706; 95%CI: 0.602-0.809). Besides, lnc-THRIL, smoke, and chronic obstructive pulmonary disease independently predicted increased risk of ARDS. As for disease severity, lnc-THRIL positively correlated with APACHE II score and SOFA score in sepsis patients. Regarding inflammation, lnc-THRIL was positively associated with CRP, PCT, TNF-α, and IL-1ß levels in sepsis patients. Additionally, the mortality rate was 30.2%, and lnc-THRIL was upregulated in non-survivors compared with survivors, presenting a good value (AUC: 0.780; 95%CI: 0.683-0.876) in predicting mortality in sepsis patients. CONCLUSION: Lnc-THRIL predicts increased risk of ARDS and positively correlates with disease severity, inflammation, and mortality in sepsis patients.

Efficacy of celastrol combined with cisplatin in enhancing the apoptosis of U-2OS osteosarcoma cells via the mitochondrial and endoplasmic reticulum pathways of apoptosis.

Osteosarcoma is a common primary malignant tumor of bone, and the poor prognosis and low 5-year survival rate have not improved for three decades. The present study aimed to study the effect a combination of celastrol and cisplatin on the human osteosarcoma cell line U-2OS, and to investigate the mechanism by which celastrol/cisplatin induces the apoptosis of osteosarcoma cells. MTT and Annexin V-FITC/PI assays were used to evaluate the effects of combined celastrol/cisplatin on growth and apoptosis, respectively, in U-2OS cells. Morphological changes accompanying cell growth inhibition were observed using a fluorescence microscope. Combination index (CI) analysis was used to evaluate the combinatorial effects of celastrol/cisplatin treatment. Western blotting was used to quantify the expression of apoptosis-associated proteins. It was identified that celastrol/cisplatin inhibited the growth of U-2OS cells in a dose-dependent manner. CI analysis revealed that combined celastrol/cisplatin demonstrated a synergistic effect in U-2OS cells, with CIs ranging from 0.80 to 0.97 at effect levels from IC10 to IC70. In addition, it was observed that celastrol/cisplatin upregulated the expression of Bcl-associated X protein, cytochrome c, caspase-3 and C/EBP homologous protein, and downregulated the expression of Bcl-2, poly(ADP-ribose) polymerase, 78 kDa glucose-regulated protein and caspase-9, whereas the expression of caspase-8 remained unchanged. To conclude, celastrol/cisplatin induced apoptosis in U-2OS cells via the mitochondrial and endoplasmic reticulum pathways, particularly in the former. Celastrol/cisplatin therefore exhibits potential as a novel therapeutic combination for the treatment of osteosarcoma.

Content Analysis of Smartphone Apps for Smoking Cessation in China: Empirical Study.

BACKGROUND: With 360 million smokers, China consumes more cigarettes than any other country in the world. Given that 620 million Chinese own smartphones, smartphone apps for smoking cessation are increasingly used in China to help smokers quit. OBJECTIVE: This study analyzed and evaluated the contents of all smoking cessation apps (iOS and Android) available in China, applying the China Clinical Smoking Cessation Guideline (CCSCG; identical to the US Clinical Practice Guideline for Treating Tobacco Use and Dependence) as a framework for analysis. METHODS: We conducted a content analysis of Chinese Android and iOS smoking cessation apps (N=64) designed to assist users in quitting smoking. Each app was independently coded by two raters for its approach to smoking cessation and adherence to the CCSCG. We also recorded the features of smoking cessation apps (eg, release date, size, frequency of downloads, user ratings, type, quality scores by raters, and designers). Linear regression was used to test predictors of popularity and user-rated quality. RESULTS: Chinese smoking cessation apps have low levels of adherence to guidelines, with an average score of 11.1 for Android and 14.6 for iOS apps on a scale of 0 to 46. There was no significant association between popularity, user rating, and the characteristics of apps. However, there was a positive relationship between popularity, user rating, and adherence score. CONCLUSIONS: Chinese apps for smoking cessation have low levels of adherence to standard clinical practice guidelines. New apps need be developed and existing apps be revised following evidence-based principles in China.

"Under the Same Quilt": The Paradoxes of Sex Between Men in the Cultural Revolution.

This article describes the paradoxes experienced by homosexual men during the Chinese Cultural Revolution. Interviews with 31 elderly Chinese gay men were carried out in four cities in China in 2011. Although homosexual men were terribly persecuted, chaotic situations and dislocations of youth from their families provided young homosexual men with a remarkable degree of personal freedom and the opportunity to explore same-sex relations. Analysis of this seemingly contradictory conflation of persecution and freedom will allow us to explore the conditions and effects of the coming of age of homosexual men in a unique epoch in Chinese history.

Correlations between the feature of sagittal spinopelvic alignment and facet joint degeneration: a retrospective study.

BACKGROUND: Sagittal spinopelvic alignment changes associated with degenerative facet joint arthritis have been assessed in a few studies. It has been documented that patients with facet joint degeneration have higher pelvic incidence, but the relationship between facet joint degeneration and other sagittal spinopelvic alignment parameters is still disputed. Our purpose was to evaluate the correlation between the features of sagittal spinopelvic alignment and facet joint degeneration. METHODS: Imaging data of 140 individuals were retrospectively analysed. Lumbar lordosis, pelvic tilt (PT), pelvic incidence (PI), sacral slope, and height of the lumbar intervertebral disc were measured on lumbar X-ray plates. Grades of facet joint degeneration were evaluated from the L2 to S1 on CT scans. Spearman's rank correlation coefficient and Student's t-test were used for statistical analyses, and a P-value <0.05 was considered statistically significant. RESULTS: PI was positively associated with degeneration of the facet joint at lower lumbar levels (p < 0.001 r = 0.50 at L5/S1 and P = 0.002 r = 0.25 at L4/5). A significant increase of PT was found in the severe degeneration group compared with the mild degeneration group: 22.0° vs 15.7°, P = 0.034 at L2/3;21.4°vs 15.1°, P = 0.006 at L3/4; 21.0° vs 13.5°, P = 0.000 at L4/5; 20.8° vs 12.1°, P = 0.000 at L5/S1. CONCLUSION: Our results indicate that a high PI is a predisposing factor for facet joint degeneration at the lower lumbar spine, and that severe facet joint degeneration may accompany with greater PT at lumbar spine.

The correlation between radiographic and pathologic grading of lumbar facet joint degeneration.

BACKGROUND: Before performing spine non-fusion surgery that retains the facet joints, choosing an accurate radiographic method to evaluate the degree of facet joint degeneration is extremely important. Therefore, the objective of this study was to determine the accuracy and reliability of different radiographic classifications by analyzing the correlation between radiographic and pathologic grading of lumbar facet joint degeneration. Taking the pathologic examination as standard, the consistency of computed tomography (CT) and magnetic resonance imaging (MRI) assessment of lumbar facet joint degeneration was compared. METHODS: A total of 74 facet joints obtained from 42 patients who underwent posterior lumbar surgery were evaluated. All patients underwent CT and MRI before surgery. The pathologic grade was evaluated with a method based on hematoxylin-eosin and toluidine blue staining. The radiographic grade was evaluated using the methods proposed by different authors. RESULTS: There was a moderate consistency between pathologic and radiographic grading for facet joint degeneration. The weighted kappa coefficients comparing pathologic with radiographic grading were 0.506 for CT, 0.561 for MRI, and 0.592 for CT combined with MRI, respectively. Taking the pathologic examination as standard, the consistency of CT and MRI examination was also moderate, and the weighted kappa coefficient was 0.459. CONCLUSION: The radiographic examination has moderate accuracy and reliability for evaluating degeneration of facet joints. Therefore, a more accurate method for evaluating the degeneration of facet joints is necessary before performing spine non-fusion surgery that retains the facet joints.

Interleukin-17A contributes to the development of post-operative atrial fibrillation by regulating inflammation and fibrosis in rats with sterile pericarditis.

Post-operative atrial fibrillation (AF) remains a common cause of morbidity. Increasing evidence indicates that inflammation and atrial fibrosis contribute to the pathogenesis of this condition. Interleukin (IL)-17A, a potent pro-inflammatory cytokine, has been implicated in the development of a number of cardiovascular diseases. However, its role in post-operative AF remains unknown. In the present study, sterile pericarditis (SP) was induced in rats by the epicardial application of sterile talc. AF was induced by transesophageal burst pacing. Western blot analysis was applied to quantify the expression of IL-17A. Quantitative PCR was used to detect the mRNA expression of IL-17A, IL-6, IL-1ß, transforming growth factor-ß1 (TGF-ß1), collagen type 1 (Col-1), collagen type 3 (Col-3) and α-smooth muscle actin (α-SMA). Gelatin zymography and reverse gelatin zymography were used to quantify the levels of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Histological analyses were performed to determine the extent of tissue inflammation and fibrosis. The rats with SP presented with a shorter refractoriness, a higher incidence and duration of AF, an enhanced susceptibility to developing AF, increased mRNA levels of AF-related pro-inflammatory cytokines (IL-6, IL-1ß and TGF-ß1), as well as marked atrial inflammation and fibrosis. The atrial IL-17A levels were elevated and correlated with the probability of developing AF. Treatment with anti-IL-17A monoclonal antibody decreased the levels of atrial IL-17A, prolonged refraction and markedly suppressed the development of AF. Simultaneously, inflammation and fibrosis were alleviated, which was further demonstrated by a decreased expression of AF-related pro-inflammatory cytokines, a downregulation in fibrosis-related mRNA expression (Col-1, Col-3 and α-SMA) and by the decreased activity of MMP-2/9 and TIMPs. Thus, the findings of our study indicate that IL-17A may play a pathogenic role in post-operative AF by inducing inflammation and fibrosis in rats with SP.

Absence of the first two zinc fingers in BCL6 causes the loss of inhibitory effects on cell growth.

BCL6ZF is a novel transcript of BCL6, which lacks the first two zinc fingers of BCL6. It has been established that BCL6 acts as a sequence­specific transcriptional repressor, however, the functions of BCL6ZF remain undefined. By generating stably overexpressed BCL6 and BCL6ZF in NCI­H1299 lung cancer cells, it was found that BCL6 suppressed the levels of cell growth associated with impaired G1 phase progression compared with those of the mock control cells. However, the effects of BCL6ZF on cell growth and the cell cycle were negligible. Further study of these results demonstrated that eight genes downstream of BCL6 were markedly downregulated by the overexpression of BCL6, whereas BCL6ZF suppressed only TGFBI, indicating that the loss of the first two zinc fingers caused the loss of the inhibitory effects on cell growth and transcriptional repression. In addition, it was determined that the BCL6ZF protein was not degraded as easily as BCL6 protein by the ubiquitin/proteasome pathway, implying that the loss of the first two zinc fingers changes the three­dimensional structure of BCL6ZF. The results demonstrated that BCL6 and BCL6ZF had different role in H1299 cells both in vitro and in vivo. The loss of its inhibitory effects on cell growth and transcriptional repressions.

Acacetin blocks kv1.3 channels and inhibits human T cell activation.

BACKGROUNDS/AIMS: Acacetin, a natural flavonoid compound, has been proven to exert anti-inflammatory and immunomodulatory effects. Kv1.3 channels, highly expressed in human T cells, are attractive therapeutic targets to treat inflammatory and immunological disorders. The present study was designed to characterize the inhibition of Kv1.3 channels by Acacetin in human T cells and examine its role in T cell activation. METHODS: Whole-cell patch-clamp was applied to record the Kv1.3 and KCa currents in human T cells; Western blot was used to detect Kv1.3 expression as well as NFAT1 and NF-κB activity; Fluo-4, CCK-8 and an ELISA kit were used to measure Ca(2+) influx, proliferation, and IL-2 secretion, respectively. RESULTS: Acacetin decreased the Kv1.3 current, accelerated the decay rate and negatively shifted the steady-state inactivation curves in a concentration-dependent manner. The IC50 values at +40 mV for peak and the current at end of pulse were 21.09 ± 2.75 and 3.63 ± 0.25 µmol/L, respectively. Treatment with Acacetin for 24 h significantly inhibited Kv1.3 protein expression. Additionally, paralleling Kv1.3 inhibition, Acacetin also inhibited Ca(2+) influx, the Ca(2+)-activated transcription factors NFAT1, NF-κB p65/p50 activity, and proliferation as well as IL-2 production. Small interfering RNA against Kv1.3 reduced the inhibitory effect of Acacetin on IL-2 secretion. CONCLUSIONS: Acacetin blocks the Kv1.3 channel and inhibits human T cell activation. This action most likely contributes to its immunomodulatory and anti-inflammatory actions.

Socio-cultural influences on the transmission of HIV among gay men in rural China.

Bisexual behaviours are relatively common among men who have sex with men in China. This pilot study aims to reveal the complex processes through which such men manage their sexuality, family responsibilities and sexual behaviours in a rural Chinese setting. A total of 15 men who have sex with men were recruited by purposive sampling. Face-to-face in-depth interviews were conducted to explore participants' views about their sexual experiences and practices. The Chinese traditional moral code, family values and gender roles that form the crucial components of Confucianism were reflected in the participants' efforts to maintain familial and social harmony through a compromised form of sexual partnership. Most study participants demonstrated a mixed experience of social stigma, sexual naiveté and ignorance of HIV and sexually transmitted infections (STIs). Under cultural and family pressure, men who have sex with men entered heterosexual marriages with the intention of maintaining a balance between their collectivist (familial) obligations and their individualistic (same-sex sexual) desires. However, the opaque nature of their concurrent sexual relationships may endanger their personal health and accelerate HIV and STI transmission. Reducing the stigma and social prejudice associated with male same-sex sexual relations is essential for any culturally sensitive HIV-prevention programme to succeed in rural China.

Qualitative exploration of HIV-related sexual behaviours and multiple partnerships among Chinese men who have sex with men living in a rural area of Yunnan Province, China.

BACKGROUND: The HIV epidemic has been spreading rapidly among men who have sex with men (MSM) in China. The present study explored the pattern of HIV-related high-risk sexual practices among MSM in a rural Chinese setting. METHODS: Data were collected by semistructured in-depth interviews conducted among 15 MSM in Yuxi Prefecture, Yunnan Province, China. Fifteen respondents were recruited through a local non-governmental organisation via purposive sampling. Thematic analysis was used. RESULTS: Technological changes, risk behaviours, social stigma and high migration rates have played a significant role in the spread of HIV among MSM in rural China. The Internet has become the primary channel for soliciting casual sex partners in the MSM community. Bisexuality and having concurrent and multiple sexual partners were common among rural MSM. A large number of sexual partners and low condom use in all MSM partnership types were noted. Due to Chinese cultural traditions and social stigma, Chinese rural MSM were reluctant to disclose their homosexuality. Rural-to-urban migrant MSM were often engaged in the commercial sex trade. CONCLUSIONS: Rural MSM is a distinctive and complex population with multiple identities in China. Concurrent multiple sexual partnerships, high mobility and low disclosure rate are the major challenges for HIV prevention and intervention programs in MSM.

Potent suppression of Kv1.3 potassium channel and IL-2 secretion by diphenyl phosphine oxide-1 in human T cells.

Diphenyl phosphine oxide-1 (DPO-1) is a potent Kv1.5 channel inhibitor that has therapeutic potential for the treatment of atrial fibrillation. Many other Kv1.5 channel blockers also potently inhibit the Kv1.3 channel, but whether DPO-1 blocks Kv1.3 channels has not been investigated. The Kv1.3 channel is highly expressed in activated T cells, which is considered a favorable target for immunomodulation. Accordingly, we hypothesized that DPO-1 may exert immunosuppressive and anti-inflammatory effects by inhibiting Kv1.3 channel activity. In this study, DPO-1 blocked Kv1.3 current in a voltage-dependent and concentration-dependent manner, with IC50 values of 2.58 µM in Jurkat cells and 3.11 µM in human peripheral blood T cells. DPO-1 also accelerated the inactivation rate and negatively shifted steady-state inactivation. Moreover, DPO-1 at 3 µM had no apparent effect on the Ca²âº activated potassium channel (K(Ca)) current in both Jurkat cells and human peripheral blood T cells. In Jurkat cells, pre-treatment with DPO-1 for 24 h decreased Kv1.3 current density, and protein expression by 48±6% and 60±9%, at 3 and 10 µM, respectively (both p<0.05). In addition, Ca²âº influx to Ca²âº-depleted cells was blunted and IL-2 production was also reduced in activated Jurkat cells. IL-2 secretion was also inhibited by the Kv1.3 inhibitors margatoxin and charybdotoxin. Our results demonstrate for the first time that that DPO-1, at clinically relevant concentrations, blocks Kv1.3 channels, decreases Kv1.3 channel expression and suppresses IL-2 secretion. Therefore, DPO-1 may be a useful treatment strategy for immunologic disorders.

18ß-Glycyrrhetinic acid potently inhibits Kv1.3 potassium channels and T cell activation in human Jurkat T cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice has been extensively used in traditional medicines for treatment of many diseases, including inflammations and immunological disorders. Recent studies have shown that the anti-inflammatory and immunomodulation activities of licorice have been attributed to its active component, glycyrretinic acid (GA). GA consists of two isoforms, 18α- and 18ß-. However, its mechanism remains poorly understood. AIM OF THE STUDY: We compared the effects of two isoforms on Kv1.3 channels in Jurkat T cells and further characterized the inhibition of Kv1.3 channels by 18ß-GA in CHO cells. In addition, we examined the effects of 18ß-GA on Kv1.3 gene expression, Ca(2+) influx, proliferation, as well as IL-2 production in Jurkat T cells. MATERIALS AND METHODS: Whole-cell patch-clamp technique was applied to record Kv1.3 currents in Jurkat T or CHO cells. Real-time PCR and Western blotting were used to detect gene expression. Fluo-4, CCK-8 kit and ELISA kit were used to measure Ca(2+) influx, proliferation, and IL-2 secretion in Jurkat T cells, respectively. RESULTS: Superfusion of 18ß-GA (10-100 µM) blocked Kv1.3 currents in Jurkat T cells, while 18α-GA at the same concentration had no effect. The 18ß-GA induced inhibition had a voltage- and concentration-dependent manner with an IC50 of 23.9±1.5 µM at +40 mV in CHO cells. Furthermore, 18ß-GA significantly inhibited Kv1.3 gene expression. In addition, paralleling Kv1.3 inhibition, 18ß-GA also inhibited Ca(2+) influx, proliferation as well as IL-2 production in Jurkat T cells. CONCLUSION: 18ß-GA blocks Kv1.3 channels, which probably involves its anti-inflammatory and immunomodulation effects.

Blocking of the human ether-à-go-go-related gene channel by imatinib mesylate.

Imatinib mesylate (IM), a widely prescribed powerful tyrosine kinase inhibitor, has been associated with increased risk of heart failure and is known to induce cell apoptosis and death in isolated cardiomyocytes. In addition to acquired long QT syndrome, pharmacological inhibition of human ether-à-go-go-related gene (HERG) channel has been reported to involve in apoptosis. The present study was undertaken to characterize the biophysical properties of IM on HERG and the molecular determinants of HERG blockade using mutant channels (Y652A and F656A). Wild type (WT) and mutant HERG channels were expressed in HEK-293 cells and Xenopus oocytes and the currents (I(HERG)) were measured using patch-clamp and two-microelectrode voltage-clamp techniques. IM inhibited WT I(HERG) in a concentration-dependent manner with an IC(50) of 19.51±2.50 µmol/L and 44.76±1.54 µmol/L in HEK-293 cells and Xenopus oocytes, respectively. The IM-induced inhibition of WT I(HERG) followed a voltage- and time-dependent manner. The blockade was enhanced by further activation of currents, which were in accordance with an open-channel blockade. The V(1/2) for steady-state activation shifted from -15.48±1.21 to -26.66±2.98 mV (p<0.05, n=6). The inactivation kinetics and voltage dependence of steady-state inactivation of the WT HERG channel were not significantly altered by IM. Two S6 domain mutants, F652A and Y656A, attenuated IM-induced inhibition of WT I(HERG). Therefore, IM preferentially blocked the open HERG channel through F652 and Y656, providing a molecular mechanism for the cardiac side effects during the clinical administration of IM.

HIV and sexually transmissible infections among money boys in China: a data synthesis and meta-analysis.

BACKGROUND: Commercial sex workers within the population of men who have sex with men (MSM) in China, known as 'money boys' (MBs), are perceived to be at higher risk for HIV and other sexually-transmissible infections (STIs). METHODS: We conducted a systematic review and meta-analyses from peer-reviewed literature accessed in two English (PubMed and Embase) and three Chinese databases (CNKI, CQVIP, Wanfang data). A data synthesis exercise was carried out to determine the extent and patterns of behaviours and HIV/STI epidemics. Pooled estimates, with 95% confidence intervals, for each study variable were calculated. RESULTS: Thirty-two eligible articles (9 in English and 23 in Chinese) were identified. Our analysis indicated that Chinese MBs are generally young, currently employed, at low literacy levels and highly mobile. The prevalence of HIV, syphilis and co-infection among MBs were estimated to be 6.0% (4.2-8.5%), 12.4% (9.9-15.3%) and 2.2% (1.1-4.1%) over the period of 2004-2011. Level of condom use among MBs is generally higher than the broader MSM population (69.2% at last act, and 48.5% consistently over the past 6 months). One-third of the Chinese MBs identified themselves as bisexual and 8.7% (5.6-13.5%) are currently married to a female. Further, 40.9% (34.5-47.7%) of MBs participated in group sex in the past 12 months and 14.8% (10.6-20.3%) concurrently use illicit drugs. CONCLUSIONS: HIV/STI epidemics have affected Chinese MBs but the evidence suggests that the extent of infections is not greater than among other MSM in China.

Hypoxia induces voltage-gated K+ (Kv) channel expression in pulmonary arterial smooth muscle cells through hypoxia-inducible factor-1 (HIF-1).

Hypoxia-inducible factor-1 (HIF-1) regulates the expression of hypoxia-inducible genes by binding erythropoietin (EPO) enhancer fragments. Of these genes, HIF-1 upregulates voltage-gated K+1.2 channels (Kv1.2) in rat PC12 cells. Whether HIF-1 regulates hypoxia-induced Kv channel expression in cultured pulmonary artery smooth muscle cells (PASMCs), however, has not been determined. In this study, we investigated the effects of hypoxia on the expression of Kv1.2 Kv1.5, Kv2.1, and Kv9.3 channels in PASMCs and examined the direct role of HIF-1 by transfecting either wild type or mutant EPO enhancer fragments. Our results showed that 18 h exposure to hypoxia significantly increased the expression of Kv1.2, Kv1.5, Kv2.1, and Kv9.3; and this hypoxia-induced upregulation was completely inhibited after transfection with the wild type but not mutant EPO enhancer fragment. These results indicate that HIF-1 regulates hypoxia-stimulated induction of Kv1.2 Kv1.5, Kv2.1, and Kv9.3 channels in cultured PASMCs.