DYNLL1 accelerates cell cycle via ILF2/CDK4 axis to promote hepatocellular carcinoma development and palbociclib sensitivity.

BACKGROUND: Disorder of cell cycle represents as a major driver of hepatocarcinogenesis and constitutes an attractive therapeutic target. However, identifying key genes that respond to cell cycle-dependent treatments still facing critical challenges in hepatocellular carcinoma (HCC). Increasing evidence indicates that dynein light chain 1 (DYNLL1) is closely related to cell cycle progression and plays a critical role in tumorigenesis. In this study, we explored the role of DYNLL1 in the regulation of cell cycle progression in HCC. METHODS: We analysed clinical specimens to assess the expression and predictive value of DYNLL1 in HCC. The oncogenic role of DYNLL1 was determined by gain or loss-of-function experiments in vitro, and xenograft tumour, liver orthotopic, and DEN/CCl4-induced mouse models in vivo. Mass spectrometry analysis, RNA sequencing, co-immunoprecipitation assays, and forward and reverse experiments were performed to clarify the mechanism by which DYNLL1 activates the interleukin-2 enhancer-binding factor 2 (ILF2)/CDK4 signalling axis. Finally, the sensitivity of HCC cells to palbociclib and sorafenib was assessed by apoptosis, cell counting kit-8, and colony formation assays in vitro, and xenograft tumour models and liver orthotopic models in vivo. RESULTS: DYNLL1 was significantly higher in HCC tissues than that in normal liver tissues and closely related to the clinicopathological features and prognosis of patients with HCC. Importantly, DYNLL1 was identified as a novel hepatocarcinogenesis gene from both in vitro and in vivo evidence. Mechanistically, DYNLL1 could interact with ILF2 and facilitate the expression of ILF2, then ILF2 could interact with CDK4 mRNA and delay its degradation, which in turn activates downstream G1/S cell cycle target genes CDK4. Furthermore, palbociclib, a selective CDK4/6 inhibitor, represents as a promising therapeutic strategy for DYNLL1-overexpressed HCC, alone or particularly in combination with sorafenib. CONCLUSIONS: Our work uncovers a novel function of DYNLL1 in orchestrating cell cycle to promote HCC development and suggests a potential synergy of CDK4/6 inhibitor and sorafenib for the treatment of HCC patients, especially those with increased DYNLL1.

Tectoridin inhibits the growth of bladder cancer by regulating PI3K/MAPK pathway through RAB27B.

Bladder cancer (BC) is a common and malignant tumor of the urinary tract, and its treatment options are limited. Tectoridin (TEC) has antitumor activity against prostate and colon cancer, but its effects on BC are poorly understood. BC cells were treated with increasing concentrations of TEC, and its effects on cell proliferation, migration, invasiveness, and apoptosis were assessed. Xenograft mouse model was used to evaluate the influences of TEC on BC tumor growth. Western blot analysis was conducted to explore the downstream pathways affected by TEC. TEC treatment decreased BC cell viability in a dose-dependent manner (IC50 ≈ 25 µM), and inhibited cell proliferation, migration, and invasiveness while promoting apoptosis. Clinical analysis revealed high expression of RAB27B in BC tumor tissues, particularly in advanced stages, correlating with an unfavorable prognosis. In vitro experiments demonstrated that TEC suppressed the PI3K/MAPK pathway by targeting RAB27B, and overexpression of RAB27B counteracted the antitumor effects of TEC. In xenograft models, TEC administration suppressed tumor growth, reduced tumor volume, inhibited cell proliferation, and suppressed the PI3K/MAPK pathway, highlighting its potential as an inhibitor of tumor growth. TEC suppresses BC tumor growth by targeting RAB27B and inactivating the PI3K/MAPK signaling and may provide a promising therapeutic target for BC treatment.

Psychological Mechanisms of Internalized HIV Stigma Affect Sleep Impairment among People Living with HIV in China: A follow-up Study.

Prior studies have demonstrated that HIV-related stigma (e.g., internalized HIV stigma) is detrimental to the physical and mental health (e.g., sleep impairment and depressive symptoms) of people living with HIV (PLWH). However, follow-up data are limited regarding the longitudinal relationships between internalized HIV stigma, future orientation, self-esteem, depressive symptoms, and sleep impairment. The present study attempted to examine a mediation model involving these variables among Chinese PLWH. A two-wave follow-up design (6 months intervals) was employed in a final sample of 1,140 Chinese PLWH (Mage = 41.63, SD = 9.29, age range: 21-67 years; 64.6% men). Participants completed Internalized HIV Stigma Scale, Optimism About the Future Scale, Rosenberg Self-Esteem Scale, Center of Epidemiological Studies Depression Scale, and an adapted version of Pittsburgh Sleep Quality Index. Results revealed that internalized HIV stigma at baseline had a significant direct relationship with sleep impairment over time, and a significant indirect relationship with increased sleep impairment over time via future orientation and depressive symptoms. Furthermore, the linkage between internalized HIV stigma and sleep impairment was serially mediated via self-esteem and depressive symptoms. This study highlights the deleterious effects of internalized HIV stigma on the physical and psychological health of PLWH. The findings suggest that interventions targeting internalized HIV stigma and related factors such as future orientation, self-esteem, and depressive symptoms may facilitate improvements in sleep quality and overall well-being among PLWH.

Longitudinal Analysis of the Relationship Between Internalized HIV Stigma, Perceived Social Support, Resilience, and Depressive Symptoms Among People Living with HIV in China: A Four-Wave Model.

Depression is one of the most common mental health problems among people living with HIV (PLWH). However, the longitudinal psychological mechanism underlying the link of internalized HIV stigma and depressive symptoms remains a research gap. This study attempted to articulate how and to what extent perceived social support and resilience mediate the longitudinal associations between internalized HIV stigma and depressive symptoms. A sample consisting of 1,098 Chinese PLWH (Mage = 38.63, SD = 9.20; 63.9% male) with a six-month interval and four waves of follow-up was used in the current study. Participants were asked to complete self-report questionnaires. The associations among main study variables were examined via a complete longitudinal mediation approach. Results indicated that the linkage between internalized HIV stigma at T1 and depressive symptoms at T4 was serially mediated by perceived social support at T2 and resilience at T3, and perceived social support at T2 and depressive symptoms at T3 serially mediated the relationship between resilience at T1 and internalized HIV stigma at T4. Depressive symptoms at a previous time point consistently predicted the levels of internalized HIV stigma at subsequent time points. The study highlights the complex interplay between internalized HIV stigma, mental health problems, and protective factors in a longitudinal context. The findings suggest the need to incorporate interventions aimed at enhancing social support and resilience in mental health programs for PLWH, as these factors may interrupt the pathway from internalized HIV stigma to depressive symptoms and potentially improve the overall psychological well-being of this population.

Psychosocial Factors Predicting HIV Disclosure Stage Transitions: An Evaluation of A Theory-Based Parental HIV Disclosure Intervention among Parents Living with HIV in China.

Appropriate parental HIV disclosures (i.e., parents living with HIV [PLH] tell their HIV diagnosis to their children) benefit parents, children, and family relations. Psychosocial factors could influence the decision-making process of parental HIV disclosure. Using the Health Action Process Approach to frame stages (pre-intention, intention, and action) in the decision-making process, this study aimed to investigate how psychosocial factors predict HIV disclosure stage transitions among PLH in China. Data were collected from a randomized clinical trial of a theory-based parental HIV disclosure intervention among 791 PLH. The predictive effects of psychosocial factors on disclosure stage transitions were examined using a Markov chain model matrix. Results showed that action self-efficacy and action planning were significant predictors of parental HIV disclosure stage transitions. Considering stage-specific psychosocial predictors may contribute to effective interventions to promote appropriate HIV disclosure among PLH in China.

Exploring the Longitudinal Influence of Perceived Social Support, HIV Stigma, and Future Orientation on Depressive Symptoms Among People Living with HIV in China.

Prior studies demonstrated that perceived social support is negatively associated with behavioral and mental health problems among people living with HIV (PLWH). However, longitudinal data regarding the associations between perceived social support, internalized HIV stigma, future orientation, and depressive symptoms are limited. The current study aimed to investigate the possible indirect relationship between these variables using four-wave follow-up data (6-month intervals) from a sample of 1,098 Chinese PLWH (Mage = 38.63, SD = 9.20, age range: 18-60 years; 63.9% men). All participants were asked to complete an adapted version of Perceived Social Support Scale, Internalized HIV Stigma Scale, Optimism About the Future Scale, and Center of Epidemiological Studies Depression Scale. Results indicated that perceived social support at baseline was negatively related to depressive symptoms at wave 4. Internalized HIV stigma at wave 2 and future orientation at wave 3 indirectly affected the linkage between perceived social support at baseline and depressive symptoms serially over time. This study highlights the essential role of perceived social support in alleviating depressive symptoms among PLWH, and underscores the complex interplay in which internalized HIV stigma and future orientation serially mediated the relationship between perceived social support and depressive symptoms. These findings suggest the need for integrated interventions to enhance social support, address HIV-related stigma, and promote positive future orientation, which could potentially alleviate depressive symptoms and promote mental well-being among PLWH.

How Does Anticipated HIV Stigma Affect Medication Adherence? A Longitudinal Path Analysis Model.

Prior research has documented that anticipated HIV stigma may play an important predictive role in medication adherence among people living with HIV (PLWH). However, longitudinal data on the mechanisms underlying this linkage are scarce. The current study aimed to explore the longitudinal mediation association among anticipated HIV stigma, medication adherence support, HIV self-management, and medication adherence. A four-wave sample consisting of 1,098 Chinese PLWH (Mage = 38.63, SD = 9.20; 63.9% male) with a six-month interval was used in the current study. Participants were asked to complete self-report questionnaires. A path analysis model was analyzed. Results indicate that anticipated HIV stigma at baseline was positively related to medication adherence at Time 4 (T4). Medication adherence support at Time 2 (T2) and HIV self-management at Time 3 (T3) serially mediated the anticipated HIV stigma at Time 1 (T1) and medication adherence at T4. These findings provide critical insights into the mediating roles of medication adherence support and HIV self-management in the relationship between anticipated HIV stigma and medication adherence over time. Such an understanding has important implications for the development of tailored interventions and public health strategies aimed at improving medication adherence among PLWH in the context of HIV-related stigma.

Psychological Distress Mediates the Relationship Between HIV-Related Stigma and Prescription Opioid Misuse Among Chinese People Living with HIV.

Prescription opioid misuse (POM) among people living with HIV (PLWH) is a serious concern due to risks related to dependence and overdose, and PLWH may be at higher risk for POM due to psychosocial stressors including psychological distress. However, scant POM research has examined the role of HIV-related stigma (e.g., internalized stigma, enacted stigma) in POM among PLWH. Guided by minority stress theory, this study examined a hypothesized serial mediation among enacted stigma, internalized stigma, psychological distress, and POM within a sample of Chinese PLWH with pain symptoms enrolled in a wave (between November 2017 and February 2018) of a longitudinal cohort study in Guangxi (n = 116). Models were tested individually for six enacted stigma experiences, controlling for key demographic and health-related variables (e.g., CD4 + count). Results showed HIV-related workplace discrimination was the most common stigma experience (12%,) and 10.3% of PLWH reported POM. Indirect effect analyses showed that internalized stigma was indirectly associated with POM through psychological distress. Internalized stigma and psychological distress mediated the association between workplace discrimination and POM. Family discrimination, gossip, and healthcare discrimination were directly associated with POM. This study suggests that Chinese PLWH may engage in POM to cope with psychological distress that is rooted in HIV-related stigma and highlights the important context of workplace discrimination for PLWH. Implications for interventions to reduce POM among PLWH are discussed.

Impact of children's age on parental HIV disclosure: a parental HIV disclosure intervention among parents living with HIV in China.

Parental HIV disclosure, where parents living with HIV (PLH) communicate their diagnosis to their children, is crucial for family communication. This study assessed intervention effects of a parental HIV disclosure intervention on psychosocial factors, focusing on child's age impact. Data from a randomized controlled trial involving 791 PLH in China were analyzed at baseline (W1), 6-month (W2), and 12-month follow-ups (W3). The study measured effects on psychosocial factors (HIV disclosure knowledge, outcome expectancy, action self-efficacy, and action planning) using the proportional latent change score method. Among PLH with children aged 6-9, the intervention yielded significant intervention effects on knowledge (ß = 0.190, p = .004), action self-efficacy (ß = 0.342, p = .001), and action planning (ß = 0.389, p < .001) from W1 to W2. For PLH with children aged 10-12, the intervention significantly enhanced action self-efficacy (ß = 0.162, p = .003) and action planning (ß = 0.367, p = .001) from W1 to W2, but there was a reduction in perceived benefits (ß = -0.175, p = 0.024) from W2 to W3. For PLH with children aged 13-15, significant intervention effects were observed on action planning, both from W1 to W2 (ß = 0.251, p = .045) and from W2 to W3 (ß = 0.321, p < .001). These findings highlight the importance of tailoring interventions to consider psychosocial factors and children's developmental stages to enhance HIV disclosure practices.

Targeting MS4A4A on tumour-associated macrophages restores CD8+ T-cell-mediated antitumour immunity.

OBJECTIVE: Checkpoint immunotherapy unleashes T-cell control of tumours but is suppressed by immunosuppressive myeloid cells. The transmembrane protein MS4A4A is selectively highly expressed in tumour-associated macrophages (TAMs). Here, we aimed to reveal the role of MS4A4A+ TAMs in regulating the immune escape of tumour cells and to develop novel therapeutic strategies targeting TAMs to enhance the efficacy of immune checkpoint inhibitor (ICI) in colorectal cancer. DESIGN: The inhibitory effect of MS4A4A blockade alone or combined with ICI treatment on tumour growth was assessed using murine subcutaneous tumour or orthotopic transplanted models. The effect of MS4A4A blockade on the tumour immune microenvironment was assessed by flow cytometry and mass cytometry. RNA sequencing and western blot analysis were used to further explore the molecular mechanism by which MS4A4A promoted macrophages M2 polarisation. RESULTS: MS4A4A is selectively expressed by TAMs in different types of tumours, and was associated with adverse clinical outcome in patients with cancer. In vivo inhibition of MS4A4A and anti-MS4A4A monoclonal antibody treatment both curb tumour growth and improve the effect of ICI therapy. MS4A4A blockade treatment reshaped the tumour immune microenvironment, resulting in reducing the infiltration of M2-TAMs and exhausted T cells, and increasing the infiltration of effector CD8+ T cells. Anti-MS4A4A plus anti-programmed cell death protein 1 (PD-1) therapy remained effective in large, treatment-resistant tumours and could induce complete regression when further combined with radiotherapy. Mechanistically, MS4A4A promoted M2 polarisation of macrophages by activating PI3K/AKT pathway and JAK/STAT6 pathway. CONCLUSION: Targeting MS4A4A could enhance the ICI efficacy and represent a new anticancer immunotherapy.

Carboxylated superparamagnetic Fe3O4 nanoparticles modified with 3-amino propanol and their application in magnetic resonance tumor imaging.

BACKGROUND: Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are of potential magnetic resonance imaging (MRI) contrast agents for tumor diagnosis. However, ultrasmall particle size or negative surface charge lead to relative short half-life which limit the utilization of USPIO for in vivo MRI contrast agents. METHODS: Superparamagnetic Fe3O4 nanoparticles coated with polyacrylic acid (PAA)were synthetized, and modified by 3-amino propanol and 3-diethyl amino propyl amine. The characteristics of superparamagnetic Fe3O4 nanoparticles were investigated through transmission electron microscopy, X-ray diffraction analysis, Zata potential analysis, thermogravimetric analysis, and relaxation properties analysis. Magnetic resonance imaging animal experiment was performed. RESULTS: The synthetized nanoparticles were irregular spherical, with small particle size, few agglomeration, and good dispersion in water. After modification, the potential fluctuation of nanoparticles was small, and the isoelectric point of nanoparticles changed to high pH. After 3-amino propanol modification, the weight loss of the curve from 820 to 940 °C was attributed to the decomposition of 3-amino propanol molecules on the surface. The T1 relaxation rate of nanoparticles changed little before and after modification, which proved that the modification didn't change the relaxation time. Brighter vascular images were observed after 3-amino propanol modification through measurement of magnetic resonance tumor imaging. CONCLUSION: These data indicated the Fe3O4 nanoparticles modified by 3-amino propanol should be a better contrast agent in the field of magnetic resonance tumor imaging.

Prescription Opioid Misuse, Pain Interference, Resilience, and Anxiety Among Chinese People Living with HIV: A Moderated Mediation Model.

Prescription opioid misuse (POM) is a concern in people living with HIV (PLWH). Pain interference is a robust factor, and its influences would occur through anxiety and resilience. Limited POM studies attend to Chinese PLWH. This study examined POM and its underlying psychological mechanism using data of PLWH with pain (n = 116) from a cohort study in Guangxi. The PROCESS macro was employed to examine a hypothesized moderated mediation model among pain interference, resilience, anxiety, and POM. Results showed 10.3% PLWH engaged in past-three-month POM. After controlling for demographics, HIV-related clinical outcomes, and pain severity, anxiety mediated the association between pain interference and POM (ß = 0.46, 95% CI = 0.01 to 10.49), and the mediation was moderated by resilience (moderated mediation index = - 0.02, 95% CI = - 0.784 to - 0.001). Chinese PLWH seem to misuse opioids to cope with pain-related anxiety. Resilience appears to offer protection.

Associations Between Internalized and Anticipated HIV Stigma and Depression Symptoms Among People Living with HIV in China: A four-wave Longitudinal Model.

Previous research has documented that HIV-related stigma (e.g., internalized and anticipated stigma) is detrimental to the mental health of people living with HIV (PLWH). However, longitudinal data on the bidirectional relationship between HIV-related stigma and depression symptoms are limited. The purpose of this study was to examine the bidirectional association among internalized and anticipated HIV stigma and depression symptoms among Chinese PLWH. A four-wave longitudinal design (6 months intervals) was employed among 1,111 Chinese PLWH (Mage = 38.58, SD = 9.16, age range: 18-60 years; 64.1% men). The bidirectional model was examined using a random-intercept cross-lagged panel model (RI-CLPM), which evaluated the within- and between-person effects of study variables. At the within-person level, results indicated that depression symptoms at T2 mediated the linkage between internalized HIV stigma at T1 and anticipated HIV stigma at T3, and that anticipated HIV stigma at both T2 and T3 mediated the relationship between depression symptoms at the previous time point and internalized HIV stigma at the subsequent time point. Furthermore, a bidirectional association was found between anticipated HIV stigma and depression symptoms across four waves. At the between-person level, internalized and anticipated HIV stigma were significantly associated with depression symptoms. This study highlights the complex interplay between different forms of HIV-related stigma and mental health problems among PLWH and underscores the importance of considering the bidirectional relationship between the development of psychopathology and stigmatization process in clinical practice.

Virologic failure and all-cause mortality among older people living with HIV/AIDS in South China.

This retrospective cohort study investigated older people living with HIV/AIDS (PLWHA) characteristics, HIV care, and treatment outcomes among all cases between 1996 and 2019 in Guangxi, China. Secondary data were extracted from two national surveillance databases. Older (≥50 years old) and younger (18-49 years old) PLWHA were compared regarding demographic and behavioral characteristics, HIV care, virologic failure, and all-cause mortality. Older PLWHA accounted for 41.6% of all HIV cases (N = 144,952) between 1996 and 2019. The proportion of older cases increased from 10.4% to 64.8% for men and from 2.4% to 66.7% for women between 2002 and 2019. Heterosexual contact accounted for 96.0% of older adults. Moreover, older PLWHA had a lower median CD4 count at the HIV diagnosis (193 vs. 212 cells/µL, p < 0.0001) and were less likely to receive antiretroviral therapy (ART) than younger adults (72.1% vs. 86.1%, p < 0.001). The all-cause mortality risk of older PLWHA was 2.87 times of younger adults [adjusted hazard ratio (AHR) 2.87; 95% confidence interval (CI) 2.76-2.98]. In addition, older PLWHA reported an 18% increase in odds for virologic failure than younger adults (AOR 1.18; 95% CI 1.08-1.30). Therefore, enhanced HIV prevention and care are urgently needed in older people.

Sexual mixing patterns in men who have sex with men: network approaches for smart resource allocation.

BACKGROUND: Age-based sexual mixing patterns in men who have sex with men (MSM) can greatly inform strategic allocation of intervention resources to subsets of the population for the purpose of preventing the greatest number of new HIV infections. METHODS: Egocentric network data collected from MSM participating in annual HIV sentinel surveillance surveys were used to assess age-dependent mixing and to explore its epidemiological implications on the risk of HIV transmission risk (among those HIV-infected) and HIV acquisition risk (among those not infected). RESULTS: Mixing in this sample of 1605 Chinese MSM is relatively age assortative (the average of values expressing the degree of preferential mixing were 2.01 in diagonal cells vs 0.87 in off-diagonal cells). Expected numbers of HIV acquisition were highest in the 20-24years age group; those for HIV transmissions were highest among 25-29year olds. The risk of both acquisition and transmission was highest in age groups that immediately follow the most commonly reported ages of sexual debut in this population (i.e. age 20). CONCLUSIONS: These findings suggest that combination prevention resources should be targeted at younger MSM who are at higher risk of both transmission and acquisition. Programs may also do well to target even younger age groups who have not yet debuted in order to establish prevention effects before risky sexual behaviours begin. More research on optimal strategies to access these harder-to-reach subsets of the MSM population is needed. Findings also support ongoing efforts for public health practitioners to collect network data in key populations to support more empirically driven strategies to target prevention resources.

Estimation of the Proportion of Potential Nondisclosed Men Who Have Sex With Men Among Self-Reported Heterosexual Men With HIV Using a Randomized Response Technique.

BACKGROUND: Because of HIV-related stigma and gender minority stigma, the number of men who have sex with men (MSM) among registered HIV/AIDS cases may be underreported in Guangxi, China. In addition to the sensitivity of direct inquiry of sexual identity and behavior, our study aims to determine the proportion of potential nondisclosed MSM (pnMSM) among self-reported heterosexual men with HIV. METHOD: The study subjects were self-reported heterosexual men with HIV who were diagnosed in recent 20 years in Guangxi, China. A randomized response technique was executed by randomly putting them to secretly answer either whether their birthday was odd or even day, or whether they experienced anal sex in the last 3 years. Personal characteristics were linked with randomized response technique answers for subgroup analysis. RESULTS: The proportion of pnMSM ever having anal sex was estimated to be 14.3% in Guangxi, China. Being younger, having a college or above education level, single, employed, of Han ethnicity, diagnosed with HIV in the past 6 years, and not on antiretroviral therapy were associated with giving positive answer. CONCLUSIONS: The reported number of MSM cases with HIV in the past may have been underestimated in Guangxi, China. Information about preexposure and postexposure prophylaxis should be provided to this stigmatized subgroup-pnMSM, especially those who are younger and with a higher socioeconomic status among self-reported heterosexual men with HIV.

HIV Service Interruptions During the COVID-19 Pandemic in China: The Role of COVID-19 Challenges and Institutional Response from Healthcare Professional's Perspective.

During the COVID-19 pandemic, HIV-related services have been unavoidably disrupted and impacted. However, the nature and scope of HIV service disruptions due to COVID-19 has rarely been characterized in China. A cross-sectional online survey was conducted among 1029 HIV healthcare providers in Guangxi, China, from April to May 2020. Latent class analysis (LCA) was first used to identify HIV service disruption levels, then hierarchical multilevel logistic regression was conducted to analyze the relationships of COVID-19 challenges, institutional responses, and HIV service disruption levels adjusting for the clustering effect of institutional ownership levels. Four classes of HIV service disruption were identified, with 22.0% complete disruption, 15.4% moderate disruption, 21.9% minor disruption, and 40.7% almost no disruption. COVID-19 challenges were positively associated with the probabilities of service disruption levels. Institutional responses were negatively associated with the probabilities of being classified as "minor disruption" and moderated the association of COVID-19 challenges with complete and moderate disruptions compared with no disruption group. To maintain continuity of core HIV services in face of a pandemic, building a resilient health care system with adequate preparedness is necessary.

The relationship of hair glucocorticoid levels to immunological and virological outcomes in a large cohort of combination antiretroviral therapy treated people living with HIV.

BACKGROUND: Existing literature mostly investigated the relationship of acute or short-term glucocorticoid exposure to HIV disease progression using cortisol levels in serum, saliva, or urine. Data are limited on the relationship of long-term glucocorticoid exposure to HIV disease progression. This study examined whether hair glucocorticoid levels, novel retrospective indicators of long-term glucocorticoid exposure, are associated with two common indicators of HIV disease progression (CD4 count and HIV viral load) among a large cohort of combination antiretroviral therapy treated Chinese people living with HIV (PLHIV). METHODS: A total of 1198 treated PLHIV provided hair samples for glucocorticoid (cortisol and cortisone) assay and completed a survey assessing sociodemographic, lifestyle, and HIV-related characteristics. Meanwhile, CD4 count and HIV viral load were retrieved from their medical records. Spearman correlation was used to examine the associations of hair cortisol and cortisone levels to continuous CD4 count and HIV viral load. Multivariate logistic regression was used to predict CD4 count < 500 cells/mm3. RESULTS: Both hair cortisol and cortisone levels were negatively associated with CD4 count but not with HIV viral load. The odds ratio for CD4 count < 500 cells/mm3 was 1.41 [95% CI 0.99-2.00] and 2.15 [95% CI 1.51-3.05] for those with hair cortisol and cortisone levels in the highest quartile compared to the lowest when controlling for sociodemographic, lifestyle, HIV-related covariates, and HIV viral load. CONCLUSION: Hair glucocorticoid levels were associated with CD4 count but not viral load in treated Chinese PLHIV. Our data furtherly supported the hypothesis that elevated glucocorticoid levels are associated with the lower CD4 count.

Metformin exerts an antitumor effect by inhibiting bladder cancer cell migration and growth, and promoting apoptosis through the PI3K/AKT/mTOR pathway.

BACKGROUND: To observe and explore the effect of metformin on the migration and proliferation of bladder cancer T24 and 5637 cells in vitro. METHODS: Bladder cancer T24 and 5637 cell lines were cultured in vitro, and were divided into group A (blank control group) and group B (metformin group: 5, 10, 15, and 20 mmol/L); both groups were plated on 6-well plates at the same time. Culture in 24-well plates was used for wound healing assays and in 96-well plates for Transwell migration and invasion, and Cell Counting Kit-8 proliferation experiments. We observed and detected the cell migration and proliferation ability of each group at 48 h, and calculated the cell migration area and survival rate. Flow cytometry was used to detect cell apoptosis in the groups. The apoptosis-related proteins, cleaved-caspase 3, cleaved-PARP, and the PI3K/AKT/mTOR signaling pathway member proteins PI3K, phosphorylated (p)-PI3K, AKT, p-AKT, mTOR, and p-mTOR were detected using western blotting. RESULTS: After 48 h of treatment with different concentrations of metformin, the cell migration and proliferation capabilities were significantly lower than those in the blank control group. The proliferation and migration abilities of T24 and 5637 cells decreased in a metformin concentration-dependent manner (P < 0.05). The apoptosis rate under different concentrations of metformin, as detected by flow cytometry, showed a significantly higher rate in the metformin group than in the control group (P < 0.05). Compared with that in the control group, the level of cleaved-caspase 3 and cleaved-PARP protein in the metformin group was increased in each treatment group, and the levels of p-mTOR, p-AKT, and p-PI3K decreased significantly compared with those in the control group (P < 0.05). CONCLUSION: Metformin inhibited bladder cancer T24 and 5637 cell migration and proliferation, and induced their apoptosis. The mechanism might involve inhibition of the activation of the PI3K/AKT/mTOR signaling pathway.

Occupational stress, burnout, and organizational readiness for change: A longitudinal study among HIV HCPs in China.

Literature suggests that organizational readiness for change (ORC) could facilitate adaptation and implementation of new projects or practices in clinical settings. Limited data are available regarding the longitudinal associations between ORC and psychosocial conditions of HCPs. Using six waves of longitudinal data collected between 2013 and 2016 from 357 HIV HCPs in Guangxi, China, we identify sociodemographic and occupational characteristics that impact ORC and examine how occupational stress and burnout affect ORC adjusting for potential cofounders. A mixed effect model was used to assess the associations of ORC with psychosocial variables controlling for key background variables, and within-cluster and within-subject correlation over time. The ORC level was stable over time. Ethnical minority HCPs reported lower ORC compared with those of Han ethnicity. HCPs with administrative responsibility reported significantly lower ORC compared with the ones without administrative responsibility. HCPs with high school education attainment showed lower ORC compared to those with some college education. The ORC level was negatively associated with occupational stress and burnout controlling all the background variables. It is important to integrate reducing stress and alleviating burnout in the workplace into efforts to promote the acceptance and adaptation of new intervention.