Molecular mechanism of regulating tat protein expression of pingganjiedu TCM in the treatment of AIDS based on network pharmacology.

AIDS is a serious disease with impaired immune function caused by human immunodeficiency virus (HIV) infection. The treatment of AIDS has always been the focus of global scientific research, and Tat protein is a key regulatory protein in the process of HIV infection. Its high expression is closely related to virus replication, disease progression, etc. The aim of this study is to explore the molecular mechanism of regulating Tat protein expression by using network pharmacology based traditional Chinese medicine for calming the liver and detoxifying. 129 AIDS patients were enrolled in the study and randomly divided into HAART combined with PGJDP treatment and HAART alone treatment groups. The virological response rate, immunological response status (CD4 + T cell level, CD4/CD8) and incidence of abnormal liver function were observed before and 48 weeks after treatment. Using the TCMSP database to obtain the chemical components and targets of the main traditional Chinese medicine components in PGJDP, clinical results indicate that the combination of HAART and PGJDP treatment can improve the virological response rate (P > 0.05); Increase the number of CD4 + T lymphocytes (P > 0.05); Significantly increased CD4/CD8 ratio (P < 0.01); Simultaneously, it significantly reduced the incidence of liver dysfunction (P < 0.01). After screening and analysis, the Chinese herbal medicine for calming liver and detoxifying has the potential to significantly regulate the expression of Tat protein. These Chinese herbal compounds can reduce the expression of Tat protein by affecting key pathways and regulating the expression of related genes, which has potential therapeutic effects on the treatment of AIDS.

Exploring disparities in HIV-1 pretreatment and acquired drug resistance in China from 2003 to 2022.

OBJECTIVES: To investigate the epidemic patterns of pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in HIV-1 sequences from China. METHODS: HIV-1 pol sequences and associated epidemiological data were collected from the Los Alamos HIV Sequence Database, NCBI, HIV Gene Sequence Database and PubMed. Genotypic resistance and subtypes were identified using the Stanford HIV Drug Resistance Database. RESULTS: A total of 36 263 sequences from ART-naïve individuals and 1548 sequences from ART-experienced individuals with virological failure were evaluated. PDR prevalence was 6.64%, initially decreasing and then increasing to 7.84% (2018-22) due to NNRTI. Pooled ADR prevalence (44.96%) increased, with NNRTI and NRTI aligning with the overall trend. The percentage of multidrug resistance was more than that of single-drug resistance in PDR and especially ADR annually. PDR was most prevalent in Central China followed by Southwest and North. ADR prevalence was highest in North China followed by Northwest and Southwest. In ADR sequences, high-level resistance was more common, especially in NRTI. PDR sequences exhibited low-level or intermediate resistance, especially PI. Drug resistance mutations revealed distinct patterns in PDR and ADR. CRF01_AE, the predominant subtype in China, exhibited the highest proportions among most ART drugs and drug resistance mutations, with a few exceptions where CRF07_BC (prominent in the Northwest), CRF55_01B and CRF08_BC (prominent in the Southwest) showed the highest proportions. CONCLUSIONS: HIV-1 PDR and ADR prevalence in China exhibited diverse epidemiological characteristics, underscoring the importance of ongoing national monitoring of PDR, ADR and subtype; patient education on adherence; and personalized regimens.

Impact of HIV-1 genetic diversity on disease progression: a prospective cohort study in Guangxi.

The high proportion of AIDS cases and mortality rates in Guangxi underscores the urgency to investigate the influence of HIV-1 genetic diversity on disease progression in this region. Newly diagnosed HIV-1 patients were enrolled from January 2016 to December 2021, and the follow-up work and detection of CD4+T lymphocytes were carried out every six months until December 2022. Multivariate logistic regression was used to analyze the factors affecting pre-treatment CD4+T lymphocyte counts, while local weighted regression models (LOESS) and generalized estimating equation models (GEE) were conducted to assess factors influencing CD4+T Lymphocyte Recovery. Cox regression analysis was utilized to examine the impact of subtypes on survival risk. Additionally, HIV-1 env sequences were utilized for predicting CXCR4 and CCR5 receptors. The study encompassed 1867 individuals with pol sequences and 281 with env sequences. Our findings indicate that age over 30, divorced/widowed, peasant, heterosexual infection, CRF01_AE, long-term infection, and Pre-treatment Viral load >10000 copies/ml were factors associated with higher risk for pre-treatment CD4+T lymphocyte decline. Specifically, male gender, age over 30, heterosexual infection (HETs), long-term infection, CRF01_AE, and Pre-treatment CD4 T cell counts below 350/µL were identified as risk factors impeding CD4+T lymphocyte recovery. Pre-treatment CD4+T lymphocyte counts and recovery in individuals infected with CRF01_AE were lower compared to CRF07_BC and CRF55_01B. Additionally, CRF01_AE and CRF08_BC subtypes exhibited higher mortality rates than CRF07_BC, CRF55_01B, and other subtypes. Notably, CRF01_AE demonstrated the highest percentage of CXCR4 affinity ratios. This research unveils the intricate influence of HIV-1 gene diversity on CD4+T lymphocyte dynamics and clinical outcomes. It highlights the multifaceted nature of HIV infection in Guangxi, providing novel insights into subtype-specific disease progression among HIV-infected individuals in this region.

Comprehensive bioinformatics analysis of human cytomegalovirus pathway genes in pan-cancer.

BACKGROUND: Human cytomegalovirus (HCMV) is a herpesvirus that can infect various cell types and modulate host gene expression and immune response. It has been associated with the pathogenesis of various cancers, but its molecular mechanisms remain elusive. METHODS: We comprehensively analyzed the expression of HCMV pathway genes across 26 cancer types using the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases. We also used bioinformatics tools to study immune invasion and tumor microenvironment in pan-cancer. Cox regression and machine learning were used to analyze prognostic genes and their relationship with drug sensitivity. RESULTS: We found that HCMV pathway genes are widely expressed in various cancers. Immune infiltration and the tumor microenvironment revealed that HCMV is involved in complex immune processes. We obtained prognostic genes for 25 cancers and significantly found 23 key genes in the HCMV pathway, which are significantly enriched in cellular chemotaxis and synaptic function and may be involved in disease progression. Notably, CaM family genes were up-regulated and AC family genes were down-regulated in most tumors. These hub genes correlate with sensitivity or resistance to various drugs, suggesting their potential as therapeutic targets. CONCLUSIONS: Our study has revealed the role of the HCMV pathway in various cancers and provided insights into its molecular mechanism and therapeutic significance. It is worth noting that the key genes of the HCMV pathway may open up new doors for cancer prevention and treatment.

Emergence of HIV-1 drug resistance mutations among children and adolescents undergoing prolonged antiretroviral therapy in Guangxi.

OBJECTIVE: Antiretroviral therapy (ART) has been implemented in Guangxi for a long time, and there are no reports of HIV drug resistance mutation (DRM) among children and adolescents experiencing virologic failure after ART. This study aimed to analyse HIV DRM prevalence, patterns, and influencing factors among children and adolescents experiencing virologic failure after ART in Guangxi. METHODS: We collected samples from a total of 491 HIV-infected individuals under 18 years old experiencing virologic failure after ART from 14 cities in Guangxi. Sequencing and DRM analysis were performed based on pol region. Multivariate logistic regression was employed to analysis the influencing factors of DRM. RESULTS: Among these patients, 396 cases were successfully sequenced. Of all, 52.53% exhibited HIV DRM, including NNRTI (48.48%), NRTI (34.85%) and PI (1.01%). NRTI and NNRTI dual-class resistance was prevalent (30.3%). M184V/I and K103N mutations were the common mutations in NRTI and NNRTI, respectively. Male sex (aOR = 2.1, 95% CI: 1.26-3.50), CRF01_AE subtype (OR = 2.50, 95% CI: 1.02-5.88), the primary regimen 3TC+AZT+NVP (OR = 10.00, 95% CI: 5.00-25.00), low pretreatment CD4+ T lymphocytes (<200 cells/mm³) (OR = 1.85, 95% CI: 1.00-3.45), and high viral load (>1000 copies/mL) (OR = 4.90, 95% CI: 1.03-23.39) showed higher risk of DRM. CONCLUSION: HIV DRM is pervasive among children and adolescents experiencing virologic failure in Guangxi. Timely HIV DRM monitoring is crucial to mitigate major mutation accumulation and inform effective treatment strategies.

Drug resistance and influencing factors in HIV-1-infected individuals under antiretroviral therapy in Guangxi, China.

OBJECTIVES: To assess the profiles and determinants of drug resistance in HIV-1-infected individuals undergoing ART in Guangxi. METHODS: Samples and data were collected from HIV-1-infected individuals experiencing virological failure post-ART from 14 cities in Guangxi. Sequencing of the HIV-1 pol gene was conducted, followed by analysis for drug resistance mutations using the Stanford University HIV Drug Resistance Database. Logistic regression was employed to identify potential risk factors associated with both HIV drug resistance and mortality. RESULTS: A total of 8963 individuals with pol sequences were included in this study. The overall prevalence of HIV-1 drug resistance (HIVDR) was 42.43% (3808/8963), showing a decrease from 59.62% to 41.40% from 2016 to 2023. Factors such as being aged ≥50 years, male, Han nationality, lower education levels, occupations including workers, peasants and children, AIDS, pre-treatment CD4 T cell counts <200 cells/mm3, infection with CRF01_AE and CRF55_01B subtypes, and ART regimen lamivudine/zidovudine/nevirapine were associated with higher susceptibility to HIVDR. The common mutations were M184V (17.38%) and K103N (22.14%). Additionally, the prevalence of M184V, S68G, M41L and G190A were different between the Han and Zhuang populations. Factors including age, gender, ethnicity, education level, occupation, infectious route, clinical stage, viral load, subtype, ART regimen and HIVDR showed significant associations with mortality. CONCLUSIONS: The factors contributing to drug resistance in the HIV-1 ART individuals in Guangxi appear to be notably intricate. Continuous reinforcement of drug resistance surveillance is imperative, accompanied by the optimization of ART regimens to mitigate virological failures effectively.

Diagnostic performance evaluation of urine HIV-1 antibody rapid test kits in a real-life routine care setting in China.

OBJECTIVES: To evaluate the diagnostic performance of urine HIV antibody rapid test kits in screening diverse populations and to analyse subjects' willingness regarding reagent types, purchase channels, acceptable prices, and self-testing. DESIGNS: Diagnostic accuracy studies PARTICIPANTS: A total of 2606 valid and eligible samples were collected in the study, including 202 samples from female sex workers (FSWs), 304 persons with injection drug use (IDU), 1000 pregnant women (PW), 100 subjects undergoing voluntary HIV counselling and testing (VCT) and 1000 students in higher education schools or colleges (STUs). Subjects should simultaneously meet the following inclusion criteria: (1) being at least 18 years old and in full civil capacity, (2) signing an informed consent form and (3) providing truthful identifying information to ensure that the subjects and their samples are unique. RESULTS: The sensitivity, specificity and area under the curve (AUC) of the urine HIV-1 antibody rapid test kits were 92.16%, 99.92% and 0.960 (95% CI: 0.952 to 0.968, p<0.001), respectively, among 2606 samples collected during on-site screenings. The kits showed good diagnostic performance in persons with IDU (AUC, 1.000; 95% CI, 1.000 to 1.000, p<0.001), PW (AUC, 0.999; 95% CI, 0.999 to 1.000, p<0.001) and FSWs (AUC, 1.000; 95% CI, 1.000 to 1.000, p<0.001). The AUC of the urine reagent kits in subjects undergoing VCT was 0.941 (95% CI: 0.876 to 0.978, p<0.001). The 'acceptable price' had the greatest influence on STUs (Pi=1.000) and PW (Pi=1.000), the 'purchase channel' had the greatest influence on subjects undergoing VCT (Pi=1.000) and persons with IDU (Pi=1.000) and the 'reagent types' had the greatest influence on FSWs (Pi=1.000). CONCLUSIONS: The rapid urine test kits showed good diagnostic validity in practical applications, despite a few cases involving misdiagnosis and underdiagnosis.

CagA-positive Helicobacter pylori may promote and aggravate scrub typhus.

Helicobacter pylori (H. pylori) infection may alter the host's resistance to tsutsugamushi disease pathogens through the Th1 immune response, leading to potential synergistic pathogenic effects. A total of 117 scrub typhus cases at Beihai People's Hospital and affiliated hospitals of Youjiang University for Nationalities and Medical Sciences were studied from January to December 2022, alongside 130 healthy individuals forming the control group. All participants underwent serum H. pylori antibody testing. The prevalence of H. pylori infection was significantly higher among scrub typhus patients (89.7%) compared to healthy individuals (54.6%) (p < 0.05). Moreover, type I H. pylori infection was notably more prevalent in scrub typhus cases (67.5%) compared to healthy individuals (30%) (p < 0.05). Multifactorial analysis demonstrated type I H. pylori infection as an independent risk factor for scrub typhus (adjusted odds ratio: 2.407, 95% confidence interval: 1.249-4.64, p = 0.009). Among scrub typhus patients with multiple organ damage, the prevalence of type I H. pylori infection was significantly higher (50.6%) than type II H. pylori infection (15.4%) (χ2 = 4.735, p = 0.030). These results highlight a higher incidence of H. pylori infection in scrub typhus patients compared to the healthy population. Additionally, type I H. pylori strain emerged as an independent risk factor for scrub typhus development. Moreover, individuals infected with type I H. pylori are more susceptible to multiple organ damage. These findings suggest a potential role of H. pylori carrying the CagA gene in promoting and exacerbating scrub typhus.

Antibiotic resistance profiles of gut microbiota across various primate species in Guangxi.

Introduction: Understanding the gut microbiota and antibiotic resistance gene (ARG) profiles in non-human primates (NHPs) is crucial for evaluating their potential impact on human health and the environment. Methods: In this study, we performed metagenomic analysis of 203 primate fecal samples, including nine NHP species and humans, to comprehensively characterize their gut microbiota and ARGs. Results: Our study reveals the prevailing phyla in primates as Firmicutes, Bacteroidetes, Euryarchaeota, and Proteobacteria. The captive NHPs exhibited higher ARG abundance compared to their wild counterparts, with tetracycline and beta-lactam resistance genes prevailing. Notably, ARG subtypes in Trachypithecus leucocephalus (T. leucocephalus) residing in karst limestone habitats displayed a more dispersed distribution compared to other species. Interestingly, ARG profiles of NHPs clustered based on geographic location and captivity status. Co-occurrence network analysis revealed intricate correlations between ARG subtypes and bacterial taxa. Procrustes analysis unveiled a significant correlation between ARGs and microbial phylogenetic community structure. Taxonomic composition analysis further highlighted differences in microbial abundance among NHPs and humans. Discussion: Our study underscores the impact of lifestyle and geographical location on NHP gut microbiota and ARGs, providing essential insights into the potential risks posed by NHPs to antibiotic resistance dissemination. This comprehensive analysis enhances our understanding of the interplay between NHPs and the gut resistome, offering a critical reference for future research on antibiotic resistance and host-microbe interactions.

Prediction of the risk of cytopenia in hospitalized HIV/AIDS patients using machine learning methods based on electronic medical records.

Background: Cytopenia is a frequent complication among HIV-infected patients who require hospitalization. It can have a negative impact on the treatment outcomes for these patients. However, by leveraging machine learning techniques and electronic medical records, a predictive model can be developed to evaluate the risk of cytopenia during hospitalization in HIV patients. Such a model is crucial for designing a more individualized and evidence-based treatment strategy for HIV patients. Method: The present study was conducted on HIV patients who were admitted to Guangxi Chest Hospital between June 2016 and October 2021. We extracted a total of 66 clinical features from the electronic medical records and employed them to train five machine learning prediction models (artificial neural network [ANN], adaptive boosting [AdaBoost], k-nearest neighbour [KNN] and support vector machine [SVM], decision tree [DT]). The models were tested using 20% of the data. The performance of the models was evaluated using indicators such as the area under the receiver operating characteristic curve (AUC). The best predictive models were interpreted using the shapley additive explanation (SHAP). Result: The ANN models have better predictive power. According to the SHAP interpretation of the ANN model, hypoproteinemia and cancer were the most important predictive features of cytopenia in HIV hospitalized patients. Meanwhile, the lower hemoglobin-to-RDW ratio (HGB/RDW), low-density lipoprotein cholesterol (LDL-C) levels, CD4+ T cell counts, and creatinine clearance (Ccr) levels increase the risk of cytopenia in HIV hospitalized patients. Conclusion: The present study constructed a risk prediction model for cytopenia in HIV patients during hospitalization with machine learning and electronic medical record information. The prediction model is important for the rational management of HIV hospitalized patients and the personalized treatment plan setting.

Disparity of HIV-1 Pretreatment Drug Resistance in Men Who Have Sex With Men and the Heterosexual Population in Guangxi, China.

Background: The prevalence of human immunodeficiency type 1 (HIV-1) pretreatment drug resistance (PDR) in men who have sex with men (MSM) in Guangxi remains unclear, and its effect on antiretroviral therapy (ART) needs to be further studied. Methods: Individuals newly diagnosed with HIV in Guangxi from 2016 to 2020, which mainly included MSM and the heterosexual (HES) population, were recruited in this study. Pol sequences were sequenced to analyze PDR and construct a genetic network. The risk factors for PDR and the effect on ART were respectively analyzed. Results: The PDR of MSM in Guangxi was 4.7% (34/716), consisting of nonnucleoside reverse transcriptase inhibitors (3.5%), protease inhibitors (0.8%), integrase strand transfer inhibitors (0.7%), and nucleoside reverse transcriptase inhibitors (0.4%), and lower than that of HES (9.3% [77/827]). The subtype was associated with PDR, and MSM was lower than HES (CRF01_AE: 3.0% vs 8.0%; CRF07_BC: 4.1% vs 7.2%). CRF55_01B (adjusted odds ratio [aOR], 3.35) was a risk factor for PDR in MSM, while CRF08_BC (aOR, 2.34) and older (aOR, 2.75) were risk factors for PDR in HES. Six of 18 (33.3%) PDR of MSM in the network connected to each other, lower than that of HES (61.1% [22/36]). CRF55_01B (aOR, 5.69) was a risk factor for PDR transmission in MSM, while CRF08_BC (aOR, 4.08) was a risk factor in HES. Pretreatment CD4+ T-cell count, age, infection route, and subtype were associated with recovery of CD4+ count and suppression of viral load. Conclusions: The prevalence of PDR was different between MSM and HES, which may be associated with subtype. Thus, the monitoring of subtype and PDR should be strengthened.

Epidemiology of extrapulmonary tuberculosis in central Guangxi from 2016 to 2021.

The burden of extrapulmonary tuberculosis (EPTB) has gradually increased in recent years, but not enough epidemiological data is available from central Guangxi. To better understand the epidemiology of EPTB in central Guangxi and identify risk factors associated with them, we retrospectively investigated the epidemiology of tuberculosis (TB), especially EPTB, among patients admitted to the Chest Hospital of Guangxi Zhuang Autonomous Region between 2016 and 2021. We excluded those infected with both pulmonary tuberculosis (PTB) and EPTB, reported the proportion and incidence of PTB or EPTB, and compared the demographic characteristics and risk factors of EPTB and PTB cases using univariate and multivariate logistic regression models. Among 30,893 TB patients, 67.25% (20,774) had PTB and 32.75% (10,119) had EPTB. Among EPTB, pleural, skeletal, lymphatic, pericardial, meningeal, genitourinary, intestinal, and peritoneal TB accounted for 49.44%, 27.20%, 8.55%, 4.39%, 3.36%, 1.48%, 0.87%, and 0.79%, respectively. Patients who were younger (age < 25), from rural areas, Zhuang and other ethnic groups, and diagnosed with anemia and HIV infection were more likely to develop EPTB. However, patients with diabetes and COPD were less likely to have EPTB. From 2016 to 2021, the proportion of PTB cases decreased from 69.73 to 64.07%. The percentage of EPTB cases increased from 30.27 to 35.93%, with the largest increase in skeletal TB from 21.48 to 34.13%. The epidemiology and risk factors of EPTB in central Guangxi are different from those of PTB. The incidence of EPTB is increasing and further studies are needed to determine the reasons for it.

Distinct Rates and Transmission Patterns of Major HIV-1 Subtypes among Men who Have Sex with Men in Guangxi, China.

The diversity and transmission patterns of major HIV-1 subtypes among MSM population in Guangxi remains unknown. Understanding the characteristics is crucial for effective intervention strategies. Between 2016 and 2021, we recruited individuals newly diagnosed with HIV-1 from MSM population in Guangxi. HIV-1 pol region was amplified and sequenced, and constructed molecular network, assessed clustering rate, cluster growth rate, spatial clustering, and calculating the basic reproductive number (R0) based on sequences data. We identified 16 prevalent HIV-1 subtypes among Guangxi MSM, with CRF07_BC (53.1%), CRF01_AE (26.23%), and CRF55_01B (12.96%) predominating. In the network, 618 individuals (66.17%) formed 59 clusters. Factors contributing to clustering included age < 30 years (AOR = 1.35), unmarried status (AOR = 1.67), CRF07_BC subtype (AOR = 3.21), and high viral load (AOR = 1.43). CRF07_BC had a higher likelihood of forming larger clusters and having higher degree than CRF01_AE and CRF55_01B. Notably, CRF07_BC has higher cluster growth rate and higher basic reproductive number than CRF01_AE and CRF55_01B. Our findings underscore CRF07_BC as a prominent driver of HIV-1 spread among Guangxi's MSM population, highlighting the viability of targeted interventions directed at specific subtypes and super clusters to control HIV-1 transmission within this population.

Anemia and opportunistic infections in hospitalized people living with HIV: a retrospective study.

BACKGROUND: There is a high prevalence of anemia among people living with HIV in Guangxi, China. Therefore, we investigated anemia and opportunistic infections in hospitalized people living with HIV and explored the risk factors related to anemia in people living with HIV to actively prevent anemia in people living with HIV. METHODS: We retrospectively studied people living with HIV admitted to Guangxi Chest Hospital from June 2016 to October 2021. Detailed information on the sociodemographic and clinical features of the participants was collected. The X2 test was used to compare the prevalence between the anemic and non-anemic groups. The logistic regression analysis was applied to exclude confounding factors and identify factors related to anemia. RESULTS: Among 5645 patients with HIV, 1525 (27.02%) had anemia. The overall prevalence of mild, moderate, and severe anemia was 4.66%, 14.08%, and 8.27%, respectively. The factors significantly related to increased risk of anemia were CD4 count < 50 cells/µl (aOR = 2.221, 95% CI = [1.775, 2.779]), CD4 count 50-199 cells/µl (aOR = 1.659, 95% CI = [1.327, 2. 073]), female (aOR = 1.644, 95% CI = [1.436, 1.881]) co-infected with HCV (aOR = 1.465, 95% CI = [1.071, 2.002]), PM (aOR = 2.356, 95% CI = [1.950, 2.849]), or TB (aOR = 1.198, 95% CI = [1.053, 1.365]). CONCLUSIONS: Within Guangxi of China, 27.02% of hospitalized people living with HIV presented with anemia. Most patients with anemia were in the mild to moderate stage. The low CD4 count, female gender, and concomitant infection with Penicillium marneffei, Hepatitis C virus, or Tuberculosis were independent correlates of anemia. Thus, these findings would be helpful to clinicians in preventing and intervening in anemia in people living with HIV.

Comparative Gut Microbiome in Trachypithecus leucocephalus and Other Primates in Guangxi, China, Based on Metagenome Sequencing.

The Trachypithecus leucocephalus (white-headed langur) is a highly endangered, karst-endemic primate species, inhabiting the karst limestone forest in Guangxi, Southwest China. How white-headed langurs adapted to karst limestone and special dietary remains unclear. It is the first time to study the correlation between the gut microbiome of primates and special dietary, and environment in Guangxi. In the study, 150 fecal samples are collected from nine primates in Guangxi, China. Metagenomic sequencing is used to analyze and compare the gut microbiome composition and diversity between white-headed langurs and other primates. Our results indicate that white-headed langurs has a higher diversity of microbiome than other primates, and the key microbiome are phylum Firmicutes, class Clostridia, family Lachnospiraceae, and genera Clostridiates and Ruminococcus, which are related to the digestion and degradation of cellulose. Ten genera are significantly more abundant in white-headed langurs and François' langur than in other primates, most of which are high-temperature microbiome. Functional analysis reveals that energy synthesis-related pathways and sugar metabolism-related pathways are less abundant in white-headed langurs and François' langur than in other primates. This phenomenon could be an adaptation mechanism of leaf-eating primates to low-energy diet. The gut microbiome of white-headed langurs is related to diet and karst limestone environment. This study could serve as a reference to design conservation breeding, manage conservation units, and determine conservation priorities.

A comprehensive cross-sectional survey to identify barriers and facilitators of cervical cancer screening in women with HIV in Guangxi, China.

BACKGROUND: Co-infection with HIV is a strong risk factor for cervical cancer development. It is unknown whether women with HIV in Guangxi, China are utilizing currently available cervical cancer screening services, what barriers they face, and if they are aware of their increased risk of developing cervical cancer. METHODS: Using a cross-sectional design, we administered a survey to women with HIV aged 21-65 years from August to October 2019 in Guangxi, China. A 100-item survey was designed in English and translated into Chinese. We assessed knowledge, attitudes, and beliefs about cervical cancer and cervical cancer screening, identified potential barriers and facilitators of cervical cancer screening programs for women with HIV, and assessed potential risk factors for cervical cancer. RESULTS: A total of 101 participants completed the survey. The median age of participants was 38 years (IQR 34.5-44 years). Forty-seven percent of the women had been screened for cervical cancer at least once. The mean score was 5.6 out of 9 (95% CI 5.3-6.0) on the knowledge about cervical cancer and screening and 6.3 out of 10 (95% CI 5.9-6.6) for cervical cancer risk factors, respectively. Facilitators of participating in cervical cancer screening included trust and openness to healthcare workers having conversations about female health concerns. Barriers identified in our study included knowledge gaps in cervical cancer risk awareness and cervical cancer screening awareness, including the lack of knowledge of available cervical cancer screening services. Women with HIV in Guangxi are under-screened for cervical cancer. CONCLUSION: When designing tailored cervical cancer screening programs for women with HIV in Guangxi, educational programs to address existing knowledge gaps will be needed to increase screening uptake in this high-risk population.

Screening and Identification of Human Endogenous Retrovirus-K mRNAs for Breast Cancer Through Integrative Analysis of Multiple Datasets.

Objective: Human endogenous retroviruses (HERVs) make up 8% of the human genome. HERVs are biologically active elements related to multiple diseases. HERV-K, a subfamily of HERVs, has been associated with certain types of cancer and suggested as an immunologic target in some tumors. The expression levels of HERV-K in breast cancer (BCa) have been studied as biomarkers and immunologic therapeutic targets. However, HERV-K has multiple copies in the human genome, and few studies determined the transcriptional profile of HERV-K copies across the human genome for BCa. Methods: Ninety-one HERV-K indexes with entire proviral sequences were used as the reference database. Nine raw sequencing datasets with 243 BCa and 137 control samples were mapped to this database by Salmon software. The differential proviral expression across several groups was analyzed by DESeq2 software. Results: First, the clustering of each dataset demonstrated that these 91 HERV-K proviruses could well cluster the BCa and control samples when the normal controls were normal cells or healthy donor tissues. Second, several common HERV-K proviruses that are closely related with BCa risk were significantly differentially expressed (p adj < 0.05 and absolute log2FC > 1.5) in the tissues and cell lines. Additionally, almost all the HERV-K proviruses had higher expression in BCa tissue than in healthy donor tissue. Notably, we first found the expression of 17p13.1 provirus that located with TP53 should regulate TP53 expression in ER+ and HER2+ BCa. Conclusion: The expression profiling of these 91 HERV-K proviruses can be used as biomarkers to distinguish individuals with BCa and healthy controls. Some proviruses, especially 17p13.1, were strongly associated with BCa risk. The results suggest that HERV-K expression profiles may be appropriate biomarkers and targets for BCa.

Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage complete SARS-CoV-2 sequences from GISAID database from January 1, 2020, to January 1, 2021, to mine the mutation hotspots associated with clinical outcome and developed a model to predict the clinical outcome in different epidemic strains. Exploring the cause of mutation based on RNA-dependent RNA polymerase (RdRp) and RNA-editing enzyme, mutation was more likely to occur in severe and mild cases than in asymptomatic cases, especially A > G, C > T, and G > A mutations. The mutations associated with asymptomatic outcome were mainly in open reading frame 1ab (ORF1ab) and N genes; especially R6997P and V30L mutations occurred together and were correlated with asymptomatic outcome with high prevalence. D614G, Q57H, and S194L mutations were correlated with mild and severe outcome with high prevalence. Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases. The expression of ADAR and APOBEC was associated with clinical outcome. The model has shown that the asymptomatic percentage has increased over time, while there is high symptomatic percentage in Alpha, Beta, and Gamma. These findings suggest that mutation in the SARS-CoV-2 genome may have a direct association with clinical outcomes and pandemic. Our result and model are helpful to predict the prevalence of epidemic strains and to further study the mechanism of mutation causing severe disease.

HIV-1 subtype diversity and transmission strain source among men who have sex with men in Guangxi, China.

With the rapid increase in HIV prevalence of men who have sex with men (MSM) in recent years and common human migration and travelling across different provinces in China, MSM are now finding it easier to meet each other, which might contribute to local HIV epidemics as well as fueling cross-province transmission. We performed a cross-sectional survey in 2018-2019 to investigate the current HIV subtype diversity and inferred HIV strain transmission origin among MSM in Guangxi province, China based on a phylogenetic analysis. Based on 238 samples, we found that the HIV-1 subtype diversity was more complicated than before, except for three major HIV subtypes/circulating recombinant forms (CRFs): CRF07_BC, CRF01_AE, CRF55_01B, five other subtypes/CRFs (CRF59_01B, B, CRF08_BC, CRF67_01B, CRF68_01B) and five unique recombinant forms (URFs) were detected. In total, 76.8% (169/220) of samples were infected with HIV from local circulating strains, while others originated from other provinces, predominantly Guangdong and Shanghai. The high diversity of HIV recombinants and complicated HIV transmission sources in Guangxi MSM indicates that there has been an active sexual network between HIV positive MSM both within and outside Guangxi without any effective prevention. Inter-province collaboration must be enforced to provide tailored HIV prevention and control services to MSM in China.