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1.
J Cell Mol Med ; 28(8): e18260, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38520216

ABSTRACT

Ovarian cancer (OC) is a deadly disease with limited treatment options and poor overall survival rates. This study aimed to investigate the role of histone modification-related genes in predicting the prognosis of OC patients. Transcriptome data from multiple cohorts, including bulk RNA-Seq data and single-cell scRNA-Seq data, were collected. Gene set enrichment analysis was used to identify enriched gene sets in the histone modification pathway. Differentially expressed genes (DEGs) between histone modification-high and histone modification-low groups were identified using Lasso regression. A prognostic model was constructed using five selected prognostic genes from the DEGs in the TCGA-OV cohort. The study found enrichment of gene sets in the histone modification pathway and identified five prognostic genes associated with OC prognosis. The constructed risk score model based on histone modification-related genes was correlated with immune infiltration of T cells and M1 macrophages. Mutations are more prevalent in the high-risk group compared to the low-risk group. Several drugs were screened against the model genes. Through in vitro experiments, we confirmed the expression patterns of the model genes. LBX2 facilitates the proliferation of OC. Histone modification-related genes have the potential to serve as biomarkers for predicting OC prognosis. Targeting these genes may lead to the development of more effective therapies for OC. Additionally, LBX2 represents a novel cell proliferation promoter in OC carcinogenesis.


Subject(s)
Histone Code , Ovarian Neoplasms , Female , Humans , Carcinogenesis , Cell Proliferation/genetics , Histone Code/genetics , Ovarian Neoplasms/genetics , Prognosis
2.
Mol Carcinog ; 63(4): 577-588, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38197493

ABSTRACT

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Herein, we investigated the role of nicotinamide mononucleotide (NMN) in HCC progression. HCC cells were treated with NMN (125, 250, and 500 µM), and then nicotinamide adenine dinucleotide (NAD+ ) and NADH levels in HCC cells were measured to calculate NAD+ /NADH ratio. Cell proliferation, apoptosis, autophagy and ferroptosis were determined. AMPK was knocked down to confirm the involvement of AMPK/mTOR signaling. Furthermore, tumor-inhibitory effect of NMN was investigated in xenograft models. Exposure to NMN dose-dependently increased NAD+ level and NAD+ /NADH ratio in HCC cells. After NMN treatment, cell proliferation was inhibited, whereas apoptosis was enhanced in both cell lines. Additionally, NMN dose-dependently enhanced autophagy/ferroptosis and activated AMPK/mTOR pathway in HCC cells. AMPK knockdown partially rescued the effects of NMN in vitro. Furthermore, NMN treatment restrained tumor growth in nude mice, activated autophagy/ferroptosis, and promoted apoptosis and necrosis in tumor tissues. The results indicate that NMN inhibits HCC progression by inducing autophagy and ferroptosis via AMPK/mTOR signaling. NMN may serve as a promising agent for HCC treatment.


Subject(s)
Carcinoma, Hepatocellular , Ferroptosis , Liver Neoplasms , Humans , Animals , Mice , Carcinoma, Hepatocellular/drug therapy , NAD , AMP-Activated Protein Kinases , Nicotinamide Mononucleotide , Mice, Nude , Liver Neoplasms/drug therapy , TOR Serine-Threonine Kinases , Nucleotides , Autophagy
4.
Chin Med J (Engl) ; 136(24): 2931-2937, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38032036

ABSTRACT

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION: The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.


Subject(s)
Anti-HIV Agents , HIV Infections , Humans , Antiretroviral Therapy, Highly Active/adverse effects , Anti-HIV Agents/adverse effects , HIV Infections/drug therapy , Tenofovir/therapeutic use , Retrospective Studies , Emtricitabine/therapeutic use , Emtricitabine/pharmacology , Adenine/therapeutic use , Lipids
5.
Emerg Microbes Infect ; 12(2): 2271068, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37824079

ABSTRACT

Immune overactivation is a hallmark of chronic HIV infection, which is critical to HIV pathogenesis and disease progression. The imbalance of helper T cell (Th) differentiation and subsequent cytokine dysregulation are generally considered to be the major drivers of excessive activation and inflammatory disorders in HIV infection. However, the accurate factors driving HIV-associated Th changes remained to be established. CD70, which was a costimulatory molecule, was found to increase on CD4+ T cells during HIV infection. Overexpression of CD70 on CD4+ T cells was recently reported to associate with highly pathogenic proinflammatory Th1/Th17 polarization in multiple sclerosis. Thus, the role of CD70 in the imbalance of Th polarization and immune overactivation during HIV infection needs to be investigated. Here, we found that the elevated frequency of CD70 + CD4+ T cells was negatively correlated with CD4 count and positively associated with immune activation in treatment-naïve people living with HIV (PLWH). More importantly, CD70 expression defined a population of proinflammatory Th1/17/22/GM subsets in PLWH. Blocking CD70 decreased the mRNA expression of subset-specific markers during Th1/17/22/GM polarization. Furthermore, we demonstrated that CD70 influenced the differentiation of these Th cells through STAT pathway. Finally, it was revealed that patients with a high baseline level of CD70 on CD4+ T cells exhibited a greater risk of poor immune reconstitution after antiretroviral therapy (ART) than those with low CD70. In general, our data highlighted the role of CD70 in Th1/17/22/GM differentiation during HIV infection and provided evidence for CD70 as a potential biomarker for predicting immune recovery.


Subject(s)
HIV Infections , Immune Reconstitution , Humans , CD4-Positive T-Lymphocytes , Disease Progression , Cell Differentiation , CD27 Ligand/genetics , CD27 Ligand/metabolism
7.
Biomed Pharmacother ; 165: 115222, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37549459

ABSTRACT

Lung cancer (LC) incidence and mortality continue to increase annually worldwide. LC is insidious and readily metastasizes and relapses. Except for its early diagnosis and surgical resection, there is no effective cure for advanced metastatic LC, and the prognosis remains dismal. Exosomes, a class of nano-sized extracellular vesicles produced by healthy or diseased cells, are coated with a bilayer lipid membrane and contain various functional molecules such as proteins, lipids, and nucleic acids. They can be used for intracellular or intercellular signaling or the transportation of biological substances. A growing body of evidence supports that exosomes play multiple crucial roles in the occurrence and metastatic progression of many malignancies, including LC. The elucidation of the potential roles of exosomes in the initiation, invasion, and metastasis of LC and their underlying molecular mechanisms may contribute to improved early diagnosis and treatment.


Subject(s)
Exosomes , Extracellular Vesicles , Lung Neoplasms , Humans , Exosomes/metabolism , Neoplasm Recurrence, Local/metabolism , Lung Neoplasms/metabolism , Extracellular Vesicles/metabolism , Biomarkers, Tumor/metabolism
9.
AIDS Res Ther ; 20(1): 49, 2023 07 15.
Article in English | MEDLINE | ID: mdl-37454082

ABSTRACT

BACKGROUND: Kidney disease is an important comorbidity in people living with HIV(PLWH), and is associated with poor outcomes. However, data on renal function of PLWH are limited in China so far. In this study we assessed the prevalence of kidney disease in patients either on antiretroviral therapy (ART) or not respectively in a single center in China and explored the possible risk factors associated. METHODS: In the cross-sectional study, we recruited hospitalized adult PLWH. Demographic characteristics, clinical information and laboratory variables were collected. Kidney disease was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and/or isolated hematuria, proteinuria, microalbuminuria. We calculated the prevalence of kidney disease and used logistic regression to assess its associated risk factors. RESULTS: A total of 501 adult PLWH were enrolled, 446 (89.0%) males and 55 (11.0%) females. The median age was 39 (IQR 30-50) years old. The prevalence of kidney disease was 19.0%, 22 (4.4%) patients with eGFR < 60 mL/min/1.73 m2, 53 (10.6%) patients with hematuria, 11 (2.2%) patients with proteinuria, and 40 (8.0%) patients with microalbuminuria. 297 (59.3%) patients were receiving ART. The patients on ART had a higher prevalence of renal disease than those had not been administrated with ART (22.6% vs. 13.7%, P = 0.013). On the multivariate logistic regression analysis among patients not on ART, lower haemoglobin (OR 0.994, 95%CI: 0.902-0.988, P = 0.013) were significantly associated with kidney disease. While among those on ART, older age (OR 1.034, 95%CI: 1.003-1.066, P = 0.032), lower haemoglobin (OR 0.968, 95%CI: 0.948-0.988, P = 0.002) and lower albumin (OR 0.912, 95%CI: 0.834-0.997, P = 0.044) were significantly associated with kidney disease. CONCLUSIONS: The prevalence of kidney disease among hospitalized PLWH in China is high, especially in patients on ART. A larger scale study on Chinese outpatient PLWH should be conducted, so as to precisely assess prevalence of kidney disease in general Chinese PLWH.


Subject(s)
HIV Infections , Kidney Diseases , Adult , Male , Female , Humans , Middle Aged , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Prevalence , Hematuria/epidemiology , Hematuria/complications , Cross-Sectional Studies , Risk Factors , Kidney Diseases/epidemiology , Glomerular Filtration Rate , Proteinuria/epidemiology , Proteinuria/complications , China/epidemiology
10.
Cell Oncol (Dordr) ; 46(5): 1181-1212, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37365450

ABSTRACT

BACKGROUND: Lung cancer (LC) is one of the most common malignancies globally. Besides early detection and surgical resection, there is currently no effective curative treatment for metastatic advanced LC. Exosomes are endogenous nano-extracellular vesicles produced by somatic cells that play an important role in the development and maintenance of normal physiology. Exosomes can carry proteins, peptides, lipids, nucleic acids, and various small molecules for intra- and intercellular material transport or signal transduction. LC cells can maintain their survival, proliferation, migration, invasion, and metastasis, by producing or interacting with exosomes. Basic and clinical data also show that exosomes can be used to suppress LC cell proliferation and viability, induce apoptosis, and enhance treatment sensitivity. Due to the high stability and target specificity, good biocompatibility, and low immunogenicity of exosomes, they show promise as vehicles of LC therapy. CONCLUSION: We have written this comprehensive review to communicate the LC treatment potential of exosomes and their underlying molecular mechanisms. We found that overall, LC cells can exchange substances or crosstalk with themselves or various other cells in the surrounding TME or distant organs through exosomes. Through this, they can modulate their survival, proliferation, stemness, migration, and invasion, EMT, metastasis, and apoptotic resistance.


Subject(s)
Exosomes , Extracellular Vesicles , Lung Neoplasms , Humans , Exosomes/metabolism , Lung Neoplasms/pathology , Signal Transduction , Apoptosis , Tumor Microenvironment
11.
Front Public Health ; 11: 1282324, 2023.
Article in English | MEDLINE | ID: mdl-38249414

ABSTRACT

Objective: The study aimed to use supervised machine learning models to predict the length and risk of prolonged hospitalization in PLWHs to help physicians timely clinical intervention and avoid waste of health resources. Methods: Regression models were established based on RF, KNN, SVM, and XGB to predict the length of hospital stay using RMSE, MAE, MAPE, and R2, while classification models were established based on RF, KNN, SVM, NN, and XGB to predict risk of prolonged hospital stay using accuracy, PPV, NPV, specificity, sensitivity, and kappa, and visualization evaluation based on AUROC, AUPRC, calibration curves and decision curves of all models were used for internally validation. Results: In regression models, XGB model performed best in the internal validation (RMSE = 16.81, MAE = 10.39, MAPE = 0.98, R2 = 0.47) to predict the length of hospital stay, while in classification models, NN model presented good fitting and stable features and performed best in testing sets, with excellent accuracy (0.7623), PPV (0.7853), NPV (0.7092), sensitivity (0.8754), specificity (0.5882), and kappa (0.4672), and further visualization evaluation indicated that the largest AUROC (0.9779), AUPRC (0.773) and well-performed calibration curve and decision curve in the internal validation. Conclusion: This study showed that XGB model was effective in predicting the length of hospital stay, while NN model was effective in predicting the risk of prolonged hospitalization in PLWH. Based on predictive models, an intelligent medical prediction system may be developed to effectively predict the length of stay and risk of HIV patients according to their medical records, which helped reduce the waste of healthcare resources.


Subject(s)
HIV Infections , Humans , Length of Stay , Retrospective Studies , HIV Infections/epidemiology , Algorithms , Supervised Machine Learning
12.
Oncol Res ; 32(2): 393-407, 2023.
Article in English | MEDLINE | ID: mdl-38186574

ABSTRACT

Advanced LUAD shows limited response to treatment including immune therapy. With the development of sequencing omics, it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers. Using GSE72094 (n = 386) and GSE31210 (n = 226) gene expression profile data in the GEO database, we identified genes associated with lung adenocarcinoma (LUAD) death using tools such as "edgeR" and "maftools" and visualized the characteristics of these genes using the "circlize" R package. We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods. By calculating the cell death index (CDI) of each individual, we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis (PCA) and Kaplan-Meier analysis. We also used the "ConsensusClusterPlus" tool for unsupervised clustering of LUAD subtypes based on model genes. In addition, we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses. We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort. Finally, we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments. The study utilized the TCGA-LUAD cohort (n = 493) and identified 2,901 genes that are differentially expressed in patients with LUAD. Through KEGG and GO enrichment analysis, these genes were found to be involved in a wide range of biological pathways. The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores. By comparing the overall survival (OS) outcomes of patients with different CDI values, it was found that increased CDI levels were significantly associated with lower OS rates. In addition, the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing. Finally, a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis. The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models. Relationship between programmed cell death (PCD) signature models and drug reactivity. After evaluating the median inhibitory concentration (IC50) of various drugs in LUAD samples, statistically significant differences in IC50 values were found in cohorts with high and low CDI status. Specifically, Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort, while Olaparib, Oxaliplatin, SB216763, and Axitinib had lower values. These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy. Therefore, this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics. The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Cell Death , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Apoptosis , Immunotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Tumor Microenvironment/genetics
13.
Front Public Health ; 10: 1000942, 2022.
Article in English | MEDLINE | ID: mdl-36424978

ABSTRACT

Background: The introduction of antiretroviral therapy (ART) has resulted in marked reductions in morbidity among people living with HIV (PLWH). Monitoring the hospitalizations of PLWH is important in evaluating the quality of healthcare and forecasting the co-morbidity pattern. We aimed to describe the trends in the rates and causes of hospitalization among PLWH who initiated ART in an HIV-designated hospital in China. Methods: PLWH who initiated ART and were hospitalized in Beijing Ditan Hospital from 2008 to 2020 were selected for the study. Hospitalizations were classified based on AIDS-defining events (ADEs), non-AIDS-defining events (nADEs), and other causes. Hospitalization rates were calculated in terms of person-years, with risk factors determined by Poisson regression. The proportion of hospitalization causes at different ART treatment statuses was also evaluated. Results: A total of 9,404 patients (94.7% were male patients) were included, contributing to 49,419 person-years. Overall, 1,551 PLWH were hospitalized for 2,667 hospitalization events, among which 60.4% of hospitalizations were due to ADEs, 11.4% were due to nADEs, and 28.2% were due to other causes. Unadjusted hospitalization rates decreased for all causes and all three diagnostic categories with year. After adjusting for the variables that changed substantially over time, ADE-related [IRR, 1.01 (0.96-1.05)] and nADE-related hospitalization rates [IRR, 0.92 (0.84-1.01)] appeared stable. Hospitalization for ADEs constituted an increasing proportion over time (36.3% in 2008-57.4% in 2020), especially in ART-naive inpatients (43.8% in 2008-83.3% in 2020). The proportion of nADE-related hospitalizations remained low (9.0% in 2008-15.4% in 2020). Hospitalization rate was highest for patients treated with ART during the first 6 months after ART initiation (46.2%) when ADEs were still the leading cause of hospitalizations (30.6%). Older age, non-men who have sex with men transmission, late presenters, HIV viral load (VL) > 50 copies/mL, and CD4 counts ≤ 200 cells/µL were associated with a higher hospitalization risk (all P < 0.05). Conclusion: Despite some progress, ADEs remain the most common and serious problem among PLWH in China. In order to avoid deteriorating to the stage of needing hospitalization, more work is needed to diagnose and treat HIV infection earlier.


Subject(s)
HIV Infections , Humans , Male , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Retrospective Studies , Hospitalization , Risk Factors , Hospitals
14.
Med Sci Monit ; 28: e937264, 2022 Oct 05.
Article in English | MEDLINE | ID: mdl-36196026

ABSTRACT

BACKGROUND There are few studies of GeneXpert MTB/RIF (hereafter referred to as Xpert) detection technology in HIV-infected people in China. Therefore, this study aimed to evaluate the value of Xpert in HIV/TB co-infected patients and to provide reference and guidance for the diagnosis of TB in HIV-infected populations. MATERIAL AND METHODS This study reviewed medical records of human immunodeficiency virus (HIV) patients hospitalized at the Infection Center of Beijing Ditan Hospital affiliated to Capital Medical University from January 2018 to May 2020, and patients diagnosed with pulmonary and extrapulmonary tuberculosis were screened as study subjects. Sensitivity and specificity of Xpert were analyzed using ROC curves. RESULTS Of the 413 HIV patients, 177 patients met the entry criteria, of which the diagnosis was active pulmonary tuberculosis (PTB): 145 and extrapulmonary tuberculosis (EPTB): 32. The sensitivity of Xpert for PTB and EPTB was 82.0% and 100%, higher than that of acid-fast bacilli (AFB) (61.0% and 58.3%), and slightly lower than that of T-SPOT.TB (91.0% and 100%); the specificity was 83.7% and 93.5%, higher than that of AFB (72.6%, 87.1%) and T-SPOT.TB (16.6%, 21.2%). The sensitivity of Xpert was 100% in bronchoalveolar lavage fluid (BALF) and 80.0% in sputum; in patients with CD4⁺ <200 cells/mm³, the sensitivity of Xpert was 90.0% and specificity was 84.8%, higher than that of AFB (60.0%, 75.5%) and T-SPOT.TB (90.0%, 21.5%). CONCLUSIONS Xpert has a high accuracy in HIV/TB co-infected patients, and Xpert still shows a high sensitivity and specificity even in HIV patients with CD4⁺ <200 cells/mm³. Xpert is recommended for the diagnosis of tuberculosis in HIV-infected patients.


Subject(s)
HIV Infections , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , HIV Infections/complications , Humans , Mycobacterium tuberculosis/genetics , Retrospective Studies , Rifampin , Sensitivity and Specificity , Sputum , Tuberculosis/complications , Tuberculosis/diagnosis , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnosis
15.
J Acquir Immune Defic Syndr ; 91(S1): S27-S34, 2022 10 01.
Article in English | MEDLINE | ID: mdl-36094512

ABSTRACT

BACKGROUND: With the increasing coverage of antiretroviral therapy, concerns for the emergence and transmission of HIV drug resistance (HIVDR) are arising. HIVDR was divided into 5 levels: sensitive, potentially resistant, low resistant, intermediate resistant, and high resistant. Most of the articles on HIVDR involved low-level, intermediate-level, and high-level drug resistance to antiretroviral drug, and few articles deal with potential drug resistance. Treatment failure associated with the level of low-level, intermediate-level, and high-level resistance to antiretroviral drug has been reported. However, whether virological failure (VF) is related to potential resistance remains unclear. In this study, we aimed to describe the situation of potential resistance to antiretroviral drug and whether it is related to VF. METHODS: We analyzed the demographic, behavioral information, medical history, and drug resistance-associated mutation data from subjects. Drug resistance mutations at baseline and time of failure in patients suffering VF were detected by using the Vela automated next-generation sequencing platform. The χ2 test or Fisher exact test and logistic regression were used to assess the risk factors that contribute to VF in the potential drug-resistant people. RESULTS: The prevalence of overall pretreatment drug resistance was 7.06% (233/3300), and the prevalence of pretreatment potential resistance was 8.79% (290/3300). All these patients with pretreatment potential first-line drugs resistance showed potential resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and some of them had potential drug resistance to NNRTIs and NRTIs or NNRTIs and PIs; among these patients, 94.71% (179/189) had V179 D/E mutations. The VF rate of first-line treatment for potentially resistant people is 17.99%. CD4+ T-cell count ≤200 cells/L at antiretroviral therapy initiation are risk factors for the failure of first-line treatment. CONCLUSIONS: The prevalence of potential drug resistance among individuals with HIV and the VF rate of first-line treatment for potential drug-resistant people were high. To better optimize clinical management, prevention, and control of HIV, attention should be devoted to the potential resistance of nonnucleoside drugs.


Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , HIV Infections , HIV-1 , Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Anti-Retroviral Agents/therapeutic use , Drug Resistance, Viral/genetics , HIV Infections/epidemiology , HIV-1/genetics , Humans , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use
16.
Front Immunol ; 13: 947647, 2022.
Article in English | MEDLINE | ID: mdl-35967422

ABSTRACT

Persistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4+ T cells depletion and AIDS progression. Furthermore, immune activation is a key factor that leads to impaired immune reconstitution after long-term effective antiretroviral therapy (ART), and is even responsible for the increased risk of developing non-AIDS co-morbidities. Therefore, it's imperative to identify an effective intervention targeting HIV-associated immune activation to improve disease management. Double negative T cells (DNT) were reported to provide immunosuppression during HIV infection, but the related mechanisms remained puzzled. Foxp3 endows Tregs with potent suppressive function to maintain immune homeostasis. However, whether DNT cells expressed Foxp3 and the accurate function of these cells urgently needed to be investigated. Here, we found that Foxp3+ DNT cells accumulated in untreated people living with HIV (PLWH) with CD4+ T cell count less than 200 cells/µl. Moreover, the frequency of Foxp3+ DNT cells was negatively correlated with CD4+ T cell count and CD4/CD8 ratio, and positively correlated with immune activation and systemic inflammation in PLWH. Of note, Foxp3+ DNT cells might exert suppressive regulation by increased expression of CD39, CD25, or vigorous proliferation (high levels of GITR and ki67) in ART-naive PLWH. Our study underlined the importance of Foxp3+ DNT cells in the HIV disease progression, and suggest that Foxp3+ DNT may be a potential target for clinical intervention for the control of immune activation during HIV infection.


Subject(s)
Forkhead Transcription Factors , HIV Infections , HIV-1 , T-Lymphocytes, Regulatory , Disease Progression , Forkhead Transcription Factors/immunology , HIV Infections/immunology , Humans , T-Lymphocytes, Regulatory/immunology
17.
Front Public Health ; 10: 916878, 2022.
Article in English | MEDLINE | ID: mdl-36033787

ABSTRACT

Background: The goal of this study was to identify potentially important factors for the dental health though heterogeneous effects of risk factors within Chinese adolescent populations with different characteristics by analyzing the repeated cross-sectional data collected in the 3rd (2005) and 4th (2015) National Oral Health Survey. Methods: We studied the relationships between the decayed, missing and filled permanent teeth (DMFT) score, which was a discrete value, with the caries risk factors (region, census type, gender, only child or not, parents' education level, tooth bushing, dentist visit history, knowledge score, sugar intake, and pit-and-fissure sealants status), though the Poisson mixture regression model, which could identify subgroups among the full population and estimate the heterogeneous effects of risk factors simultaneously. We performed a series of tests and trend analysis based on the model fitting results to explore the primary causes for the dental caries issue clearly and intuitively. Results: A total of 39,049 teenagers aged 12 years were involved in the analysis. The Poisson mixture regression model clustered all individuals into three subgroups, where the mean values (standard deviations) of DMFT were 0.18 (0.56), 1.31 (1.49), and 2.91 (1.89), respectively. Model fitting results indicated that the heterogeneous effects of the involved risk factors were significant. In addition, we also found significant differences in the distributions and trends of DMFT within different categories of selected risk factors (region, census type, gender and dentist visiting history) from the projection analysis results. The estimated and projected proportions showed that the proportion of high caries risk population in the southwestern region increased by 31.8%, and will become even more severe as it will be the major component of high caries risk population in 2025. Conclusions: We found that the trends for the developments and changes of dental caries within populations with different characteristics were inequality. The regional difference is the primary factor for diversified changes in DMFT. The findings in this study provide support for intervention and prevention policies for the deterioration of dental caries risk within different adolescent populations.


Subject(s)
Dental Caries , Adolescent , Child , Cross-Sectional Studies , Humans , Pit and Fissure Sealants , Risk Factors
18.
HIV Med ; 23 Suppl 1: 32-41, 2022 03.
Article in English | MEDLINE | ID: mdl-35293109

ABSTRACT

OBJECTIVES: We aimed to analyze the incidence rates of new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury during antiretroviral therapy (ART) among people living with HIV (PLWH) and determine the associated risk factors. METHODS: This study included PLWH enrolled from Beijing Ditan Hospital from November 11, 2004, to December 29, 2018. The incidence rates of new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury were calculated and stratified based on ART regimen, CD4 count, and HIV-RNA. Risk factors were determined using Cox regression analysis. RESULTS: Overall, 6747 participants were included. Moreover, 4.5%, 43.3%, 25.4%, 11.2%, and 6.2% of patients developed new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury, respectively, with incidence rates of 1.7, 26.9, 10.2, 3.9, and 5.5 per 100 person-years, respectively. Longitudinally, the incidence rates and percentages of these outcomes were highest in the first year of ART. The percentage of dyslipidemia was significantly higher in protease inhibitor (PI)-based regimen than in non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. However, the percentage of liver injury was significantly higher in NNRTI-based regimen than in PI-based regimen. In multivariate Cox regression analysis, low CD4 count (<200 cells/µL, adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.15-1.57) and high HIV-RNA (>105 copies/mL, aHR = 1.26, 95% CI 1.08-1.48) were risk factors for hypertriglyceridemia. CONCLUSIONS: Clinical outcomes, including new-onset diabetes, dyslipidemia, and liver and renal injuries, are common in PLWH. Regular glucose, lipid, liver, and renal function monitoring is required during ART, especially in high-risk patients.


Subject(s)
Anti-HIV Agents , Dyslipidemias , HIV Infections , Hypercholesterolemia , Hypertriglyceridemia , Anti-HIV Agents/adverse effects , CD4 Lymphocyte Count , Dyslipidemias/chemically induced , Dyslipidemias/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , Humans , Hypercholesterolemia/drug therapy , Hypertriglyceridemia/chemically induced , Hypertriglyceridemia/drug therapy , Hypertriglyceridemia/epidemiology , RNA/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Viral Load
19.
BMC Infect Dis ; 22(1): 4, 2022 Jan 04.
Article in English | MEDLINE | ID: mdl-34983408

ABSTRACT

BACKGROUND: We aimed to clarify the characteristics, risk factors, and prognosis of stroke among HAART-naive people living with HIV (PLWH) in China. METHODS: We selected HAART-naive PLWH admitted to Beijing Ditan Hospital, Capital Medical University, from 1 January 2009 to 31 December 2019. Demographic and clinical data were obtained by searching an anonymous electronic case system. Descriptive analysis and logistic regression and Cox proportional hazard models were used to determine the characteristics and predictors of stroke among all HAART-naive PLWH and evaluate the risk factors of mortality in HAART-naive PLWH with stroke. RESULTS: Stroke was diagnosed in 105 cases (3.7%) of 2867 HAART-naive PLWH. Multivariate logistic regression indicated that age of 30-55 years (OR 1.903, 95% CI 1.005-3.603, p = 0.048), age of ≥ 55 years (OR 4.104, 95% CI 1.928-8.737, p < 0.001), and CD4 count of < 200 cells/µL (OR 2.005, 95% CI 1.008-3.985, p = 0.047) were associated with increased odds of stroke. Diabetes (OR 3.268, 95% CI 1.744-6.125, p < 0.001), hypertension (OR 2.301, 95% CI 1.425-3.717, p = 0.001), syphilis (OR 2.003, 95% CI 1.300-3.089, p = 0.002), and complicated AIDS-defining CNS diseases (OR 7.719, 95% CI 4.348-13.703, p < 0.001) were risk factors for stroke. Of the 105 stroke patients, 12 (11.4%) died during hospitalisation, and the risk factors for mortality among patients with stroke were age of > 65 years (AHR: 8.783, 95% CI 1.522-50.668, p = 0.015), complicated severe pneumonia (AHR: 3.940, 95% CI 1.106-14.029, p = 0.034), and AIDS-defining CNS diseases (AHR: 19.766, 95% CI 3.586-108.961, p = 0.001). CONCLUSIONS: For HAART-naive people living with HIV (PLWH), stroke occurred in various age groups, and early screening for stroke, timely intervention for risk factors among patients in various age groups, and controlling the CD4 count are extremely important in reducing the burden of stroke.


Subject(s)
HIV Infections , Stroke , Adult , Aged , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , China/epidemiology , HIV , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Stroke/epidemiology , Stroke/etiology
20.
Infect Med (Beijing) ; 1(4): 281-284, 2022 Dec.
Article in English | MEDLINE | ID: mdl-38075403

ABSTRACT

Rhodococcus equi is a zoonotic opportunistic pathogen that mainly infects immunodeficient individuals, such as those with HIV infection. In R. equi-infected individuals, serious lung lesions can develop and death may result without appropriate antiviral treatment. This bacterium is rare in clinic and there is little information regarding its diagnosis and treatment. To improve our understanding, this case report describes the diagnosis and treatment of a patient with HIV complicated with R. equi infection from Ditan Hospital, Beijing, China.

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