Pathological proliferation: a potential mechanism for poor CD4+ T cell recovery in people living with HIV.

Background: People living with HIV (PLWH) fail to achieve normalization of CD4+ T cell counts and function, especially in immunological non-responders (INRs). The frequencies of Ki67+CD4+ T cells were inversely associated with CD4+ T cell counts in HIV infected patients. Early ART did not normalize CD4+ T cell proliferation. However, the features of the abnormal proliferation CD4+ T cell in INRs are far from known. Method: PLWH were divided into INRs (n= 16) and immunological responders (IRs, n= 53) groups. Mass cytometry was applied to peripheral blood T cells to profile the immune cells and liquid chip technique was used to measure plasma levels of cytokines and chemokines. Correlation analyses were conducted to evaluate associations between the degree of CD4+ T cell proliferation and immune function. Results: The percentage of Ki67+ CD4+ T cells were significant higher in INRs, and we defined these cells with significant higher level of Ki67, as over-proliferating cells. No significant difference of markers' expression (HLA-DR, CD38, CD57, PD-1, PD-L1, CD107a, perforin) was found between INRs and IRs. Compared with naïve CD4+ T cells in INRs, Ki67+ CD4+ T cells exhibited lower levels of CD57 and CD38. Whereas Ki67+ T cells exhibited higher levels of CD38 and CD57 and activation compared with differentiated mature central memory CD4+ T cells and effector memory CD4+ T cells. Ki67+ cells did not show higher levels of senescence and activation compared to certain Ki67- CD4+ central memory T cells in IRs. Furthermore, Ki67+ CD4+ Tcm cells exhibited positive correlations with pro-inflammatory cytokines. Conclusion: We proposed and validated the hypothesis of "pathological proliferation" in INRs: excessive proliferation of CD4+ T cells in INRs may be accompanied by aberrant activation, senescence and loss of immune function. Eventually, such over-proliferating but poor-quality cells in INRs result in incomplete recovery of both CD4+ T cell counts and function. An intervention that enhancing the proliferative capacity or functional ability or both of CD4+ T cell in INRs might therefore be beneficial.

People who living with HIV/AIDS also have a high prevalence of anxiety disorders: a systematic review and meta-analysis.

Background: An estimated 301 million people worldwide suffer from anxiety disorders. People living with HIV/AIDS (PLWHA) are particularly prone to anxiety disorders that could interfere with the important developmental process in an individual's development and ultimately result in a wide range of negative mental, physical, and psychosocial consequences, as well as poor quality of life in those population groups. Early intervention for anxiety disorders can reverse some of the physical damage caused by anxiety. However, based on systematic reviews and meta-analyses, the specific prevalence of anxiety disorders in PLWHA remains unknown. Method: We conducted a literature search on PubMed, Embase, and Web of Science up to 22 October 2022. A random-effects meta-analysis was used to pool prevalence rates from the included studies. Sensitivity and subgroup analyses were performed to identify the possible sources of heterogeneity and to compare the prevalence estimates across groups. The Joanna Briggs Institute's Quality Assessment Checklist was used to assess the quality of the included studies. Cochran's Q and I2 tests were used to assess the between-study heterogeneity. Results: Ten studies with a total of 238,570 cases were included for the final analysis. Results showed that 15.5% of HIV/AIDS patients had anxiety disorders. The prevalence was higher in females (20.8%) than males (20.7%). The mean age of PLWHA with anxiety disorders was 46.58 ± 11.15 years in these included studies. The subgroup analyses showed significant higher prevalence in non-heterosexual (32.1%). Conclusion: We attempted to quantify literature that could allow for stronger inferences to be made regarding the significantly higher prevalence of anxiety disorders in PLWHA, a finding that suggests the imperativeness of intervention strategies to alleviate suffering and reduce the probable negative ramifications. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023442219, identifier CRD42023442219.

Mitochondrial Metabolism in Alveolar Macrophages of Patients Infected with HIV, Tuberculosis, and HIV/Tuberculosis.

Tuberculosis (TB) is one of the most common opportunistic infections and is a leading cause of mortality in patients with HIV and AIDS. HIV infection causes serious defects in the host immune system and increases the risk of active TB. TB infection promotes HIV replication and aggravates host damage in patients with HIV/AIDS. Alveolar macrophages (AMs) are essential immune cells during TB and HIV infections. AMs undergo a shift in mitochondrial metabolism during TB or HIV infection, that is, metabolic reprogramming, allowing them to act in the form of classical activated macrophages (M1) and alternative activated macrophages (M2) at different stages of infection. We reviewed the alterations in the mitochondrial energy metabolism of AMs in patients with HIV, TB, and HIV/TB to provide ideas for further research on the role of metabolic reprogramming by AMs in the pathogeneses of HIV, TB, and HIV/TB coinfection.

Disruption of blood-brain barrier: effects of HIV Tat on brain microvascular endothelial cells and tight junction proteins.

Although the widespread use of antiretroviral therapy (ART) has prolonged the life span of people living with HIV (PLWH), the incidence of HIV-associated neurocognitive disorders (HAND) in PLWH is also gradually increasing, seriously affecting the quality of life for PLWH. However, the pathogenesis of HAND has not been elucidated, which leaves HAND without effective treatment. HIV protein transactivator of transcription (Tat), as an important regulatory protein, is crucial in the pathogenesis of HAND, and its mechanism of HAND has received widespread attention. The blood-brain barrier (BBB) and its cellular component brain microvascular endothelial cells (BMVECs) play a necessary role in protecting the central nervous system (CNS), and their damage associated with Tat is a potential therapeutic target of HAND. In this review, we will study the Tat-mediated damage mechanism of the BBB and present multiple lines of evidence related to BMVEC damage caused by Tat.

Clinical characteristics of adult inpatients with Measles in Beijing from 2010 to 2021: a retrospective analysis.

BACKGROUND: With the measles vaccine coverage rate gradually increasing, adult patients' epidemiological and clinical characteristics have changed. AIMS: To analyze the clinical characteristics of adult measles patients in Beijing Youan Hospital. METHODS: We retrospectively reviewed the electronic medical records of 818 patients diagnosed with measles at Beijing Youan Hospital between June 2010 and October 2021. We divided all hospitalized patients into two demographics groups, using 14 years of age as the cut-off. RESULTS: Of the adult inpatients, 110 (74.83%) were aged 20-40. There was an overall peak incidence in 2014, and yearly peaks came in April. Fever, cough, erythema, and Koplik's spots were present in 79.59%, 82.1%, 99.3%, and 59.8% of the adult group, respectively, compared to 75.26%, 92.0%, 99.9%, and 39.0% of the pediatric group. Decreased lymphocytes and hepatic impairment were common in adults. The adult group's median level of C-reactive protein was higher than that of the pediatric group (p < 0.05). The positive rate of measles antibody (IgM) detection was 64.6% in the adults and 78.8% in the pediatric group (p < 0.05). Of the adults, 46.9%, 8.8%, and 66% had pneumonia, gastroenteritis, and antibiotic use, compared to 89.6%, 2.7%, and 83.2% of the pediatric patients. The duration of symptoms before admission and the average length of hospital stay was approximately six days in both groups. CONCLUSIONS: Koplik's spots are more likely to be detected by clinicians in adult patients admitted to the hospital. Active surveillance is helpful for adults who are negative for IgM on admission. Although the proportion of adult measles patients with liver injury is high, the disease is generally mild. Measles significantly impacts peripheral blood lymphocytes in adults, but adults are at lower risk of concurrent pneumonia than the pediatric group. Clinicians need to pay attention to the appropriate use of antibiotics. Expanding the coverage of the measles vaccination in high-risk areas is beneficial for preventing measles in adults.

Clinical Features of Human Brucellosis and Risk Factors for Focal Complications: A Retrospective Analysis in a Tertiary-Care Hospital in Beijing, China.

Purpose: Brucellosis is an ongoing zoonotic disease in China, but there are few data in Beijing. This study was designed to illustrate clinical characteristics of patients with brucellosis in Beijing, China and explore the risk factors for focal brucellosis. Patients and Methods: Data of patients with brucellosis were retrospectively collected from the patients' electronic medical records in Beijing Youan Hospital during 2010 to 2021, including epidemiological, demographic and clinical features. Risk factors for focal brucellosis were identified by multivariable logistic regression models. Results: A total of 197 patients were included in the study, with 165 (83.8%) cases in acute phase and 32 (16.2%) cases in chronic phase. Patients in acute phase were more likely to have splenomegaly (24.2% vs 3.1%, p=0.007) than those in chronic phase, but had less arthralgia (62.4% vs 81.3%, p=0.040). The median level of alanine aminotransferase (36.9 vs 20.7, p=0.001) was higher in patients at acute stage than those at chronic stage. Of all the patients, 76 (38.6%) were reported with focal complications, including 16 (8.1%) peripheral arthritis, 36 (18.3%) spondylitis, 17 (8.6%) epididymoorchitis, 8 (4.1%) meningitis and 3 (1.3%) endocarditis. Additionally, male (OR 2.76, 95% CI 1.15-6.64, p = 0.023), arthralgia (OR 6.23, 95% CI 2.36-16.43, p < 0.001) and higher level of platelets (OR 1.01, 95% CI 1.00-1.01, p < 0.001) were the independent risk factors for focal brucellosis. Conclusion: The control of human brucellosis still cannot be ignored due to the re-emerging cases in Beijing, which are more likely to present splenomegaly and abnormal liver function in acute phase. Moreover, male, arthralgia and high level of platelets were the independent risk factors for focal brucellosis.

Duration of SARS-CoV-2 RNA shedding and factors associated with prolonged viral shedding in patients with COVID-19.

To investigate the factors associated with the duration of severe acute respiratory syndrome coronavirus 2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). A retrospective cohort of COVID-19 patients admitted to a designated hospital in Beijing was analyzed to study the factors affecting the duration of viral shedding. The median duration of viral shedding was 11 days (IQR, 8-14.3 days) as measured from illness onset. Univariate regression analysis showed that disease severity, corticosteroid therapy, fever (temperature>38.5°C), and time from onset to hospitalization were associated with prolonged duration of viral shedding (P < .05). Multivariate regression analysis showed that fever (temperature>38.5°C) (OR, 5.1, 95%CI: 1.5-18.1), corticosteroid therapy (OR, 6.3, 95%CI: 1.5-27.8), and time from onset to hospitalization (OR, 1.8, 95%CI: 1.19-2.7) were associated with increased odds of prolonged duration of viral shedding. Corticosteroid treatment, fever (temperature>38.5°C), and longer time from onset to hospitalization were associated with prolonged viral shedding in COVID-19 patients.

Clinical characteristics of Coronavirus Disease 2019 patients in Beijing, China.

The outbreak of Coronavirus Disease (COVID-19) in Wuhan have affected more than 250 countries and regions worldwide. However, most of the clinical studies have been focused on Wuhan, and little is known about the disease outside of Wuhan in China. In this retrospective cohort study, we report the early clinical features of 80 patients with COVID-19 admitted to the hospital in Beijing. The results show that 27 (33.8%) patients had severe illness. Six (7.5%) patients were admitted to the ICU, and 3 (3.8%) patients died. Forty-eight percent (39/80) of the patients had a history of living/traveling in Wuhan. Patients with severe- illness were significantly older (average age, 71 years old vs 44 years old) and had a high incidence of expectoration (59.3% vs 34.0%), shortness of breath (92.6% vs 9.4%), anorexia (51.9% vs 18.9%) and confusion(18.5% vs 0%) compared with nonsevere patients. The systolic blood pressure (median, 130 mmHg vs 120 mmHg) was higher and the oxygen saturation (median, 98.3% vs 92.0%) was significantly lower in severe patients than nonsevere patients. In addition, myoglobin (median, 56.0 ng/mL vs 35.0 ng/mL), troponin I (median, 0.02 pg/mL vs 0.01 pg/mL), C-reactive protein (median, 69.7 mg/L vs 12.9 mg/L) and neutrophils (median, 3.3×109/L vs 2.2×109/L) were significantly increased, while lymphocytes (median, 0.8×109/L vs 1.2×109/L), albumin (mean, 32.8 g/L vs 36.8 g/L) and the creatinine clearance rate (median, 91.2 vs 108.2 ml/min/1.73m2) were significantly decreased among severe patients. Our study revealed that older patients with high levels of C-reactive protein, myoglobin, troponin I, and neutrophil and high systolic blood pressure as well as low levels of lymphocytes, and albumin and a low creatinine clearance rate and oxygen saturation were more likely to have severe disease.

Clinical features and outcomes of 210 patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a lethal chronic interstitial lung disease (ILD) of unknown cause and having a variable and unpredictable course. This study aimed to summarize the clinical features and follow-up outcomes and to identify potential factors useful for the assessment of prognosis in IPF. METHODS: Two hundred and ten patients hospitalized and diagnosed as IPF in our unit from January 1999 to June 2007 were enrolled into this study. The baseline demographic, clinical, radiologic and physiologic characteristics were summarized. Clinical follow-up data until February 2010 were collected, and the median survival time and 1-, 2-, and 5-year survival rates, as well as the influences of the summarized baseline variables on the prognosis were analyzed. RESULTS: The age at diagnosis as IPF was (64 ± 10) years, the duration before diagnosis of 106 patients (50%) was shorter than 2 years, and 73% were males. One hundred and forty-five patients (69%) had a history of smoking with a median pack-year of 18. Eighty-nine patients (42%) had emphysema and 62 patients (29%) pulmonary arterial hypertension (PAH). One hundred and twenty-four patients were followed up, of which 99 patients died from various causes including respiratory failure related to IPF (93%). The follow-up period was (21 ± 23) months. The median survival time was 38 months. The 1-, 2-, and 5-year survival rates were 61%, 52%, and 39%, respectively. Multivariate analysis showed clubbing, PAH, duration from initial onset to diagnosis, and forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) were independent prognostic indicators of IPF. CONCLUSION: IPF patients who have clubbing, PAH, a higher FEV1/FVC, and a short duration from initial onset to diagnosis have a poorer outcome.

CCL18 in serum, BAL fluid and alveolar macrophage culture supernatant in interstitial lung diseases.

BACKGROUND: CCL18 is a CC chemokine produced mainly by antigen-presenting cells, and is chemotactic predominantly for T-lymphocytes. CCL18 can stimulate pulmonary fibroblasts and increase the collagen production in vitro. OBJECTIVES: This study aimed to compare the CCL18 levels in a variety of human biological fluids between various interstitial lung diseases (ILDs), and to reveal potential correlations with BAL cell differentials. METHODS: Serum and bronchoalveolar lavage fluid (BALF) samples were collected from 199 patients with idiopathic pulmonary fibrosis (IPF), idiopathic non-specific interstitial pneumonia (iNSIP), respiratory bronchiolitis interstitial lung disease/desquamative interstitial pneumonia (RB-ILD/DIP), cryptogenic organizing pneumonia (COP), hypersensitivity pneumonitis (HP) or sarcoidosis. Alveolar macrophage (AM) culture was performed in 44 patients with IPF, iNSIP, COP, HP, sarcoidosis or non-ILDs. The CCL18 levels in serum, BALF and AM culture supernatant were measured with ELISA. RESULTS: Both serum and BALF CCL18 levels in all ILDs were higher than in controls (all p < 0.005). In HP, CCL18 serum levels were the highest of all ILDs, and its BALF levels were significantly higher than in other ILDs except iNSIP. The BALF CCL18 levels markedly correlated with BAL cell differentials, especially with the percentage of BAL lymphocytes. In AM culture supernatant, the spontaneous CCL18 production was higher in HP and COP than in IPF and controls. CONCLUSION: CCL18 levels in serum, BALF and AM culture supernatant are markedly increased in various inflammatory and fibrotic ILDs. However, the CCL18 level being highest in HP among the investigated ILDs suggests that CCL18 may be more profoundly involved in inflammatory immune responses.

Macrolides inhibit cytokine production by alveolar macrophages in bronchiolitis obliterans organizing pneumonia.

BACKGROUND AND OBJECTIVE: Bronchiolitis obliterans organizing pneumonia (BOOP) is a distinct clinicopathological entity histologically characterized by intra-alveolar granulation tissue and absence of extensive fibrotic lesions. Effective macrolide treatment of BOOP has been reported anecdotally. This study aimed to investigate whether alveolar macrophages (AMs) produce aberrant proinflammatory cytokines in BOOP and whether this can be inhibited by clarithromycin (CAM) or azithromycin (AZM). METHODS: AMs collected by bronchoalveolar lavage (BAL) from 6 BOOP patients and 8 non-ILD controls were cultured for 24h in the presence or absence of CAM, AZM, lipopolysaccharide (LPS), or dexamethasone (DEX). Tumor necrosis factor alpha (TNF-α), soluble TNF receptor 1 (sTNFR1), sTNFR2, interleukin 1beta (IL-1ß), IL-6, IL-8, IL-10, interferon gamma inducible protein 10 (IP-10) and CC chemokine ligand 18 (CCL18) were measured in the culture supernatant by ELISA. RESULTS: The spontaneous and LPS-stimulated production of all investigated cytokines by AMs was significantly increased in BOOP compared to controls. CAM and AZM induced a dose-dependent suppression of spontaneous TNF-α, sTNFR2, IL-6, IL-8 and CCL18 production (p<0.05). CAM also inhibited the IL-1ß production. CAM and AZM significantly and dose-dependently attenuated the LPS-stimulated production of sTNFR1, sTNFR2, IL-8 and CCL18 (p<0.05). CAM also inhibited the LPS-stimulated TNF-α, IL-1ß, IL-6 and IL-10 production. CONCLUSIONS: AMs from BOOP patients produce abundant proinflammatory cytokines which may be pivotal in the disease pathogenesis. Macrolides inhibit this cytokine production, CAM more efficiently than AZM.