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Abstract Purpose Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. Method We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. Results As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. Conclusion In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

Abstract Background Stroke is a common complication of hypertension, but the predictive value of metabolic syndrome parameters' variability on stroke risk in individuals with hypertension remains unclear. Therefore, our objective was to investigate the relationship between metabolic syndrome parameters' variability and the risk of total stroke and its subtypes in hypertensive patients. Methods This prospective cohort study included 17,789 individuals with hypertension from the Kailuan study since 2006. Metabolic syndrome parameters, including waist circumference (WC), fasting blood glucose (FBG), systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), were collected at three follow-up visits in the 2006, 2008, and 2010 surveys. We assess the variability utilizing the coefficient of variation (CV), standard deviation (SD), average real variation (ARV), and variability independent of the mean (VIM), with CV initially assessed. Participants were categorized based on the number of high-variability metabolic syndrome parameters (0, 1, 2, ≥ 3). Stroke cases were identified by reviewing medical records. The associations between variability in metabolic syndrome parameters and the risk of total stroke and its subtypes were analyzed using Cox proportional hazard regression models. Results During a median follow-up of 9.32 years, 1223 cases of stroke were recorded. Participants with ≥ 3 high-variability metabolic syndrome parameters had an increased risk of total stroke (HR: 1.29, 95%CI 1.09–1.52), as well as an increased risk of ischemic stroke (HR: 1.31, 95%CI 1.05–1.63) compared to those without high-variability parameters. The study also examined variability in each metabolic syndrome parameter, and significant associations with an increased risk of total stroke were observed for variability in SBP (HR: 1.24, 95%CI 1.05–1.46) and HDL-C (HR: 1.34, 95%CI 1.09–1.64). Conclusions Long-term fluctuations in metabolic syndrome parameters significantly increase the risk of total stroke, especially ischemic stroke. Maintaining low variability in metabolic syndrome parameters could benefit health, and hypertensive individuals must be regularly monitored.

Human immunodeficiency virus (HIV) infection has evolved into an established global pandemic over the past four decades; however, despite massive research investment globally, the precise underlying mechanisms which are fundamental to HIV-related pathogenesis remain unclear. Single cell ribonucleic acid (RNA) sequencing methods are increasingly being used for the identification of specific cell-type transcriptional changes in HIV infection. In this scoping review, we have considered information extracted from fourteen published HIV-associated single-cell RNA sequencing-related studies, hoping to throw light on the underlying mechanisms of HIV infection and pathogenesis, and to explore potential candidate biomarkers for HIV disease progression and antiviral treatment. Generally, HIV positive individuals tend to manifest disturbances of frequency of multiple cellular types, and specifically exhibit diminished levels of CD4+ T-cells and enriched numbers of CD8+ T-cells. Cell-specific transcriptional changes tend to be linked to cell permissiveness, hyperacute or acute HIV infection, viremia, and cell productivity. The transcriptomes of CD4+ T-cell and CD8+ T-cell subpopulations are also observed to change in HIV-positive diabetic individuals, spontaneous HIV controllers, individuals with high levels of HIV viremia, and those in an acute phase of HIV infection. The transcriptional changes seen in B cells, natural killer (NK) cells, and myeloid dendritic cells (mDCs) of HIV-infected individuals demonstrate that the humoral immune response, antiviral response, and immune response regulation, respectively, are all altered following HIV infection. Antiretroviral therapy (ART) plays a crucial role in achieving immune reconstitution, in improving immunological disruption, and in mitigating immune system imbalances in HIV-infected individuals, while not fully restoring inherent cellular transcription to levels seen in HIV-negative individuals. The preceding observations not only illustrate compelling advances in the understanding of HIV-associated immunopathogenesis, but also identify specific cell-type transcriptional changes that may serve as potential biomarkers for HIV disease monitoring and therapeutic targeting.

IntroductionWith the discovery of extracorporeal membrane oxygenation (ECMO), it is considered as a valuable tool for supporting the treatment of severe acute respiratory distress syndrome (ARDS). It has gained increasing attention, particularly during the COVID-19 epidemic. However, to date, no relevant bibliometric research on the association between ECMO and ARDS (ECMO-ARDS) has been reported. Our study aimed to summarize the knowledge structure and research focus of ECMO-ARDS through a bibliometric analysis.MethodPublications related to ECMO-ARDS from 2000 to 2022 were obtained from the Web of Science Core Collection (WoSCC). Research data underwent bibliometric and visual analysis by using CiteSpace, VOSviewer, and one online analysis platform. By analyzing the countries, institutions, journals, authors, the geographic distribution of research contributions as well as the leading institutions and researchers in this field were identified. Additionally, prominent journals and highly cited publications were highlighted, indicating their influence and significance in the field. Moreover, the co-citation references and co-occurring keywords provided valuable information on the major research topics, trends, and potential emerging frontiers.ResultsA total of 1,565 publications from 60 countries/regions were retrieved. The annual publication number over time revealed exponential growth trends (R2 = 0.9511). The United States was dominant in ECMO-ARDS research, whereas the Univ Toronto was most productive institution. Prof Combes A published the most publications in this area. ASAIO Journal and Intensive Care Medicine were the most active and co-cited journals, respectively. Reference co-citation analysis showed that current research focus has shifted to COVID-related ARDS, multi-center studies, as well as prone positioning. Apart from the keywords “ECMO” and “ARDS”, other keywords appearing at high frequency in the research field were “COVID-19”, “mechanical ventilation”, “extracorporeal life support”, “respiratory failure”, “veno-venous ECMO”, “SARS-CoV-2”, “outcome”. Among them, keywords like “mortality”, “veno-venous ECMO”, “epidemiology”, “obesity”, “coagulopathy”, “lung ultrasound”, “inhalation injury”, “noninvasive ventilation”, “diagnosis”, “heparin”, “cytokine storm” has received growing interest in current research and also has the potential to continue to become research hotspots in the near future.ConclusionThis bibliometric analysis offers a comprehensive understanding of the current state of ECMO-ARDS research and can serve as a valuable resource for researchers, policymakers, and stakeholders in exploring future research directions and fostering collaborations in this critical field.

Abstract Background This study’s objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis. Methods A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020. Results Approximately 42.9%, 20.6%, and 10.6% of the enrolled patients developed severe anemia, severe leukopenia, and severe thrombocytopenia, respectively. Baseline hemoglobin level 73.4 µmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST/ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/liter (OR = 4.342, 95% CI: 1.747 ~ 10.789), and a dose of amphotericin B deoxycholate > 0.58 mg/kg/d (OR = 2.504, 95% CI:1.066 ~ 5.882) were observed to be independent risk factors associated with the development of severe anemia. Co-infection with tuberculosis (OR = 3.307, 95% CI: 1.050 ~ 10.420), and platelet level (per 10 × 109 /L) (OR = 0.952, 95% CI: 0.911 ~ 0.996) were shown to be independent risk factors associated with the development of severe leukopenia. Platelet level

Background: Globally, China bears the highest stroke burden, emphasizing the paramount importance of comprehending the influencing factors on family resilience among patients with ischemic stroke to promote their physical and mental well-being, as well as enhance the quality of their life. This understanding can concurrently assist healthcare professionals in formulating interventions aimed at fostering healthy family functioning. Objective: To investigate the level of family resilience in patients with ischemic stroke and its predictive factors. Methods: A total of 310 inpatients with ischemic stroke were recruited from three tertiary general hospitals in China between May and November 2021. The study employed a range of instruments for data collection, including the General data questionnaire, Family Resilience Rating Scale, Simplified Coping Style Questionnaire, Perceived Social Support Scale and Connor-Davidsion Re-silience Scale. Data analysis was conducted using SPSS 22.0 statistical software. Non-parametric tests, Spearman analysis, and multiple stepwise regression were employed to investigate the predictive variables of family resilience. Results: A total of 303 patients successfully completed the investigation, yielding an efficacy rate of 97.74 %. The total scores for family resilience spanned from 87 to 245, with a median (P25, P75) of 187 (160, 200). The highest scores were observed in the dimension of dilemma interpretation, while the lowest scores were recorded in the dimension of social support. Family relationship (β = 0.459, P

Objective: The aim of this study was to assess the effect of modified high-flow oxygen therapy on end-expiratory lung volume (EELV) and positive end-expiratory pressure (PEEP) in tracheotomized patients with normal pulmonary, acute hypoxic respiratory failure (AHRF) or chronic obstructive pulmonary disease (COPD). Methods: A ventilator and an artificial lung model were used to simulate the normal or strong inspiratory effort state of normal lung, AHRF and COPD patients. The traditional high-flow respiratory humidification therapy device connected with a standard interface (group A), and the modified therapy device added two types of resistance valves (group B, inner diameter 7.7 mm, length 24.0 mm; group C, inner diameter 7.7 mm, length 34.0 mm) to the exhalation end of the standard interface. The changes of end-expiratory lung volume (ΔEELV) and PEEP with the increase of flow rate (10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min) in the three groups was recorded. Results: Under simulated conditions of normal lung, AHRF and COPD, as the flow rate increased by using the modified therapy device, the PEEP values in all groups showed an exponential increasing trend, and the ΔEELV also increased accordingly. In addition, under the same flow rate level, the PEEP values of the two modified high-flow oxygen therapies (Group B and Group C) were significantly higher than those of the standard high-flow oxygen therapy (Group A) (p

Abstract. Background:. The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE. Methods:. This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks. Results:. A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen A vs. 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3% (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44] vs. 70.2% [33/47], P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6. Conclusions:. Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation. Trial Registration:. ChiCTR.org.cn, ChiCTR1900021195.

Abstract. Background:. A more comprehensive understanding of the trends of incidence, prevalence, and mortality in human immunodeficiency virus (HIV), and their complex interrelationships, may provide important evidence for decision-making related to HIV prevention and control. The variances in these indices between different population groups, genders, and ages are critical to decipher evolving patterns of the HIV epidemic in specific populations. Methods:. A secondary analysis of relevant data was conducted using data extracted from the Global Burden of Disease study of 2019. HIV/acquired immune deficiency syndrome (AIDS) incidence, prevalence, AIDS-related mortality, and mortality-to-prevalence ratio (MPR) for annual percentage change, average annual percentage change (AAPC), and corresponding 95% confidence intervals (CIs) were calculated using joinpoint regression statistical analysis. Results:. The AAPC of HIV/AIDS incidence, prevalence, AIDS-related mortality rate, and MPR were –1.4 (95% CI: –1.6, –1.2), 4.1 (95% CI: 4.0, 4.3), 2.0 (95% CI: 1.7, 2.3), and –2.1 (95% CI: –2.3, –1.8) between 1990 and 2019 globally, and were 3.5 (95% CI: 2.2, 4.8), 6.9 (95% CI: 6.8, 7.0), 8.1 (95% CI: 7.1, 9.1), and 1.2 (95% CI: 0.1, 2.3) in China during the same period. In terms of differences in the preceding indicators by gender, we observed a similar pattern of trends for male and female genders both globally and in China during the entire study period. Each specific age group exhibits a distinct pattern in terms of incidence, prevalence, mortality rate, and MPR both globally and in China. Conclusions:. Prevalence and mortality rates of HIV/AIDS have increased between 1990 and 2019 globally and in China. While the incidence rate and MPR have declined globally over the past three decades, these two indicators are observed to present an increasing trend in China. There is a high HIV burden among young and middle-aged adults globally; however, the elderly have a high HIV burden in China. HIV screening at older age should be scaled up, and patients with advanced HIV disease should be provided early with additional care and health resources.

Abstract Background The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective. Methods A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups. Results Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p

Background: Ultrasound-triggered sonodynamic therapy (SDT), as a non-invasive approach, has attracted considerable attention in a wide variety of malignant tumors and other diseases. Over the past 2 decades, the number of scientific publications on SDT has increased rapidly. However, there is still a lack of one comprehensive report that summarizes the global research trends and knowledge landscapes in the field of SDT in detail. Thus, we performed a bibliometric analysis on SDT from 2000 to 2021 to track the current hotspots and highlight future directions.Methods: We collected publications on SDT research from the Web of Science Core Collection database. The annual number of publications and citations, major contributors, popular journals, international collaborations, co-cited references and co-occurrence keywords were analyzed and visualized with CiteSpace, VOSviewer, and R-bibliometrix.Results: A total of 701 publications were included. The annual publication output increased from 5 in 2000 to 175 in 2021, and the average growth rate was 18.4%. China was the most productive country with 463 documents (66.05%), and Harbin Medical University was the most prolific institution (N = 73). Ultrasound in Medicine and Biology published the most papers related to SDT. Materials Science, and Chemistry were the research areas receiving the most interest. All the keywords were divided into four different clusters including studies on mechanisms, studies on drug delivery and nanoparticles, studies on cancer therapy, as well as studies on ultrasound and sonosensitizers. In addition to nanomaterials-related studies including nanoparticles, mesoporous silica nanoparticles, nanosheets, liposomes, microbubble and TiO2 nanoparticle, the following research directions such as immunogenic cell death, metal-organic framework, photothermal therapy, hypoxia, tumor microenvironment, chemodynamic therapy, combination therapy, tumor resistance, intensity focused ultrasound, drug delivery, and Staphylococcus aureus also deserve further attention and may continue to explode in the future.Conclusion: SDT has a bright future in the field of cancer treatment, and nanomaterials have increasingly influenced the SDT field with the development of nano-technology. Overall, this comprehensive bibliometric study was the first attempt to analyze the field of SDT, which could provide valuable references for later researchers to better understand the global research trends, hotspots and frontiers in this domain.

Abstract Background It remains challenging to differentiate tuberculosis (TB) from non-TB pulmonary infections in HIV-infected patients. Herein, we developed a scoring system aimed to rapidly determine the likelihood of TB or non-TB pathology in HIV-infected patients presenting with pulmonary infections. Methods We collected and collated data of hospitalized HIV-infected patients with pulmonary infections, followed by univariate and multivariate data analyses to determine risk variables that were significantly different between HIV/TB patients and HIV/non-TB patients. Subsequently, a regression coefficient was calculated for each variable, and a score was assigned to each variable in line with its regression coefficient. The sum of the scores for each variable in our scoring model was used to predict the likelihood of TB or non-TB pulmonary infection in each patient. Finally, we tested the diagnostic accuracy of the scoring system in our retrospective cohort, as well as in a prospective cohort. Results A total of 598 HIV-infected patients were enrolled in our retrospective cohort, among whom 288 had TB and 310 had non-TB pulmonary infections. Eight variables, including fever, highest body temperature, erythrocyte sedimentation rate (ESR), cervical lymphadenopathy, hilar and/or mediastinum lymphadenopathy, pulmonary cavitation, pleural effusion, and miliary nodules, were found to be mathematically significantly different via univariate analysis and multivariate logistic regression analysis. After regression coefficient calculation followed by score assignment, a receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) was calculated to be 0.902. When the total score for a patient is > 12, the sensitivity and specificity for TB prediction using our scoring system were 76.4% and 87.7% respectively in the retrospective cohort, and its diagnostic accuracy was 82.7% in the prospective cohort. Conclusions Our results demonstrate that our proposed diagnostic scoring system could be helpful in differentiating pulmonary TB from non-TB pulmonary infections in HIV-infected patients.

BackgroundCentral nervous system tumor (CNST) is one of the most complicated and lethal forms of human tumors with very limited treatment options. In recent years, growing evidence indicates that oncolytic virotherapy (OVT) has emerged as a promising therapeutic strategy for CNSTs. And a considerable amount of literature on OVT-CNSTs has been published. However, there are still no studies summarizing the global research trends and hotspots of this field through a bibliometric approach. To fulfill this knowledge gap, bibliometric analysis was conducted based on all publications relating to OVT-CNSTs since 2000s.MethodsWe searched the Web of Science Core Collection for all relevant studies published between 2000 and 2022. Four different tools (online analysis platform, R-bibliometrix, CiteSpace and VOSviewer) were used to perform bibliometric analysis and network visualization, including annual publication output, active journals, contribution of countries, institutions, and authors, references, as well as keywords.ResultsA total of 473 articles and reviews were included. The annual number of publications on OVT-CNSTs showed a significant increasing trend. Molecular Therapy and Cancer Research were the most active and co-cited journals, respectively. In terms of contributions, there is no doubt that the United States occupied a leading position with the most publications (n=307, 64.9%) and the highest H-index (57). The institution and author that contributed the largest number of publications were Ohio State University and Chiocca EA, respectively. As can be seen from citation analysis, the current studies mainly focused on preclinical and phase I/II clinical results of various oncolytic virus for CNSTs treatment. Keywords co-occurrence and burst analysis revealed that the following research topics including immunotherapy, T-cells, tumor microenvironment, vaccine, blood-brain-barrier, checkpoint inhibitors, macrophage, stem cell, and recurrent glioblastoma have been research frontiers of this field and also have great potential to continue to be research hotspots in the future.ConclusionThere has been increasing attention on oncolytic viruses for use as CNSTs therapeutics. Oncolytic immunotherapy is a topic of great concern in this field. This bibliometric study provides a comprehensive analysis of the knowledge base, research hotspots, development perspective in the field of OVT-CNSTs, which could become an essential reference for scholars in this area.

Iron metabolism is vital for the survival of both humans and microorganisms. Heme oxygenase-1 (HO-1) is an essential stress-response enzyme highly expressed in the lungs, and catabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV)/bilirubin (BR), especially in pathological conditions which cause oxidative stress and inflammation. Ferrous iron (Fe2+) is an important raw material for the synthesis of hemoglobin in red blood cells, and patients with iron deficiency are often associated with decreased cellular immunity. CO and BR can inhibit oxidative stress and inflammation. Thus, HO-1 is regarded as a cytoprotective molecule during the infection process. However, recent study has unveiled new information regarding HO-1. Being a highly infectious pathogenic bacterium, Mycobacterium tuberculosis (MTB) infection causes acute oxidative stress, and increases the expression of HO-1, which may in turn facilitate MTB survival and growth due to increased iron availability. Moreover, in severe cases of MTB infection, excessive reactive oxygen species (ROS) and free iron (Fe2+) due to high levels of HO-1 can lead to lipid peroxidation and ferroptosis, which may promote further MTB dissemination from cells undergoing ferroptosis. Therefore, it is important to understand and illustrate the dual role of HO-1 in tuberculosis. Herein, we critically review the interplay among HO-1, tuberculosis, and the host, thus paving the way for development of potential strategies for modulating HO-1 and iron metabolism.

Abstract Background Pneumocystis pneumonia (PCP) is a common acquired immune deficiency syndrome (AIDS)-related opportunistic infection. Recent reports estimate that more than 400,000 patients with human immunodeficiency virus (HIV) develop PCP each year globally. However, the timing of antiretroviral therapy (ART) initiation for HIV-infected patients with PCP is still controversial, and the benefits and risks of early initiation of ART are not completely clear. We thus designed this study in order to determine the optimal timing for ART initiation for HIV-positive patients with moderate to severe PCP. Methods This study will be an open-label, multi-centre, prospective randomised controlled trial. A total of 200 subjects will be randomly assigned to an early ART initiation group (≤14 days after PCP diagnosis) and a deferred ART initiation group (>14 days after PCP diagnosis) at a 1:1 ratio. All subjects will be followed up for 48 weeks after starting ART. The primary endpoint is incidence of disease progression (including new or relapsing opportunistic infections and death) at week 48. The secondary endpoints are the changes in CD4 counts from baseline at weeks 12, 24 and 48; the degree of virological suppression (HIV RNA

Background: Tenofovir disoproxil fumarate (TDF) can cause renal and bone toxicity, which is associated with high plasma tenofovir concentrations in antiretroviral treatment of HIV-1 infected patients. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. We aimed to assess the non-inferiority of a TAF-containing combination regimen versus a TDF-containing fixed-dose single-tablet regimen in the antiretroviral-treatment-naive, HIV-1-infected patients. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Trial Registry, from January 2001 to July 2019, using relevant keywords. Available data were extracted from eligible randomized trials (RCTs) and pooled as risk ratios (RRs) or standardized mean differences (SMDs) in a meta-analysis model using Stata/SE. Results: We included seven eligible randomized controlled trials (RCTs) with a total of 6269 participants. Patients who were antiretroviral-naive adults with HIV-1 on both the TAF-containing regimens and the TDF-containing regimens had similar virologic suppression effects (RR, 1.02; 95% CI, 1.00–1.04; p > 0.05) at week 24 (93.99% vs. 94.20%), week 48 (90.71% vs. 89.54%), and week 96 (86.16% vs. 84.80%). Both groups had no significant improvements in CD4 cell count for the naive patients during 48 weeks of therapy (SMD, 0.09; 95% CI, 0.01 to 0.16; p < 0.05). Both treatments were safe and well-tolerated, and most adverse events were similar as mild to moderate in severity. Moreover, compared with the TDF-containing regimens, the TAF-containing regimens in patients had significantly smaller reductions in both hip (RR, 0.33; 95CI, 0.29-0.39; p < 0.05) and spine (RR, 0.58; 95CI, 0.51–0.65; p < 0.05). Additionally, the TAF-containing regimens in patients had significantly fewer increases for renal events than those of the TDF-containing regimens through 48 weeks (0.31; 95% CI, 0.18–0.55; p < 0.05). Conclusions: Our meta-analysis indicated that efficacy, safety, and tolerability of TAF-containing regimens were non-inferior in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection. Furthermore, compared with those receiving the TDF-containing regimens, patients on the TAF-containing regimens had significant advantages in renal function, bone parameters, and lipid profile for the naive patients. Keywords: HIV-1, Tenofovir alafenamide (TAF), Tenofovir disoproxil fumarate (TDF), Antiretroviral regimens, Meta-analysis

Background: To investigate whether TDF-containing regimens significantly benefited efficacy, safety, and tolerability in TAF-containing regimens in virologically suppressed HIV-infected patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Trial Registry were systematically searched for eligible studies. We extracted and evaluated the pooled data from available randomized controlled trials (RCTs). Results: Eight eligible RCTs were included. In the intention-to-treat (ITT) analysis, patients who switched to TAF-containing regimens had significantly better viral suppression than those continuing TDF-containing regimens at weeks 48 and 96 (RR, 1.02; 95CI, 1.00–1.03; p 0.05). Compared with those receiving the TDF-containing regimens, virologically suppressed HIV-infected patients on the TAF-containing regimens had significant increases in CD4 cell counts (SMD, 0.12; 95CI, 0.08 to 0.17; p

ABSTRACT The dynamics of quasispecies afford RNA viruses a great fitness on cell tropism and host range. To study the quasispecies features and the intra-host evolution of SARS-CoV-2, we collected nine confirmed patients and sequenced the haplotypes of spike gene using a single-molecule real-time platform. Fourteen samples were extracted from sputum, nasopharyngeal swabs, or stool, which in total produced 283,655 high-quality circular consensus sequences. We observed a stable quasispecies structure that one master mutant (mean abundance ∼0.70), followed by numerous minor mutants (mean abundance ∼1.21 × 10−3). Under high selective pressure, minor mutants may obtain a fitness advantage and become the master ones. The later predominant substitution D614G existed in the minor mutants of more than one early patient. An epidemic variant had a possibility to be independently originated from multiple hosts. The mutant spectrums covered ∼85% amino acid variations of public genomes (GISAID; frequency ≥ 0.1) and likely provided an advantage mutation pool for the current/future epidemic variants. Notably, 32 of 35 collected antibody escape substitutions were preexistent in the early quasispecies. Virus populations in different tissues/organs revealed potentially independent replications. The quasispecies complexity of sputum samples was significantly lower than that of nasopharyngeal swabs (P = 0.02). Evolution analysis revealed that three continuous S2 domains (HR1, CH, and CD) had undergone a positive selection. Cell fusion-related domains may play a crucial role in adapting to the intrahost immune system. Our findings suggested that future epidemiologic investigations and clinical interventions should consider the quasispecies information that has missed by routine single consensus genome. IMPORTANCE RNA virus population in a host does not consist of a consensus single haplotype but rather an ensemble of related sequences termed quasispecies. The dynamics of quasispecies afford SARS-CoV-2 a great ability on genetic fitness during intrahost evolution. The process is likely achieved by changing the genetic characteristics of key functional genes, such as the spike glycoprotein. Previous studies have applied the next-generation sequencing (NGS) technology to evaluate the quasispecies of SARS-CoV-2, and results indicated a low genetic diversity of the spike gene. However, the NGS platform cannot directly obtain the full haplotypes without assembling, and it is also difficult to predict the extremely low-frequency variations. Therefore, we introduced a single-molecule real-time technology to directly obtain the haplotypes of the RNA population and further study the quasispecies features and intrahost evolution of the spike gene.

Objective: We intend to investigate the relapse of HIV-associated cryptococcal meningitis (CM), assess potential predictors and conduct survival analysis, with a view to establishing a valid reference for the management of the relapse of CM.Method: This is a retrospective study in Chinese patients with HIV-associated CM and those who experience relapse of CM. Baseline demographic, laboratory and clinical characteristics of patients with HIV-associated CM were collected. Predictors for relapse of HIV-associated CM were analyzed using univariate and multivariate logistic regression. Survival probability in relapse cases was determined by Kaplan-Meier survival curves.Results: During the study period, 87 of 348 (25.0%) HIV patients experienced the relapse of CM. CD4+ T-cell counts, antiretroviral therapy (ART) status and the time from symptom onset to presentation were all statistically associated with the relapse of CM (p = 0.013, 0.018 and 0.042, respectively). The overall survival among 46 HIV CM relapse patients whose survival information were obtained, was 78.3%. The proportion of patients who died after antifungal treatment for CM was greater in those whose interval from symptom onset to presentation ≥4 weeks, compared with those

Background: People living with HIV (PLWH) are aging worldwide, and different management strategies may be required for older and younger PLWH. However, demographic characteristics, illness distribution, mortality, and independent risk factors in the PLWH population in China are not yet fully understood, especially in patients aged 50 years or older.Methods: We conducted a retrospective analysis of 4445 HIV-positive Chinese inpatients in Chongqing, China.Results: The mortality rate in patients 50 years or older (the older group) was significantly higher than that in those under 50 years (the younger group) (p < 0.001). In the younger group, independent risk factors for death included: nadir CD4+ T-cell counts

The expansion of separation demands at molecular and ionic levels has triggered extensive research to explore new materials as promising practical membranes for separations. Owing to their dimension-related properties of two-dimensional (2D) porous organic polymers (POPs), promising research on the construction of 2D POPs into membranes has emerged and progressed rapidly, offering membranes with highly tunable pores/channels, robust frameworks/networks, intrinsic flexibility, and light weight for multiple separation purposes. In this review, up-to-date strategies for processing of 2D POPs into diverse continuous membranes and engineering of their nanochannels are highlighted. The 2D POPs materials discussed include the examples of 2D covalent organic frameworks (COFs), 2D covalent triazine frameworks (CTFs) and 2D conjugated microporous polymers (CMPs). Case studies on these materials for potential membrane applications including gas separation, water treatment, organic solvent nanofiltration (OSN), pervaporation are summarized. Finally, the critical challenges and futuristic upgrades of research directions and opportunities of 2D POPs based advanced membranes are outlined.

Background: The efficacy and side effects of voriconazole plus 5-flucytosine (Vori + 5-FC) versus amphotericin B deoxycholate plus 5-flucytosine (AmBd + 5-FC) as an induction treatment for cryptococcal meningitis are unknown. Methods: Forty-seven patients treated with Vori + 5-FC and 92 patients treated with AmBd + 5-FC were included in the current study after propensity score matching (PSM) at a ratio of 1:2. Two-week laboratory test results and 90-day mortality were compared between the two groups. Results: After 2 weeks of induction treatment, the CSF Cryptococcus sterile culture rate was 57.1% in the Vori + 5-FC group and 76.5% in the AmBd + 5-FC group (p = .026). No difference was found in the normalization of CSF indicators (glucose, total protein, intracranial pressure and India ink sterile rate) between the two groups. Both the Vori + 5FC regimen and AmBd + 5-FC regimen obviously decreased haemoglobin concentrations, platelet counts and serum potassium levels (all p = .010). Notably, the Vori + 5FC regimen did not influence serum creatinine levels (p = .263), while AmBd + 5FC increased serum creatinine levels (p = .019) after 2-week induction treatment. The Vori + 5-FC group and AmBd + 5-FC group had similar 90-day cumulative survival rates (89.9% vs. 87.8%, p = .926). Conclusion: The Vori + 5-FC regimen was associated with low 2-week CSF sterile culture and was not superior to AmBd + 5-FC as induction therapy in terms of the 90-day cumulative survival rate of CM patients. [ABSTRACT FROM AUTHOR]