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Background: Long-term nucleos(t)ide analogue (NA) treatment can reverse liver fibrosis in chronic hepatitis B (CHB), but its effect on fibrosis regression remains limited. Biejia-Ruangan (BR) has been approved in China as an antifibrotic traditional Chinese medicine drug in patients with chronic liver diseases. A multicenter randomized controlled trial aims to evaluate the effect of BR on fibrosis regression in CHB patients treated with NAs.Methods: CHB patients with histologically confirmed advanced fibrosis or cirrhosis were randomly assigned to receive entecavir (ETV) (0.5 mg per day) plus BR (2 g 3 times a day) or placebo for 72 weeks. Liver fibrosis regression was defined as a reduction of ≥ 1 point by the Ishak fibrosis stage (IFS).Results: Overall, 500 patients were enrolled in each group as the intention-to-treat population. The rate of fibrosis regression after 72 weeks of treatment was significantly higher in the ETV + BR group (40% vs 31.8%; P = .0069). Among 388 patients with cirrhosis (ie, IFS ≥ 5) at baseline, the rate of cirrhosis reversal (ie, IFS ≤ 4) was significantly higher in the ETV + BR group (41.5% vs 30.7%; P = .0103).Conclusions: Addition of BR to the current standard treatment with NAs in CHB patients with advanced fibrosis or cirrhosis can improve liver fibrosis regression.Clinical Trials Registration: NCT01965418. [ABSTRACT FROM AUTHOR]

Strains of the HIV-1 circulating recombinant forms (CRFs) 06_cpx and 56_cpx were identified for the first time in Guangzhou, China. The nearly full-length genome (NFLG) sequence was amplified, and the PCR products were sequenced by the Sanger method. The CRF06_cpx and CRF56_cpx strains were identified using the Basic Local Alignment Search Tool (BLAST) and confirmed by neighbour-joining (NJ) phylogenetic analysis. Additionally, these strains were found to contain transmitted drug resistance mutations that have little effect on first-line efavirenz (EFV)-based treatment. Genetic analysis of the detailed sequence data will provide more information on the HIV-1 epidemic in China. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19) is an emerging, rapidly evolving pandemic, hypertension is one of the most common co‐existing chronic conditions and a risk factor for mortality. Nearly one‐third of the adult population is hypertensive worldwide, it is urgent to identify the factors that determine the clinical course and outcomes of COVID‐19 patients with hypertension. Methods and results: 148 COVID‐19 patients with pre‐existing hypertension with clarified outcomes (discharge or deceased) from a national cohort in China were included in this study, of whom 103 were discharged and 45 died in hospital. Multivariate regression showed higher odds of in‐hospital death associated with high‐sensitivity cardiac troponin (hs‐cTn) > 28 pg/ml (hazard ratio [HR]: 3.27, 95% confidence interval [CI]: 1.55–6.91) and interleukin‐6 (IL‐6) > 7 pg/ml (HR: 3.63, 95% CI:1.54–8.55) at admission. Patients with uncontrolled blood pressure (BP) (n = 52) which were defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg for more than once (≥2 times) during hospitalization, were more likely to have ICU admission (p = 0.037), invasive mechanical ventilation (p = 0.028), and renal injury (p = 0.005). A stricter BP control with the threshold of 130/80 mm Hg was associated with lower mortality. Treatment with renin‐angiotensin‐aldosterone system (RAAS) suppressors, including angiotensin‐converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and spironolactone, was associated with a lower rate of ICU admission compared to other types of anti‐hypertensive medications (8 (22.9%) vs. 25 (43.1%), p = 0.048). Conclusion: Among COVID‐19 patients with pre‐existing hypertension, elevated hs‐cTn and IL‐6 could help clinicians to identify patients with fatal outcomes at an early stage, blood pressure control is associated with better clinical outcomes, and RAAS suppressors do not increase mortality and may decrease the need for ICU admission. [ABSTRACT FROM AUTHOR]

Background: Guangdong, located in South China, is one of the areas heavily affected by HIV-1 in China. The transmission of HIV-1 among men who have sex with men (MSM) has gradually been increasing in Guangdong. Objective: To investigate the characteristics of the HIV-1 drug resistance, and genetic transmission networks in MSM with antiretroviral therapy (ART) failure from 2014 to 2019 in Guangdong. Methods: HIV-1 pol gene sequences were amplified. An online subtyping tool was used to determine the genotype, and a maximum likelihood phylogenetic tree was reconstructed to confirm the genotype results. The Stanford University HIV Drug Resistance Database was used to analyse the sequences of drug resistance mutations (DRMs) and drug resistance profiles. A pairwise Tamura-Nei 93 genetic distance-based method was used to analyse the genetic transmission networks. Results: Of 393 sequences isolated from HIV-infected MSM with ART failure, CRF01_AE (47.3%), CRF07_BC (21.4%) and CRF55_01B (21.4%) were the top three strains. 55.2% individuals harboured NRTI DRMs, whereas 67.4% carried NNRTI DRMs. 96.8% cases harboured mutations resistance to NRTIs or NNRTIs at high-level. The most common DRMs were M184I/V (42.2%), followed by V179D/E (37.9%) and K65R (27.2%). Of the subtype B sequences, no sequence fell into a cluster. Of the CRF01_AE, CRF55_01B, and CRF59_01B sequences, 14.5%, 61.9%, and 33.3% fell into clusters, respectively. Of the CRF07_BC sequences, 39.3% fell into clusters. The majority of MSM in transmission networks were concentrated at age below 35 years old, with multiple links. Moreover, approximately 54.8% of MSM had more than 2 potential transmission partners. Conclusion: Drug resistance mutations more frequently occurred in NNRTIs among MSM with ART failure in Guangdong Province. Transmission network analysis revealed a complex transmission pattern, and more attention should be given to younger HIV-1-infected MSM with multiple links. [ABSTRACT FROM AUTHOR]

The phenomenon of COVID-19 patients tested positive for SARS-CoV-2 after discharge (redetectable as positive, RP) emerged globally. The data of incidence rate and risk factors for RP event and the clinical features of RP patients may provide recommendations for virus containment and cases management for COVID-19. We prospectively collected and analyzed the epidemiological, clinical and virological data from 285 adult patients with COVID-19 and acquired their definite clinical outcome (getting PCR positive or not during post-discharge surveillance). By March 10, 27 (9.5%) discharged patients had tested positive for SARS-CoV-2 in their nasopharyngeal swab after a median duration of 7·0 days (IQR 5·0–8·0). Compared to first admission, RP patients generally had milder clinical symptoms, lower viral load, shorter length of stay and improved pulmonary conditions at readmission (p<0.05). Elder RP patients (≥ 60 years old) were more likely to be symptomatic compared to younger patients (7/8, 87.5% vs. 3/19, 18.8%, p = 0.001) at readmission. Age, sex, epidemiological history, clinical symptoms and underlying diseases were similar between RP and non-RP patients (p>0.05). A prolonged duration of viral shedding (>10 days) during the first hospitalization [adjusted odds ratio [aOR]: 5.82, 95% confidence interval [CI]: 2.50–13.57 for N gene; aOR: 9.64, 95% CI: 3.91–23.73 for ORF gene] and higher Ct value (ORF) in the third week of the first hospitalization (aOR: 0.69; 95% CI: 0.50–0.95) were associated with RP events. In conclusion, RP events occurred in nearly 10% of COVID-19 patients shortly after the negative tests, were not associated with worsening symptoms and unlikely reflect reinfection. Patients' lack of efficiency in virus clearance was a risk factor for RP result. It is noteworthy that elder RP patients (≥ 60 years old) were more susceptible to clinical symptoms at readmission. Author summary: The baseline enrolled 285 patients admitted to Guangzhou Eighth People's Hospital (Guangzhou, Guangdong) with a diagnosis of COVID-19. We reported the epidemiology, clinical laboratory, radiological characteristics, virological results, treatment, and definite outcomes (getting PCR retested positive (RP) or not during post-discharge surveillance) of the cases. RP events occurred in nearly 10% of cases, were not associated with worsening symptoms and unlikely reflect reinfection. The lack of efficiency in virus clearance was a risk factor for RP result. Elder RP patients (≥ 60 years old) were more susceptible to clinical symptom at readmission. In the context of numerous COVID-19 cases showed SARS-CoV-2 positive again after discharged, the data in China may provide recommendations for post-discharge management, especially for other developing countries. [ABSTRACT FROM AUTHOR]

Background: The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain.Research Question: The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model.Study Design and Methods: A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19.Results: In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age ≥ 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation.Interpretation: The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk. [ABSTRACT FROM AUTHOR]

Background: Monkeypox virus (MPXV) is spreading globally and nearly half of the infected people were human immunodeficiency virus (HIV) positive. Therefore, an in-depth understanding of the effects of HIV infection on the outcomes of MPXV infection is urgently needed. This study aimed to explore the clinical features, viral dynamics, and antibody response to MPXV infections in men who had sex with men (MSM) with and without HIV co-infection., Design or Methods: MPXV-infected patients diagnosed by PCR were recruited in this study and were divided into MPXV and MPXV + HIV groups based on whether they were co-infected with HIV. Clinical data and samples were collected during of the hospital stay and follow up interviews. The symptoms and signs, laboratory examinations, viral shedding in various body fluids or swabs, antibody dynamics were tracked and compared between the two groups., Results: A total of 41 MPXV patients were recruited through June 2023 to September 2023 in Guangzhou. The MPXV group and MPXV + HIV group comprised 20 and 21 MSM, respectively. Patients in the two groups exhibited similar clinical characteristics except for pruritus and eschar, both were significantly fewer in MPXV + HIV group than in MPXV only group. Among the 355 clinical samples collected, MPXV DNA was detected in 100% of scabs, 97.4% of skin swabs, and 92.3% of exudate swabs from lesions, while the positive rate was 87.5% from oropharyngeal swabs, 59% from saliva, 51.3% from anal swabs, 50% from feces, 30.6% from urine samples, 37.5% of semen, and 28.2% from sera. Dynamics analysis revealed that viral DNA was undetectable in most patients 20 days after symptom onset. IgM and IgG antibodies to MPXV were detected in all patients with 3-5 days earlier in the MPXV group than in the MPXV + HIV group., Conclusion: This cohort analysis based on a large outbreak among MSM in Guangzhou indicated no obvious differences in clinical symptoms, viral DNA data, but antibody responses were 3-5 days later in mpox patients with HIV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Xie, Zeng, Cao, Fan, Jiang, Lei, Wang, Li, Tang, Yu and Li.)

The wide variety of new HIV-1 recombinant variants are a predominant challenge for understanding the molecular epidemiology and preventing the spread of the HIV-1 epidemic. In this study, we confirmed a novel HIV-1 unique B/C recombinant (ZLQ01186) isolated from a male patient infected with HIV-1 through injection drug use in Foshan city, Guangdong Province. The near full-length genome was amplified, and then the polymerase chain reaction products were sequenced by Sanger sequencing. The genomic sequence of the strain, with two subtype B segments inserted into the subtype C backbone, was 8,953 bp in length, extending from 647 to 9,599 bp according to the HXB2 genome. In addition, this B/C recombinant strain contained the non-nucleoside reverse transcriptase inhibitor resistance mutation K103N and the integrase strand transfer inhibitor other resistance mutation L74I according to the Stanford University HIV Drug Resistance Database program. The drug resistance profile indicates high-level resistance against efavirenz and rilpivirine. This study identified a recombinant between the main circulating strains, indicating a more complicated trend of the HIV-1 epidemic in Guangdong, China.

Background: Coronavirus Disease 2019 (COVID-19) is threatening billions of people. We described the clinical characteristics and explore virological and immunological factors associated with clinical outcomes., Methods: 297 COVID-19 patients hospitalized in Guangzhou Eighth People's Hospital between January 20 and February 20, 2020 were included. Epidemiological, clinical and laboratory data were collected and analyzed. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in respiratory tract, blood samples and digestive tract was detected and lymphocyte subsets were tested periodically., Result: Among the 297 patients (median age of 48 years), 154 (51.9 %) were female, 245 (82.5 %) mild/moderate cases, and 52 (17.5 %) severe/critical cases. 270 patients were detected for SARS-CoV-2 RNA in anal swabs and/or blood samples, and the overall positive rate was 23.0 % (62/270), higher in severe/critical cases than in mild/moderate cases (52.0 % vs. 16.4 %, P < 0.001). The CD4/CD8 ratio on admission was significantly higher in severe/critical cases than in mild/moderate cases (1.84 vs. 1.50, P = 0.022). During a median follow-up period of 17 days, 36 (12.1 %) patients were admitted to intensive care unit (ICU), 16 (5.4 %) patients developed respiratory failure and underwent mechanical ventilation, four (1.3 %) patients needed extracorporeal membrane oxygenation (ECMO), only one (0.34 %) patients died of multiple organ failure. Detectable SARS-CoV-2 RNA in anal swabs and/or blood samples, as well as higher CD4/CD8 ratio were independent risk factors of respiratory failure and ICU admission., Conclusions: Most of COVID-19 patients in Guangzhou are mild/moderate, and presence of extrapulmonary virus and higher CD4/CD8 ratio are associated with higher risk of worse outcomes., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Crucial roles of hematologic and immunologic responses in progression of coronavirus disease 2019 (COVID-19) remain largely unclear., Objective: We sought to address the dynamic changes in hematologic and immunologic biomarkers and their associations with severity and outcomes of COVID-19., Methods: A retrospective study including 548 patients with COVID-19 with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed., Results: On admission, the counts of lymphocytes, T-cell subsets, eosinophils, and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or nonsurvivors. During hospitalization, eosinophils, lymphocytes, and platelets showed an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in nonsurvivors. Nonsurvivors kept a high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein, and C-reactive protein, which were kept stable or showed a downward trend in survivors. Positive correlation between CD8 + T-cell and lymphocytes count was found in survivors but not in nonsurvivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils, and platelets could serve as predictors for recovery, whereas progressive increases in neutrophils, basophils, and IL-6 were associated with fatal outcome., Conclusions: Hematologic and immunologic impairment showed a significantly different profile between survivors and nonsurvivors in patients with COVID-19 with different severity. The longitudinal variations in these biomarkers could serve to predict recovery or fatal outcome., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis., Methods/design: This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival., Discussion: Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China., Trial Registration: ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013.