ABSTRACT
BACKGROUND@#Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China.@*METHODS@#This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs).@*RESULTS@#We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain.@*CONCLUSIONS@#In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.
Subject(s)
Adult , Humans , Anti-HIV Agents/therapeutic use , China , Emtricitabine/pharmacology , HIV Infections/drug therapy , HIV-1 , Lamivudine/pharmacology , Lipids , Retrospective StudiesABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.
ABSTRACT
Objective@#To investigate the risk factors of scrub typhus complicated with acute respiratory distress syndrome (ARDS) and provide help for the prevention and treatment of this severe disease.@*Methods@#A retrospective analysis on the clinical data of 176 scrub typhus patients in the First Affiliated Hospital of Guangxi Medical University from 2009 to 2016 was conducted. The patients were divided into ARDS group (n=25) and non-ARDS group (n=151). Age, sex, the time from onset to diagnosis, clinical characteristics, laboratory examinations within 24 hours of admission, and acute physiology and chronic health evaluation (APACHE)Ⅱscore were recorded. The differences of clinical characteristics between two groups were compared, and the relevant factors were analyzed. Chi-square test, t-test, and Mann-Whitney U test were chosen for the comparison of categorical data and measurement data of normal or non-normal distribution, respectively, then statistically significant variables were included into logistic regression analysis.@*Results@#Fever (100.0%) was the most common clinical feature and elevated alanine aminotransferase (95.4%) was the most frequent laboratory abnormality. Age (t=3.055), APACHEⅡscore (t=5.592), D-dimer (t=2.704), the time from onset to diagnosis (t=5.719), serum level of creatinine (t=4.099), and the incidence of hepatosplenomegaly (χ2=5.202) in ARDS group were all higher than those in non-ARDS group (all P<0.05), while the platelet count, serum level of albumin in ARDS group were both lower than those in non-ARDS group (both P<0.05). Multiple factor logistic regression analysis demonstrated that age, APACHEⅡscore, D-dimer, the time from onset to diagnosis, and the platelet count were independent risk factors for scrub typhus complicated with ARDS. Fifteen patients died among the 176 cases, with eight (32%) in the ARDS group and seven (4.6%) in the non-ARDS group, the difference between the two groups was statistically significant (χ2=20.6, P<0.01).@*Conclusion@#Patients with scrub typhus should be definitely diagnosed at an early stage. Meanwhile, monitoring the risk factors of scrub typhus patients complicated with ARDS, and taking effective treatment can improve the prognosis of scrub typhus patients.
ABSTRACT
Objective To investigate the effect of Th1/Th2 cytokines and immune state on the occurrence and familial aggregation of hepatocellular carcinoma(HCC).Methods Ninety-five members whose families have had two or even more HCC patients(high-occurrence families) were selected as the case group,by matching with the same nationality,gender,residential area,age±5 years old,95 members whose families had no any cancer were selected as the control.The level of peripheral blood Th1 type cytokines such as interferon-γ(IFN-γ),interleukin-2(IL-2) and Th2 type cytokines such as interleukin-4(IL-4),interleukin-10 (IL-10) were detected by enzyme linked immunosorbent assay(ELISA).Results There was a Th1/Th2 serum cytokine imbalance profile in members of HCC high-occurrence family.The levels of IFN-γ and IL-2 were significantly lower in members of HCC high-occurrence family than that of the controls.The levels of IL-4 and IL-10 were higher in members of HCC high-occurrence family than that of the controls.Conclusion There was a poor cellular immune state in members of HCC in the high-occurrence families.Th1 type cytokines was inhibited,and Th2 type cytokines was enhanced,so more susceptible to HBV chronic infection.It might be the mechanism of HCC occurrence and familial aggregation.
ABSTRACT
Biological invasions are increasingly attracting the ecologists’ attention. Invasive plants threaten the natural ecosystems not only by competing with the native plants, but also by altering the structure and function of soil microbial communities belowground. In this study, we studied the effects of the invasive plant Coreopsis grandiflora (C. grandiflora) on the functional diversity of soil microbial communities in Laoshan mountain in the province of Shandong, North of China. We sampled soil from plots that were invaded or not invaded by C. grandiflora. The functional diversity of microbial communities in the sampled soils was assessed by the Biolog procedure test. By the ANOVA analysis of average well color development (AWCD), Shannon index (H’ ), Shannon evenness (E), principle components analysis of the level physiological profiles (CLPP) and correlation analysis between the studied parameters, we found that the invasive species C. grandiflora enhanced the functional diversity of soil microbial communities where the habitat was invaded by the C. grandiflora. The study indicated that the successful invasive plants have profound effects on the function of soil microbial communities.
ABSTRACT
ObjectiveTo elucidate the association of immune response to hepatitis B vaccination with HLA-DRB1 * 12 allele as well as the level of IL-4 and IFN-γ.MethodsSeventy-four healthy college students from Guangxi province who had non- or hypor -response to recombinant hepatitis B vaccination and 64 medium- or hyper-responders with the conditions of similar were selected randomly and involved in this study.HLA-DRB1 * 12 was detected by PCR-SSP,the level of IFN-γ and IL-4 cytokines were examined by ELISA.Results(1)The allelic frequencies of HLA-DRB1 * 12 was lower in the non- or hypor-responders than that in the medium- or hyper-responders ( 10.8％ vs 32.8％,P=0.002) ; (2)The expression level of IFN-γ in the non- or hypor-responders ( 7.21±7.92 ) ng/ml was much less than that of the medium- or hyper- responders ( 16.36± 11.00) ng/ml ( P=0.000).(3) The expression level of IL-4 in the non- or hyporresponders (3.18±4.45) ng/ml was much less than that of the medium- or hyper- responders (7.76±5.71 ) ng/ml(P=0.000).(4)No significant differences was seen between the expression level of IFN-γ in the HLA-DRB1 * 12 positive ( 13.18± 11.24) ng/ml and the negative ( 11.00± 10.29 ) ng/ml ( P =0.349 ).(5)No significant differences was seen between the expression level of IL-4 in the HLA-DRB1 * 12 positive (5.947±4.530) ng/ml and the negative (5.132±5.800) ng/ml (P=0.423).ConclusionHLA-DRB1 * 12 might be the allele enhanced immune response to hepatitis B vaccination.The expression levels of IFN-γand IL-4 correlating to Thl/Th2 cells might affect on the immune response to hepatitis B vaccination.
ABSTRACT
Objective:To investigate the effect of HLA-DRB1*07,13 allelic genes on the immune response to hepatitis B vaccination.Methods:896 healthy college students of Han nationality from Guangxi province,who had received standard courses of vaccination with recombinant hepatitis B virus vaccine,were tested the level of anti-HBs with ELISA method at the sixth month after their last vaccination.The non- or hypo-responders were selected to receive another 20 μg doses of recombinant vaccine and were examined anti-HBs once more four weeks later.99 non- or hypo-responders and 136 medium or hyper-responders were selected for the study subjects.HLA-DRB1*07,13 allelic genes of the subjects were detected by polymerase chain reaction using sequence specific primer (PCR-SSP) method.Results:The frequencies of HLA-DRB1*07 gene in the non- or hypo-responders group were significantly higher than that in the medium or hyper-responder group (16.16% vs 4.41%,P＜0.05). No significant difference of HLA-DRB1*13 gene between the two groups (1.01% vs 3.68%,P=0.389).Conclusion:There is a close relationship between the expression of HLA-DRB1*07 gene and the non- or hypo-response to HB vaccine;No relationship between HLA-DRB1*13 gene expression and the response to HB vaccine is found.