Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

ObjectiveTo investigate the status of different antiretroviral therapy（ART） initiation times in patients with HIV/AIDS and analyze the relevant characteristics and influencing factors of delayed ART. MethodsFrom December 2018 to December 2020， a survey was conducted among adult HIV/AIDS patients treated in 28 designated AIDS prevention and treatment institutions in Beijing， Shanghai， Guangdong， Jiangsu， Henan， Jiangxi， Guangxi， Yunnan and other places. Data of the basic demographic information， lifestyle and chronic disease prevalence， and characteristics of diagnosis and treatment were collected. The characteristics and related factors of delayed ART were compared and analyzed. ResultsThe median age of 1 741 patients was 41 years old （IQR： 32‒52）. The initial CD4 count of most patients was less than 200 cells·μL^-1（51.4%）. Among them， 1 027 patients had delayed ART （59.0%）， and the association between ART initiation time and initial CD4 count varied with the time of diagnosis of HIV infection. Multivariate logistic analysis showed that the older age （aOR=0.99， 95%CI： 0.98‒0.99） was associated with a higher rate of starting ART within 1 month after diagnosis， while those diagnosed before 2017 and with the initial CD4 count >200 cells·μL^-1 were more likely to delay ART. Delayed initiation of ART may be a risk factor for poor sleep quality and co-infection in HIV/AIDS patients. ConclusionWith the expansion of free ART in China， the proportion of delayed ART with HIV/AIDS shows a downward trend. Timely ART management should be strengthened for the young HIV/AIDS patients and patients with high CD4 counts.

Objective:To explore the clinical characteristics of acquired immunodeficiency syndrome (AIDS) complicated with nontuberculous mycobacteria (NTM) disease.Methods:The clinical data of 190 patients with AIDS complicated with NTM disease diagnosed by Shanghai Public Health Clinical Center, Fudan University from January 1, 2019 to December 31, 2021 were analyzed retrospectively. NTM diseases were divided into disseminated NTM disease group and non-disseminated NTM disease group. The independent sample t test, Mann Whitney U test and chi-square test were used for statistical analysis. Results:The 190 patients with AIDS complicated with NTM disease included 182 males and eight females. The age was (42±13) years old, and the first hospital stay was 15(6, 26) days. Pneumocystis carinii pneumonia was the most common co-infection in 12.1%(23/190) of patients, 87 cases (45.8%) were disseminated NTM disease. The clinical symptoms of patients were common in fever (55.8%(106/190)), cough (50.0%(95/190)), and expectoration (28.9%(55/190)). The proportions of fatigue (31.0%(27/87) vs 7.8%(8/103)), poor appetite (21.8%(19/87) vs 10.7%(11/103)) in the AIDS patients with disseminated NTM disease group were higher than those in the non-disseminated NTM disease group, and the differences were statistically significant ( χ2=16.99, P<0.001 and χ2=4.42, P=0.036, respectively). There was no significant difference in the proportions of deaths between AIDS patients with disseminated NTM disease and those without disseminated NTM disease (17.2%(15/87) vs 12.6%(13/103), χ2=0.80, P=0.371). The most common NTM species was Mycobacterium avium (67.1%(49/190)), followed by Mycobacterium kansasii (15.1%(11/190)). Hemoglobin ((90.3±23.9) g/L vs (110.1±24.2) g/L), albumin ((29.7±5.5) g/L vs (34.7±5.6) g/L), CD4 + T lymphocyte count (11(5, 30)/μL vs 52(16, 96)/μL) and CD8 + T lymphocyte count ((362±320)/μL vs (496±352)/μL) in the disseminated NTM disease group were lower than those in non-disseminated NTM disease group ( t=-5.63, P<0.001; t=-6.18, P<0.001; Z=-5.90, P<0.001; and t=-2.73, P=0.007, respectively), while procalcitonin (0.24(0.10, 0.77) μg/L vs 0.10 (0.04, 0.51) μg/L) was higher than that in the non-disseminated NTM disease group ( Z=-3.09, P=0.002), with statistical significance. The most common imaging features were lung patch and strip shadow (67.4%(128/190)). Conclusions:The most common type of AIDS patients complicated with NTM disease is disseminated NTM disease, and Mycobacterium avium is the most common NTM species. The clinical manifestations (fatigue, anorexia) and laboratory tests (hemoglobin, albumin, procalcitonin, CD4 + T lymphocyte count, CD8 + T lymphocyte count) of AIDS patients with disseminated NTM disease and non-disseminated NTM disease are different, while the prognosis is not significantly different.

Humans ; Cost-Benefit Analysis ; HIV Infections/drug therapy* ; Cost-Effectiveness Analysis ; Decision Trees

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

Since the end of 2019, the COVID-19 caused by 2019-nCoV has emerged and the pandemic ravaged the world, which seriously threatens global public health security and economic development. 2019-nCoV vaccine is an effective weapon to combat the viral infection, however, studies have shown that vaccine-induced immune protection decreases over time, coupled with some novel and immune escape variants continual emerging. Therefore, it is urgent to complete booster immunization to improve protection. At present, 2019-nCoV vaccines based on a variety of technical platforms have been approved and available in China. Therefore, we developed this sequential vaccination strategy guide to provide documentation guidance for the prevention and control of the epidemic caused by 2019-nCoV and its variant strains.

The study analyzed the application of failure mode and effect analysis(FMEA)in the emergency management of emergent infectious diseases. In February 2020, optimization of emergency management procedures for emergent infectious diseases was identified as the research theme. Subsequently, FMEA was applied to study the emergency management process of emergent infectious diseases and analyze corresponding potential failure modes in an infectious disease hospital. The appraisal identified four prioritized risk exposures to correct, including non-standardized personnel protection, delayed personnel arrival, unqualified specimens and inadequate ward preparation. Accordingly pertinent countermeasures were formulated. Three months after measures were taken, the risk priority numbers of the above four risks were decreased significantly. On the other hand, evident increase was found in the on-duty rate of emergency personnel, the rate of standard protection, the qualification rate of sample collection and disposal, as well as the serviceability rate of respirators, ECG monitors and protective equipment in emergency wards. The application of FMEA is conducive to optimizing the emergency response process of emergent infectious diseases, and to upgrading emergency management at large.

Objective:To assess the value of CD4 + and CD8 + T-lymphocyte counts for the diagnostic classification and prognosis of coronavirus disease 2019 (COVID-19). Methods:A total of 95 COVID-19 adult patients admitted to Shanghai Public Health Clinical Center, Fudan University from January to March 2020 were recruited. The CD4 + and CD8 + T-lymphocyte counts among ordinary, severe and critical patients, as well among the cured, improved, unimproved and death patients were compared. The area under receiver operating characteristic curve (AUROC) was used to evaluate the value of CD4 + and CD8 + T-lymphocyte counts for the clinical diagnosis and prognosis of COVID-19. The comparison among groups was performed by Mann-Whitney U test. Results:A total of 95 COVID-19 cases including 68 common, 11 severe and 16 critical cases were enrolled. The counts of CD4 + and CD8 + T-lymphocyte of patients in common, severe and critical groups were 419 (309, 612), 267 (212, 540), 141 (77, 201)/μL, and 238 (153, 375), 128 (96, 172), 92 (51, 144)/μL, respectively, with significant differences ( Z=24.322 and 15.956, respectively, both P<0.01). The counts of CD4 + and CD8 + T-lymphocyte of the death, unimproved, improved, and cured patients were 149 (143, 349), 315 (116, 414), 344 (294, 426), 745 (611, 966)/μL, and 106 (43, 501), 176(67, 279), 194(188, 432), 429(276, 564)/μL, respectively, with significant differences ( Z=36.083 and 16.658, respectively, both P<0.01). The optimal cut-off point of CD4 + T-lymphocyte counts was 237/μL for critical COVID-19 with AUROC 0.911 (95% confidence interval ( CI) 0.833-0.989, P<0.01), with the sensitivity of 86.1% and specificity of 87.5%. For predicting severe and critical cases, the optimal cut-off point of CD4 + T-lymphocyte counts was 405/μL with AUROC 0.863 (95% CI 0.727-0.999, P=0.001), with the sensitivity of 78.6% and specificity of 74.6%. Conclusions:The conditions of patients with COVID-19 are aggravated with CD4 + and CD8 + T-lymphocyte counts decreasing. CD4 + T-lymphocyte counts may be an indicator for diagnostic classification of COVID-19 and prognostic indicator for severe and critical patients.

The outbreak of COVID-19 occurred in January 2020, the epidemic is still rampant around the world. The Shanghai Expert Consensus on Comprehensive Treatment and Management of Corona Virus Disease 2019 was issued in early March 2020, which provided the guidance of the standardized treatment and rational medication for COVID-19. The administration of " four agents (glucocorticoids, heparin, high-dose vitamin C, Interferon-κ) and one peptide (thymic peptide)" recommended by the consensus is the key to successfully block and treat critical illness.

Administration, Intravenous ; Ascorbic Acid/therapeutic use* ; COVID-19 ; Humans ; Pneumonia ; SARS-CoV-2