Exosomal microRNAs associated with tuberculosis among people living with human immunodeficiency virus.

Objective: To investigate the diagnostic value of selected exosomal miRNAs for Tuberculosis (TB) among people living with human immunodeficiency virus (PLHIV). Methods: A total of 43 adult HIV patients, including 20 diagnosed with TB and 23 controls, were enrolled. The levels of six exosomal miRNAs (miR-20a, miR-20b, miR-26a, miR-106a, miR-191, and miR-486) were measured using qRT-PCR. Results: The levels of these six exosomal miRNAs (miR-20a, miR-20b, miR-26a, miR-106a, miR-191, and miR-486) were significantly higher in the plasma of TB patients compared to controls among PLHIV. The Receiver Operating Characteristic (ROC) curve of these six miRNAs showed a fair performance in distinguishing TB patients from controls, with Area Under Curve (AUC) values of 0.78 (95 %CI 0.63-0.93), 0.81 (95 %CI 0.67-0.95), 0.77 (95 %CI 0.61-0.93), 0.84 (95 %CI 0.70-0.98), 0.82 (95 %CI 0.68-0.95) and 0.79 (95 %CI 0.65-0.93), respectively. These miRNAs showed higher AUC values for extrapulmonary tuberculosis compared to pulmonary tuberculosis. An analysis of subgroups was performed based on CD4 + T cell count (＜200 and ≥ 200 cells·µL-1). In the high CD4 count group, all these six exosomal miRNAs appeared to have higher AUC values compared to the low CD4 count group. Conclusions: These six exosomal miRNAs could serve as potential biomarkers for diagnosing TB among PLHIV.

Prognostic value of the neutrophil-to-lymphocyte ratio and C-reactive-protein-to-prealbumin ratio in hospitalized older patients with coronavirus disease 2019.

The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-prealbumin ratio (CPAR) are novel markers of inflammation. The CPAR is an indicator of inflammation and malnutrition. We evaluated NLR and CPAR in combination as indicators of disease severity and prognosis in hospitalized older patients with coronavirus disease 2019 (COVID-19). A total of 222 hospitalized patients with COVID-19 (aged > 60 years) were divided into non-severe and severe groups. The severe group was subdivided into the surviving and deceased subgroups. We retrospectively assessed the predictive power of NLR and CPAR in combination (NLR + CPAR) to determine the prognosis of hospitalized older patients with COVID-19. The NLR and CPAR were significantly higher in the severe group than in the non-severe group (P < .001). Furthermore, the NLR and CPAR were higher in the deceased subgroup than in the surviving subgroup (P < .001). Pearson correlation analysis showed a highly significant positive correlation between NLR and CPAR (P < .001, r = 0.530). NLR + CPAR showed an area under the curve of 0.827 and sensitivity of 83.9% in the severe group; the area under the curve was larger (0.925) and sensitivity was higher (87.1%) in the deceased subgroup. The receiver operating characteristic curve of NLR + CPAR was significantly different from the receiver operating characteristic curves of either biomarker alone (P < .001). Kaplan-Meier analysis showed that patients in the severe group with elevated NLR + CPAR had a significantly lower 90-day survival rate than patients who lacked this finding (odds ratio 7.87, P < .001). NLR + CPAR may enable early diagnosis and assessment of disease severity in hospitalized older patients with COVID-19. This may also enable the identification of high-risk older patients with COVID-19 at the time of admission.

Diagnostic of FibroTouch and six serological models in assessing the degree of liver fibrosis among patients with chronic hepatic disease: A single-center retrospective study.

BACKGROUND AND AIMS: The aim of this study was to evaluate the diagnostic value of FibroTouch and serological models on staging hepatic fibrosis in chronic liver diseases. METHODS: We recruited 850 patients undergoing liver biopsy and received FibroTouch test before or after liver biopsy within one week, blood was taken for the routine inspection before the operation within one week. The serological models were calculated by the blood results and routine clinical information. The diagnostic value of FibroTouch and six serological models was analyzed by receiver operating characteristic curve (ROC). RESULTS: Patients with severe liver fibrosis had significantly higher AST, ALT, GGT, RDW, ALP, and FT-LSM. The area under the receiver operating characteristic curve (AUROC) of FT-LSM for the liver diagnosis of S≥2, S≥3 and S = 4 was 0.75(95% confidence interval [CI]:0.72-0.78), 0.83(95% CI: 0.80-0.86), and 0.85 (95% CI: 0.81-0.89), respectively. The optimal cut-off of FT-LSM for diagnosing S≥2, S≥3 and S = 4 was 8.7, 10.7, and 12.3, respectively. CONCLUSIONS: Our study showed the FibroTouch has a higher diagnostic value compared with the non-invasive serological models in staging the fibrosis stage. The cut-off of FibroTouch and five serological models (APRI, FIB-4, S-index, Forns, and PRP) increased with the severe of fibrosis stage.

Spatiotemporal characteristics and the epidemiology of tuberculosis in China from 2004 to 2017 by the nationwide surveillance system.

BACKGROUND: China has always been one of the countries with the most serious Tuberculosis epidemic in the world. Our study was to observe the Spatial-temporal characteristics and the epidemiology of Tuberculosis in China from 2004 to 2017 with Joinpoint regression analysis, Seasonal Autoregressive integrated moving average (SARIMA) model, geographic cluster, and multivariate time series model. METHODS: The data of TB from January 2004 to December 2017 were obtained from the notifiable infectious disease reporting system supplied by the Chinese Center for Disease Control and Prevention. The incidence trend of TB was observed by the Joinpoint regression analysis. The Seasonal autoregressive integrated moving average (SARIMA) model was used to predict the monthly incidence. Geographic clusters was employed to analyze the spatial autocorrelation. The relative importance component of TB was detected by the multivariate time series model. RESULTS: We included 13,991,850 TB cases from January 2004 to December 2017, with a yearly average morbidity of 999,417 cases. The final selected model was the 0 Joinpoint model (P = 0.0001) with an annual average percent change (AAPC) of - 3.3 (95% CI: - 4.3 to - 2.2, P < 0.001). A seasonality was observed across the 14 years, and the seasonal peaks were in January and March every year. The best SARIMA model was (0, 1, 1) X (0, 1, 1)12 which can be written as (1-B) (1-B12) Xt = (1-0.42349B) (1-0.43338B12) εt, with a minimum AIC (880.5) and SBC (886.4). The predicted value and the original incidence data of 2017 were well matched. The MSE, RMSE, MAE, and MAPE of the modelling performance were 201.76, 14.2, 8.4 and 0.06, respectively. The provinces with a high incidence were located in the northwest (Xinjiang, Tibet) and south (Guangxi, Guizhou, Hainan) of China. The hotspot of TB transmission was mainly located at southern region of China from 2004 to 2008, including Hainan, Guangxi, Guizhou, and Chongqing, which disappeared in the later years. The autoregressive component had a leading role in the incidence of TB which accounted for 81.5-84.5% of the patients on average. The endemic component was about twice as large in the western provinces as the average while the spatial-temporal component was less important there. Most of the high incidences (> 70 cases per 100,000) were influenced by the autoregressive component for the past 14 years. CONCLUSION: In a word, China still has a high TB incidence. However, the incidence rate of TB was significantly decreasing from 2004 to 2017 in China. Seasonal peaks were in January and March every year. Obvious geographical clusters were observed in Tibet and Xinjiang Province. The relative importance component of TB driving transmission was distinguished from the multivariate time series model. For every provinces over the past 14 years, the autoregressive component played a leading role in the incidence of TB which need us to enhance the early protective implementation.

Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression.

OBJECTIVES: To explore the epidemiological information, clinical characteristics, therapeutic outcomes and temporal progression of laboratory findings in 2019-coronavirus disease (COVID-19) patients exposed to lopinavir. METHODS: We collected data from ten COVID-19 patients admitted between January 22, 2020 and February 11, 2020 at Xixi hospital in Hangzhou, China. RESULTS: Of ten patients, secondary, tertiary and quartus patients emerged; the incubation period was 3-7 days. Mainly initial symptoms were cough and low fever (37.3-38.0°C). An asymptomatic case presented normal radiography, the others had ground glass opacities. All cases (three transferred, seven discharged) were exposed to lopinavir on initial hospitalization. Three patients stopped lopinavir because of adverse effects, two of them deteriorated, one was hospitalized longer than others who with sustained lopinavir use. Levels of potassium, albumin, and lymphocytes were low, but increased persistently after treatment. Eosinophil values were low on initial hospitalization, then all returned to normal before discharge. Viral load of SARS-CoV-2, radiography and eosinophil improved continuously in 3-14, 6-8 and 7-9 days, respectively. CONCLUSIONS: Increasing eosinophils may be an indicator of COVID-19 improvement. The COVID-19 patients may benefit from sustained lopinavir use. More research on a larger scale is needed to verify these points.

Retinoblastoma binding protein 4 represses HIV-1 long terminal repeat-mediated transcription by recruiting NR2F1 and histone deacetylase.

Human immunodeficiency virus (HIV) transcription is closely associated with chromatin remodeling. Retinoblastoma binding protein 4 (RBBP4) is a histone chaperone implicated in chromatin remodeling. However, the role of RBBP4 in HIV-1 infection and the underlying mechanism remain elusive. In the present study, we showed that RBBP4 plays a negative regulatory role during HIV-1 infection. RBBP4 expression was significantly increased in HIV-1-infected T cells. RBBP4 binds to the HIV-1 long terminal repeat (LTR)， represses HIV-1 LTR-mediated transcription through recruiting nuclear receptor subfamily 2 group F member 1(NR2F1) and histone deacetylase 1 and 2 (HDAC1/2) to HIV-1 LTR, and further controls local histone 3 (H3) deacetylation and chromatin compaction. Furthermore, the occupancy of RBBP4, HDAC1/2, and NR2F1 on LTR in HIV-latent J-lat cells was significantly higher than that in HIV-1-activated cells. In conclusion, our results establish RBBP4 as a new potent antiretroviral factor, which may provide theoretical basis for the treatment of HIV in the future.