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.

Antimitochondrial antibody associated with liver cirrhosis in patients with primary biliary cholangitis.

Antimitochondrial antibody (AMA) serves as a serological marker for diagnosing primary biliary cholangitis (PBC). However, the association between AMA and prognosis for PBC patients remains unclear. The objective of this study was to investigate the relationship between AMA and cirrhosis in PBC patients. This retrospective study enrolled 225 PBC patients, including 127 with liver cirrhosis and 98 without cirrhosis. AMA was tested by indirect immunofluorescence (IIF) with rat kidney as the substrate. AMA-M2 and M2-3E were detected by line immunoassay (LIA). The overall positivity rate for AMA detection in PBC patients was 80.9%. The positivity rates of IIF-AMA, AMA-M2, and M2-3E were significantly higher in patients with liver cirrhosis than in those without cirrhosis (73.2% vs. 52.0%, 74.0% vs. 51.0%, and 80.3% vs. 60.2%, respectively). In multivariate logistic regression, IIF-AMA (OR: 3.05, 95% CI: 1.59-5.87), AMA-M2 (OR: 3.11, 95% CI: 1.61-6.01), and M2-3E (OR: 3.29, 95% CI: 1.63-6.66) remained significantly associated with an increased incidence of liver cirrhosis. Moreover, in multinomial logistic regression, IIF-AMA (compensated cirrhosis, OR: 3.55, 95% CI: 1.49-8.44; decompensated cirrhosis, OR: 2.86, 95% CI: 1.32-6.18), AMA-M2 (compensated cirrhosis, OR: 4.74, 95% CI: 1.94-11.58; decompensated cirrhosis, OR: 2.51, 95% CI: 1.19-5.33), and M2-3E (compensated cirrhosis, OR: 4.92, 95% CI: 1.74-13.96; decompensated cirrhosis, OR: 2.91, 95% CI: 1.28-6.64) were all found to be associated with different stages of liver cirrhosis. AMA was found to be associated with the occurrence of liver cirrhosis in PBC patients. Additionally, AMA was also related to different stages of liver cirrhosis, including compensated and decompensated cirrhosis.

A long trend of sexually transmitted diseases before and after the COVID-19 pandemic in China (2010-21).

BACKGROUND: The longer ongoing benefits of coronavirus disease 2019 (COVID-19) non-pharmaceutical interventions (NPIs) for sexually transmitted diseases (STDs) in China are still unclear. We aimed to explore the changes in five STDs (AIDS, hepatitis B, hepatitis C, gonorrhoea, and syphilis) before, during, and after the COVID-19 pandemic in mainland China, from 2010 to 2021. METHODS: The number of the monthly reported cases of the five STDs were extracted from the website to construct the Joinpoint regression and autoregressive integrated moving average (ARIMA) models. Eight indicators reflecting NPIs were chosen from the COVID-19 Government Response Tracker system. The STDs and eight indicators were used to establish the Multivariable generalised linear model (GLM) to calculate the incidence rate ratios (IRRs). RESULTS: With the exception of hepatitis B, the other four STDs (AIDS, hepatitis C, gonorrhoea, and syphilis) had a positive average annual percent change over the past 12years. All the ARIMA models had passed the Ljung-Box test, and the predicted data fit well with the data from 2010 to 2019. All five STDs were significantly reduced in 2020 compared with 2019, with significant estimated IRRs ranging from 0.88 to 0.92. In the GLM, using data for the years 2020 (February-December) and 2021, the IRRs were not significant after adjusting for the eight indicators in multivariate analysis. CONCLUSION: Our study demonstrated that the incidence of the five STDs decreased rapidly during the COVID-19 pandemic in 2020. A recovery of STDs in 2021 was found to occur compared with that in 2020, but the rising trend disappeared after adjusting for the NPIs. Our study demonstrated that NPIs have an effect on STDs, but the relaxation of NPI usage might lead to a resurgence.

Trends in respiratory diseases before and after the COVID-19 pandemic in China from 2010 to 2021.

BACKGROUND: The ongoing benefits of coronavirus disease 2019 (COVID-19) nonpharmaceutical interventions (NPIs) for respiratory infectious diseases in China are still unclear. We aimed to explore the changes in seven respiratory infectious diseases before, during, and after COVID-19 in China from 2010 to 2021. METHODS: The monthly case numbers of seven respiratory infectious diseases were extracted to construct autoregressive integrated moving average (ARIMA) models. Eight indicators of NPIs were chosen from the COVID-19 Government Response Tracker system. The monthly case numbers of the respiratory diseases and the eight indicators were used to establish the Multivariable generalized linear model (GLM) to calculate the incidence rate ratios (IRRs). RESULTS: Compared with the year 2019, the percentage changes in 2020 and 2021 were all below 100% ranging from 3.81 to 84.71%. Pertussis and Scarlet fever started to increase in 2021 compared with 2020, with a percentage change of 183.46 and 171.49%. The ARIMA model showed a good fit, and the predicted data fitted well with the actual data from 2010 to 2019, but the predicted data was bigger than the actual number in 2020 and 2021. All eight indicators could negatively affect the incidence of respiratory diseases. The seven respiratory diseases were significantly reduced during the COVID-19 pandemic in 2020 and 2021 compared with 2019, with significant estimated IRRs ranging from 0.06 to 0.85. In the GLM using data for the year 2020 and 2021, the IRRs were not significant after adjusting for the eight indicators in multivariate analysis. CONCLUSION: Our study demonstrated the incidence of the seven respiratory diseases decreased rapidly during the COVID-19 pandemic in 2020 and 2021. At the end of 2021, we did see a rising trend for the seven respiratory diseases compared to the year 2020 when the NPIs relaxed in China, but the rising trend was not significant after adjusting for the NPIs indicators. Our study showed that NPIs have an effect on respiratory diseases, but Relaxation of NPIs might lead to the resurgence of respiratory diseases.

Determinants and Incidence of Chronic Kidney Disease with Tenofovir- Based Antiretroviral Therapy Regimens: A Cohort Study in HIV-Infected Adults in South China.

BACKGROUND: The data of the impact of tenofovir (TDF) on kidney damage in Chinese HIV-1 infected patients are limited. OBJECTIVE: The study aims to evaluate the incidence and risk factors of stage 3 chronic kidney disease (CKD) and rapid kidney function decline (RKFD) among Chinese HIV-1 infected patients starting with a TDF-based regimen. METHODS: We enrolled 797 TDF-initiated HIV-1-infected patients in a Chinese cohort. Kidney dysfunctions were defined as stage 3 CKD (eGFR < 60 mL/min/1.73 m2 during follow-up) and RKFD (eGFR decline > 10 mL/min/1.73 m2/year). A linear mixed-effects model was used to quantify the average eGFR change per 48 weeks. A generalized estimating equation regression analysis was conducted to determine the risk factors associated with renal dysfunction. The method of multiple imputations was used to reduce the bias caused by missing data. RESULTS: In this retrospective study, 14 (2%) patients experienced stage 3 CKD, and 272 (34%) individuals experienced RKFD during a median of 26 (IQR, 4-78; maximum 325) weeks follow-up period. The mean loss in eGFR per 48 weeks increased consistently over time, from -2.59 mL/min/1.73 m2 before 48 weeks to -17.61 mL/min/1.73 m2 after 288 weeks. For every 10 mL/min/1.73 m2 increase of eGFR, the risk of RKFD increased by 29% (95%CI: 18%, 40%). Each 10 years older and every 10 mL/min/1.73 m2 higher in baseline eGFR, the risk of stage 3 CKD increased to 1.56 (95% CI: 1.00, 2.43) and decreased by 65% (95% CI: 48%, 76%), respectively. Anemia and higher viral load were significantly associated with RKFD. The results were robust across a range of multiple imputation analyses. CONCLUSION: TDF-associated CKD is rare in HIV-1 infected Chinese adults. Longer TDF-exposed patients are more likely to have renal dysfunction, especially those with older age, anemia, lower baseline eGFR, and higher viral load.

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.

Longitudinal Progression of Estimated GFR in HIV-1-Infected Patients with Normal Renal Function on Tenofovir-Based Therapy in China.

PURPOSE: Estimated glomerular filtration rate (eGFR) decline in HIV-1-infected patients exposure to tenofovir disoproxil fumarate (TDF) has been widely assessed using linear models, but nonlinear assumption is not well validated. We constructed a retrospective cohort study to assess whether eGFR decline follows nonlinearity during antiviral therapy. PATIENTS AND METHODS: We examined 823 (299 of TDF users and 524 of non-TDF users) treatment-naïve HIV-1-infected participants (age ≥ 17 years, initial eGFR ≥ 90 mL/min/1.73m2). Estimated GFR trajectories were compared by one-linear and piecewise-linear mixed effects models, before and after propensity score matching, respectively. Whether the incidence of renal dysfunction (reduced renal function [RRF], eGFR < 90 mL/min/1.73 m2 and rapid kidney function decline [RKFD], eGFR > -3 mL/min/1.73 m2/year) follows nonlinearity was assessed by logistic regression. RESULTS: The median follow-up time of this study was 10 (interquartile range, 2-20) months, during which 178 (21.6%) experienced RRF, and 451 (54.8%) experienced RKFD. The slopes (mL/min/1.73 m2/year) of eGFR were -5.31 (95% CI: -6.57, -4.06) before 1.40 years, 4.83 (95% CI: 1.38, 8.28) from years 1.40 to 2.30 and -3.71 (95% CI: -5.97, -1.45) after 2.30 years among TDF users. Within years 1.40-2.30, each year of TDF exposure was associated with a 78% decreased risk of RKFD (95% CI: -91%, -49%). In comparison, eGFR increased slightly at the initiation of antiviral therapy, declined after 2.15 years (-4.96; 95% CI: -5.76, -4.17) among non-TDF users. Such a progression nonlinear trajectory was missed on the assumption of one-linearity, whether in TDF or non-TDF users. CONCLUSION: Over the piecewise mixed-effects analyses with the advantage of revealing the true nature of the exposure outcome relationships, an interesting reverse S-shaped relationship was observed. A routine screen based on nonlinearity could be more helpful for patient management.

Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019.

OBJECTIVE: To investigate the diagnostic value of serological testing and dynamic variance of serum antibody in coronavirus disease 2019 (COVID-19). METHODS: This study retrospectively included 43 patients with a laboratory-confirmed infection and 33 patients with a suspected infection, in whom the disease was eventually excluded. The IgM/IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was measured by chemiluminescence immunoassay analysis. RESULTS: Compared to molecular detection, the sensitivities of serum IgM and IgG antibodies to diagnose COVID-19 were 48.1% and 88.9%, and the specificities were 100% and 90.9%, respectively.In the COVID-19 group, the IgM-positive rate increased slightly at first and then decreased over time; in contrast, the IgG-positive rate increased to 100% and was higher than IgM at all times. The IgM-positive rate and titer were not significantly different before and after conversion to virus-negative. The IgG-positive rate was up to 90% and not significantly different before and after conversion to virus-negative. However, the median IgG titer after conversion to virus-negative was double that before, and the difference was significant. CONCLUSIONS: Viral serological testing is an effective means of diagnosis for SARS-CoV-2 infection. The positive rate and titer variance of IgG are higher than those of IgM in COVID-19.

[Analysis of the test results of HBV serum markers and HBV DNA of the neonates born to HBsAg-positive mothers].

OBJECTIVE: To observe the HBV serum markers and HBV DNA expressions of the neonates born to the HBsAg-positive mothers. METHODS: By detecting serum immunity markers of hepatitis B virus (5 items) and serum HBV DNA of 283 neonates (a pair of twins) born to 282 HBsAg-positive mothers. RESULTS: 12 patterns emerge from the study of the hepatitis B serum markers of 283 neonates. Topping the list is the combination of HBeAg and anti-HBc positive accounting for 48.41% (137/283), followed by the combination of anti-HBe and anti-HBc positive accounting for 22.26% (62/283). The third highest combination is that of HBsAg, HBeAg and anti-HBc positive accounting for 12.37% (35/283). There are five combinations accounting for 16.61% (47/283), each with HBsAg-positive. No case is found of the five items all negative or only HBsAb positive. Five cases are detected of serum HBV DNA > or = 1 x 103 IU/ml accounting for 1.77%. CONCLUSIONS: Neonates born to HBsAg-positive mothers display complex patterns of serum hepatitis B markers, the dominant pattern being the combination of HBeAg and anti-HBc positive. Cases of serum HBV DNA > or = 1 x 10(3) IU/ml are rare.

[Clinical application studies on AFP-L3 detected by micro-spin column method].

OBJECTIVE: To explore the clinical value of Lens culinaris agglutinin-reactive alpha-fetoprotein in the differentiation diagnosis between benign and malignant liver diseases, as well as the early warning of hepatocellular carcinoma. METHODS: Alpha-fetoprotein variants from 300 patients with liver diseases were isolated with micro-spin column equipped lens culinaris agglutinin (LCA). The AFP and AFP-L3 were detected by the electrochemical luminescence (ECL) method, and the proportions of AFP-L3 were calculated. RESULTS: The positive rates of AFP-L3 of HCC patients and chronic liver disease patients were 95% and 64% respectively, there were significant difference in two groups (chi2 = 134.72, P < 0.01), the HCC incidence rates of AFP-L3 positive and negative chronic liver disease patients showed significant difference (chi2 = 80.158, P < 0.01). there were no correlations between the proportion of AFP-L3 and AFP consistency(r = 0.046, P > 0.05). CONCLUSIONS: The detection of AFP-L3 by micro-spin column assay show great clinical value in the differentiation diagnosis of benign and malignant liver diseases, as well as the early warning of hepatocellular carcinoma.

[Detection of peripheral blood HBV-LHBs transactivation function and its relationship with anti-viral efficacy].

OBJECTIVE: Explore the serum of patients with CHB of HBV large envelope protein (HBV-LHBs) trans-activation function and antiviral therapy effect relationship. METHODS: 60 cases of anti-viral treatment of patients with chronic hepatitis B to take every 3 months HBVDNA, HBV-LHBs, as well as detection of hepatitis B immune markers to observe the changes in indexes. RESULTS: Income group 60 cases of anti-virus group HBVDNA with HBV-LHBs have a higher detection rate of the consistency of the results found no statistical significance (P > 0.05), HBV-LHBs-positive rate and positive rate of HBeAg differences (chi2 = 4.08, P < 0.05). After 24 months of antiviral therapy HBV-LHBs expression always HBVDNA in 29 cases of which occurred 24 months after the negative reaction of the 20 cases, continuous positive were seven cases of non-negative. 60 cases of patients 24 months found no HBsAg seroconversion, four cases of emergence of HBeAg seroconversion. CONCLUSION: (1) detection of serum HBV-LHBs to reflect the hepatitis B virus replication with HBVDNA good correlation. (2) anti-viral treatment of dynamic observation of the process of HBV-LHBs expression can predict the effectiveness of anti-viral therapy.

[Subject diagnostic value of detecting a1pha-fetoprotein variants with a new microspincolumn method in hepatocellular carcinoma].

OBJECTIVE: To evaluate the usefulness of new microspincolumn method for the measurement of a1pha-fetoprotein variant AFP-L3 in differentiation of benign and malignant liver disease and the warming for liver cancer. METHODS: AFP-L3 was isolated by using microspincolumn coupled with lens culinaris agglutinin (LCA), AFP and AFP-L3 were determined with chemiluminescent immunoassay, the proportion of AFP-L3 levels AFP-L3(%) were calculated, and the relationship between the elevated AFP-L3(%) levels and benign and malignant liver disease was analyzed. RESULTS: The levels of AFP-L3(%) in serum of patients with hepatocellular carcinoma was significantly higher than those in the patients with other liver diseases (P < 0.001). Taking AFP-L3(%) >or= 10% as the diagnostic criteria, the sensitivity for diagnosis of liver cancer was 90.9%. CONCLUSION: Detection of AFP-L3 seemed to be of clinical value in diagnosis and differential diagnosis of hepatocellular carcinoma; it may be especially important for identifying patients with hepatocellular carcinoma whose a1pha-fetoprotein level is low.