Appraisal of evidence reliability and applicability of Paxlovid as treatment for SARS-COV-2 infection: A systematic review.

This study aimed to clarify the beneficial effect and the clinical application value of Paxlovid in the treatment of coronavirus disease-19 (COVID-19) through a systematic review. Databases including PubMed, Cochrane Library, Chinese Clinical Trial Registry, and ClinicalTrials.gov were systematically searched for interventional or observational studies on the efficacy and safety of Paxlovid in the treatment of SARS-COV-2. The relative and absolute effect sizes for the outcomes were calculated based on the data reported in the original intervention literature. The external applicability of the evidence was analysed in terms of clinical application scenarios, patient willingness, and cost utility. One interventional and three observational studies were conducted. Four studies published in 2022, had participation sample sizes ranging 1780-109,254. Based on the randomised controlled trial data, the risk of all-cause mortality, all-cause death, and hospitalisation was significantly reduced in the Paxlovid group. Serious adverse events were reduced during the study. Based on observational studies, Paxlovid can significantly reduce the risk of death and hospitalisation in older patients with COVID-19 (moderate certainty) and improve in-hospital disease progression, composite disease progression, and viral load (low certainty). Paxlovid did not improve the outcomes of death and hospitalisation (low certainty) in patients aged <65 years. As per the economic utility analysis, the economic cost of reducing one death dramatically decreased with increasing age. Early use of Paxlovid in the older adult population with COVID-19 is beneficial. However, in the setting of limited resources, Paxlovid should be prioritised for older patients.

Global burden and trends of rotavirus infection-associated deaths from 1990 to 2019: an observational trend study.

BACKGROUND: Rotavirus is the leading global pathogen of diarrhea-associated mortality and poses a great threat to public health in all age groups. This study aimed to explore the global burden and 30-year change patterns of rotavirus infection-associated deaths. METHODS: Based on the Global Burden of Disease 2019 Study (GBD 2019), we analyzed the age-standardized death rate (ASDR) of rotavirus infection by sex, geographical region, and sociodemographic index (SDI) from 1990 to 2019. A Joinpoint regression model was used to analyze the global trends in rotavirus infection over the 30 years, SaTScan software was used to detect the spatial and temporal aggregations, and a generalized linear model to explore the relationship between sociodemographic factors and death rates of rotavirus infection. RESULTS: Globally, rotavirus infection was the leading cause of diarrheal deaths, accounting for 19.11% of deaths from diarrhea in 2019. Rotavirus caused a higher death burden in African, Oceanian, and South Asian countries in the past three decades. The ASDR of rotavirus declined from 11.39 (95% uncertainty interval [95% UI] 5.46-19.48) per 100,000 people in 1990 to 3.41 (95% UI 1.60-6.01) per 100,000 people in 2019, with an average annual percentage change (AAPC) (- 4.07%, P < 0.05). However, a significant uptrend was found in high-income North America (AAPC = 1.79%, P < 0.05). The death rate was the highest among children under 5 years worldwide. However, the death rates of elderly individuals over 70 years were higher than those of children under 5 years in 2019 among high, high-middle, middle, and low-middle SDI regions. Current health expenditure, gross domestic product per capita, and the number of physicians per 1000 people were significantly negatively correlated with death rates of rotavirus. CONCLUSIONS: Although the global trends in the rotavirus burden have decreased substantially over the past three decades, the burden of rotavirus remained high in Africa, Oceania, and South Asia. Children under 5 years and elderly individuals over 70 years were the populations most at risk for rotavirus infection-associated deaths, especially elderly individuals over 70 years in relatively high SDI regions. More attention should be paid to these areas and populations, and effective public health policies should be implemented in the future.

Value of Xpert MTB/RIF Using Bronchoalveolar Lavage Fluid for the Diagnosis of Pulmonary Tuberculosis: a Systematic Review and Meta-analysis.

The performance of Xpert MTB/RIF using bronchoalveolar lavage fluid (BAL) for the diagnosis of pulmonary tuberculosis (PTB) remains unclear. Therefore, a systematic review/meta-analysis was conducted. Studies published before 31 December 2019 were retrieved from the PubMed, Embase, and Web of Science databases using the keywords "pulmonary tuberculosis," "Xpert MTB/RIF," and "BAL." Two independent evaluators extracted the data and assessed the bias risk of the included studies. A random-effects model was used to calculate the overall sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic odds ratio (DOR), and the area under the curve (AUC), as well as the respective 95% confidence intervals (CIs). Nineteen trials involving 3,019 participants met the inclusion criteria. Compared to the culture method, the pooled sensitivity, specificity, PLR, NLR, DOR, and the AUC with 95% CIs of Xpert MTB/RIF were 0.87 (0.84 to 0.90), 0.92 (0.91 to 0.93), 10.21 (5.78 to 18.02), 0.16 (0.12 to 0.22), 78.95 (38.59 to 161.53), and 0.9467 (0.9462 to 0.9472), respectively. Relative to the composite reference standard, the observed values were 0.69 (0.65 to 0.72), 0.98 (0.98 to 0.99), 37.50 (18.59 to 75.62), 0.30 (0.21 to 0.43), 171.98 (80.82 to 365.96), and 0.9691 (0.9683 to 0.9699), respectively. All subgroups, except children, showed high sensitivity and specificity. In conclusion, the use of Xpert MTB/RIF in the context of BAL samples has a high diagnostic performance for PTB (except for children) and may serve as an alternative rapid diagnostic tool.

Use of thiazide diuretics for the prevention of recurrent kidney calculi: a systematic review and meta-analysis.

BACKGROUND: Thiazide diuretics reduce the risk of recurrent kidney calculi in patients with kidney calculi or hypercalciuria. However, whether thiazide diuretics can definitely prevent recurrent kidney calculi remains unclear. We aimed to evaluate the effect and safety of thiazide diuretics on recurrent kidney calculi. METHODS: The PubMed, Cochrane Library, and EMBASE databases were systematically searched using the keywords thiazide diuretics and kidney calculi to identify randomized controlled trials (RCTs). The primary outcome was the incidence of recurrent kidney calculi, and the secondary outcome was the 24-h urinary calcium level. The pooled risk ratio (RR), risk difference (RD), standardized mean difference (SMD), and 95% confidence interval (CI) were calculated. The evidence quality was graded using the GRADE criteria, and recommendations for recurrent kidney calculus prevention using thiazide diuretics were reassessed. RESULTS: Eight RCTs involving 571 patients were included. The pooled RR for the incidence of kidney calculi in the thiazide diuretic groups was 0.44 (95% CI 0.33-0.58, P < 0.0001) compared to that in the placebo and untreated groups; the pooled RD was - 0.23 (95% CI - 0.30 to - 0.16, P < 0.0001). The pooled SMD for the 24-h urinary calcium level was - 18.59 (95% CI - 25.11 to - 12.08, P < 0.0001). The thiazide diuretic groups had a high incidence of adverse reactions and low tolerance. The evidence quality for decrease in kidney calculus incidence using thiazide diuretics was low, while that for the 24-h urinary calcium level decrease among those with recurrent kidney calculi was moderate, and that for the decrease in kidney calculus incidence using short-acting and long-acting thiazide diuretics was low. The overall strength of recommendation for prevention of recurrent renal calculi using thiazide diuretics was not recommended. The subgroup and sensitivity analysis findings were robust. CONCLUSIONS: Long-term use of thiazide diuretics reduces the incidence of recurrent renal calculi and 24-h urinary calcium level. However, the benefits are insufficient, and the evidence quality is low. Considering the adverse effects, poor patient compliance, and economic burden of long-term medication, their use in preventing recurrent kidney calculi is not recommended.

Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19).

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.

Pyrosequencing for rapid detection of tuberculosis resistance in clinical isolates and sputum samples from re-treatment pulmonary tuberculosis patients.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. Early diagnosis of MDR-TB patients is essential for minimizing the risk of Mycobacterium tuberculosis (MTB) transmission. The conventional drug susceptibility testing (DST) methods for detection of drug-resistant M. tuberculosis are laborious and cannot provide the rapid detection for clinical practice. METHODS: The aim of this study was to develop a pyrosequencing approach for the simultaneous detection of resistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and amikacin (AMK) in M. tuberculosis clinical isolates and sputum samples from re-treatment pulmonary tuberculosis (PTB) patients. We identified the optimum conditions for detection mutation of rpoB, katG, rpsl, embB, gyrA and rrs gene by pyrosequencing. Then this approach was applied to detect 205 clinical isolates and 24 sputum samples of M. tuberculosis from re-treatment PTB patients. RESULTS: The mutations of rpoB and gyrA gene were detected by pyrosequencig with the SQA mode, and the mutations of katG, rpsl, embB, gyrA and rrs gene were detected by pyrosequencing with SNP mode. Compared with the Bactec MGIT 960 mycobacterial detection system, the accuracy of pyrosequencing for the detection of RIF, INH, EMB, SM, AMK and OFL resistance in clinical isolates was 95.0%, 79.2%, 70.3%, 84.5%, 96.5% and 91.1%, respectively. In sputum samples the accuracy was 83.3%, 83.3%, 60.9%, 83.3%, 87.5% and 91.7%, respectively. CONCLUSIONS: The newly established pyrosequencing assay is a rapid and high-throughput method for the detection of resistance to RIF, INH, SM, EMB, OFL and AMK in M. tuberculosis. Pyrosequencing can be used as a practical molecular diagnostic tool for screening and predicting the resistance of re-treatment pulmonary tuberculosis patients.

Intensity and drivers of subtypes interference between seasonal influenza viruses in mainland China: A modeling study.

Subtype interference has a significant impact on the epidemiological patterns of seasonal influenza viruses (SIVs). We used attributable risk percent [the absolute value of the ratio of the effective reproduction number (Rₑ) of different subtypes minus one] to quantify interference intensity between A/H1N1 and A/H3N2, as well as B/Victoria and B/Yamagata. The interference intensity between A/H1N1 and A/H3N2 was higher in southern China 0.26 (IQR: 0.11-0.46) than in northern China 0.17 (IQR: 0.07-0.24). Similarly, interference intensity between B/Victoria and B/Yamagata was also higher in southern China 0.14 (IQR: 0.07-0.24) than in norther China 0.10 (IQR: 0.04-0.18). High relative humidity significantly increased subtype interference, with the highest relative risk reaching 20.59 (95% CI: 6.12-69.33) in southern China. Southern China exhibited higher levels of subtype interference, particularly between A/H1N1 and A/H3N2. Higher relative humidity has a more pronounced promoting effect on subtype interference.

The silence of MUC2 mRNA induced by promoter hypermethylation associated with HBV in Hepatocellular Carcinoma.

BACKGROUND: To evaluate the promoter methylation status of MUC2 gene and mRNA expression in patients with hepatocellular carcinoma. METHODS: We analyzed MUC2 methylation by MSP, and MUC2 mRNA by real-time PCR in 74 HCC. RESULTS: MUC2 mRNA were lower in HCC tissues (Mean -ΔCt = -4.70) than that in Non-HCC tissues (Mean -ΔCt = -2.98). Expression of MUC2 was elevated in only 23 (31.08%) of the 74 HCC patients. MUC2 promoter was hypermethylated in 62.2% (46/74) of HCCs, and in only 18.9% (14/74) of non-tumor samples. MUC2 mRNA were lower in HCC patients with hypermethylation (Mean -ΔΔCt = -2.25) than those with demethylation (Mean -ΔΔCt = -0.22), and there is a decreased tendency for MUC2 mRNA in HCC patients with promoter hypermethylation (p = 0.011). There was a significantly correlation found between MUC2 mRNA and HBV and AFP in HCC. The loss of MUC2 mRNA and hypermethylation could be poor prognostic factors. After treated by 5-Aza-CdR and TSA, we found that MUC2 mRNA induced significantly in 7721, Huh7 and HepG2 cells. CONCLUSION: The results suggested that MUC2 mRNA silenced by promoter hypermethylation is associated with high levels HBV in HCC.

An anoikis-related lncRNA signature is a useful tool for predicting the prognosis of patients with lung adenocarcinoma.

Background: Anoikis-related long non-coding RNAs (ARLs) play a critical role in tumor metastasis and progression, suggesting that they may serve as risk markers for cancer. This study aimed to investigate the prognostic value of ARLs in patients with lung adenocarcinoma (LUAD). Methods: Clinical data, RNA sequencing (RNA-seq) data, and mutation data from the LUAD project were obtained from The Cancer Genome Atlas (TCGA) database. The Molecular Signatures Database (MSigDB) and the GeneCard database were used to collect an anoikis-related gene (ARG) set. Pearson correlation analysis was performed to identify ARLs. LASSO and Cox regression were then used to establish a prognostic risk signature for ARLs. The median risk score served as the basis for categorizing patients into high and low-risk groups. Kaplan-Meier analysis was utilized to compare the prognosis between these two groups. The study also examined the associations between risk scores and prognosis, clinicopathological characteristics, immune status, tumor mutation burden (TMB), and chemotherapeutic agents. LncRNA expression was assessed using quantitative real-time PCR (qRT-PCR). Results: A total of 480 RNA expression profiles, 501 ARGs, and 2698 ARLs were obtained from the database. A prognostic ARL signature for LUAD was established, consisting of 9 lncRNAs. Patients in the low-risk group exhibited significantly better prognosis compared to those in the high-risk group (P < 0.001). The 9 lncRNAs from the ARL signature were identified as independent prognostic factors (P < 0.001). The signature demonstrated high accuracy in predicting LUAD prognosis, with area under the curve values exceeding 0.7. The risk scores for ARLs showed strong negative correlations with stroma score (P = 5.9E-07, R = -0.23), immune score (P = 9.7E-09, R = -0.26), and microenvironment score (P = 8E-11, R = -0.29). Additionally, the low-risk group exhibited significantly higher TMB compared to the high-risk group (P = 4.6E-05). High-risk status was significantly associated with lower half-maximal inhibitory concentrations for most chemotherapeutic drugs. Conclusion: This newly constructed signature based on nine ARLs is a useful instrument for the risk stratification of LUAD patients. The signature has potential clinical significance for predicting the prognosis of LUAD patients and guiding personalized immunotherapy.

Evaluation of the clinical value of ELISA based on MPT64 antibody aptamer for serological diagnosis of pulmonary tuberculosis.

BACKGROUND: Presently, tuberculosis (TB) poses a global threat to human health. The development of reliable laboratory tools is vital to the diagnosis and treatment of TB. MPT64, a protein secreted by Mycobacterium tuberculosis complex, is highly specific for TB, making antibody to MPT64 a reagent specific for the diagnosis of TB. METHOD: Antibody to MPT64 was obtained by a combination of genetic engineering and immunization by the system evolution of ligands by exponential enrichment. A high-affinity aptamer of antibody to MPT64 was selected from a random single-stranded DNA library, and a sandwich ELISA method based on this aptamer was developed. This ELISA method was used to detect TB in 328 serum samples, 160 from patients with pulmonary TB (PTB) and 168 from non-tuberculous controls. RESULTS: The minimum limit of detection of the ELISA method was 2.5 mg/L, and its linear range varied from 10 mg/L to 800 mg/L. Its sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve, with 95 % confidence intervals, were 64.4 % (56.7 %-71.4 %), 99.4 % (96.7 %-99.9 %), 108.2 (15.3-765.9), 0.350 (0.291-0.442) and 0.819 (0.770-0.868), respectively. No significant difference in sensitivity was observed between sputum smear positive (73/112, 65.2 %) and negative (30/48, 62.5 %) individuals. CONCLUSIONS: This sandwich ELISA based on an MPT64 antibody aptamer may be useful for the serological diagnosis of PTB, both in sputum smear positive and negative patients.

Clinical value of ELISA-MPT64 for the diagnosis of tuberculous pleurisy.

Tuberculous pleurisy is one of the common extrapulmonary tuberculosis diseases. However, the diagnosis of tuberculous pleurisy still lacks a useful and effective tool, mainly due to paucity of Mycobacterium tuberculosis organisms in pleural effusion. Previous studies have confirmed that the MPT64 protein is highly specific and is secreted only by M. tuberculosis (MTB) complex. Therefore, in this study, we developed ELISA based on recombinantly expressed MPT64 in combination with rabbit polyclonal antibodies. The ELISA-MPT64 method was validated using MTB strains and tested against clinical samples. Nested PCR, Löwenstein-Jensen (L-J) culture and smear microscopy were employed as the comparative tools for assessing the performance of the assay. Our results demonstrate that the newly established ELISA-MPT64 technique is a rapid and useful tool for the diagnosis of tuberculous pleurisy.

Treatment for Triple-Negative Breast Cancer: An Umbrella Review of Meta-Analyses.

Purpose: In recent years, many meta-analyses of triple-negative breast cancer (TNBC) treatment have been published; however, these studies still lack systematic summary. Therefore, the aim of this study is to summarize and evaluate the evidence level and efficacy of treatment for TNBC. Materials and Methods: Retrospective and prospective studies on treatment of TNBC were searched in the PubMed, Embase, and Cochrane Library databases. The literature search deadline was June 30, 2021. Two investigators independently screened the literature and extracted the data. In addition, the joint World Health Organization-United Nations Food and Agriculture Organization expert consultation was used to evaluate the validity of the evidence. Results: A total of 28 meta-analyses were included in this study. The treatment interventions for TNBC mainly included surgery, chemotherapy (CT), radiotherapy, molecular targeted therapy, immunotherapy, zoledronic acid, and gonadotropin-releasing hormone (GnRH) analog. Platinum improves the pathological complete response (PCR) rate of patients treated with neoadjuvant chemotherapy (NACT), the objective remission rate (ORR) and overall survival (OS) in patients with metastatic triple-negative breast cancer. Capecitabine improves disease-free survival (DFS) and OS in patients treated with adjuvant CT. Bevacizumab was added to NACT to improve the PCR rate in patients. Immunotherapy improves the PCR rate in patients treated with NACT. The improvement in PCR rate in patients with high Ki67 expression treated with neoadjuvant therapy is highly suggestive. Other interventions had suggestive or weak evidence. Conclusion: Among the strategies for treating TNBC, platinum, bevacizumab, and immunotherapy can lead to better PCR rates as part of a NACT regimen. Capecitabine as adjuvant CT and platinum in the treatment of metastatic TNBC can benefit patients' survival. However, the effectiveness of other interventions for TNBC is not yet clear. Further research is needed in the future to obtain more reliable clinical evidence.

Changing trends in clinical research literature on PubMed database from 1991 to 2020.

BACKGROUND: Clinical research publications have become the dominant source and basis of clinical evidence-based decision-making. Exploring the type and quantity of clinical research publications in the PubMed database is useful for clarifying the changing trends of clinical research development in recent years. Therefore, a longitudinal analysis of the type and quantity of clinical research publications in the PubMed database over three decades was conducted. METHODS: The PubMed database was searched to retrieve clinical research according to the type and year of publication from January 1, 1991 to December 31, 2020. The research types were classified as primary and secondary literature. RESULTS: A total of 1,078,404 primary literatures were retrieved and the constituent proportions were ranked from high to low as case report/series (27.54%), randomized clinical trials (RCTs) (23.62%), cohort studies (21.05%), cross-sectional studies (17.49%), case control studies (9.15%), non-RCTs (1.01%), and pragmatic clinical trials (PCTs) (0.15%). Correspondingly, 1,302,173 secondary literatures were retrieved and ranked as narrative review (70.88%), systematic review (15.02%), systematic review and meta-analyses (13.89%), traditional meta-analyses (4.48%), expert consensus (2.31%), guidelines (1.49%), scoping reviews (0.68%), net meta-analyses (0.40%), and umbrella reviews (0.04%). The average annual growth rate for the primary literature was 10.28%, and ranked from high to low as PCTs (83.68%), cohort studies (17.74%), cross-sectional studies (17.61%), non-RCTs (12.11%), case control studies (8.86%), RCTs (7.68%), case report/series (7.51%); while that for the secondary literature was 10.57%, and ranked from high to low as net meta-analyses (48.97%), umbrella reviews (47.09%), scoping reviews (41.92%), systematic reviews and meta-analyses (33.44%), systematic reviews (33.05%), traditional meta-analyses (12.49%), expert consensuses (9.22%), narrative review (8.72%), and guidelines (2.82%). CONCLUSION: Both the composition and number of clinical studies changed significantly from 1991 to 2020. Based on the trend, the case report/series, case control study, and narrative review are on the decline, while cohort study, cross-sectional study, systematic reviews, and systematic review and meta-analysis literature have increased. To improve the quality of clinical evidence, we recommend RCT and cohort study give priority to access to allocated research resources in future.

Global influenza vaccination rates and factors associated with influenza vaccination.

OBJECTIVES: Influenza vaccination is an effective method for preventing influenza virus infection. Herein, we performed a meta-analysis to quantify global influenza vaccination rates (IVRs) and the factors influencing its uptake in the general population, individuals with chronic diseases, pregnant women, and healthcare workers. METHODS: Related articles were obtained from online databases and screened according to the inclusion criteria. The pooled IVRs were calculated using the random effects model. Subgroup analyses and multivariate meta-regression were performed to determine the factors associated with influenza vaccine uptake. RESULTS: We included 522 studies from 68 countries/regions. Most studies were conducted in the European region (247 studies), followed by the Western Pacific (135 studies) and American regions (100 studies). The IVRs with 95% confidence intervals (CIs) in the general population were lower (24.96%, 23.45%-26.50%) than in individuals with chronic diseases (41.65%, 40.08%-43.23%), healthcare workers (36.57%, 33.74%-39.44%), and pregnant women (25.92%, 23.18%-28.75%). The IVRs in high-income countries/regions were significantly higher than that in middle-income countries/regions. A free national or regional vaccination policy, perception of influenza vaccine efficacy and disease severity, a recommendation from healthcare workers, and having a history of influenza vaccination were positive factors for vaccine uptake (P <0.01). CONCLUSION: Overall, global IVRs were low, especially in the general population. The studies on the IVRs, especially for priority populations, should be strengthened in Eastern Mediterranean, South-East Asian, and African regions. Free vaccination policies and the dissemination of continuous awareness campaigns are effective measures to enhance vaccination uptake.

Accuracy of multitarget indirect enzyme-linked immunoassay assay for detection of tuberculosis antibody.

BACKGROUND: Diagnosis of tuberculosis (TB) is still difficult. The development of rapid and sensitive laboratory tools for the diagnosis of tuberculosis is a priority. This study aimed to develop an indirect enzyme-linked immunoassay (ELISA) assay for detection of TB antibody and explore its diagnostic value in patients with pulmonary tuberculosis (PTB) via a multi-center clinical evaluation. METHODS: The specific antigen, fusion antigen, and specific antibody peptide were obtained using molecular cloning and phage peptide library screening. An indirect ELISA assay was developed using multiple target materials. Further, the assay was validated in six institutions with clinically confirmed TB patients, non-TB patients with pulmonary disease, and healthy controls as research subjects. RESULTS: An indirect ELISA assay was developed with 16 kD antigen, 11,488 (CFP10-MPT48-TB8.4) fusion antigen, and TB18 and pl2 as target antigens against TB antibody. The results of this multicenter study showed that the sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) of the assay were 48.25% [95% confidence interval (CI): 45.5-51.1%], 92.20% (95% CI: 90.7-93.5%) and 0.724 (95% CI: 0.707-0.741), respectively, and the cut-off value was 0.119. According to the meta-analysis, the combined ROC was 0.736 (95% CI: 0.692-0.779), I2=83.73%. The sensitivity of the sputum-positive PTB group (culture or smear positive) was 58.75% (95% CI: 52.96-65.00%); the sensitivity in sputum-negative group (culture or smear negative) was 37.38% (95% CI: 32.71-42.52%), respectively; the sensitivity of the sputum-positive group was significantly higher than that of sputum-negative group (OR =1.57, 95% CI: 1.29-1.92, P<0.001). CONCLUSIONS: Multitarget indirect ELISA assay based on specific-TB antigen, fusion antigen, and antibody peptide is of value for the diagnosis of PTB and can be used as an auxiliary rapid diagnostic tool to improve the sensitivity of sputum-negative TB.

Diagnostic performance of microRNAs in testicular germ cell tumors: a systematic review and meta-analysis.

The sensitivity (Sen) of classic biomarkers for the diagnosis of testicular germ cell tumors (TGCTs) is currently low. Previous studies have shown the diagnostic potential of microRNAs (miRNAs) for TGCTs; however, the results of these studies are inconsistent. Therefore, we conducted a systematic review and meta-analysis to evaluate their diagnostic value. PubMed, EMBASE, Cochrane Library, and Web of Science databases were systematically searched until September 30, 2020 and 18 trials from 11 studies involving 2,068 participants were included in this meta-analysis. Using a bivariate mixed-effects meta-analysis model, the pooled Sen, specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) with 95% confidence interval values of total miRNAs were 0.83 (0.73-0.90), 0.95 (0.89-0.98), 15.79 (7.41-33.66), 0.18 (0.11-0.29), 87.13 (41.99-180.82), and 0.95 (0.93-0.97), respectively; however, the observed values of single miR-371a-3p were 0.84 (0.76-0.90), 0.95 (0.91-0.98), 18.41 (9.69-34.97), 0.17 (0.11-0.26), 111.56 (47.72-260.80), and 0.97 (0.95-0.98), respectively. Subgroup analysis revealed that miRNAs that included miR-371a-3p showed higher predictive performance than those that did not (P < 0.05). This research identified that miR-371a-3p has a high diagnostic value for TGCTs, except teratoma.

The Role of ß-Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis.

ß-Catenin is a key molecule of canonical Wnt/ß-catenin pathway. Its roles and expression profiles in T cells of tuberculosis (TB) remain unclear. The aim of this study was to explore the role of ß-catenin in CD4+ T cells and its expression characteristics in patients with pulmonary tuberculosis (PTB). In this study, CD4+ T cell-specific ß-catenin conditional knockout mice (ß-CAT-cKO mice) were aerosol infected with Mycobacteria tuberculosis (Mtb) H37RV with wild-type mice as controls. Four weeks after infection, the mRNA expression of IFN-γ, TNF-α, and TCF-7 in the lungs of mice was measured. CD4, CD8, ß-catenin, IFN-γ, and TNF-α in mononuclear cells from the lungs and spleens were measured by flow cytometry, and the pathological changes of lungs were also observed. Patients with PTB were enrolled, with blood samples collected and PBMCs isolated. The expressions of ß-catenin, IFN-γ, TNF-α, and PD-1 in CD4+ and CD8+ T cells were measured by flow cytometry. Results showed a decreased frequency of and reduced IFN-γ/TNF-α mRNA expression and secretion by CD4+ T cells in the lungs of infected ß-CAT-cKO mice compared with infected wild-type controls, and only slightly more inflammatory changes were observed in the lungs. ß-catenin expressions in CD4+ and CD8+ T cells were significantly decreased in blood cells of patients with severe PTB compared with those in mild PTB. The stimulation of peripheral blood mononuclear cells (PBMCs) with lithium chloride (LiCl), a stimulant of ß-catenin, resulted in the increase in CD4+ T cell frequency, as well as their secretion of IFN-γ and TNF-α. ß-Catenin demonstrated a moderately positive correlation with PD-1 in CD4+ T cells. ß-Catenin along with PD-1 and IFN-γ in CD4+ T cells had a high correlation with those in CD8+ T cells. In conclusion, ß-catenin may be involved in the regulation of Th1 response and CD4+ T cell frequency in TB.

The epidemiological and radiographical characteristics of asymptomatic infections with the novel coronavirus (COVID-19): A systematic review and meta-analysis.

OBJECTIVES: The role of asymptomatic infections in the transmission of COVID-19 have drawn considerable attention. Here, we performed a meta-analysis to summarize the epidemiological and radiographical characteristics of asymptomatic infections associated with COVID-19. METHODS: Data on the epidemiological and radiographical characteristics of asymptomatic infections were extracted from the existing literature. Pooled proportions with 95% confidence intervals were then calculated using a random effects model. RESULTS: A total of 104 studies involving 20,152 cases were included. The proportion of asymptomatic individuals among those with COVID-19 was 13.34% (10.86%-16.29%), among which presymptomatic and covert infections accounted for 7.64% (4.02%-14.04%) and 8.44% (5.12%-13.62%), respectively. The proportions of asymptomatic infections among infected children and healthcare workers were 32.24% (23.08%-42.13%) and 36.96% (18.51%-60.21%), respectively. The proportion of asymptomatic infections was significantly higher after 2020/02/29 than before (33.53% vs 10.19%) and in non-Asian regions than in Asia (28.76% vs 11.54%). The median viral shedding duration of asymptomatic infections was 14.14 days (11.25-17.04). A total of 47.62% (31.13%-72.87%) of asymptomatic infections showed lung abnormalities, especially ground-glass opacity (41.11% 19.7%-85.79%). CONCLUSIONS: Asymptomatic infections were more commonly found in infected children and healthcare workers and increased after 2020/02/29 and in non-Asian regions. Chest radiographical imaging could be conducive to the early identification of asymptomatic infections.

Comparison of HBV-DNA and HBeAg as antiviral therapeutic indicators among HBV-infected pregnant women: a systematic review and meta-analysis.

BACKGROUND: Hepatitis B virus deoxyribonucleic acid level (HBV-DNA) ≥5.3 log10IU/mL among pregnant women was recommended as an antiviral therapeutic indicator. However, implementation of HBV-DNA testing has varying difficulties in places. In this study, we explored the implementation rate of HBV-DNA testing worldwide, and possibility of hepatitis B e antigen (HBeAg) testing replacing HBV-DNA as an antiviral treatment indicator during pregnancy. METHODS: We searched five electronic databases including PubMed, Embase, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) for studies published between Jan 1, 2000, and Nov 16, 2020. Studies were eligible for inclusion if HBV DNA testing implementation rate is available, or if maternal HBV DNA level could be analyzed by HBeAg status. The rates were pooled after data was made a Freeman-Tukey double arcsine transformation. This study is registered with PROSPERO, CRD42021235711. RESULTS: A total of 9,575 studies were identified, 79 were finally included in this study. The HBV-DNA testing implementation rate was 36.6% (95% CI, 28.3-45.3%) globally. The rate of HBV-DNA ≥5.3 log10IU/mL was 81.51% (95% CI, 71.68-89.74%) among HBeAg positive pregnant women, and was 4.08% (95% CI, 2.14-6.54%) in HBeAg negative pregnant women. Even if infants were immunized with hepatitis B vaccine and hepatitis B immunoglobulin, the rate of mother-to-child transmission was still 4.87% (95% CI, 4.10-5.68%) among HBeAg positive mothers, and was 0 (95% CI, 0-0.07%) among HBeAg negative mothers, with a RR of 30.40 (95% CI, 11.31-81.72). CONCLUSIONS: The implementation rate of HBV DNA testing varies from region to region. Limited studies show that HBV DNA testing does not cover all pregnant women with hepatitis B. When HBV-DNA testing is not available, it is worth considering to use HBeAg positivity as an antiviral therapeutic indicator among HBV-infected pregnant women for preventing MTCT.

Concurrence and impact of hepatic steatosis on chronic hepatitis B patients: a systematic review and meta-analysis.

BACKGROUND: The association between hepatic steatosis (HS) and chronic hepatitis B (CHB) remains controversial. We performed a systematic review and meta-analysis to investigate the latest concurrence rate and impact of HS on CHB patients. METHODS: Relevant studies were identified by searching PubMed, EMBASE, and the Cochrane Library from January 1, 2000 to December 2, 2020. We calculated the pooled prevalence of HS in CHB patients using a random effects model. A subgroup analysis was performed to explore the impact of HS on CHB patients. This study is registered with PROSPERO (No. CRD42021242584). RESULTS: A total of 98 studies with a population of 48,472 patients were included. The global prevalence of HS in CHB patients was 34.93% [95% confidence interval (CI): 32.01-37.90%]. Overweight status, hypertension, diabetes, hyperlipidemia, and metabolic syndrome showed a higher risk for developing HS in CHB patients, while positive hepatitis B e antigen (HBeAg) status was negatively associated with the presence of HS [odds ratio (OR) =0.81, 95% CI: 0.70-0.93]. The pooled analysis showed no significant association between HS and fibrosis progression (OR =0.68, 95% CI: 0.44-1.05). However, the coexistence of HS was negatively associated with the antiviral therapy response in CHB patients, including virological response (OR =0.69, 95% CI: 0.48-0.99) and alanine aminotransferase (ALT) normalization (OR =0.44, 95% CI: 0.28-0.69). DISCUSSION: The global prevalence of HS in CHB patients is higher than previously estimated. The concurrence of HS could impact the replication of HBV and the effectiveness of antiviral therapy in CHB patients. However, coexistence with HS did not show a higher risk of developing advanced fibrosis in CHB patients.