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.

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.

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.

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.

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.

Effects of inflammatory and anti-inflammatory environments on the macrophage mitochondrial function.

Mitochondrial response to inflammation is crucial in the metabolic adaptation to infection. This study aimed to explore the mitochondrial response under inflammatory and anti-inflammatory environments, with a focus on the tricarboxylic acid (TCA) cycle. Expression levels of key TCA cycle enzymes and the autophagy-related protein light chain 3b (LC3b) were determined in raw 264.7 cells treated with lipopolysaccharide (LPS) and metformin (Met). Additionally, reactive oxygen species (ROS) levels and mitochondrial membrane potential were assessed using flow cytometry. Moreover, 8-week-old C57BL/6J mice were intraperitoneally injected with LPS and Met to assess the mitochondrial response in vivo. Upon LPS stimulation, the expression of key TCA enzymes, including citrate synthase, α-ketoglutarate dehydrogenase, and isocitrate dehydrogenase 2, and the mitochondrial membrane potential decreased, whereas the levels of LC3b and ROS increased. However, treatment with Met inhibited the reduction of LPS-induced enzyme levels as well as the elevation of LC3b and ROS levels. In conclusion, the mitochondrial TCA cycle is affected by the inflammatory environment, and the LPS-induced effects can be reversed by Met treatment.

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.

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.

Comparative efficacy and safety of low-intensity warfarin therapy in preventing unprovoked recurrent venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Although there exists potential risk of bleeding, extended 'lifelong' conventional-intensity [international normalized ratio (INR): 2.0-3.0] warfarin anticoagulation is recommended for unprovoked venous thromboembolism (VTE) patients because of risk of recurrent VTE. Whether long-term low-intensity (INR: 1.5-2.0) warfarin therapy reduced the risk of major bleeding without substantially lowered antithrombotic efficacy is not well understood. The aim of this study was to perform a systematic review and meta-analysis to evaluate the risk-benefits of low-intensity warfarin therapy. METHODS: We conducted a comprehensive search of electronic databases and included randomized control trials (RCTs) that reported efficacy (recurrent VTE) and safety (bleeding episodes) of low-intensity warfarin therapy compared with conventional-intensity warfarin or placebo from inception through Jun 2016. RESULTS: Four RCTs reporting high GRADE quality evidence were included. Although the relative risk of recurrent VTE with low-intensity therapy was significantly increased [2.96 (95% CI: 1.40 to 6.24), P < .004] compared to conventional-intensity warfarin, there was significant decrease of relative risk when compared with placebo [0.37 (95% CI: 0.24 to 0.56), P < .00001]. As per included publications, no significant major bleeding episodes were observed in low-intensity warfarin group. CONCLUSIONS: Although less effective than conventional-intensity warfarin therapy this meta-analysis indicates that long-term low-intensity warfarin therapy is highly effective for preventing recurrent VTE than placebo, along with reduced risks of major bleeding and minimizing potential complications.

Comparative effectiveness of sildenafil for pulmonary hypertension due to left heart disease with HFrEF.

There is no cure for pulmonary hypertension due to left heart disease (PH-LHD), but the rationale for using sildenafil to treat pulmonary arterial hypertension with heart failure with reduced ejection fraction (HFrEF) has been supported by short-term studies. We performed a meta-analysis to evaluate the effectiveness of sildenafil for PH-LHD with HFrEF. A systematic literature search of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials was conducted from inception through October 2014 for randomized trials and for observational studies with control groups, evaluating the effectiveness of sildenafil to treat PH-LHD with HFrEF. Sildenafil therapy decreased pulmonary arterial systolic pressure both at the acute phase and at the 6-month follow-up (weighted mean difference (WMD): -6.03 mm Hg, P=0.02; WMD: -11.47 mm Hg, P<0.00001, respectively). Sildenafil was found to reduce mean pulmonary artery pressure (WMD: -3 mm Hg, P=0.0004) and pulmonary vascular resistance (WMD: -60.0 dynes cm(-5), P=0.01) at the 3-month follow-up. Oxygen consumption at peak significantly increased to 3.66 ml min(-1) kg(-1) (P<0.00001), 3.36 ml min(-1) kg(-1) (P<0.00001) and 2.60 ml min(-1) kg(-1) (P=0.03) at 3, 6 and 12 months, respectively. There were significant reductions in ventilation to CO2 production slope of -2.00, -4.68 and -7.12 at 3, 6 and 12 months, respectively (P<0.00001). Sildenafil was superior to placebo regarding left ventricular ejection fraction at the 6-month follow-up (WMD: 4.35, P<0.00001), and it significantly improved quality of life. Sildenafil therapy could effectively improve pulmonary hemodynamics and cardiopulmonary exercise testing measurements of PH-LHD with HFrEF, regardless of acute or chronic treatment.

Genetic polymorphisms of ERCC1­118, XRCC1­399 and GSTP1­105 are associated with the clinical outcome of gastric cancer patients receiving oxaliplatin­based adjuvant chemotherapy.

The aim of the present study was to determine whether specific molecular parameters may serve as predictors of treatment outcomes and toxicity of oxaliplatin (OXA)­based chemotherapy, which is used as an adjuvant treatment in resected gastric cancer. All gastric cancer patients examined in the study received an OXA/5­fluorouracil chemotherapeutic regimen. Genetic polymorphisms of certain platinum­related genes were determined by the TaqMan 5' nuclease assay and direct sequencing. Relapse­free survival (RFS), overall survival (OS) and toxicity were evaluated according to each genotype. Following adjustment for the most relevant clinical variables, excision repair cross­complimentary group 1 (ERCC1)­118 and X-ray repair cross-complementing protein 1 (XRCC1­399) demonstrated significant predictive value for RFS and OS. We also demonstrated that carrying at least one variant XRCC1 Arg399Gln or glutathione S-transferase π 1 (GSTP1) Ile105Val allele significantly increased the risk of any grade 3 or 4 hematological toxicity. In particular, carrying at least one variant GSTP1 Ile105Val allele was also significantly correlated with an increased risk of grade 3 or 4 gastrointestinal toxicity and neurotoxicity. Our data suggested that gastric cancer patients harboring ERCC1­118 C/C and XRCC1­399 A/G or A/A genotypes may benefit from receiving OXA­based adjuvant chemotherapy, and carrying at least one variant XRCC1 Arg399Gln or GSTP1 Ile105Val allele may contribute to the occurrence of adverse drug effects associated with OXA­based chemotherapy.

The effects of ERCC1 expression levels on the chemosensitivity of gastric cancer cells to platinum agents and survival in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy.

Excision repair cross-complementing 1 (ERCC1) is reported to be involved in the sensitivity of cancer cells to platinum-based chemotherapy. The present study was designed to evaluate the effects of ERCC1 expression on the chemosensitivity of platinum agents in gastric cancer cell lines, and on survival in gastric cancer patients treated with surgery followed by oxaliplatin-based adjuvant chemotherapy. ERCC1 expression levels were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. The chemosensitivity of a series of gastric cancer cell lines to platinum agents in vitro was evaluated using CellTiter 96 Aqueous One Solution Cell Proliferation Assay kit. The apoptotic effect of the drugs was evaluated by double staining with Annexin-V-fluorescein isothiocyanate (FITC) and propidium iodide (PI). The results demonstrated that the expression levels of ERCC1 mRNA were correlated with the chemosensitivity of platinum agents, and depletion of ERCC1 sensitized the relatively resistant MKN45 cells to cisplatin and oxaliplatin. Univariate analyses revealed that patients with low ERCC1 levels had longer relapse-free survival (RFS) and overall survival (OS) than those with high ERCC1 levels (median RFS, 18 vs. 7 months, P=0.001; median OS, 27 vs. 11 months, P=0.001). Multivariate analyses suggested that high ERCC1 expression is an independent prognostic marker of poor RFS [hazard ratio (HR), 2.16; 95% confidence interval (CI), 1.09-4.25; P= 0.026] and OS (HR, 2.21; 95% CI, 1.07-4.55; P=0.031). These results suggest that overexpression of ERCC1 is correlated with platinum drug resistance in gastric cancer cells, and that depletion of ERCC1 sensitizes gastric cancer cell lines to cisplatin and oxaliplatin. Gastric cancer patients with low levels of ERCC1 expression demonstrate a benefit from oxaliplatin-based adjuvant chemotherapy.

Characteristics of general distribution of hepatitis B virus genotypes in China.

BACKGROUND: Based on differences in the virus nucleotide sequence, hepatitis B virus (HBV) genotypes are presently divided into genotypes A-H. The geographic distributions of HBV genotypes differ in countries and regions. To determine the general characteristics of their distributions in the mainland of China, we reviewed articles on HBV genotypes published in China. METHODS: The Wanfang Database and the CNKI Database were searched for original articles involving HBV in China, and then the data from the articles were classified according to genotype and latitude and analyzed using SPSS 11.0. RESULTS: The main HBV genotypes were C, B and BC, and their rates were 50.99%, 35.58%, 6.07%, respectively; other genotypes were rare. There was a negative correlation between latitude and the rate of genotype B (r=-0.782, P<0.01), while a positive correlation existed between latitude and the rate of genotype C (r=0.646, P<0.01). No correlation was observed between latitude and the rates of other genotypes (r=0.294, P>0.05). CONCLUSIONS: In China, HBV genotype C predominates, followed by genotype C and mixed genotype BC; genotypes A, D and others are rare. With an increasing latitude, the distribution of genotype B decreases gradually, while that of genotype C tends to increase. The other genotypes do not show any changes.