Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Differences in epidemiological and clinical features between adult and pediatric tracheobronchial tuberculosis patients in Southwest China.

Background: Tracheobronchial tuberculosis (TBTB) is a common form of extrapulmonary tuberculosis that affects the tracheobronchial tree. However, the mechanism has not been fully elucidated. Comparisons of clinical characteristics in various age groups can aid in the understanding of TBTB. Methods: This retrospective study was conducted at the Public Health Clinical Center of Chengdu between July 2017 and December 2021, including adults and children with TBTB. Clinical data were extracted from medical records. T/T' test, Mann-Whitney U test, Chi-square test, or Fisher's exact test were used in this study. Results: This study enrolled 347 patients with TBTB (175 adults and 172 children). Adult females were more susceptible to TBTB, whereas gender-based differences were not observed in children. Children had a higher occurrence of irritant dry cough and fever, and acute hematogenous disseminated PTB, and specific types of EPTB, but a shorter interval before diagnosis, and lower diagnostic yields compared to adults (P < 0.05). Adults presented more extensive lung lesions and cavitations as compared to children. Granulation hyperplasia and lymph fistula were more frequently observed in children, as well as airway stenosis, but less severe. Conclusions: The study revealed important variations exist in multiple respects between adults and children with TBTB.

Expression Pattern and Prognostic Analysis of Branched-Chain Amino Acid Catabolism-Related Genes in Non-Small Cell Lung Cancer.

BACKGROUND: The purpose of our study is to analyze the expression pattern and prognostic value of catabolism-related enzymes of branched-chain amino acids (BCAAs) in non-small cell lung cancer (NSCLC). METHODS: Differential expression analysis, mutation, copy number variation (CNV), methylation analysis, and survival analysis of BCAAs catabolism-related enzymes in NSCLC were performed using the Cancer Genome Atlas (TCGA) database. RESULTS: Six and seven differentially expressed genes were obtained in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively. IL4I1 was located at the core regulatory nodes in the gene co-expression networks of both LUAD and LUSC. The AOX1 mutation rate was the highest in both LUAD and LUSC. For CNV, IL4I1 was up-regulated in both LUAD and LUSC with an increase in copy number, whereas AOX1 and ALDH2 were differentially regulated in the two subtypes of lung cancer. In patients with NSCLC, high expression of IL4I1 was associated with lower overall survival (OS), and low expression of ALDH2 predicted shorter disease-free survival (DFS). ALDH2 expression was related with LUSC survival. CONCLUSIONS: This study explored the biomarkers of BCAAs catabolism related to the prognosis of NSCLC, which provided a theoretical foundation to guide the clinical diagnosis and treatment of NSCLC.

Clinical-pathological features and perioperative outcomes of mediastinoscopy vs. thoracoscopy esophagectomy in esophageal cancer: A meta-analysis.

Objective: To compare the clinicopathological features and perioperative outcomes of video-assisted mediastinoscopy esophagectomy (VAME) compared to video-assisted thoracoscopy esophagectomy (VATE) in esophageal cancer. Methods: We comprehensively searched online databases (PubMed, Embase, Web of Science and Wiley online library) to find available studies exploring the clinicopathological features and perioperative outcomes between VAME and VATE in esophageal cancer. Relative risk (RR) with 95% confidence interval (CI) and standardized mean difference (SMD) with 95% CI were used to evaluate the perioperative outcomes and clinicopathological features. Results: A total of seven observational studies and one randomized controlled trial involving 733 patients were considered eligible for this meta-analysis, of which 350 patients underwent VAME in contrast to 383 patients underwent VATE. Patients in the VAME group had more pulmonary comorbidities (RR = 2.18, 95% CI 1.37-3.46, P = 0.001). The pooled results showed that VAME shortened the operation time (SMD = -1.53, 95% CI -2.308--0.76, P = 0.000), and retrieved less total lymph nodes (SMD = -0.70, 95% CI -0.90--0.50, P = 0.000). No differences were observed in other clinicopathological features, postoperative complications or mortality. Conclusions: This meta-analysis revealed that patients in the VAME group had more pulmonary disease before surgery. The VAME approach significantly shortened the operation time and retrieved less total lymph nodes and did not increase intra- or postoperative complications.

A one-year follow-up study on dynamic changes of leukocyte subsets and virus-specific antibodies of patients with COVID-19 in Sichuan, China.

Background: SARS-CoV-2 infection causes immune response and produces protective antibodies, and these changes may persist after patients discharged from hospital. Methods: This study conducted a one-year follow-up study on patients with COVID-19 to observe the dynamic changes of circulating leukocyte subsets and virus-specific antibodies. Results: A total of 66 patients with COVID-19 and 213 healthy patients with inactivated SARS-CoV-2 vaccination were included. The virus-specific total antibody, IgG and IgM antibody of patients after one year of recovery were higher than those of healthy vaccinated participants (94.13 vs 4.65, 2.67 vs 0.44, 0.09 vs 0.06, respectively) (P < 0.001). Neutrophil count (OR = 1.73, 95% CI: 1.10-2.70, P = 0.016) and neutrophil-to-lymphocyte ratio (OR = 1.59, 95% CI: 1.05-2.41, P = 0.030) at discharge were the influencing factors for the positivity of virus-specific IgG antibody in patients after one year of recovery. The counts of CD4+ and CD8+ T, B and NK cells increased with the time of recovery, and remained basically stable from 9 to 12 months after discharge. After 12 months, the positivity of IgG antibody was 85.3% and IgM was 11.8%, while the virus-specific antibody changed dynamically in patients within one year after discharge. Conclusions: The SARS-CoV-2 specific antibody of recovered patients showed dynamic fluctuation after discharge, while the leukocyte subsets gradually increased and basically stabilized after 9 months.

High Number and Specific Comorbidities Could Impact the Immune Response in COVID-19 Patients.

Background: Cellular immunodeficiency and comorbidities are common in COVID-19 patients. Aim: The purpose of this study was to investigate comorbidities impacting on the cellular immunity in COVID-19 patients. Methods: The research objects included 55 healthy controls and 718 COVID-19 patients who divided into the control group and the COVID-19 group, respectively. Those in the COVID-19 group were divided into subgroups on the basis of the number and types of comorbidities present. Lymphocyte itself and its subsets were compared between the control group and the COVID-19 group, the groups with comorbidities based on the different number and types of comorbidities, and the relationship between the lymphocyte counts and subsets with the number and types of comorbidities was investigated. Results: Compared with the control group, the lymphocyte counts and T cell subsets were significantly increased in the groups with comorbidities, but both B and NK cell subsets were significantly decreased in the no comorbidity group and in most of the groups with comorbidities (all P<0.05). In the three comorbidities group, the lymphocyte counts and T cell subsets were all significantly decreased, but the CD56+ percentage was obviously increased (all P<0.05). The number of comorbidities was negatively correlated with the lymphocyte counts and the T and NK cell subsets. A negative correlation also existed between cancer and both the lymphocyte counts and the T cell subsets, between chronic hepatitis B and the lymphocyte counts, and between chronic kidney disease and the CD3+ counts. A positive correlation existed between nonalcoholic fatty liver disease (NAFLD) disease and both lymphocyte and CD3+ counts. The risk factors were number of comorbidities for the lymphocyte count, CD3+CD4+ and CD3+CD8+ percentages, NAFLD for the lymphocyte and CD3+ counts, cardiovascular diseases for CD3+CD4+ and CD3+CD8+ percentages, diabetes mellitus for the CD3+CD8+ percentage, and cancer for the CD3+ percentage, respectively. Conclusions: High numbers of comorbidities and specific comorbidities could impact the immune response of COVID-19 patients. This study provides a reference for clinicians in the identification of suitable and timely immunotherapy for COVID-19 patients. Clinical Trial Registry: https://www.chictr.org.cn/enindex.aspx, identifier ChiCTR2000034563.

Bioinformatics Analysis to Reveal Potential Differentially Expressed Long Non-Coding RNAs and Genes Associated with Tumour Metastasis in Lung Adenocarcinoma.

BACKGROUND: Due to the onset of metastases, the survival rate of lung adenocarcinoma (LUAD) is still low. In view of this, we performed this study to screen metastasis-associated genes and lncRNAs in LUAD. METHODS: The mRNA and lncRNA expression profiles of 185 metastatic LUAD and 217 non-metastatic LAUD samples were retrieved from the TCGA database and included in this study. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between metastatic samples and non-metastatic samples of LAUD, as well as the cis nearby-targeted DEmRNAs of DElncRNAs and the DElncRNA-DEmRNA co-expression network, were obtained. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of selected DEmRNAs. Survival analysis of selected DElncRNAs and DEmRNAs was performed. RESULTS: In total, 1351 DEmRNAs and 627 DElncRNAs were screened between the LUAD primary tissue samples and metastatic samples. Then, 194 DElncRNA-nearby-targeted DEmRNA pairs and 191 DElncRNA-DEmRNA co-expression pairs were detected. Except for RHCG and KRT81, the expression of the other six DEmRNAs in the qRT-PCR results generally exhibited the same pattern as that in our integrated analysis. The expression of CRHR2, FAM83A-AS1, FAM83A and Z83843.1 was significantly correlated with the overall survival time of patients with metastatic LUAD. CONCLUSION: We speculate that two interaction pairs (FAM83A-AS1-FAM83A and Z83843.1-MATR3) and four genes (CRHR2, UGT2B15, CHGB and NEFL) are closely associated with the metastasis of LUAD.