Efficacy and Safety of Chinese Medicine Resuscitation Pack for Enhanced Recovery after Bronchoscopy: A Randomized, Single-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS: Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).

The ethnopharmacology, phytochemistry, pharmacology and toxicology of the genus Erycibe (Convolvulaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Erycibe belongs to the Convolvulaceae family that contains approximately 70 species mainly distributed from tropical and subtropical Asia to north of Australia. Several Erycibe species are traditionally used in folk medicine for the treatment of various ailments, including rheumatic arthralgia, primary glaucoma, hepatopathies, and infectious and malignant diseases. AIM OF THE REVIEW: This review aims to summarize comprehensive and updated information on traditional medicinal uses, phytochemistry, pharmacology, and toxicology of Erycibe species to provide a reference for the further research and application of the Erycibe genus. MATERIALS AND METHODS: The scientific and extensive literatures between 1975 and 2020 were systematically gathered from scientific databases such as SciFinder Scholar, Science Direct, Web of Science, PubMed, Google Scholar, Scopus, Springer Link and China National Knowledge Infrastructure (CNKI), as well as Chinese herbal classic books, PhD and MSc theses, and several official websites. RESULTS: Erycibe species have been used for the treatment of various rheumatoid diseases, glaucoma, a variety of hepatic diseases, infectious diseases and various malignancies in the traditional and local medicine. Since the 1970s, 153 compounds, including coumarins, quinic acid derivatives, flavonoids, alkaloids, lignans, and others have been isolated from five species of the Erycibe genus. Pharmacological studies have shown that these extracts and compounds from the Erycibe genus have extensive activities consistent with the traditional and local applications, such as anti-glaucoma, anti-arthritic, hepatoprotective and anti-cancer activities, as well as anti-inflammatory, anti-respiratory syncytial virus (RSV), and neuroprotective properties. CONCLUSIONS: Although there are extensive data on the genus Erycibe, certain specific gaps still exist. For herbal preparations containing Erycibe species, clinical toxicological investigation is required for the safety of these herbal preparation therapies, as well as further investigations on pharmacokinetics and bioavailability for guideline for clinical application. Furthermore, more detailed pharmacological, toxicological and clinical researches are needed to assess the alternatives to Erycibe species. Systematic and comprehensive pre-clinical studies are similarly required to estimate the possibility of extracts and compounds from the genus Erycibe with bioactivity developing into new drugs.

Herbal Medicine for Adult Patients with Cough Variant Asthma: A Systematic Review and Meta-Analysis.

INTRODUCTION: Herbal medicine is commonly used by patients with chronic cough, but the role of herbal medicine for cough variant asthma (CVA) has not yet been clearly defined. For the first time, we performed a meta-analysis to integrate the current evidence of randomized controlled trials (RCTs) on this topic and assess the efficacy of herbal medicine in adults with CVA. METHODS: A comprehensive search was conducted in electronic databases to identify RCTs of herbal medicine for adult CVA. Cochrane systematic review methods were followed, and the Grading of Recommendations Assessment, Development, and Evaluation was performed to evaluate the quality of evidence. RESULTS: Twenty-eight RCTs were included. Compared with placebo, moderate-quality evidence from two studies showed that herbal medicine was associated with reduced cough symptom score (CSS) (MD -1.15 points; 95% CI, -1.67 to -0.63) and visual analogue scale (VAS) (MD -1.76 points; 95% CI, -2.66 to -0.86). Compared with montelukast, low- to moderate-quality evidence from 11 studies indicated that herbal medicine was associated with improved Leicester Cough Questionnaire (LCQ) (MD 2.38 points; 95% CI, 1.32 to 3.44), reduced CSS (SMD -0.81 points; 95% CI, -1.09 to -0.53), and VAS (MD -1.34 points; 95% CI, -1.82 to -0.86). There were no significant differences between herbal medicine and ICS plus bronchodilator. CONCLUSIONS: In adults with CVA, herbal medicine may result in improved quality of life and reduced cough frequency and severity scores compared with placebo or montelukast. Herbal medicine was not better than ICS plus a bronchodilator but the evidence is very uncertain.

Diagnostic value of the hypertonic saline bronchial provocation test in children with asthma using the high-power aerosol provocation system.

Objective: This study aimed to evaluate the diagnostic value of the modified hypertonic saline bronchial provocation test (HS-BPT) for children with asthma by using the high-power Aerosol Provocation System (APS).Methods: A total of 330 children suspected of having asthma and receiving HS-BPT-APS were included in this prospective survey conducted in Guangzhou, China from February 2017 to September 2018. The positive rate of HS-BPT-APS and the volume and types of adverse reactions were observed. There was also a retrospective cohort of 123 children with suspected asthma who underwent a methacholine BPT from 2015 to 2017. Using the method of nearest neighbor matching, a comparison was made of the positive rate and adverse reaction between the methacholine BPT group and HS-BPT-APS group.Results: The total positive rate of HS-BPT-APS was 43.9%. Common adverse reactions included cough, wheezing and chest tightness. There were no serious adverse reactions. Results of nearest neighbor matching showed a difference in the positive rate between the methacholine BPT group and HS-BPT-APS group (8.1% vs 18.2%, p = 0.026), but there was no statistically significant difference between the age groups in patients who received the methacholine BPT or HS-BPT-APS. There was a similar adverse reaction rate in the two groups (p = 0.609).Conclusions: HS-BPT-APS is simple, safe, and time-saving, with few adverse reactions. The positive rate of HS-BPT-APS was higher than that of methacholine BPT in children with asthma. HS-BPT-APS may be a valuable tool in the diagnosis of children with asthma, and further study is required.

Is Chinese Medicine Injection Applicable for Treating Acute Lung Injury and Acute Respiratory Distress Syndrome? A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the efficacy and safety of Chinese medicine injection (CMI) for treating acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Randomized controlled trials (RCTs) were identified by searching 3 English databases and 4 Chinese databases from their inceptions until February 2019. The Cochrane Handbook was used to evaluate risk of bias in the included studies. Data analysis was conducted using RevMan 5.3.3 software. RESULTS: A total of 19 eligible RCTs involving 1,334 participants was included in this systematic review and meta-analysis. The main meta-analysis showed that CMI combined with conventional therapy (CT) was more effective than CT alone in reducing the acute physiology and chronic health evaluation (APACHE) H score [mean difference (MD): -1.74 points, 95% confidence interval (CI): -2.77 to -0.71, I2=0] and increasing the total effective rate [relative risk (RR): 1.35, 95% CI: 1.17 to 1.56, I2=37%]. Compared with CT, CMI combined with CT showed improvements in the arterial partial pressure of oxygen (PaO2, MD: 9.25 mm Hg, 95% CI: 0.87 to 17.63, I2=98%) and oxygenation index [arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2), MD: 50.75 mm Hg, 95% CI: 35.18 to 66.31, I2=94%]. CMI plus CT was superior to CT in reducing the systemic inflammatory response syndrome (SIRS) score (MD: -0.84 points, 95% CI: -1.26 to -0.42, I2=65%), length of hospital stay (MD: -4.22 days, 95% CI: -6.49 to -1.95, I2=92%), and duration of mechanical ventilation (MD: -2.94 days, 95% CI: -4.68 to -1.21, I2=89%). Only 1 study reported adverse events. CONCLUSIONS: CMI as an adjuvant therapy showed great potential benefits for the treatment of ALI/ARDS. However, we could not make a definite conclusion due to low quality of included studies and uncertain security. Future studies should focus on improving research design, especially in blindness and placebo. The reporting of adverse events was also needed.

ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC), one of the most aggressive cancers, is characterized by heterogeneous genetic and epigenetic changes. Recently, A-to-I RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), was found to be aberrantly regulated during tumorigenesis. We previously reported that ADAR2 was downregulated in ESCC but its role was unclear. Thus, we report here that overexpression of ADAR2 can induce apoptosis in ESCC cell lines and inhibit tumor growth in vitro and in vivo. ADAR2 knockdown inhibited apoptosis in ADAR2 highly expressing tumor cells. RNA-seq assay showed that ADAR2, not ADAR1 or active-site-mutated ADAR2, could edit insulin-like growth factor binding protein 7 (IGFBP7) mRNA in ESCC. IGFBP7 knockdown or ADAR2 catalytic activity destruction abolished the pro-apoptotic function of ADAR2. Mechanistically, RNA editing may stabilize IGFBP7 protein by changing the protease recognition site of matriptase and this is essential for IGFBP7 to induce apoptosis. Western blotting revealed that ADAR2 overexpression could induce IGFBP7-dependent inhibition of Akt signaling. Thus, our data indicate that ADAR2 suppresses tumor growth and induces apoptosis by editing and stabilizing IGFBP7 in ESCC, and this may represent a novel therapeutic target for treating ESCC.

A comprehensive genomic characterization of esophageal squamous cell carcinoma: from prognostic analysis to in vivo assay.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide and is characterized by numerous genetic mutations. TNM staging is not sufficient for predicting patient outcomes. Additionally, ESCC shows poor responsiveness to chemotherapy and radiation. Thus, there is an urgent need to find efficient therapy targets. Previous ESCC high-throughput genomic studies have lacked intensive survival analysis, particularly for copy number variation (CNV) and the genes involved. MAIN BODY: In the study "Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis" recently published in the American Journal of Human Genetics, we comprehensively analyzed the effects of CNVs, mutations, and relative gene expression on patient outcomes. To validate our findings for our 67 sequencing samples, we collected a 321-patient retrospective cohort with detailed 5-year follow-up information and carried out univariate and multivariate survival analyses. In addition, the biological functions of the survival predictors in ESCC were investigated both in vitro and in vivo. CONCLUSIONS: We found the independent ESCC survival predictors and potential therapy targets. Nevertheless, the effects of numerous low-frequency mutations need to be explored using larger sample sequencing. Overall, constructing multi-gene prognostic signatures will remain a great challenge in the future.

Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis.

The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.

Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients.

Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/ß-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16(INK4a). Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway.

Long non-coding RNAs (LncRNAs) have been recently found to be pervasively transcribed in the genome and critical regulators of the epigenome. HOTAIR, as a well-known LncRNA, has been found to play important roles in several tumors. Herein, the clinical application value and biological functions of HOTAIR were focused and explored in esophageal squamous cell carcinoma (ESCC). It was found that there was a great upregulation of HOTAIR in ESCC compared to their adjacent normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a significantly poorer prognosis than those with low expression. Moreover, HOTAIR was further validated to promote migration and invasion of ESCC cells in vitro. Then some specific molecules with great significance were investigated after HOTAIR overexpression using microarray and quantitative real time-polymerase chain reaction (qPCR). WIF-1 playing an important role in Wnt/ß-catenin signaling pathway was selected and further tested by immunehistochemistry. Generally, inverse correlation between HOTAIR and WIF-1 expression was demonstrated both in ESCC cells and tissues. Mechanistically, HOTAIR directly decreased WIF-1 expression by promoting its histone H3K27 methylation in the promoter region and then activated the Wnt/ß-catenin signaling pathway. This newly identified HOTAIR/WIF-1 axis clarified the molecular mechanism of ESCC cell metastasis and represented a novel therapeutic target in patients with ESCC.

[Effect of Nervilla fordii on lung aquaporin 1 and 5 expression in endotoxin-induced acute lung injury rat].

OBJECTIVE: To explore the protective mechanism of Nervilia fordii (NF) by observing the effect of its pretreatment on lung aquaporin 1 and 5 (AQP-1, AQP-5) expression in rats with endotoxin-induced acute lung injury (ALI). METHODS: Twenty-four SD rats were randomly divided into 3 groups, the normal group (A), the NF pre-intervention group (B) and the endotoxin model group (C). Rats in Group B and C were made into ALI by endotoxin (5 mg/kg) injection via sublingual vein, and NF pretreatment was applied to Group B. Animals were sacrificed at the 8 h after modeling, their lung were taken for observing the water permeability change by wet/dry weight ratio (W/D) measuring, pathological feature by HE staining, and the expression of AQP-1, AQP-5 was detected by immunohistochemistry and RT-PCR. RESULTS: The W/D ratio of lung was higher in model rats than in normal rats, but as compared with Group C, it was significantly lower (P < 0.05) in Group B. The pulmonary edematous change was significantly mild and the AQP-1 and AQP-5 protein expressions were significantly higher in Group B than in Group C (P < 0.05). CONCLUSION: NF pretreatment can promote lung AQP-1 and AQP-5 expression up-regulation, increase lung water clearance and transportation to improve the water balance and eliminate pulmonary edema, so as to effectively protect lung from acute injury.