Wenyang Huazhuo Tuihuang Formula Inhibits the Th17/Treg Cell Imbalance and Protects against Acute-on-Chronic Liver Failure.

Objective: Acute-on-chronic liver failure (ACLF) is a group of chronic liver diseases and caused by acute internal and external liver injury. Wenyang Huazhuo Tuihuang (WYHZTH) formula had a good clinical effect on promoting the resolution of jaundice. The aim of this study is to further investigate the mechanism of the WYHZTH formula in the ACLF rat model. Methods: The ACLF rat model was constructed by combining human serum albumin with LPS and D-gal. WYHZTH was used to intervene and treat. The cytokines IL-17, IL-23, IL-10, and TGF-ß were detected by ELISA and fluorescence-quantitative PCR. Flow cytometry was used to detect the percentage of Th17 and Treg cells in the peripheral blood and liver tissues of each group of rats. The pathological changes in the liver tissue were detected by hematoxylin-eosin staining, immunohistochemistry, and electron microscopy. Results: Compared with the ACLF group, the WYHZTH formula and Thy significantly decreased the levels of ALT, AST, and CHE in the ACLF group. After drug intervention, apoptosis was significantly reduced. The PCNA expression decreased in the ACLF model group but increased in the WYHZTH or Thy group. Under transmission electron microscope, hepatocytes in the ACLF group showed obvious necrosis. After drug intervention, hepatocyte necrosis was reduced with most of the structure returning to normal. Conclusion: This present study demonstrated that WYHZTH formula may protect against acute-on-chronic liver failure, which may be related to the inhibition of Th17/Treg cell imbalance.

SNHG17 upregulates WLS expression to accelerate lung adenocarcinoma progression by sponging miR-485-5p.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been uncovered to be essential regulators in the biological processes of human cancers, including lung adenocarcinoma (LUAD). Recently, small nucleolar RNA host gene 17 (SNHG17) has been identified as one novel oncogenic lncRNA in gastric cancer. However, it remains unclear whether SNHG7 exert functions in LUAD progression. METHODS: The expression levels of SNHG17, miR-485-5p and Wnt ligand secretion mediator (WLS) in LUAD cells was evaluated by RT-qPCR. The effect of SNHG7 silencing on LUAD cell proliferation was assessed by colony formation and EdU assays. The apoptosis of LUAD cells was measured by flow cytometry analysis. Transwell assays were applied to detect cell migration and invasion. The relationship between SNHG17 and miR-485-5p was validated by RIP, RNA pull down and luciferase reporter assays. RESULTS: SNHG17 and WLS were up-regulated in LUAD cell lines. Down-regulation of SNHG17 curbed LUAD cell proliferation, migration and invasion but facilitated apoptosis. SNHG17 acted as miR-485-5p sponge to upregulate WLS expression. CONCLUSION: SNHG17 triggers the progression of LUAD via sponging miR-485-5p to upregulate WLS expression.

Efficacy and safety of Qing-Feng-Gan-Ke Granules in patients with postinfectious cough: study protocol of a novel-design phase III placebo-controlled, double-blind randomized trial.

BACKGROUND: Postinfectious cough (PIC) is a common condition that affects millions of people worldwide every year. There is Western medicine for this condition but the treatment effect is often incomplete. Traditional Chinese medicine (TCM) has been increasingly prescribed for patients with PIC. Preliminary trials on Qing-Feng-Gan-Ke-Granules (QFGKG) conveyed promising results in treating PIC. This protocol describes an ongoing phase III randomized controlled clinical trial, designed according to a novel methodology of "one study, one primary outcome", with the objective of evaluating the efficacy and safety of QFGKG in patients suffering from PIC. METHODS/DESIGN: This is a multicenter, phase III, randomized, double-blind, parallel-group, placebo-controlled clinical trial, comprising two simultaneously conducted study parts, part A and part B, intending to investigate two primary outcomes, i.e. time to cough resolution and cough symptom score, respectively. A total of 480 patients, aged 18 to 65 years, who complain of an ongoing persistent cough that has been lasting ≥ 3 weeks, will be recruited from six participating sites and then randomized to receive QFGKG 12.0 g twice daily or placebo 12.0 g twice daily. Each part will enroll 240 patients, with 180 patients being allocated to the QFGKG group and 60 to the placebo group. DISCUSSION: Although traditional Chinese medicine is a structured intervention that has shown some promise in treating persistent cough, existing unconvincing evidence has noted limitations. This is a rare well-designed and rigorously-controlled, randomized, double-blind trial to evaluate the effects and safety of a Chinese herbal medicine in patients with postinfectious cough, providing tangible benefits for clinical research. Results of this trial are inclined to be conjectured as more truthful by implementing separate study parts that specifically estimate exclusive primary outcome. It will not only provide robust clinical evidence on the efficacy and safety of QFGKG for postinfectious cough, but will also provide a critical piece of information on the availability and superiority of a novel methodology for future clinical trials. The current trial is ongoing with recruitment of the predetermined number of patients being in progress. TRIAL REGISTRATION: The two parts of this trial were separately registered with the Chinese Clinical Trial Registry: ChiCTR-TRC-13003278 (part A); and ChiCTR-TRC-13003337 (part B).

Baicalin Inhibits Lipopolysaccharide-Induced Inflammation Through Signaling NF-κB Pathway in HBE16 Airway Epithelial Cells.

Baicalin, a flavonoid monomer derived from Scutellaria baicalensis called Huangqin in mandarin, is the main active ingredient contributing to S. baicalensis' efficacy. It is known in China that baicalin has potential therapeutic effects on inflammatory diseases. However, its anti-inflammatory mechanism has still not been fully interpreted. We aim to investigate the anti-inflammatory effect of baicalin on lipopolysaccharide (LPS)-induced inflammation in HBE16 airway epithelial cells and also to explore the underlying signaling mechanisms. The anti-inflammatory action of baicalin was evaluated in human airway epithelial cells HBE16 treated with LPS. Airway epithelial cells HBE16 were pretreated with a range of concentrations of baicalin for 30 min and then stimulated with 10 µg/ml LPS. The secretions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in cell culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of IL-6, IL-8, and TNF-α were tested by quantitative real-time polymerase chain reaction (real-time RT-PCR). Furthermore, Western blotting was used to determine whether the signaling pathway NF-κB was involved in the anti-inflammatory action of baicalin. The inflammatory cell model was successfully built with 10 µg/ml LPS for 24 h in our in vitro experiments. Both the secretions and the mRNA expressions of IL-6, IL-8, and TNF-α were significantly inhibited by baicalin. Moreover, the expression levels of phospho-IKKα/ß and phospho-NF-κB p65 were downregulated, and the phospho-IκB-α level was upregulated by baicalin. These findings suggest that the anti-inflammatory properties of baicalin may be resulted from the inhibition of IL-6, IL-8, and TNF-α expression via preventing signaling NF-κB pathway in HBE16 airway epithelial cells. In addition, this study provides evidence to understand the therapeutic effects of baicalin on inflammatory diseases in clinical practice.

Modified Yupingfeng formula for the treatment of stable chronic obstructive pulmonary disease: a systematic review of randomized controlled trials.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), is a very common disease of respiratory system. An increasing number of clinical trials on Yupingfeng formula in the management of stable COPD have been performed. However, the evidence base for it remains unknown. This review aims at assessing the efficacy, and safety of modified Yupingfeng formula in the treatment of stable COPD through a systematic review of all available randomized controlled trials. MATERIALS AND METHODS: Literature retrieval was conducted using four English databases (CENTRAL, PubMed, EMBASE, and ISI Web of Science), and four Chinese databases (CBM, CNKI, VIP, and WANFANG), from respective inception to January 2013, and supplemented with a manual search. Review authors independently extracted the trial data, and assessed the quality of each trial. Methodological quality was assessed by Cochrane risk of bias and Jadad's scale. The following outcomes were evaluated: (1) lung function; (2) 6-minute walk distance (6MWD); (3) effective rate; (4) serum levels of IgA, IgG and IgE; and (5) adverse events. Data were analyzed using STATA 12.0 software. RESULTS: A total of nine studies involving 660, stable COPD patients were identified. Patients from all studies included in this review were randomized to receive Yupingfeng formula combined with Western medications in comparison with Western medications. In general, the methodological quality of the included trials was poor. The results of this systematic review indicates that, compared with Western medications alone, the use of Yupingfeng formula, if combined with Western medications could significantly improve FEV1 (WMD = 0.30L; 95%CI: 0.19, 0.42), FEV1/FVC ratio (SMD = 0.69; 95%CI: 0.48, 0.91), 6MWD (WMD = 31.73m; 95% CI: 19.29, 44.17), and effective rate (RR = 1.24; 95% CI: 1.10, 1.41), and increase the serum levels of IgA (WMD = 0.25; 95%CI: 0.16, 0.34) and IgG (WMD = 1.10; 95%CI: 0.53, 1.68), but no difference was found in the serum IgE levels (WMD = 0.47; 95%CI: -0.32, 1.27) between the two groups. No serious adverse events were reported. CONCLUSIONS: Within the limitations of this systematic review, we may conclude that compared with Western medications alone, Yupingfeng formula, when combined with Western medications can provide more benefits for patients with stable COPD, without any serious adverse reactions being identified. However, these benefits need to be further confirmed through high-quality prospective placebo-controlled trials that should be strictly conducted in accordance with methodological principles and procedures.

Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

OBJECTIVE: To assess the effect of Tanreqing injection on airway inflammation in rats. METHODS: A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. RESULTS: LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. CONCLUSION: Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

Tanreqing injection combined with conventional Western medicine for acute exacerbations of chronic obstructive pulmonary disease: a systematic review.

OBJECTIVE: In China, most patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) are usually treated with Tanreqing injection plus conventional Western medicine. However, the value of its use remains uncertain. The objective of this systematic review is to compare the efficacy of Tanreqing injection plus conventional Western medicine with that of conventional Western medicine alone (therapy A versus therapy B, respectively) in the management of acute exacerbations of COPD. METHODS: Literature retrieval was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,(®) EMBASE, Chinese Biomedical Database (CBM), and other electronically available databases from respective inception to August 2009. In addition, manual search of some traditional Chinese journals was performed to identify potential studies. Review authors independently extracted the trial data and assessed the quality of each trial. The following outcomes were evaluated: (1) forced expiratory volume in 1 second as a percentage of the predicted value; (2) arterial partial pressure of oxygen (Po(2)); (3) arterial partial pressure of carbon dioxide (Pco(2)); (4) length of hospital stay; (5) marked efficacy rate; (6) interleukin-8; and (7) adverse events. RESULTS: Based on the search strategy, 14 trials involving 954 patients were finally included. Our results showed that compared with therapy B, therapy A improved Po(2), clinical efficacy, and lung function, reduced Pco(2), shortened the length of hospital stay, and was thus more therapeutically beneficial. No serious adverse events were reported. CONCLUSIONS: Within the limitations of this systematic review, we can conclude that compared with therapy B, therapy A may provide more benefits for patients with acute exacerbations of COPD. Further large-scale high-quality trials are warranted.

The reporting quality, scientific rigor, and ethics of randomized placebo-controlled trials of traditional Chinese medicine compound formulations and the differences between Chinese and non-Chinese trials.

BACKGROUND: An increasing number of randomized placebo-controlled trials involving traditional Chinese medicine (TCM) compound formulations have been implemented worldwide. OBJECTIVE: The aim of this study was to assess the reporting quality, scientific rigor, and ethics of randomized placebo-controlled trials of TCM compound formulations and compare these differences between Chinese and non-Chinese trials. METHODS: English-language databases included the following: PubMed, OVID, EMBASE, and Science Citation Index Expanded. Chinese-language databases included the following: Chinese Biomedical Literature Database, Wanfang Database, Chinese Scientific and Technological Periodical Database, and the China National Knowledge Infrastructure. All were searched from respective inception to March 2009 to identify randomized placebo-controlled trials involving TCM compound prescriptions. Two reviewers independently assessed the retrieved trials via a modified Consolidated Standard of Reporting Trials (CONSORT) checklist and some evaluation indices that embodied the TCM characteristics or the scientific rigor and ethics of placebo-controlled trials. Trial publishing time was divided into 3 intervals: phase 1 (≤1999); phase 2 (2000-2004); and phase 3 (2005-2009). The number and percentage of trials reporting each item and the corresponding differences between Chinese (mainland China, Hong Kong, and Taiwan) and non-Chinese (eg, Japan, United States, Australia, Korea, and United Kingdom) trials were calculated. Moreover, the influence of trial publishing time on the reporting of CONSORT items and the differences in the number of items reported for each time interval between Chinese and non-Chinese trials were assessed. RESULTS: A total of 324 trials from China and 51 trials from other countries were included. A mean of 39.7% of the CONSORT items across all Chinese trials and 50.2% of the items across all non-Chinese trials were reported. The number of the reported CONSORT items all increased over time in both groups and the gap between Chinese articles and non-Chinese articles gradually decreased. Additionally, of the 324 Chinese articles, 137 (42.28%) reported TCM syndrome type, 113 (34.88%) reported the diagnostic criteria of diseases for TCM, and 69 (21.30%) reported efficacy evaluation indices of TCM. Of the non-Chinese articles, 3 (5.88%) reported TCM syndrome type and 1 (1.96%) reported the diagnostic criteria of diseases and evaluation indices of efficacy for TCM. It was found that 45.37% and 6.17% of Chinese articles reported the standard intervention for the diseases being treated and the emergency plan, respectively, compared with 23.53% and 9.80% for the non-Chinese articles; 33.02% and 10.49% of Chinese articles reported informed consent and ethics committee approval, respectively, compared with 92.16% and 82.35% for the non-Chinese articles. With regard to placebo ethics, 38.89% of the Chinese trials and 23.53% of the non-Chinese trials found it would not be ethically acceptable to use placebo alone in the control group. CONCLUSIONS: The data indicate that the reporting quality of the included trials on TCM compounds has improved over time, but still remains poor regardless of Chinese or non-Chinese trials. Across all trials, particularly Chinese trials, the reporting of the CONSORT items was inadequate (39.7%). The difference in the mean number of the reported CONSORT items between Chinese trials and non-Chinese trials narrowed from phase 1 (10.0 vs 13.8) to phase 3 (14.4 vs 17.4). Moreover, a large number of trials, especially non-Chinese trials (94.1%), were lacking syndrome differentiation of TCM. More importantly, in many placebo-controlled trials, especially Chinese trials, the use of placebo was not justified and was ethically contradictory.

[Chinese medicine for acute upper respiratory tract infection: a systematic review of randomized controlled trials].

OBJECTIVE: To evaluate the efficacy and safety of new drugs of traditional Chinese medicine (TCM) for acute upper respiratory tract infection (common cold). METHODS: Reports regarding randomized controlled trials of Chinese medicine for common cold were reviewed. Related reports were selected and the methodological quality of the trials was assessed by the Jadad scale. Meanwhile, the stratified analysis was made according to different TCM syndrome types of common cold. RESULTS: Thirteen randomized controlled trials consistent with the inclusion criteria were selected and reviewed. As TCM treatment group was compared with control group, the meta analysis indicated that the relative risk (RR) for obviously effective rate was 1.10, and the 95% confidence interval (CI) was [1.05, 1.16]; the weighted mean difference (WMD) of the onset time of lowering body temperature was -1.70, and the 95% CI was [-2.76, -0.65]. There were significant differences in the above evaluation indexes between the two groups (P=0.000 2, P=0.002). The WMD of disappearing time of fever was -1.32, and the 95% CI was [-3.14, 0.49], while there was no significant difference between the two groups (P=0.15). As the common cold patients with wind-heat syndrome in the TCM treatment group were compared with those in the control group, the meta analysis indicated that the RR for obviously effective rate was 1.11, the 95% CI was [1.05, 1.19], and there was significant difference between the two groups (P=0.000 7). As the common cold patients with wind-cold syndrome in the TCM treatment group were compared with those in the control group, the meta analysis indicated that the RR for obviously effective rate was 1.07, the 95% CI was [0.99, 1.16], and there was no significant difference between the two groups (P=0.10). Serious adverse reactions had not been reported in the trials. CONCLUSION: TCM new drugs developed in recent years for preventing and treating common cold have better therapeutic effects than the old ones. They can accelerate the onset time of lowering body temperature and improve the symptoms of common cold without any significant adverse reactions. Because of lacking of placebo-controlled and blank-controlled studies, further high-quality trials are still needed.

[Tanreqing Injection for community-acquired pneumonia: a systematic review of randomized evidence].

OBJECTIVE: To evaluate the efficacy and safety of Tanreqing Injection, a compound traditional Chinese herbal medicine, for community-acquired pneumonia. METHODS: Literatures about randomized controlled trials of Tanreqing Injection for community-acquired pneumonia were reviewed. Related literatures were selected and analyzed according to different treatment strategies of the trials. The methodological quality of the trials was assessed by the Jadad scale, and evaluation was performed. RESULTS: Twelve randomized controlled trials meeting the inclusion criteria were selected and reviewed. As Tanreqing combined group (Tanreqing Injection plus antibiotics and basic therapy) was compared with antibiotics group (antibiotics plus basic therapy), the meta-analysis indicated that the relative risk (RR) for the total cure rate was 1.51, and 95% confidence interval (CI) was [1.29, 1.77]; RR for the total obvious effect rate was 1.31,ls and 95% CI was [1.20,1.43]; RR for the effective rate was 1.17, and 95% CI was [1.11, 1.23]. The weighted mean difference (WMD) in disappearance time of fever between the two groups was -1.24, and 95% CI was [-1.71, -0.76]. The RR values between the two groups for the total obvious effect rate of cough and expectoration were 1.42 and 1.27, and 95% CIs were [1.16, 1.74] and [1.04, 1.55] respectively. The RR values between the two groups in absorption of chest X-ray shadow and neutrophil number were 1.19, 1.10 and 95% CIs were [1.09, 1.30], [1.03, 1.17] respectively. The differences were all statistically significant. Serious systematic adverse reactions had not been reported in the trials. CONCLUSION: The effect of combined therapy with Tanreqing Injection plus antibiotics and basic therapy is better than that of antibiotics plus basic therapy. Tanreqing Injection can improve the symptoms of cough and expectoration, shorten the fever time and facilitate the absorption of chest X-ray shadow, without any significant adverse reactions. However, further high-quality trials are needed.