Mechanism of Chinese botanical drug Dizhi pill for myopia: An integrated study based on bioinformatics and network analysis.

To identify the active constituents, core targets, immunomodulatory functions and potential mechanisms of Dizhi pill (DZP) in the treatment of myopia. The active constituents and drug targets of DZP were searched in the TCMSP, Herb databases and correlational studies. The targets of myopia were searched in the TTD, Genecards, OMIM and Drugbank databases. Gene expression profile data of GSE136701 were downloaded from the GEO database and subjected to WGCNA and DEG analysis to screen for significant modules and targets of myopia. Intersectional targets of myopia and DZP and core targets of myopia were analyzed through the String database. The GO and KEGG enrichment analyses of the interested targets were conducted. Cibersort algorithm was used for immune infiltration analysis to investigate the immunomodulatory functions of DZP on myopia. Autodock was used to dock the important targets and active constituents. Eight targets (STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, HSP90AA1, MIP, and LGSN) and 5 active constituents (Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester, and Naringenin) were identified from DZP. In pathways identified by the GO and KEGG enrichment analyses, "ATP metabolic process" and "AGE-RAGE diabetes complication signaling" pathways were closely related to the mechanisms of DZP in the treatment of myopia. Molecular docking showed that both the intersectional targets and core targets of myopia could bind stably and spontaneously with the active constituents of DZP. This study suggested that the mechanisms of DZP in the treatment of myopia were related to active constituents: Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester and Naringenin, intersectional targets: STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, and HSP90AA1, core targets of myopia: MIP and LGSN, AGE-RAGE signaling pathway, positive regulation of ATP metabolic process pathway and immunomodulatory functions.

Effectiveness and safety of Linggui Zhugan decoction for the treatment of premature contraction in patients with coronary heart disease: A systematic review and meta-analysis.

Objective: To evaluate the effectiveness and safety of Linggui Zhugan decoction (LZD) as an adjunct treatment of premature contraction in patients with coronary heart disease. Methods: PubMed, Embase, Web of Science, ClinicalTrials.gov Cochrane Library, Chinese Knowledge Infrastructure, Wanfang database, Sino Med, and VIP database were searched from inception until July 2022. Two reviewers independently selected randomized controlled trials assessing the effectiveness of LZD combined with conventional antiarrhythmic drugs in treating premature contraction in patients with coronary heart disease compared to conventional antiarrhythmic drugs only. The clinical effectiveness was considered as the primary outcome, and the times of premature junctional beats in 24 h after treatment along with adverse reactions were considered secondary outcomes. The Cochrane risk of bias 2 tool was used for the risk of bias assessment. Meta-analysis was conducted using RevMan 5.4.1. and RStudio software. Results: A total of 14 studies including 1,236 participants were included. The primary outcome indicated that, compared with antiarrhythmic drugs alone (especially ß receptor blockers), the combination of LZD and conventional antiarrhythmic drugs resulted in higher clinical effectiveness (RR = 1.29, 95% CI: [1.22,1.36]) and lower number of premature junctional beats in 24 h (MD = -71.14, 95% CI: [-76.23, -66.06]) at end-of-intervention. The differences in adverse reactions (RR = 0.42, 95%CI: [0.15, 1.14], p = 0.09) were not significant. The risk of bias was marginally high among the studies. Funnel plot and Harbord's test (t = 1.63, p = 0.1346) indicated no existence of publication bias. Conclusion: The current evidence shows that LZD can increase the effectiveness of conventional antiarrhythmic drugs for treating premature contraction in patients with coronary heart disease. However, the results should be interpreted with caution because of the high overall risk of bias. Future studies with appropriate randomization and double-blind methods are warranted to confirm these findings. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=296628], identifier [CRD42022296628].

Zao Ren An Shen capsule for insomnia: a double-blind, randomized, placebo-controlled trial.

STUDY OBJECTIVES: The aim of this study was to test the efficacy and safety of Zao Ren An Shen (ZRAS) capsule, a Chinese herbal medicine product, for the treatment of insomnia. METHODS: We conducted a double-blind randomized placebo-controlled trial. After a one-week placebo run-in, a total of 85 people with insomnia were randomly allocated to receive ZRAS or placebo for 4 weeks. The primary outcomes were insomnia severity assessed with the Insomnia Severity Index (ISI) and the number of participants with adverse events (AEs). Secondary outcomes included objective and subjective sleep parameters, psychological status, fatigue level, quality of life, acceptability, and tolerability. RESULTS: A nonsignificant (p > .05) difference of 0.7 points in ISI in favor of ZRAS capsule was found at the end of the treatment. The number of participants with AEs was not significantly different (p > .05) between the two groups. Except for subjective sleep onset latency, which had a nonsignificant (p > .05) medium effect (Cohen's d = 0.5), the effects in secondary efficacy outcomes were all small (Cohen's d < .4) and nonsignificant (p > .05). The acceptability and tolerability were high in the active group. CONCLUSIONS: ZRAS capsule is safe, acceptable, and tolerable, yet not more effective than placebo in the treatment of insomnia. As previous evidence showed that Chinese herbal medicine was effective for insomnia, these results may be explained by the dose of the product, which was lower than the dose generally used in the clinic.Registration: This clinical trial was registered in Australia New Zealand Clinical Trial Registry (registration number ACTRN12619000140156) under the name "Impact of Zao Ren An Shen (ZRAS) capsule on chronic insomnia patients' insomnia severity: A randomized-controlled trial" (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376730&isReview=true).

Mind-Body Therapies for Cancer Patients Living with Depression, Anxiety or Insomnia (MIRACLE): A Systematic Review with Individual Participant Data Network Meta-Analysis.

Depression, anxiety, and insomnia are common in cancer patients. Mind-body therapies (MBTs) are promising forms of treatment for cancer patients living with depression, anxiety, and insomnia. The objective of this study is to assess the effectiveness and acceptability of MBTs in cancer patients living with depression, anxiety, or insomnia. EMBase, PubMed, Cinahl, PsychINFO, IndMED, CSI-NISCAIR, CNKI, Clinicaltrial.gov, ChiCTR, and CTRI will be searched until October 2020 for relevant studies. Randomized controlled studies in which MBTs were tested in a cancer population will be selected. The authors of the selected studies will be contacted to obtain individual participant data. The participants who reached a defined clinical threshold for depression, anxiety, or insomnia will be selected for the three sub-studies on depression, anxiety, and insomnia, respectively. Pairwise and network meta-analyses will be used to assess the changes in depression, anxiety, sleep quality, and completion rate. We will assess the effect of the treatment dose (number and frequency of interventions) on effectiveness. The results of this study will inform clinical decision-making for the treatment of psychological disturbances in cancer patients. If MBTs are found effective, they will potentially be recommended as treatments for cancer patients with psychological symptoms.

Prognostic Value of EZH2 in Non-Small-Cell Lung Cancers: A Meta-Analysis and Bioinformatics Analysis.

BACKGROUND: The prognosis of non-small-cell lung cancer (NSCLC) has not been significantly improved. In the past several years, research on epigenetics is in full swing. There is a focus on the gene EZH2; however, its role as a predictor of the prognosis of NSCLC is in the debate. OBJECTIVE: To clarify if the expression level of EZH2 can influence the prognosis of NSCLC and explain its prognostic value. METHODS: We have systematically searched PubMed, Web of Science, and Cochrane library, screened relevant articles, and conducted a meta-analysis on the expression level of EZH2 in NSCLC. We collected the hazard ratio (HR) and the 95% confidence interval (CI) and used STATA 12.0 to calculate the combined result of EZH2 overall survival. In addition, we conducted subgroup analyses, a sensitivity analysis, and a funnel plot to test the reliability of the results. We further validated these meta-analysis results using the Kaplan-Meier plotter database and The Cancer Genome Atlas (TCGA) database. In addition, we have investigated the correlation between EZH2 expression and EGFR expression, KRAS expression, BRAF expression, and smoking in TCGA database to further explore the mechanism behind the influence of high EZH2 expression on lung cancer prognosis. RESULTS: 13 studies including 2180 participants were included in the meta-analysis. We found that high expression of EZH2 indicates a poor prognosis of NSCLC (HR = 1.65 and 95% CI 1.16-2.35; p ≤ 0.001). Subgroup analyses showed high heterogeneity in stages I-IV (I 2 = 85.1% and p ≤ 0.001) and stages I-III (I 2 = 66.9% and p = 0.029) but not in stage I (I 2 = 0.00% and p = 0.589). In the Kaplan-Meier plotter database, there was a high expression in 963 cases and low expression in 964 cases (HR = 1.31 and 95% CI 1.15-1.48; p < 0.05). Further analysis found that the high expression of EZH2 was statistically significant in lung adenocarcinoma (HR = 1.27and 95% CI 1.01-1.6; p = 0.045), but not in lung squamous cell carcinoma (HR = 1.03 and 95% CI 0.81-1.3; p = 0.820). The results of the TCGA database showed that the expression of EZH2 in normal tissues was lower than that in lung cancer tissues (p < 0.05). Smoking was associated with high expression of EZH2 (p < 0.001). EZH2 was also highly expressed in lung cancers with positive KRAS expression, and the correlation was positive in lung adenocarcinoma (r = 0.3129 and p < 0.001). The correlation was also positive in lung squamous cell carcinoma (r = 0.3567 and p < 0.001). EZH2 expression was positively correlated with BRAF expression (r = 0.2397 and p < 0.001), especially in lung squamous cell carcinoma (r = 0.3662 and p < 0.001). In lung squamous cell carcinoma, a positive yet weak correlation was observed between EZH2 expression and EGFR expression (r = 0.1122 and p < 0.001). CONCLUSIONS: The high expression of EZH2 indicates a poor prognosis of NSCLC, which may be related to tumor stage or cancer type. EZH2 may be an independent prognostic factor for NSCLC. EZH2 high expression or its synergistic action with KRAS and BRAF mutations affects the prognosis of non-small-cell lung cancer.

Acupuncture for Cancer Related Pain: Protocol for a Pragmatic Randomised Wait-List Controlled Trial.

BACKGROUND: Acupuncture has been proved effective for cancer related pain (CRP) in China, America and some other countries. However, there is relative lack of evidence to support the use of acupuncture for CRP in Australia. OBJECTIVES: To assess the effectiveness and safety of acupuncture for management of CRP in a real-world setting and to understand cancer patients' experience of undergoing acupuncture for CRP. METHODS: A pragmatic randomised controlled trial will be conducted in South Western Sydney Local Health District (SWSLHD) in NSW, Australia. Adults with cancer related pain (n = 106) will be randomised in a 1:1 ratio to receive the acupuncture intervention up front versus after a wait list period of 4 weeks. Pain level (by Numerical Rating Scale), analgesic use, auricular acupressure frequency and adverse events will be assessed at baseline, mid-treatment and post-treatment. Expectancy on trial outcome (by Credibility and Expectancy questionnaire) will be assessed at baseline. The perspective of the participants (by an interview) will be recorded after the last intervention. EXPECTED OUTCOMES: We hypothesise that acupuncture will relieve cancer related pain at mid-treatment and post-treatment. We also hypothesise that few adverse events will be provoked by acupuncture. TRIAL REGISTRATION: Australia New-Zealand Clinical Trial Registry (ACTRN12620000325909).

Zao Ren An Shen for insomnia: a systematic review with meta-analysis.

OBJECTIVE: To assess the effectiveness and safety of Zao Ren An Shen (ZRAS), a Chinese herbal medicine formula, for the treatment of insomnia. METHODS: Seven databases (ie, EMBASE, PubMed, the Cochrane library, and PsycINFO, Chinese National Knowledge Infrastructure, Wanfang and Chongqing VIP) were searched from their inception to 6 November 2018. Controlled trials comparing the effectiveness or safety of ZRAS to conventional treatments, a placebo or no-treatment in an insomnia population were selected. Primary outcomes were: sleep quality (assessed with the Pittsburgh Sleep Quality Index, PSQI), and the number of adverse events at post-treatment. The risk of bias was assessed with the Cochrane Collaboration's tool and meta-analyses were performed using RevMan 5.3. RESULTS: A total of 19 studies (1780 participants) were included. The effect of ZRAS on sleep quality (mean difference) was found to be superior compared to placebo in the sole placebo-controlled study located [-0.90 (-1.56, -0.24; 95% CI), p = 0.007] and similar to Benzodiazepine Receptor Agonists (BzRAs) [0.17 (-0.29, 0.64); 95% CI, p = 0.46]. The number of adverse events (relative risk) was lower for ZRAS than BzRAs [0.16 (0.12, 0.23; 95% CI), p < 0.001]. An overall high risk of bias was found in the selected studies. CONCLUSIONS: The results favor ZRAS against BzRAs and placebo for the treatment of insomnia. However, the poor methodology of the studies prevents strong recommendations for ZRAS. Clinical trials with higher quality designs are required.

Is insomnia disorder associated with time in bed extension?

OBJECTIVE: There is a lack of evidence for extension of time in bed behaviors (i.e., getting to bed earlier, going out of bed later, staying in bed while awake and napping) as perpetuating factors of insomnia. The aim of this study is to assess if insomnia disorder is associated with extension of time in bed behaviors. METHODS: 150 good sleepers and 173 insomniacs were recruited between December 2017 and June 2018. A cross-sectional survey was performed using the Wang Insomnia Integrated Questionnaire. RESULTS: Bedtime, rising time and time in bed were not different between good sleepers and insomniacs (Cohen's d, <0.01, 0.07, 0.07, respectively; all p>0.05) and were not correlated with insomnia severity (all p>0.05). Staying in bed while awake during the night and in the morning where both different between good sleepers and insomniacs (Cohen's d, 1.33 and 0.85, respectively; all p<0.001) and were positively correlated with insomnia severity (all p<0.001). Napping was more frequent (p<0.01) among good sleepers (63.3%) than insomniacs (48.6%) and a predictor of good sleep (p<0.01). CONCLUSION: Going to bed earlier and getting out of bed later do not seem to be associated with insomnia. Staying in bed while awake during the night and in the morning are associated with insomnia but could be only signs of insomnia symptoms. Limiting time in bed to prevent insomnia might and suppressing insomniacs' napping behavior to treat insomnia might not be effective.

Zao Ren An Shen capsule for chronic insomnia: Study protocol for a randomized, placebo-controlled trial.

BACKGROUND: Zao Ren An Shen (ZRAS), a Chinese Herbal Medicine product, has been proposed as an alternative to recommended treatments for chronic insomnia. There is a lack of strong evidence supporting this proposition. AIMS: To assess the efficacy and safety of ZRAS capsule for chronic insomnia compared to placebo. METHODS: A parallel-group, double-blind, randomized-controlled trial will be performed in Western Sydney University, Australia. After a 1-week placebo run-in, adults with chronic insomnia (n = 90) will be randomized in a 1:1 ratio to receive either ZRAS capsule or placebo for 4 weeks. Insomnia severity (Insomnia Severity Scale score), sleep parameters (measured with the Consensus Sleep Diary and actigraphy), fatigue levels (Fatigue Severity Scale score), psychological status (Depression Anxiety Stress Scale score), quality of life (Assessment of Quality of Life score), and adverse events will be assessed at baseline, mid-treatment, post-treatment and at a 1-month follow-up. EXPECTED OUTCOMES: We hypothesize that ZRAS capsule will improve insomnia severity, sleep parameters, fatigue levels, psychological status, and quality of life better than placebo at mid-treatment, post-treatment, and follow-up. We also hypothesize that the number of adverse events provoked by ZRAS capsule will be similar to placebo at these time-points. TRIAL REGISTRATION: Australia New-Zealand Clinical Trial Registry (Registration number ACTRN12619000140156).

L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial.

Partial or non-response to antidepressants in Generalized Anxiety Disorder (GAD) is common in clinical settings, and adjunctive biological interventions may be required. Adjunctive herbal and nutraceutical treatments are a novel and promising treatment option. L-theanine is a non-protein amino acid derived most-commonly from tea (Camellia sinensis) leaves, which may be beneficial in the treatment of anxiety and sleep disturbance as suggested by preliminary evidence. We conducted a 10-week study (consisting of an 8-week double-blind placebo-controlled period, and 1-week pre-study and 2-week post-study single-blinded observational periods) involving 46 participants with a DSM-5 diagnosis of GAD. Participants received adjunctive L-theanine (450-900 mg) or matching placebo with their current stable antidepressant treatment, and were assessed on anxiety, sleep quality, and cognition outcomes. Results revealed that adjunctive L-theanine did not outperform placebo for anxiety reduction on the HAMA (p = 0.73) nor insomnia severity on the Insomnia Severity Index (ISI; p = 0.35). However, LT treated participants reported greater self-reported sleep satisfaction than placebo (ISI item 4; p = 0.015). Further, a separation in favour of L-theanine was noted on the ISI in those with non-clinical levels of insomnia symptoms (ISI ≤ 14; p = 0.007). No significant cognitive effects (trail making time and the modified emotional Stroop) were revealed. While this preliminary study did not support the efficacy of L-theanine in the treatment of anxiety symptoms in GAD, further studies to explore the application of L-theanine in sleep disturbance are warranted.

Culturally Adapted CBTI for Chinese Insomnia Patients: a One-Arm Pilot Trial.

PURPOSE: Insomnia is a common mental disorder with severe consequences. Cognitive-behavioral therapy for insomnia (CBTI) has been proved effective against insomnia, but most of the research is limited to Western countries. This trial objective is to develop a Chinese culture-adapted CBTI program and assess its efficacy. METHOD: An 8-week culturally adapted CBTI program was developed that included mixed group and individual session and culturally adapted relaxation and cognitive restructuring treatment components. A one-arm clinical trial was conducted at a public hospital between March 2016 and January 2017. Seventy-two Chinese adults (15 males, 57 females; mean age, 50 years) with insomnia disorder underwent the culturally adapted CBTI program. Sleep diaries and self-report scales, as well as polysomnography (PSG, for a subgroup only), were used to assess qualitative and quantitative measures of sleep, mental health status, and quality of life at baseline, post-treatment, and 4-month follow-up. RESULTS: Pre-post analyses showed significant changes in sleep diary sleep onset latency (SOL), wake after sleep onset (WASO), and total sleep time of respectively - 37.03 min (CI, - 48.90 to - 25.16), - 28.16 min (CI, - 40.22 to - 16.10), and + 27.49 min (CI, 10.51 to 44.47). Self-reported sleep quality, mental health, and quality of life improved compared to baseline. The self-reported outcomes were mainly stable at follow-up. PSG outcomes globally failed to show improvement. CONCLUSION: The design of a CBTI program adapted to Chinese population was achieved. Culturally adapted CBTI showed promising results. More rigorously designed studies are needed to ensure efficacy.