Variation in Placebo Effect Sizes in Clinical Trials of Oral Interventions for Management of the Behavioral and Psychological Symptoms of Dementia (BPSD): A Systematic Review and Meta-Analysis.

Increasing placebo effect sizes over time have been reported in randomized controlled trials (RCTs) for outcomes related to psychiatric symptoms. The Neuropsychiatric Inventory (NPI) is a key outcome measure in clinical trials of the behavioral and psychological symptoms of dementia (BPSD). Accurate placebo effect size estimates for NPI are needed for sample size calculations in order to adequately power future studies. This study investigated variation in placebo effect sizes for NPI in RCTs testing oral interventions for BPSD. A search of PubMed was conducted in April 2016 for two-armed, double-blinded, placebo-controlled RCTs testing any oral intervention for management of BPSD using the NPI. Meta-analysis was conducted of baseline versus end of treatment placebo group data of included studies. Twenty-five RCTs published from 2000 to 2015 were included. Substantial variation in placebo effect sizes was detected. Participants in placebo groups showed greater improvements in recent studies compared with earlier studies. Subgroup analyses indicated robustness of this finding. From 2000 to 2008 there was no significant change in total NPI scores within placebo groups (12 studies; 1,056 participants), whereas from 2009 to 2015 there was significant improvement (mean difference: -2.68; 95% confidence interval: -4.38, -0.99; z = 3.10; p = 0.002, random effects; I2 = 76%; 13 studies; 1,170 participants). This increase in NPI effect sizes in placebo groups has important implications for power calculations for future clinical trials of BPSD. Effect size estimates for NPI need to be based on more recent studies.

Electroacupuncture for Poststroke Spasticity: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effects and safety of electroacupuncture (EA) for stroke patients with spasticity. DATA SOURCES: Five English databases (PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database) and 4 Chinese databases (Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Chongqing VIP Database, Wanfang Database) were searched from their inception to September 2016. STUDY SELECTION: Randomized controlled trials were included if they measured spasticity with the Modified Ashworth Scale (MAS) in stroke patients and investigated the add-on effects of electroacupuncture to routine pharmacotherapy and rehabilitation therapies. DATA EXTRACTION: Information on patients, study design, treatment details and outcomes assessing spasticity severity, motor function, and activities of daily living was extracted. DATA SYNTHESIS: In total, 22 trials involving 1425 participants met the search criteria and were included. The estimated add-on effects of EA to reduce spasticity in the upper limbs as measured by the MAS (standardized mean difference [SMD]=-.57; 95% confidence interval [CI], -.84 to -.29), and to improve overall motor function as measured by the Fugl-Meyer Assessment of Sensorimotor Recovery (mean difference [MD]=10.60; 95% CI, 8.67-12.53) were significant. Significant add-on effects of EA were also shown for spasticity in the lower limbs, lower-limb motor function, and activities of daily living ([SMD=-.88; 95% CI, -1.42 to -.35;], [MD=4.42; 95% CI, .06-8.78], and [MD=6.85; 95% CI, 3.64-10.05], respectively), although with high heterogeneity. For upper-limb motor function, no significant add-on effects of EA were found. CONCLUSIONS: EA combined with conventional routine care has the potential of reducing spasticity in the upper and lower limbs and improving overall and lower extremity motor function and activities of daily living for patients with spasticity, within 180 days poststroke. Further studies of high methodological and reporting quality are needed to confirm the effects and safety of EA, and to explore the adequate and optimal protocol of EA for poststroke spasticity, incorporating a group of comprehensive outcome measures in different populations.

Potential effectiveness of Chinese herbal medicine Yu ping feng san for adult allergic rhinitis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chinese herbal medicine formula Yu ping feng san (YPFS) is commonly used for allergic rhinitis (AR). Previous review had summarized the effectiveness and safety of YPFS, however without any subgroup analysis performed to provide detailed evidence for guiding clinical practice. YPFS was recommended for the management of AR by Chinese medicine clinical practice guideline, but the treatment duration of YPFS was also not specified. The aim of this study is to evaluate the effectiveness and safety of YPFS in treating adult AR with the most recent evidence, and attempt to specify the duration of utilisation through subgroup meta-analyses. METHODS: Seven databases were searched from their inceptions to September 2017. Randomized controlled trials (RCTs) evaluating YPFS for adult AR were included. Methodological quality of studies was assessed using the Cochrane risk of bias tool. Meta-analysis and subgroup meta-analyses were conducted for evaluating the effectiveness of YPFS. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence. RESULTS: Twenty-two RCTs involving 23 comparisons were included in this review. YPFS was compared to placebo, pharmacotherapy, and used as an add-on treatment compared to pharmacotherapy. Meta-analyses were feasible for the outcomes of four individual nasal symptom scores and "effective rate". Four individual nasal symptom scores decreased after YPFS' combination treatment: itchy nose (MD-0.46, 95% CI[-0.50, -0.42]), sneezing (MD-0.41, 95% CI[-0.47, -0.35]), blocked nose (MD-0.46, 95% CI[-0.54, -0.39]) and runny nose (MD-0.42, 95% CI[-0.58, -0.26]). Based on "effective rate", meta-analysis showed that YPFS did not achieve better effect than pharmacotherapy (RR1.07, 95%CI [0.94, 1.22), but its combination with pharmacotherapy seemed more effective than pharmacotherapy alone (RR1.27, 95%CI [1.19, 1.34]) (low quality). Subgroup analysis suggested that YPFS was not superior to the second-generation antihistamine (RR1.04, 95%CI [0.90, 1.19]) (low quality). Further, YPFS' combination treatment seemed more beneficial when it was used for more than three weeks (RR1.15, 95%CI [1.01, 1.32]). In addition, YPFS was well-tolerated for treating adult AR. CONCLUSION: Chinese herbal medicine formula YPFS seems beneficial for adult AR. This potential benefit need to be further evaluated by more rigorous RCTs.

Gentiana scabra Bunge. Formula for Herpes Zoster: Biological Actions of Key Herbs and Systematic Review of Efficacy and Safety.

This study reviewed the biological action of key herbs and evaluated systematically the efficacy and safety of oral Gentiana formula for herpes zoster (HZ). Experimental studies relevant to HZ were identified in PubMed. Randomized controlled trials using Gentiana formula for HZ were identified from nine English and Chinese databases. The primary outcome was evaluation of pain. Potential risk of bias was assessed. Meta-analysis was conducted using mean difference or risk ratio with 95% confidence intervals. Key herbs Gentiana scabra Bunge, Gentiana triflora Pall, Scutellaria baicalensis Georgi, and Gardenia jasminoides Ellis have shown antiinflammatory actions through inhibition of inflammatory cytokines and pro-inflammatory enzymes. Twenty-six clinical studies, involving 2955 participants, were included. Modified Gentiana formula resolved pain earlier than pharmacotherapy when used alone or combined with topical Chinese herbal medicine. Incidence of postherpetic neuralgia was lower (risk ratio 0.14, 95% confidence interval 0.03 to 0.74) with modified Gentiana formula plus topical Chinese herbal medicine. Mild adverse events were reported. Antiinflammatory actions of key herbs of Gentiana formula may explain clinical benefit in hastening pain relief and decreasing postherpetic neuralgia. Few adverse events were reported. Findings were limited by study quality and diversity in intervention and comparator dosage. Copyright © 2017 John Wiley & Sons, Ltd.

A Pharmacological Review of Bioactive Constituents of Paeonia lactiflora Pallas and Paeonia veitchii Lynch.

The roots of two peony species, Paeonia lactiflora Pallas and Paeonia veitchii Lynch are routinely referred to as either chishao () or baishao (). This paper reviews the botanical origins and traditional medicinal usage of each species, as well as pharmacological like activity of their constituents. A search of herbal pharmacological encyclopaedia, PubChem and PubMed databases identified their known constituents. The biological data for these constituents were evaluated and classified according to pharmacological-like activity, with emphasis on compounds of greatest concentration and bioavailability. It was found that P. lactiflora and P. veitchii have some common compounds; however, their phytochemical bioavailability varies. Furthermore, a larger number of compounds have been identified in P. lactiflora. These have greater potential for antiinflammatory, antiviral, antibacterial and antioxidant therapeutic activity compared with P. veitchii. However, evidence indicates both species are similarly indicated for antiviral and glycaemic activity. Major compounds of each are classified as flavonoids, hydrolysable tannins (polyphenols) and monoterpene glycosides. The evidence suggests both species, when administered in entire botanical form, have an excellent safety profile; however, constituent toxicity risk evidence is limited, requiring further investigation. Although experiments show many compounds have biological activity, further investigation of their therapeutic potential is needed. Copyright © 2016 John Wiley & Sons, Ltd.

Chinese Herbal Medicine for Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Cognitive Outcomes.

Mild cognitive impairment (MCI) is a condition that may be prodromal to the development of dementia. There remain, as yet, no approved pharmaceutical interventions for MCI. Chinese herbal medicines (CHMs) have a long history of use for cognitive impairments and some plant ingredients have shown neuroprotective actions in experimental studies. This review assesses the current clinical evidence from controlled clinical trials for the effects of CHMs on cognitive outcomes as measured by Mini-mental state examination (MMSE) or Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Fifty one studies (4026 participants) were included. These compared CHM with placebo, supportive care, pharmaceutical treatment or combined CHM with a pharmaceutical in an integrative setting. For the eight randomised controlled trials (RCTs) of comparisons with placebo, MMSE was significantly higher in the CHM groups (MD 1.56 [0.78, 2.34] I2 = 85%, n = 503), similarly for eight RCTs of comparisons with supportive care (MD 1.77 [1.33, 2.21] I2 = 0%, n = 555). Benefits were also evident in comparisons with some pharmaceuticals and with integrative treatment. The small size of most studies and methodological weaknesses mean that these results should be interpreted with caution. Further studies employing rigorous methods are required to investigate the potential benefits of these CHMs for MCI. Copyright © 2016 John Wiley & Sons, Ltd.

Acupuncture for seasonal allergic rhinitis: a randomized controlled trial.

BACKGROUND: Seasonal allergic rhinitis (SAR) is a common condition with relatively high prevalence in Australia. It causes a significant impact on sufferers' quality of life (QoL). Meta-analysis has shown that the efficacy of acupuncture for SAR is uncertain. OBJECTIVE: To evaluate the efficacy and safety of 12 sessions of acupuncture treatment during 4 weeks for SAR in a randomized, subject- and assessor-blinded, sham-controlled trial conducted during the pollen seasons in 2009 through 2011 in Melbourne. METHODS: Patients diagnosed with SAR and confirmed allergic to rye grass pollen were randomly allocated to receive real acupuncture (RA) or sham acupuncture (SA) treatment. RA was delivered manually, whereas SA involved superficial needling at non-acupoints without additional stimulation. Severity of SAR symptoms was the primary outcome measurement. Secondary outcomes were QoL, global change, SAR-related medication usage, and adverse events. Analysis of covariance using pollen count as a covariate was used to analyze outcome data. RESULTS: A total of 175 participants were included in this trial. RA was significantly better than SA for decreasing SAR symptom severity (sneezing, mean difference -0.28, 95% confidence interval -0.51 to -0.05; itchiness of ears and palate, mean difference -0.40, 95% confidence interval -0.69 to -0.11) at the end of treatment and improving participants' QoL at the end of the treatment and follow-up phases. Furthermore, the acupuncture treatment was safe and well tolerated. CONCLUSION: Four weeks of acupuncture treatment is a safe and effective option for clinical management of SAR in the Melbourne area for patients' symptom relief and QoL improvement.

Natural products for chronic cough: Text mining the East Asian historical literature for future therapeutics.

Chronic cough is a significant health burden. Patients experience variable benefits from over the counter and prescribed products, but there is an unmet need to provide more effective treatments. Natural products have been used to treat cough and some plant compounds such as pseudoephedrine from ephedra and codeine from opium poppy have been developed into drugs. Text mining historical literature may offer new insight for future therapeutic development. We identified natural products used in the East Asian historical literature to treat chronic cough. Evaluation of the historical literature revealed 331 natural products used to treat chronic cough. Products included plants, minerals and animal substances. These natural products were found in 75 different books published between AD 363 and 1911. Of the 331 products, the 10 most frequently and continually used products were examined, taking into consideration findings from contemporary experimental studies. The natural products identified are promising and offer new directions in therapeutic development for treating chronic cough.

Topical application of Chinese herbal medicine for atopic eczema: a systematic review with a meta-analysis.

BACKGROUND: Atopic eczema (AE) affects 10-20% of children in industrialised countries. OBJECTIVE: This review systematically evaluated the effects and safety of topical use of Chinese herbal medicine (CHM) for AE. METHODS: Randomised controlled trials on topical use of CHM were identified through searching electronic databases. Their risk of bias was assessed. Meta-analysis was conducted by employing the RevMan 5.2 software. RESULTS: Ten studies involving 1,058 participants were included. These studies had high risk of bias in randomisation, blinding and outcome data. Meta-analysis showed that topical applications of CHM were superior to conventional medications in total effectiveness rate (risk ratio 1.19; 95% confidence interval 1.04 to 1.36). No significant difference was observed in overall skin lesion score (standardised mean difference -0.05; 95% confidence interval -0.88 to 0.78) compared to corticosteroid creams. CONCLUSIONS: There was no conclusive evidence to demonstrate that topical application of CHM for AE was superior to other control interventions due to methodological weaknesses of the included randomised controlled trials.

Acupuncture therapies for chronic obstructive pulmonary disease: a systematic review of randomized, controlled trials.

CONTEXT: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality and is projected to be the third leading cause of death by 2030. Acupuncture, a traditional Chinese therapy, has been used for more than 2000 years to treat respiratory conditions and may treat COPD effectively. In previous literature reviews, researchers have noted significant heterogeneity among the included studies, and none of the reviewers found convincing evidence to recommend routine use of acupuncture therapies for COPD. OBJECTIVE: This literature review examined the efficacy and safety of acupuncture therapies for patients with COPD in improving lung function, increasing exercise capacity, creating positive subjective changes in symptoms, and enhancing health-related quality of life (QoL). DESIGN: The research team searched the following electronic databases from inception to April 2013: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), Embase (Elsevier), the China National Knowledge Infrastructure (CNKI), Chongqing VIP Information Company (CQVIP), the Chinese Biomedical Literature Database (CBM), and Wanfang Data. The review included randomized, controlled trials (RCTs) that examined the benefits of acupuncture or other related therapies for treatment of COPD. Data were extracted into a predefined form; risk of bias was assessed according to the Cochrane Risk of Bias tool; and statistical analyses were made. RESULTS: In total, 16 studies were included in the review. The research team found that the acupuncture therapies used in these studies improved health-related QoL. The team's conclusions, comparing results from the interventions with placebo, were based on data from 3 questionnaires that the studies used: (1) the St George's Respiratory Questionnaire (SGRQ), with a mean difference (MD) of -8.33 units (95% CI, -13.13 to -3.53); (2) dyspnea on the Medical Research Council's (MRC's) dyspnea scale, with an MD of -0.34 units (95% CI, -0.38 to -0.30); and (3) the Dyspnea Visual Analogue Scale (DVAS), with an MD of -8.85 mm (95% CI, -11.81 to -5.89). Compared with placebo, acupuncture therapies also increased the distance walked in 6 min (6MWT), with an MD of -28.14 (95% CI, 23.92 to 32.36) compared with placebo. No benefit was seen on measures of lung function when acupuncture therapies were compared with either placebo or drug therapy. CONCLUSION: Acupuncture therapies may result in clinically important improvements in QoL and dyspnea. Future high-quality RCTs should be undertaken to provide conclusive evidence concerning the benefits of acupuncture therapies in the treatment of COPD.

The efficacy and safety of Chinese herbal medicine for mild cognitive impairment: a systematic review and meta-analysis of randomized placebo-controlled trials.

Objective: Effective and safe treatments for mild cognitive impairment (MCI) are limited. Chinese herbal medicine (CHM) is commonly used in China to manage MCI. However, its efficacy and safety remain uncertain. This review aims to evaluate the efficacy and safety of CHM for MCI. Methods: Nine databases were searched from their inceptions to January 2023. Randomized, placebo-controlled trials of oral CHM for MCI were included. Study quality was assessed using the Cochrane risk-of-bias tool 2.0, and the certainty of evidence was evaluated via the GRADE approach. Results: Thirteen studies, involving 1,043 participants, were analyzed. Most of the studies (10 out of 13) were associated with "some concerns" regarding the overall risk of bias. Meta-analyses results indicated that CHM significantly improved cognitive function compared to placebo in terms of Mini-Mental State Examination (MMSE) (MD: 1.90 [1.22, 2.58], I2 = 87%, 11 studies, 823 participants) and Montreal Cognitive Assessment (MoCA) (MD: 2.88 [1.69, 4.06], I2 = 81%, 3 studies, 241 participants). The certainty of evidence for MMSE was assessed as "moderate", while it was "low" for MoCA. One study did not report adverse events (AEs), one study reported no statistical difference between the groups in terms of AEs, and 11 studies provided detailed numbers of AE cases where gastrointestinal symptoms were the most commonly reported AEs. Two studies reported no SAEs among participants and one study found no significant difference in SAEs proportions between groups. The meta-analysis revealed no significant difference in AEs between the two groups (RR: 1.31 [0.92, 1.87), I2 = 0%, 11 studies, 839 participants). The cognitive-enhancing function of commonly used herbs (Panax ginseng C.A.Mey., Acorus calamus var. angustatus Besser, and Polygala tenuifolia Willd.) may be attributed to mechanisms including antioxidant, anti-apoptotic, anti-neurotoxic, anti-cytotoxic, and anti-inflammatory actions. Conclusion: Chinese herbal medicine holds potential as an effective intervention to improve cognitive function in MCI patients, supported by meta-analyses evidence of low to moderate certainty. Although current data suggests CHM is generally safe, caution is advised due to the lack of AE reporting or detailed information in some instances. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=400292, identifier [CRD42023400292].

Adding Chinese herbal medicine bath therapy to conventional therapies for psoriasis vulgaris: A systematic review with meta-analysis of randomised controlled trials.

BACKGROUND: Chinese herbal medicine (CHM) bath is commonly used in China as an adjuvant therapy for managing psoriasis vulgaris. Previous systematic reviews showed that CHM bath therapy was effective and safe for psoriasis vulgaris, however, without exploration of the specifics of CHM bath therapy such as the optimal temperature, duration of each session, and the total treatment duration. PURPOSE: To evaluate the add-on effects of CHM bath therapy to conventional therapies for adult psoriasis vulgaris. METHODS: We conducted a comprehensive search in nine medical databases from inception to September 2022 to identify relevant randomised controlled trials (RCTs) published in Chinese or English. The included studies compared the combination of CHM bath therapy and conventional therapies to conventional therapies alone for adult psoriasis vulgaris. Methodological quality assessment of the included RCTs was performed using the Cochrane risk-of-bias tool 2 (RoB 2). Statistical analysis was carried out using RevMan 5.4, R 4.2.3 and Stata 12.0 software. The certainty of evidence of outcome measures was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation Working Group (GRADE) system. RESULTS: A total of 23 RCTs involving 2,183 participants were included in this systematic review. Findings suggested that the combination of CHM bath therapy and conventional therapies was more effective in reducing Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and itch visual analogue scale, compared to using conventional therapies alone. These enhanced effects were notably observed when the CHM bath was set above 38 °C and had a duration of 20 and 30 min, as assessed by DLQI. Moreover, an eight-week treatment duration resulted in better effects for PASI compared to shorter durations. Additionally, the top ten frequently used herbs in the included studies were identified. Despite the findings, the certainty of evidence was rated as 'low' or 'moderate' based on the GRADE assessment, and significant heterogeneity was detected in subgroup and sensitivity analyses. CONCLUSION: The CHM bath therapy combined with conventional therapies is more effective and safer than conventional therapies alone for adult psoriasis vulgaris. The results suggest a potential correlation between treatment effects and factors such as extended treatment duration, increased bath temperature, and longer bath sessions. However, the certainty of evidence was downgraded due to methodological limitations of the included studies. To confirm the findings of this systematic review, a double-blinded, placebo-controlled RCT is needed in the future.

Oral Chinese herbal medicine combined with donepezil for mild cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: This study aims to evaluate the add-on effects of oral Chinese herbal medicine (CHM) for mild cognitive impairment (MCI), when used in addition to donepezil compared to donepezil alone. METHODS: Randomized controlled trials comparing these treatments across all types of MCI were identified from nine databases and three registers until August 2023. Outcome measures were Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and adverse events (AEs). Methodological quality was assessed using Cochrane risk-of-bias tool, and evidence certainty was evaluated using the GRADE method. RESULTS: Involving 1611 participants across 20 studies, meta-analysis results indicate that oral CHM combined with donepezil significantly improved cognitive function in MCI patients compared to donepezil alone, as evidenced by MMSE (1.88 [1.52, 2.24], I2 = 41%, 12 studies, 993 participants) and MoCA (MD: 2.01 [1.57, 2.44], I2 = 52%, 11 studies, 854 participants). Eleven studies reported details of AEs, identifying gastrointestinal symptoms and insomnia as the most common symptoms. No significant difference in AEs frequency was found between the groups (RR: 0.91 [0.59, 1.39], I2 = 4%, 11 studies, 808 participants). All 20 studies were evaluated as having "some concerns" regarding the overall risk of bias. The certainty of evidence for MMSE was "moderate" and "low" for MoCA. From frequently utilized herbs, two classical CHM formulae were identified: Kai xin san and Si wu decoction. The observed treatment effects of commonly used herbs may be exerted through multiple pharmacological mechanisms, including anti-inflammatory, anti-oxidative stress, anti-apoptotic actions, promotion of neuronal survival and modulation of the cholinergic system. CONCLUSIONS: The concurrent use of oral CHM and donepezil appears to be more effective than donepezil alone in improving the cognitive function of MCI, without leading to an increase in AEs. While recognizing concerns of overall methodological quality, this combined therapy should be considered as an alternative option for clinical practice.

Real-world observations and impacts of Chinese herbal medicine for migraine: results of a registry-based cohort study.

Background: Migraine is a prevalent, recurrent condition with substantial disease burden. Chinese herbal medicine (CHM) has been used frequently for migraine in controlled clinical settings. This study is to summarise the characteristics of patients who seek clinical care in a tertiary Chinese medicine hospital in China; to gather their preferences and values of using CHM; to explore the effect of CHM for migraine and its comorbidities in a real-world setting, and to collect first-hand expertise of clinicians' practice pattern in prescribing CHM for migraine. Methods: This registry-based cohort study was prospectively conducted at Guangdong Provincial Hospital of Chinese Medicine from December 2020 to May 2022. Adult migraine patients seeking their initial anti-migraine clinical care at the hospital were consecutively recruited and followed up for 12 weeks. Practitioners specialised in headache management prescribed individualised treatments without research interference. Standardised case report forms were employed to gather information on patients' preferences and perspective of seeking clinical care, as well as to assess participants' migraine severity, comorbidities, and quality of life, at 4-weeks intervals. Various analytical methods were utilised based on the computed data. Results: In this study, we observed 248 participants. Of these, 73 received CHM treatment for 28 days or longer. Notably, these participants exhibited a greater disease severity, compared to those treated with CHM for less than 28 days. Of the 248 participants, 83.47% of them expected CHM would effectively reduce the severity of their migraine, around 50% expected effects for migraine-associated comorbidities, while 51.61% expressing concerns about potential side effects. CHM appeared to be effective in reducing monthly migraine days and pain intensity, improving patients' quality of life, and potentially reducing comorbid anxiety, with a minimum of 28 days CHM treatment. Herbs such as gan cao, gui zhi, chuan xiong, fu ling, bai zhu, yan hu suo, etc. were frequently prescribed for migraine, based on patients' specific symptoms. Conclusion: CHM appeared to be beneficial for migraine and comorbid anxiety in real-world clinical practice when used continuously for 28 days or more. Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR2000041003.

Add-on effects of Chinese herbal medicine external application (FZHFZY) to topical urea for mild-to-moderate psoriasis vulgaris: Protocol for a double-blinded randomized controlled pilot trial embedded with a qualitative study.

Psoriasis vulgaris is a chronic dermatological disease with a high global prevalence. It significantly reduces patients' quality of life and is associated with a substantial economic burden. Conventional therapies for mild-to-moderate psoriasis are often associated with insufficient long-term symptomatic relief and side effects. Chinese herbal medicine (CHM) is commonly used for psoriasis management. A CHM formula, namely Fu zheng he fu zhi yang (FZHFZY), has shown promising treatment effects in clinical practice when used as a bath therapy. However, its efficacy and safety has not been evaluated by a rigorous randomized controlled trial (RCT). Therefore, we designed a double-blinded pilot RCT embedded with a qualitative study on CHM formula FZHFZY plus topical urea for mild-to-moderate psoriasis vulgaris to advance the evidence development and practice of CHM external application for psoriasis. This will be a mixed-method design consisting of a pilot RCT and a qualitative study. The pilot RCT is a two-arm, parallel, placebo-controlled, double-blinded trial. Sixty eligible participants will be randomized at a 1:1 ratio to receive eight weeks' treatment of either FZHFZY plus 10% urea cream, or placebo plus 10% urea cream, with 12-week follow-up visits after the treatment phase. The CHM or placebo will be administered externally as a bath therapy. Outcome measures include trial feasibility, efficacy and safety. The primary efficacy outcome will be Psoriasis Area Severity Index (PASI). Secondary efficacy outcomes include Physician Global Assessment, PASI-75, PASI-50, Body Surface Area, Dermatology Life Quality Index, Skindex-16, itch visual analogue scale and relapse. The qualitative study will be conducted to collect participants' feedback on CHM external application and their experience with the pilot RCT. This study will advance the evidence-based clinical practice of using CHM for psoriasis vulgaris and then to support translation of findings into clinical practice in the future. Trial registration number: ChiCTR2200064092.

Renal-protective effects of Chinese medicinal herbs and compounds for diabetic kidney disease in animal models: protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic kidney disease (DKD) is a common and severe complication of diabetes that can lead to end-stage renal disease with no cure. The first-line drugs recommended by clinical guidelines fail to achieve satisfactory effects for people with DKD. A Chinese herbal medicine Tangshen Qushi Formula (TQF) shows preliminary efficacy and safety in preserving renal function for people with DKD, but the effects on comprehensive renal outcomes remain unclear. We will conduct a systematic review and meta-analysis to evaluate the effects of TQF herbs and their compounds identified from ultra-high performance liquid chromatography-MS/MS in diabetic animal models with renal outcomes. METHODS: This protocol complies with the guideline Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will include studies investigating the effects of TQF herbs and compounds on diabetic rats or mice with renal outcomes. Six electronic databases will be searched from their inception to February 2023. Quality assessment will be conducted using SYRCLE's risk of bias tool. Standardized or weighted mean differences will be estimated for renal outcomes (creatinine, urea, proteinuria, histological changes, oxidative stress, inflammation, and kidney fibrosis). Data will be pooled using random-effects models. Heterogeneity across studies will be expressed as I2. Sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots and Egger's test will be used to explore publication bias. DISCUSSION: The results of this review will provide valuable insights into the potential effects of TQF in managing DKD. The limitation is that the included studies will be animal studies from specific databases, and the interpretation of the findings must be cautious. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023432895. Registered on 19 July 2023 ( https://www.crd.york.ac.uk/PROSPERO/#recordDetails ).

Renal protective effects and mechanisms of Astragalus membranaceus for diabetic kidney disease in animal models: An updated systematic review and meta-analysis.

BACKGROUND: Astragalus membranaceus (AM) shows potential therapeutic benefits for managing diabetic kidney disease (DKD), a leading cause of kidney failure with no cure. However, its comprehensive effects on renal outcomes and plausible mechanisms remain unclear. PURPOSE: This systematic review and meta-analysis aimed to synthesize the effects and mechanisms of AM on renal outcomes in DKD animal models. METHODS: Seven electronic databases were searched for animal studies until September 2023. Risk of bias was assessed based on SYRCLE's Risk of Bias tool. Standardized mean difference (SMD) or mean difference (MD) were estimated for the effects of AM on serum creatinine (SCr), blood urea nitrogen (BUN), albuminuria, histological changes, oxidative stress, inflammation, fibrosis and glucolipids. Effects were pooled using random-effects models. Heterogeneity was presented as I2. Subgroup analysis investigated treatment- and animal-related factors for renal outcomes. Publication bias was assessed using funnel plots and Egger's test. Sensitivity analysis was performed to assess the results' robustness. RevMan 5.3 and Stata MP 15 software were used for statistical analysis. RESULTS: Forty studies involving 1543 animals were identified for analysis. AM treatment significantly decreased SCr (MD = -19.12 µmol/l, 95 % CI: -25.02 to -13.23), BUN (MD = -6.72 mmol/l, 95 % CI: -9.32 to -4.12), urinary albumin excretion rate (SMD = -2.74, 95 % CI: -3.57, -1.90), histological changes (SMD = -2.25, 95 % CI: -3.19 to -1.32). AM treatment significantly improved anti-oxidative stress expression (SMD = 1.69, 95 % CI: 0.97 to 2.41), and decreased inflammation biomarkers (SMD = -3.58, 95 % CI: -5.21 to -1.95). AM treatment also decreased fibrosis markers (i.e. TGF-ß1, CTGF, collagen IV, Wnt4 and ß-catenin) and increased anti-fibrosis marker BMP-7. Blood glucose, lipids and kidney size were also improved compared with the DM control group. CONCLUSION: AM could improve renal outcomes and alleviate injury through multiple signaling pathways. This indicates AM may be an option to consider for the development of future DKD therapeutics.

Oral Chinese Herbal Medicine plus usual care for diabetic kidney disease: study protocol for a randomized, double-blind, placebo-controlled pilot trial.

Background: Diabetic kidney disease (DKD) has become the leading cause of kidney failure, causing a significant socioeconomic burden worldwide. The usual care for DKD fails to achieve satisfactory effects in delaying the persistent loss of renal function. A Chinese herbal medicine, Tangshen Qushi Formula (TQF), showed preliminary clinical benefits with a sound safety profile for people with stage 2-4 DKD. We present the protocol of an ongoing clinical trial investigating the feasibility, efficacy, and safety of TQF compared to placebo in delaying the progressive decline of renal function for people with stage 2-4 DKD. Methods: A mixed methods research design will be used in this study. A randomized, double-blind, placebo-controlled pilot trial will evaluate the feasibility, efficacy, and safety of TQF compared to placebo on kidney function for people with stage 2-4 DKD. An embedded semi-structured interview will explore the acceptability of TQF granules and trial procedures from the participant's perspective. Sixty eligible participants with stage 2-4 DKD will be randomly allocated to the treatment group (TQF plus usual care) or the control group (TQF placebo plus usual care) at a 1:1 ratio for 48-week treatment and 12-week follow-up. Participants will be assessed every 12 weeks. The feasibility will be assessed as the primary outcome. The changes in the estimated glomerular filtration rate, urinary protein/albumin, renal function, glycemic and lipid markers, renal composite endpoint events, and dampness syndrome of Chinese medicine will be assessed as the efficacy outcomes. Safety outcomes such as liver function, serum potassium, and adverse events will also be evaluated. The data and safety monitoring board will be responsible for the participants' benefits, the data's credibility, and the results' validity. The intent-to-treat and per-protocol analysis will be performed as the primary statistical strategy. Discussion: Conducting a rigorously designed pilot trial will be a significant step toward establishing the feasibility and acceptability of TQF and trial design. The study will also provide critical information for future full-scale trial design to further generate new evidence supporting clinical practice for people with stage 2-4 DKD. Trial registration number: https://www.chictr.org.cn/, identifier ChiCTR2200062786.

Chinese herbal medicine for atopic dermatitis: a systematic review.

BACKGROUND: Atopic dermatitis (AD) is a chronic, itching skin disease, and conventional therapies offer inadequate symptom management. Patients with AD are increasingly turning to Chinese medicine. OBJECTIVE: We systematically evaluated the clinical evidence of the efficacy and safety of oral Chinese herbal medicine for AD. METHODS: Searches were conducted on major electronic databases using the following key words: "randomized controlled trials," "atopic dermatitis," "traditional Chinese medicine," "traditional East Asian medicine," "herbal medicine," "Chinese herbal drugs," "medicinal plants," "phytotherapy," "Kampo medicine," and "Korean traditional medicine." The results were screened to include English/Chinese randomized controlled trials. A metaanalysis was conducted on suitable outcome measures. RESULTS: Seven randomized controlled trials were included (1 comparing Chinese herbal medicine and Western medicine with Western medicine alone; 6 comparing Chinese herbal medicine with placebo). Combined Chinese herbal medicine with Western medicine was superior to Western medicine alone. Three placebo controlled trials showed significant treatment efficacy and 2 showed significantly reduced concurrent therapy with Chinese herbal medicine. No abnormalities in safety profile or severe adverse events were reported. LIMITATIONS: A metaanalysis of all included studies could not be conducted because of study heterogeneity. CONCLUSIONS: Chinese herbal medicine significantly improved symptom severity of AD and was reported as well tolerated. However, the poor quality of studies did not allow for valid conclusions to support its tolerability and routine use. Additional studies addressing the methodologic issues are warranted to determine the therapeutic benefit of Chinese herbal medicine for AD.

Oral Chinese herbal medicine in reducing the recurrence of colorectal adenoma after polypectomy: A protocol for the systematic review and meta-analysis.

BACKGROUND: Colorectal adenoma (CRA) is a significant precancerous lesion of sporadic colorectal cancer (CRC). CRA is likely to recur after polypectomy, increasing the risk of CRC. Chinese herbal medicine (CHM) has been used to reduce CRA recurrence. This review aims to evaluate the effectiveness and safety of oral CHM in reducing CRA recurrence compared to other treatments (placebo, routine care, no treatment, and conventional medicine). METHODS: We will search for randomised controlled trials (RCTs) from nine major biomedical databases in English and Chinese from their inception to July 2023. The RCTs that investigate the effects of oral CHM in reducing CRA recurrence compared to other treatments will be involved. We will exclude trials using CHM extract or external application of CHM, cohort study and cross-section study. The Cochrane Risk of Bias Tool version 2 will be used to assess the quality of included studies. Data will be analysed using Review Manager software 5.4 and STATA. The random effect model will be used. The heterogeneity of intervention effects will be tested by Chi2 (Cochrane Q) and I2 statistics. Funnel plots will assess publication bias if more than ten studies are included. Subgroup and sensitivity analysis will be conducted when possible. DISCUSSION: This review will discuss the effectiveness and safety of oral CHM in reducing CRA recurrence. It will show the critical information for clinicians in the decision-making process and countries to develop clinical guidelines on CRA management. Systematic review registration PROSPERO CRD42023324197.