Chinese herbal medicine bath therapy for psoriasis vulgaris using topical calcipotriol as the comparator: A systematic review with meta-analysis and association rule analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory skin disease. Vitamin D analogues are the first-line topical agents for the long-term management of psoriasis. Chinese herbal medicine (CHM) bath therapy is commonly employed for psoriasis. However, the effects and safety of CHM bath therapy for psoriasis vulgaris, using topical calcipotriol as the comparator, remain inconclusive. Furthermore, the combination of herbs, a distinctive feature of CHM, is essential for its therapeutic effects due to the individual and synergistic properties of the herbs involved. AIM OF THE STUDY: The review was conducted to evaluate the effectiveness and safety of CHM bath therapy for psoriasis vulgaris, using calcipotriol as the comparator. Potential herbs and herb combinations of CHM bath therapy were also explored for further drug discovery. MATERIALS AND METHODS: Nine databases were searched from inception until March 05, 2024. Randomised controlled trials (RCTs) investigating CHM bath therapy, using calcipotriol as the comparator, were included. Statistical analyses were performed using RevMan 5.4, Stata 12.0 and SPSS Clementine 12.0 software. The evidence certainty for outcomes was assessed using the approach proposed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group. Moreover, association rule analysis on herbs identified in the systematic review was conducted to explore the potential herbs and herb combinations. RESULTS: A total of 17 RCTs involving 1,379 participants were included in this systematic review. The findings of this review revealed that: 1) CHM bath therapy produced comparable effects to calcipotriol in reducing Psoriasis Area and Severity Index (PASI), Psoriasis Scalp Severity Index (PSSI), and itch visual analogue scale (VAS) at the end of the treatment phase; as well as exhibited a superior long-term effect than calcipotriol through decreasing relapse rates at the end of the follow-up phase; 2) CHM bath therapy showed an additional benefit when combined with calcipotriol in managing psoriasis vulgaris at the end of the treatment phase, in terms of PASI, PSSI, itch VAS, IL-17, IL-23, CD3+ and CD4+ T cells. The certainty of the evidence was rated as 'very low', 'low' or 'moderate' based on the GRADE assessment, considering some concerns or high risk of bias of included studies, substantial heterogeneity, and existing publication bias of some outcomes. Additionally, the proportions of participants reporting adverse events were similar in both groups. Association rule analysis of all included herbs identified 23 herb combinations including Prunus persica (L.) Batsch and Carthamus tinctorius L., as well as 11 frequently used herbs, such as Kochia scoparia (L.) Schrad., Dictamnus dasycarpus Turcz. And Sophora flavescens Ait. CONCLUSIONS: The effects of CHM bath therapy were comparable with those of topical calcipotriol but demonstrated a longer-lasting effect. Combining CHM bath therapy with calcipotriol also provided an additional benefit for adult psoriasis vulgaris. However, the certainty of the evidence was downgraded due to the methodological limitations of included studies. To confirm the findings of this review, future investigations should involve double-blinded, placebo-controlled RCTs. Importantly, it appears worthwhile to consider further research for drug development utilising the identified herbs or herb combinations.

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.

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.

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.

Acupuncture for premature ventricular complexes without ischemic or structural heart diseases: A systematic review and meta-analysis of clinical and pre-clinical evidence.

Background: With increasing evidence suggesting potential benefits, acupuncture is often applied to the treatment of premature ventricular complexes (PVCs), particularly in symptomatic patients who fail or are unsuitable for medications or refuse catheter ablation. However, the existing clinical evidence is inconsistent. Objectives: This review aims to systematically evaluate the effectiveness and safety of acupuncture therapies for PVCs without ischemic or structural heart diseases, when it is compared with sham/placebo acupuncture or usual care, or used as an add-on therapy to routine care; and to summarize existing pre-clinical research evidence supporting the effects of acupuncture therapies for this clinical condition. Methods: Four English-language databases, four Chinese-language databases and seven clinical registries were searched from their inceptions to May 21, 2021 and updated to November 01, 2022. Trials comparing acupuncture with sham acupuncture or evaluating the add-on effects of acupuncture were included. Primary outcomes are the number of premature ventricular beats (PVBs) and effective rate defined as "the proportion of participants with over 50% decrease in the number of PVBs from baseline to the end of treatment measured by 24-h Holter". Results: A total of 479 records were identified with nine trials involving 847 participants included in this review. Meta-analysis on two sham-control trials with low risk of bias for all domains suggested that acupuncture could significantly reduce the number of PVBs (RR 3.83, 95% CI [2.19, 6.7], I 2 = 0%). Moreover, the combination of acupuncture and standard treatment was superior to standard treatment alone in reducing the burden of PVBs (RR 1.21, 95% CI [1.08, 1.36], I 2 = 0%). Though no treatment protocol consensus was announced, body acupuncture on point PC6, HT7, DU10, DU11, and ST36 with duration of needle retention ranging from 15 to 30 min for a 4-week treatment period is broadly used by the included trials. For experimental evidence, five studies explored the mechanisms of acupuncture for PVCs were eventually included into analysis and PC6 was the most frequently studied acupuncture point. Moreover, a reduction of electrical activity of sympathetic nerves in experimental animals undergoing electro-acupuncture was observed by four of these studies. Conclusion: Sham-controlled RCT evidence with moderate-level certainty suggested that acupuncture could be a therapeutic option to reduce the burden of PVBs in patients without ischemic or structural heart diseases. Further clinical studies using validated and reliable outcome measurement instruments and bench research to unveil the mechanisms of acupuncture stimulation and point-specific effects for PVCs are needed. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=262132], identifier [CRD42021262132].

Chinese herbal medicine for migraine management: A hospital-based retrospective analysis of electronic medical records.

Background: Migraine is a chronic neurological disease causing significant socioeconomic burden and impaired quality of life. Chinese medicine is commonly used for migraine in China. Clinical trials have generated evidence of the effectiveness of Chinese medicine therapies for migraine. However, little is known about how to use these therapies to treat migraine in real-world clinical settings. Methods: In this retrospective study, we analyzed data from the electronic medical records (EMRs) of 2,023 migraine patients who attended the Guangdong Provincial Hospital of Chinese Medicine (GPHCM) between July 2018 and July 2020. Results: More than three-quarters (77.21%) of the patients were female. Most (78.20%) of the patients were aged between 18 and 50 years, 18.49% were aged above 50 years, and the remaining 3.31% were under 18 years. Sleep disorders were the most documented comorbidity occurring in 27.29% of patients, and more common in females (29.77%) than male (18.87%). Fatigue was the most frequently reported trigger of migraine attacks among all patients (9.39%), while menstruation was the most common trigger for female patients (10.24%). Less than a quarter of patients (21.01%) reported a history of taking analgesic medication for their migraine. The median treatment duration reported by the patients was 10 days. Chinese herbal medicine (CHM) was the predominant treatment for migraine at the hospital (88.48%), while pharmacotherapies were prescribed to 28.97% of the patients. CHM was prescribed more often as a sole treatment (53.58% of patients) than combined with pharmacotherapies (27.39% of patients). Among patients who reported improvements after taking CHM, the most frequently used herbs were fu ling and chuan xiong, the most frequent patented CHM product was tong tian oral solution, and the main herbal formulae were chuan xiong cha tiao san and yi qi cong ming tang. Conclusion: CHM formulae, such as chuan xiong cha tiao san and yi qi cong ming tang, patented CHM product tong tian oral solution, and some herbs are potentially effective treatments for migraine. As such, CHM can be used as an alternative to conventional pharmacotherapies for migraine and is worth further evaluation in randomized controlled trials.

Natural products for migraine: Data-mining analyses of Chinese Medicine classical literature.

Background: Treatment effect of current pharmacotherapies for migraine is unsatisfying. Discovering new anti-migraine natural products and nutraceuticals from large collections of Chinese medicine classical literature may assist to address this gap. Methods: We conducted a comprehensive search in the Encyclopedia of Traditional Chinese Medicine (version 5.0) to obtain migraine-related citations, then screened and scored these citations to identify clinical management of migraine using oral herbal medicine in history. Information of formulae, herbs and symptoms were further extracted. After standardisation, these data were analysed using frequency analysis and the Apriori algorithm. Anti-migraine effects and mechanisms of actions of the main herbs and formula were summarised. Results: Among 614 eligible citations, the most frequently used formula was chuan xiong cha tiao san (CXCTS), and the most frequently used herb was chuan xiong. Dietary medicinal herbs including gan cao, bai zhi, bo he, tian ma and sheng jiang were identified. Strong associations were constructed among the herb ingredients of CXCTS formula. Symptoms of chronic duration and unilateral headache were closely related with herbs of chuan xiong, gan cao, fang feng, qiang huo and cha. Symptoms of vomiting and nausea were specifically related to herbs of sheng jiang and ban xia. Conclusion: The herb ingredients of CXCTS which presented anti-migraine effects with reliable evidence of anti-migraine actions can be selected as potential drug discovery candidates, while dietary medicinal herbs including sheng jiang, bo he, cha, bai zhi, tian ma, and gan cao can be further explored as nutraceuticals for migraine.

Acupuncture for menstruation-related migraine prophylaxis: A multicenter randomized controlled trial.

Objective: The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM). Patients and methods: This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1-3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1-3 and 4-6. Results: A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17-0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82-1.07) in the acupuncture group and 0.61 (95% CI, 0.50-0.71) in the medication group over cycles 1-3. Conclusion: This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles. Clinical trial registration: [https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606].

Fire Needling Acupuncture for Adult Patients with Acute Herpes Zoster: Protocol of a Systematic Review and Meta-Analysis.

Background: Acute herpes zoster (HZ) is characterized as a vesicular rash with unilateral distribution produced by the reactivation of varicella zoster virus. It can induce various comorbidities that can adversely influence the quality of life of patients. The purpose of this systematic review is to assess the effect and safety of fire needling acupuncture on acute HZ. Methods: Three English databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials) and four Chinese Databases (China National Knowledge Infrastructure, Wanfang database, Chongqing VIP database, and China Biology Medicine database) will be searched from their inceptions to July 2022. Randomized controlled trials investigating fire needling acupuncture therapy for acute HZ will be included, regardless of publication status. Two reviewers will independently conduct the study screening, data extraction, and research quality assessments. The primary outcome measures are the Pain Visual Analogue Scale and the occurrence of postherpetic neuralgia. Secondary outcomes measures are the evaluation of skin lesions, time to resolution of pain, tolerance evaluation, total effective rate, adverse events and changes in inflammatory and immune suppression markers in peripheral plasma. All included studies will be assessed for methodological quality via the Cochrane Collaboration's bias risk assessment tool. Meta-analyses will be undertaken using Review Manager V.5.3 software. The findings will be reported as the risk ratio of the binary data and the mean difference (MD) or standardized MD of the continuous data. Subgroup analyses and sensitivity analyses will be conducted where appropriate. The Grading of Recommendations Assessment, Development, and Evaluation will be used to assess evidence certainty. Results: From the study, we will ascertain the effects and safety of fire needling acupuncture on acute HZ. Conclusion: This study will validate the effects and safety of fire needling acupuncture in the management of acute HZ, generating new evidence to guide acupuncture interventions for acute HZ in the future. Registration Number: PROSPERO CRD42020199047.

Efficacy and Safety of Oral Chinese Herbal Medicine for Migraine: A Systematic Review and Meta-Analyses Using Robust Variance Estimation Model.

Background: Migraine is a prevalent headache disorder with significant impacts on patients' quality of life and economic burden. Chinese herbal medicine (CHM) is commonly prescribed for migraine in China. This review aimed to provide a rigorous evaluation of evidence on the efficacy of oral CHM for migraine and explore the correlation between its effect size and treatment duration. Methods: We searched nine digital databases (PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, AMED, BioMedical Literature, CNKI, CQVIP, and Wanfang Data) from their inceptions to May 2021, with the language being restricted to Chinese and English. Randomized, placebo-controlled trials using oral CHM to treat adult migraine were included. Data screening and extraction were conducted by two independent reviewers. The methodological quality of randomized controlled trials (RCTs) was assessed using the Cochrane Risk of Bias tool. Meta-analyses were conducted to estimate the effect size using a random effect model, and a robust variance estimation (RVE) model was constructed to explore the correlation between treatment effects and treatment duration. The certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation. Publication bias was tested using a funnel plot and Egger's test. Results: A total of 18 RCTs involving 3,015 participants were included. Results of the meta-analyses showed that, at the end of the treatment phase, CHM was more efficacious than placebo in reducing migraine frequency, migraine days, and pain severity, and increasing response rate. Additionally, CHM showed superior effects to placebo in lowering migraine frequency and pain severity at the end of the 4-week follow-up. The RVE model suggested that the benefits of CHM for migraine frequency and pain intensity increased as treatment duration extended. The number of adverse events reported by the CHM and placebo groups was comparable. The certainty of the evidence was graded as "moderate." No publication bias was detected. Conclusion: Oral CHM appeared to be more efficacious than placebo for reducing migraine frequency and pain severity. Greater treatment effects were associated with longer treatment duration. The oral CHM was well tolerated. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021270719.

Migraine patients visiting Chinese medicine hospital: Protocol for a prospective, registry-based, real-world observational cohort study.

INTRODUCTION: Migraine is a disabling, recurrent headache disorder with complex comorbidities. Conventional treatments for migraine are unsatisfactory, with side effects and limited effectiveness. Chinese herbal medicine (CHM) has been used as an alternative or complementary treatment option for migraine in China. Currently, the existing evidence of benefit of CHM for migraine has been generated from randomised clinical trials using standardised intervention with a focus on internal validity hence with limited external validity. Moreover, CHM individualised intervention design, patients' preferences and concerns, and clinicians' experience are critical to clinical decision making and therapeutic success. This real-world observational study aims to gather practice-based evidence of effects and safety of CHM for migraine in the context of integrating Chinese medicine diagnostic procedures, patients' preferences and matters relevant to clinical decision making. METHODS AND ANALYSIS: The study is being undertaken at the Guangdong Provincial Hospital of Chinese Medicine (GPHCM) from December 2020 to May 2022. We anticipate that approximately 400 adult migraineurs will be enrolled and observed on their migraine severity, analgesic consumption, quality of life, anxiety, depression and insomnia at baseline and then every four weeks over 12 weeks. Treatments, diagnostic information, and patient-reported most bothersome symptoms will be collected from patient clinical records. Patient's demographic data, preferences and concerns on CHM treatments will also be gathered at baseline and be analysed. Factors related to clinical outcomes will be explored with multiple correlation and multivariable regression analyses. Effects of CHM will be evaluated using generalised estimated equation, based on clinical outcome data. DISCUSSION: This study will provide comprehensive evidence of CHM for migraine in the context of evidence-based practice. TRIAL REGISTRATION NUMBER: ChiCTR2000041003.

Determining 5HT7R's Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine.

Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT7 receptor (5-HT7R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT7R could influence phosphorylation of protein kinase A (PKA)- or extracellular signal-regulated kinase1 / 2 (ERK1 / 2)-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT7R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK1 / 2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 min every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT7R antagonist (SB269970) or 5-HT7R agonist (AS19) was administered intrathecally before each IS application at 2-day intervals during the 7-day injection protocol. The changes in 5-HT7R and 5-HT7R-associated signaling pathway were examined by real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) analyses. When compared with IS group, mechanical and thermal pain thresholds of the IS + EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT7R mRNA expression and protein levels were detected in the IS + EA group. More importantly, 5-HT7R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK1 / 2. Injecting 5-HT7R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK1 / 2. Our findings indicate that 5-HT7R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK1 / 2 in TG and TNC.

Add-on effect of PSORI-CM01 to topical calcipotriol for moderate psoriasis vulgaris: A multi-center, randomized, double-blind pilot study.

BACKGROUND: Mild-moderate psoriasis vulgaris is a common dermatological autoimmune condition with limited conventional therapeutic options. Safe and effective adjunct therapies to topical non-steroidal antipsoriatic therapy are needed. The oral Chinese herbal medicine (CHM) formula PSORI-CM01 has been evidenced potential antipsoriatic pharmacological activity. This article reports a pilot study which was designed as a double-blinded, placebo-controlled randomized controlled trial (RCT) evaluating the effects of PSORI-CM01 when added to topical calcipotriol cream. METHODS: People with moderate psoriasis vulgaris were randomized to receive oral PSORI-CM01 or placebo administered for 12 weeks in combination with calcipotriol. The primary clinical outcome was the change of psoriasis area severity index (PASI) score at week 12 and week 24. Secondary clinical outcomes were PASI75, PASI50, relapse rate, change in body surface area, dermatology life quality index and Skindex29, and adverse events (AEs). Participants' satisfaction and willingness to repeat were also assessed. RESULTS: The pilot study was conducted in Australia and China, 29 participants were randomized with 26 completed the treatment and follow-up. Participants' baseline basic characteristics were comparable. No between-group statistical significance was found on pre-defined clinical outcome measures, although there seemed a trend of treatment effects favoring the combination of PSORI-CM01 with calcipotriol. Frequency and severity of AEs were similar between two groups, with no severe AEs reported. CONCLUSIONS: The design and duration of the study appears feasible. A proper powered RCT with slight adjustments in the methods is needed to reveal the add-on effects of oral CHM PSORI-CM01. The experience and results from this pilot study will contribute to the refine of objectives and design of a future study, and assist the sample size calculation for the full-scale RCT.

Electroacupuncture for Poststroke Spasticity: Results of a Pilot Pragmatic Randomized Controlled Trial.

CONTEXT: People with spasticity that occurred between 30 days and one year after stroke onset with a baseline Modified Ashworth Scale (MAS) ≥1. OBJECTIVES: To determine the practicality of a pragmatic parallel-group open-labeled randomized controlled trial and to collect preliminary data of effectiveness and safety of electroacupuncture (EA) for poststroke spasticity. METHODS: Eligible participants were randomly allocated to the intervention group (EA plus usual care) or the control group (usual care alone) at a 1:1 ratio with block sizes of six. Participants received EA three times a week for four weeks, then were followed up for another four weeks. Participants' retention and adherence in the trial were assessed to determine the practicality of trial design. Clinical outcome measures were the change scores of MAS, Fugl-Meyer Assessment of motor performance and Barthel Index, and adverse events. RESULTS: Seventy-two people were screened for eligibility, and 30 of them were recruited and randomized. At the end, 25 participants followed the trial protocol and were included in our final data analyses using an intention-to-treat approach. No significant between-group difference was detected for the change scores of MAS, Fugl-Meyer Assessment, or Barthel Index at the end of treatment or end of follow-up. Eighteen participants reported 37 adverse events, but none of the participants was deemed related to EA. CONCLUSION: It is feasible to conduct a full-scale trial to precisely evaluate the effectiveness and safety of EA for treating poststroke spasticity; however, longer treatment and follow-up phases should be considered in the full-scale trial.

Mechanism of Traditional Chinese Medicine in Treating Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a degenerative disease, making a unique contribution to chronic pain, edema, and limited mobility of knee joint. Traditional Chinese Medicine (TCM) is a common complementary therapy for KOA and has been found effective. The aim of this review is to consolidate the current knowledge about the mechanism of four interventions of TCM: acupuncture, moxibustion, herbs, and massage in treating KOA, and how they alleviate symptoms such as pain, swelling, and dysfunction. Furthermore, this review highlights that four therapies have different mechanisms but all of them can manage KOA through inhibiting inflammation, which indicates that alternative therapies should be considered as a viable complementary treatment for pain management in clinical practice.

Electro-acupuncture inhibits C-fiber-evoked WDR neuronal activity of the trigeminocervical complex: Neurophysiological hypothesis of a complementary therapy for acute migraine modeled rats.

INTRODUCTION: Acupuncture has become a relevant complementary and alternative treatment for acute migraine; however, the neurophysiological mechanism (C-fibers) underlying this effect remains unclear. C-fibers play a crucial role for diffuse noxious inhibitory controls (DNIC) at wide dynamic range (WDR) neurons in the trigeminocervical complex (TCC) in migraine attacks, and we supposed that this may be the mechanism of acupuncture analgesia. This study aimed to examine the neurophysiology of acupuncture intervention in an acute migraine rat model. METHODS: Inflammatory soup (IS) or saline was injected into the dura mater to establish a migraine and control model in rats. To explore the neurobiological mechanism of acupuncture for migraine, we implemented electro-acupuncture (EA), non-electric-stimulation acupuncture, and no-acupuncture in IS and saline injected rats, and recorded the single-cell extraneural neurophysiology of the atlas (C1) spinal dorsal horn neurons in the TCC. RESULTS: Our research shows that electro-acupuncture at GB8 (Shuaigu), located in the periorbital region receptive field of the trigeminal nerve, may rapidly reduce the C-fiber evoked WDR neuronal discharges of the TCC within 60 s. DISCUSSION: This study provides pioneering evidence of a potential neurobiological mechanism for the analgesic effect on migraine attacks achieved by electro-acupuncture intervention via DNIC. The data indicates that EA may become a crucial supplementary and alternative therapy for migraineurs that failed to respond to acute medications, e.g., fremanezumab, which achieves its analgesic effect via modulating Aσ-fibers, not C-fibers.

Oral Chinese Herbal Medicine as Prophylactic Treatment for Episodic Migraine in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The prophylactic effects of Chinese herbal medicine (CHM) for migraine were examined in numerous clinical trials. This review aimed to analyze the effectiveness and safety of CHM as prophylactic treatment of migraine compared to flunarizine. METHODS: Nine databases were searched for randomized controlled trials (RCTs) that evaluated effects of CHM for episodic migraine prophylaxis compared to flunarizine, published before March 2019. RESULTS: Thirty-five RCTs with 2,840 participants met the inclusion criteria, and 31 of them were included in meta-analyses. The overall meta-analysis indicated that, when compared to flunarizine, CHM reduced the frequency of migraine attacks at the end of treatment (EoT) (21 studies, mean difference (MD) -1.23, 95% confidence interval (CI) (-1.69, -0.76)) and at the end of follow-up (EoFU) (five studies, MD -0.96, 95% CI (-1.70, -0.21)). Subgroup analyses based on the treatment duration, follow-up duration, and the dosage of flunarizine showed that CHM was superior to or comparable with flunarizine in reducing migraine frequency. Similar results were also found for secondary outcomes such as the pain visual analogue scale, migraine duration, responder rate, and acute medication usage. In particular, the studies that used CHM containing herb pairs (Chuan Xiong plus Bai Zhi and Chuan Xiong plus Tian Ma) showed promising results. However, the certainty of this evidence was evaluated as "low" or "very low" using the Grading of Recommendations, Assessment, Development and Evaluations approach. CONCLUSION: CHM appeared to be comparable with flunarizine in reducing the frequency of episodic migraine attacks in adults at EoT and EoFU and well-tolerated by participants, regardless of the treatment duration, follow-up duration, and dosage of flunarizine. Due to the low certainty of the evidence, the suggested promising prophylactic outcomes require higher quality evidence from further rigorous RCTs.

Add-On Effects of Chinese Herbal Medicine for Post-Stroke Spasticity: A Systematic Review and Meta-Analysis.

Background: Treatment for post-stroke spasticity (PSS) remains a major challenge in clinical practice. Chinese herbal medicine (CHM) is often administered to assist in routine care (RC) in the treatment of PSS, with increasing numbers of clinical research and preclinical studies suggesting that it has potential benefits. Therefore, we conducted a systematic review and meta-analysis to evaluate the add-on effects and safety of CHM for PSS. Methods: Five English and four Chinese databases were searched from their respective inception to 28 February 2018. We included randomized controlled trials that evaluated the add-on effects of CHM for PSS, based on changes in the scores of the (Modified) Ashworth Scale (AS or MAS), Fugl-Meyer Assessment of Sensorimotor Recovery (FMA), and Barthel Index (BI). Results: Thirty-five trials involving 2,457 patients were included. For upper-limb AS or MAS, the estimated add-on effects of CHM to RC were significantly better when using oral (SMD -1.79, 95% CI: -3.00 to -0.57) or topical CHM (SMD -1.06, 95% CI: -1.40 to -0.72). For lower-limb AS or MAS, significant add-on benefits to RC were also detected (SMD -1.01, 95% CI: -1.43 to -0.59 and SMD -1.16, 95% CI: -1.83 to -0.49) using oral and topical CHM, respectively. For FMA and BI, better results were detected when adding CHM to RC, except for the subgroup of oral CHM for upper-limb FMA. Ten of the 35 included studies reported safety information, with two of them mentioning two mild adverse events. Conclusions: Noting the quality concerns of the included trials, this review suggests that CHM appears to be a well-tolerated therapy for patients with PSS, and the potential add-on effects of CHM in reducing spasticity and improving the daily activities of patients with PSS require further rigorous assessment.

Acupuncture for Post-stroke Shoulder-Hand Syndrome: A Systematic Review and Meta-Analysis.

Background: Shoulder-hand syndrome (SHS) is prevalent in hemiplegic patients after stroke. Potential benefits of acupuncture were shown in recent clinical trials. This systematic review aimed to comprehensively evaluate the safety and efficacy of acupuncture for SHS in stroke patients. Methods: Five English databases (PubMed, Embase, CINAHL, CENTRAL, and AMED) and four Chinese databases (CBM, CNKI, CQVIP, and Wanfang) were searched from their inceptions to January 2019. Randomized, controlled trials that evaluated the add-on effects of acupuncture to rehabilitation for post-stroke SHS were identified. Results: Thirty-eight studies involving 3,184 participants fulfilled the eligible criteria and were included in the review. The overall meta-analysis showed that acupuncture combined with rehabilitation significantly improved motor function (upper-limb Fugl-Meyer Assessment (FMA): 34 studies, mean difference (MD) 8.01, 95% confidence interval (CI) [6.69,9.33]), and reduced pain (visual analog scale (VAS): 25 studies, MD -1.59, 95%CI [-1.86,-1.32]). It also improved activities of daily living (ADL) when compared with rehabilitation alone (ADL: 11 studies, MD 9.99, 95%CI [5.91,14.06]). However, the certainty of evidence of all these outcomes was assessed as "low." Subgroup analyses of acupuncture stimulation types and treatment duration all showed significant add-on effects comparing with rehabilitation alone. The safety of acupuncture was unclear because there is a lack of detailed reporting of adverse events in most of the included studies. Conclusions: Acupuncture therapy seems effective for motor function, pain relief and activities of daily living in stroke patients with mild SHS, when it is used in combination with rehabilitation. The low certainty of evidence downgrades our confidence in making recommendations to clinical practice.