An AGS-associated mutation in ADAR1 catalytic domain results in early-onset and MDA5-dependent encephalopathy with IFN pathway activation in the brain.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a severe neurodegenerative disease with clinical features of early-onset encephalopathy and progressive loss of intellectual abilities and motor control. Gene mutations in seven protein-coding genes have been found to be associated with AGS. However, the causative role of these mutations in the early-onset neuropathogenesis has not been demonstrated in animal models, and the mechanism of neurodegeneration of AGS remains ambiguous. METHODS: Via CRISPR/Cas-9 technology, we established a mutant mouse model in which a genetic mutation found in AGS patients at the ADAR1 coding gene (Adar) loci was introduced into the mouse genome. A mouse model carrying double gene mutations encoding ADAR1 and MDA-5 was prepared using a breeding strategy. Phenotype, gene expression, RNA sequencing, innate immune pathway activation, and pathologic studies including RNA in situ hybridization (ISH) and immunohistochemistry were used for characterization of the mouse models to determine potential disease mechanisms. RESULTS: We established a mouse model bearing a mutation in the catalytic domain of ADAR1, the D1113H mutation found in AGS patients. With this mouse model, we demonstrated a causative role of this mutation for the early-onset brain injuries in AGS and determined the signaling pathway underlying the neuropathogenesis. First, this mutation altered the RNA editing profile in neural transcripts and led to robust IFN-stimulated gene (ISG) expression in the brain. By ISH, the brains of mutant mice showed an unusual, multifocal increased expression of ISGs that was cell-type dependent. Early-onset astrocytosis and microgliosis and later stage calcification in the deep white matter areas were observed in the mutant mice. Brain ISG activation and neuroglial reaction were completely prevented in the Adar D1113H mutant mice by blocking RNA sensing through deletion of the cytosolic RNA receptor MDA-5. CONCLUSIONS: The Adar D1113H mutation in the ADAR1 catalytic domain results in early-onset and MDA5-dependent encephalopathy with IFN pathway activation in the mouse brain.

A Lorentz Force EMAT Design with Racetrack Coil and Periodic Permanent Magnets for Selective Enhancement of Ultrasonic Lamb Wave Generation.

This article proposes an electromagnetic acoustic transducer (EMAT) for selectively improving the purity and amplitude of ultrasonic Lamb waves in non-ferromagnetic plates. The developed EMAT consists of a racetrack coil and a group of periodic permanent magnets (PPMs). Two-dimensional finite element simulations and experiments are implemented to analyze the working mechanism and performance of the PPM EMAT. Thanks to the specific design, the eddy currents increase with increasing wire density and the directions of the magnetic fields and Lorentz forces alternate according to the polarities of the magnet units. Wires laid uniformly beneath the magnets, and the gaps between adjacent magnets generate tangential and normal Lorentz forces, resulting in-plane (IP) and out-of-plane (OP) displacements, respectively. The constructive interference occurs when the wavelength of the generated Lamb wave is twice the spacing of the magnets, leading to large amplitudes of the targeted ultrasonic Lamb waves. Therefore, the PPM EMAT is capable of generating pure symmetric or antisymmetric mode Lamb waves at respective frequencies. The results prove that the developed PPM EMAT can generate pure either S0 or A0 mode Lamb waves at respective frequencies. The increase in wire width and wire density further increases the signal amplitudes. Compared with the case of conventional meander-line-coil (MLC) EMAT, the amplitudes of the A0 and S0 mode Lamb waves of our PPM EMAT are increased to 880% and 328%, respectively.

Aicardi-Goutières syndrome-associated mutation at ADAR1 gene locus activates innate immune response in mouse brain.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a severe infant or juvenile-onset autoimmune disease characterized by inflammatory encephalopathy with an elevated type 1 interferon-stimulated gene (ISG) expression signature in the brain. Mutations in seven different protein-coding genes, all linked to DNA/RNA metabolism or sensing, have been identified in AGS patients, but none of them has been demonstrated to activate the IFN pathway in the brain of an animal. The molecular mechanism of inflammatory encephalopathy in AGS has not been well defined. Adenosine Deaminase Acting on RNA 1 (ADAR1) is one of the AGS-associated genes. It carries out A-to-I RNA editing that converts adenosine to inosine at double-stranded RNA regions. Whether an AGS-associated mutation in ADAR1 activates the IFN pathway and causes autoimmune pathogenesis in the brain is yet to be determined. METHODS: Mutations in the ADAR1 gene found in AGS patients were introduced into the mouse genome via CRISPR/Cas9 technology. Molecular activities of the specific p.K999N mutation were investigated by measuring the RNA editing levels in brain mRNA substrates of ADAR1 through RNA sequencing analysis. IFN pathway activation in the brain was assessed by measuring ISG expression at the mRNA and protein level through real-time RT-PCR and Luminex assays, respectively. The locations in the brain and neural cell types that express ISGs were determined by RNA in situ hybridization (ISH). Potential AGS-related brain morphologic changes were assessed with immunohistological analysis. Von Kossa and Luxol Fast Blue staining was performed on brain tissue to assess calcification and myelin, respectively. RESULTS: Mice bearing the ADAR1 p.K999N were viable though smaller than wild type sibs. RNA sequencing analysis of neuron-specific RNA substrates revealed altered RNA editing activities of the mutant ADAR1 protein. Mutant mice exhibited dramatically elevated levels of multiple ISGs within the brain. RNA ISH of brain sections showed selective activation of ISG expression in neurons and microglia in a patchy pattern. ISG-15 mRNA was upregulated in ADAR1 mutant brain neurons whereas CXCL10 mRNA was elevated in adjacent astroglia. No calcification or gliosis was detected in the mutant brain. CONCLUSIONS: We demonstrated that an AGS-associated mutation in ADAR1, specifically the p.K999N mutation, activates the IFN pathway in the mouse brain. The ADAR1 p.K999N mutant mouse replicates aspects of the brain interferonopathy of AGS. Neurons and microglia express different ISGs. Basal ganglia calcification and leukodystrophy seen in AGS patients were not observed in K999N mutant mice, indicating that development of the full clinical phenotype may need an additional stimulus besides AGS mutations. This mutant mouse presents a robust tool for the investigation of AGS and neuroinflammatory diseases including the modeling of potential "second hits" that enable severe phenotypes of clinically variable diseases.

[Proposal of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19].

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.

Comparative effectiveness of six Chinese herb formulas for acute exacerbation of chronic obstructive pulmonary disease: a systematic review and network meta-analysis.

BACKGROUND: Six Chinese herb formulas, namely, the Weijing decoction (WJ), the Maxingshigan decoction (MXSG), the Yuebijiabanxia decoction (YBBX), the Qingqihuatan decoction (QQHT), the Dingchuan decoction (DC) and the Sangbaipi decoction (SBP), are commonly used, along with routine pharmacotherapy, to manage the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). In this study, we conducted a systematic review to summarize the efficacy of these six formulas, and we also conducted a network meta-analysis (NMA) to rank these formulas. METHODS: We searched five English databases and four Chinese databases, with dates ranging from the starting dates of these databases to December 2016. Randomized controlled trials that evaluated any of the six Chinese herb formulas combined with the use of pharmacotherapy for AECOPD were identified. RESULTS: Fifty-five studies involving 4560 participants were included. The pairwise meta-analyses showed that WJ and QQHT had superior effects on the improvement of lung function (forced expiratory volume in 1 seconds; FEV1) (mean difference (MD): 0.25, 95% confidence interval (CI): 0.19-0.30 and 0.34, 95%CI: 0.10-0.58). MXSG, WJ and QQHT were found to be more effective for improving arterial blood gases (PaO2 and PaCO2). In terms of effective rates, all of these formulas had additional favourable effects compared to routine pharmacotherapy. The results of the NMA analyses indicated that only MXSG showed superior add-on effects for the improvement of FEV1 (MD: 0.37, 95% credible interval (CrI): 0.03-0.72). Most of the formulas combined with routine pharmacotherapy were superior to pharmacotherapy alone for the improvement of arterial blood gases and effective rates. The ranking tests suggested that QQHT and MXSG combined with routine pharmacotherapy might be optimal options for the treatment of AECOPD. CONCLUSIONS: This NMA indicated that QQHT and MXSG might be more effective treatment regimens for AECOPD. Further well-designed studies that specifically examine the direct comparisons of these formulas are needed to support our conclusions.

Comparisons between traditional medicines and pharmacotherapies for Alzheimer disease: A systematic review and meta-analysis of cognitive outcomes.

OBJECTIVES: To evaluate the clinical evidence for traditional medicines (TMs) used in East Asia on measures of cognition in Alzheimer disease, determine the effect sizes at different time points for the TMs and pharmacotherapies, and assess the tolerability of the TMs. METHODS: We searched 12 databases in English, Chinese, and Japanese for eligible randomised controlled trials that compared orally administered TMs with pharmacotherapy and reported cognitive outcomes. Meta-analyses were conducted for Alzheimer's Disease Assessment Scale-cognitive subscale and/or Mini-Mental State Examination (MMSE). Mean differences and 95% confidence intervals were calculated to evaluate treatment effects. RESULTS: Thirty randomised controlled trials met inclusion criteria. Twenty-nine compared TMs with donepezil. Single studies provided comparisons with galantamine, rivastigmine, or memantine. There were no significant differences between the TM and donepezil groups at 12 or 24 weeks for Alzheimer's Disease Assessment Scale-cognitive subscale or MMSE. Improvements over baseline were significant for MMSE at 12 and 24 weeks within the TM and donepezil groups and remained significant at 1 year. Effect sizes were reduced in the 3 double-blind studies. At 24 weeks, donepezil 10 mg/d generally produced greater improvements in MMSE than 5 mg/d. Tolerability reporting was incomplete and inconsistent between studies. CONCLUSIONS: The results suggested that the clinical benefits of the TMs were not less than donepezil at comparable time points, with both groups showing improvements. However, lack of blinding in most studies and other design and measurement issues are likely to have resulted in overestimation of effect sizes in both groups. Further well-designed studies are needed.

Acupuncture plus moxibustion for herpes zoster: A systematic review and meta-analysis of randomized controlled trials.

Herpes zoster is an acute inflammatory condition which can have a significant impact on quality of life. Antiviral therapies are effective, but do not meet patients' expectations of symptomatic relief. Acupuncture and moxibustion have been used for herpes zoster; this systematic review evaluated their efficacy and safety. Nine English and Chinese databases were searched from their inceptions to March 2016. Randomized controlled trials evaluating the combination of acupuncture plus moxibustion in adult herpes zoster were included. Outcomes included pain intensity and duration, quality of life and adverse events. Meta-analysis was performed using RevMan software (version 5.3). Nine studies (945 participants) were included. Studies were of low to moderate methodological quality based on risk of bias assessment. Pain intensity (visual analogue scale) was lower among those who received acupuncture plus moxibustion compared with pharmacotherapy (one study; MD -8.25 mm, 95% CI -12.36 to -4.14). The clinical significance of this result is yet to be established. Some benefits were seen for other pain and cutaneous outcomes, and global improvement in symptoms. Mild adverse events were reported in the intervention groups. Acupuncture plus moxibustion may improve pain and cutaneous outcomes, although current evidence is limited by the number of studies and methodological shortcomings.

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.

Herbal medicine for adults with asthma: A systematic review.

BACKGROUND: Many people with asthma use herbal medicines to help reduce symptoms and improve asthma control. OBJECTIVE: To update the systematic review and meta-analysis of randomised controlled trials of herbal medicine for adult asthma. DATA SOURCES: Nine English and Chinese databases were searched (PubMed, Embase, CINAHL, CENTRAL, AMED, CBM, CNKI, CQVIP, Wanfang). STUDY SELECTIONS: Herbal medicines combined with routine pharmacotherapies compared with the same pharmacotherapies alone or placebo. Cochrane Risk of Bias Tool and GRADE Summary of Findings tables were used to evaluate methodological quality. RESULTS: Twenty-nine (29) studies involving 3,001 participants were included. Herbal interventions used multi-ingredients such as licorice root, crow-dipper, astragali, and angelica. Compared with routine pharmacotherapies alone, herbal medicines as add-on therapy improved lung function (FEV1: MD 7.81%, 95% CI 5.79, 9.83, I(2) = 63%; PEFR: MD 65.14 L/min, 95% CI 58.87, 71.41, I(2) = 21%); asthma control (MD 2.47 points, 95% CI 1.64, 3.29, I(2) = 55%); reduced salbutamol usage (MD -1.14 puffs/day, 95% CI -2.20, -0.09, I(2) = 92%); and reduced acute asthma exacerbations over one year (MD -1.20, 95% CI -1.82, -0.58, one study). Compared with placebo plus pharmacotherapies herbal medicines as add-on therapy improved lung function (FEV1: MD 15.83%, 95% CI 13.54, 18.12 and PEFR: MD 55.20 L/min, 95% CI 33.41, 76.99). Other outcomes were not reported in these placebo studies. Included studies were low to moderate quality. Adverse events were rare. CONCLUSIONS: Herbal medicines combined with routine pharmacotherapies improved asthma outcomes greater than pharmacotherapies alone. Included studies did not blind participants therefore more studies that address such weaknesses are warranted.

Oral Astragalus (Huang qi) for preventing frequent episodes of acute respiratory tract infection in children.

BACKGROUND: Acute respiratory tract infections (ARTIs) are common in children and can involve both upper and lower airways. Many children experience frequent ARTI episodes or recurrent respiratory tract infections (RRTIs) in early life, which creates challenges for paediatricians, primary care physicians, parents and carers of children.In China, Astragalus (Huang qi), alone or in combination with other herbs, is used by Traditional Chinese Medicine (TCM) practitioners in the form of a water extract, to reduce the risk of ARTIs; it is believed to stimulate the immune system. Better understanding of the therapeutic mechanisms of Astragalus may provide insights into ARTI prevention, and consequently reduced antibiotic use. OBJECTIVES: To assess the effectiveness and safety of oral Astragalus for preventing frequent episodes of acute respiratory tract infections (ARTIs) in children in community settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 12, 2015), MEDLINE (Ovid) (1946 to 31 December 2015), Embase (Elsevier) (1974 to 31 December 2015), AMED (Ovid) (1985 to 31 December 2015), Chinese National Knowledge Infrastructure (CNKI) (1979 to 31 December 2015) and Chinese Scientific Journals full text database (CQVIP) (1989 to 31 December 2015), China Biology Medicine disc (CBM 1976 to 31 December 2015) and Wanfang Data Knowledge Service Platform (WanFang) (1998 to 31 December 2015). SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing oral Astragalus as a sole Chinese herbal preparation with placebo to prevent frequent episodes of ARTIs in children. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures for this review. We assessed search results to identify relevant studies. We planned to extract data using standardised forms. Disagreements were to be resolved through discussion. Risk of bias was to be assessed using the Cochrane 'Risk of bias' tool. We planned to use mean difference (MD) or standardised mean difference (SMD) for continuous data and risk ratio (RR) or odds ratio (OR) to analyse dichotomous data, both with 95% confidence intervals (CIs). MAIN RESULTS: We identified 6080 records: 3352 from English language databases, 2724 from Chinese databases, and four from other sources. Following initial screening and deduplication, we obtained 120 full-text papers for assessment. Of these, 21 were not RCTs; 55 did not meet the inclusion criteria because: participants were aged over 14 years; definition was not included for recurrent or frequent episodes;Astragalus preparation was not an intervention; Astragalus preparation was in the formula but was not the sole agent; the Astragalus preparation was not administered orally; or Astragalus was used for treatment rather than prevention of ARTI. A further 44 studies were excluded because they were not placebo-controlled, although other inclusion criteria were fulfilled.No RCTs met our inclusion criteria. AUTHORS' CONCLUSIONS: We found insufficient evidence to enable assessment of the effectiveness and safety of oral Astragalus as a sole intervention to prevent frequent ARTIs in children aged up to 14 years.

Bioassay-guided isolation of an active compound with protein tyrosine phosphatase 1B inhibitory activity from Sargassum fusiforme by high-speed counter-current chromatography.

A rapid and efficient method using high-speed counter-current chromatography was established for the bioassay-guided separation of an active compound with protein tyrosine phosphatase 1B inhibitory activity from Sargassum fusiforme. Under the bioassay guidance, the ethyl acetate extract with the best IC50 value of 0.37 ± 0.07 µg/mL exhibited a potential protein tyrosine phosphatase 1B inhibitory activity, which was further separated by high-speed counter-current chromatography. The separation was performed with a two-phase solvent system composed of n-hexane/methanol/water (5:4:1, v/v). As a result, dibutyl phthalate (19.7 mg) with the purity of 95.3% was obtained from 200 mg of the ethyl acetate extract. Its IC50 was 14.05 ± 0.06 µM, which was further explained by molecular docking. The result of molecular docking showed that dibutyl phthalate enfolded in the catalytic site of protein tyrosine phosphatase 1B. The main force between dibutyl phthalate and protein tyrosine phosphatase 1B was the hydrogen bond interaction with Gln266. In addition, hydrogen bond, van der Waals force and hydrophobic interaction with the amino acids (Ala217, Ile219, and Gly220) were also responsible for the stable protein-ligand complex.

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.

[Reporting quality and effect size comparison in randomized controlled trials of bo's abdominal acupuncture using CONSORT statement and STRICTA].

OBJECTIVE: To evaluate the reporting quality of randomized controlled trials (RCT) that compared Bo's abdominal acupuncture with conventional body acupuncture, and compare the efficacy and safety between them by performing a Meta-analysis. METHODS: All RCTs comparing Bo's abdominal acupuncture with conventional body acupuncture were included. English and Chinese databases were searched from their respective inceptions to March 2014. The reporting quality was assessed according to the "Consolidated Standards of Reporting Trials" (CONSORT) checklist for parallel RCTs and the revised "Standards for Reporting Interventions in Clinical Trials of Acupuncture" (STRICTA). A Meta-analysis was conducted to synthesize the effect sizes, and publication bias was evaluated by the Egger linear regression test using Stata. RESULTS: Ninety-seven studies were included, of which most lacked adequate reporting information, and 80.4% showed that the efficacy of abdominal acupuncture is superior to conventional body acupuncture, especially for the following diseases: lumbar disc herniation, cervical spondylosis, omarthritis and cervical vertigo, except simple obesity. Effect-sizes were controversial when evaluating different outcomes. CONCLUSION: The international standard CONORT statement and STRICTA guidelines should be strictly applied when reporting acupuncture RCTs in the future. Abdominal acupuncture appears to be more effective compared with conventional body acupuncture for some diseases. However, fur-her high quality blind RCTs using validated out-ome indexes and standard reporting are warranted.

Dietary interventions for mineral and bone disorder in people with chronic kidney disease.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic dysfunction of mineral and bone metabolism in people with CKD. Recent research shows that phosphate retention plays a significant role in the development of CKD-MBD. Compared with drug therapies, dietary interventions may be simple, inexpensive and feasible for phosphate retention. However, there is little evidence to support these interventions. OBJECTIVES: Our objective was to assess the benefits and harms of any dietary intervention for preventing and treating CKD-MBD. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 27 August 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We also searched the Chinese Biomedicine Database (CBM) (1976 to August 2015), China Knowledge Resource Integrated Database (CNKI) (1979 to August 2015), and VIP (1989 to August 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs looking at dietary interventions for prevention or treatment of CKD-MBD were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the eligibility, methodological quality, and extracted data. Continuous outcomes (serum calcium level, serum phosphorus level, calcium × phosphate product, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23) and alkaline phosphatase) were expressed as mean difference (MD) with 95% confidence interval (CI). Dichotomous outcomes (mortality) were expressed as risk ratio (RR) with 95% CI. We used a random-effects model to meta-analyse studies. MAIN RESULTS: Nine studies were included in this review which analysed 634 participants. Study duration ranged from 4 to 24 weeks. The interventions included calcium-enriched bread, low phosphorus intake, low protein intake, very low protein intake, post haemodialysis supplements and hypolipaemic diet. Only one study reported death; none of the included studies reported cardiovascular events or fractures. There was insufficient reporting of design and methodological aspects among the included studies to enable robust assessment of risk of bias.There was limited and low-quality evidence to indicate that calcium-enriched bread increased serum calcium (1 study, 53 participants: MD -0.16 mmol/L, 95% CI -0.51 to -0.31), decreased serum phosphorus (53 participants: MD -0.41 mmol/L, 95% CI -0.51 to -0.31) and decreased the calcium × phosphate product (53 participants: MD -0.62 mmol²/L², 95% CI -0.77 to -0.47).Very low protein intake was not superior to conventional low protein intake in terms of effect on serum phosphorus (2 studies, 41 participants: MD -0.12 mmol/L, 95% CI -0.50 to 0.25), serum calcium (MD 0.00 mmol/L, 95% CI -0.17 to 0.17), or alkaline phosphatase (MD -22.00 U/L, 95% CI -78.25 to 34.25). PTH was significantly lower in the very low protein intake group (2 studies, 41 participants: MD -69.64 pmol/L, 95% CI -139.83 to 0.54).One study reported no significant difference in the number of deaths between low phosphorus intake and normal diet (279 participants: RR 0.18, 95% CI 0.01 to 3.82). Low phosphorus intake decreased serum phosphorus (2 studies, 359 participants: MD -0.18 mmol/L, 95% CI -0.29 to -0.07; I(2) = 0%).One study reported post-haemodialysis supplements did not increase serum phosphorus compared to normal diet (40 participants: MD 0.12 mmol/L, 95% CI -0.24 to 0.49).One study reported low phosphorus intake plus lanthanum carbonate significantly decreased FGF-23 (19 participants: MD -333.80 RU/mL, 95% CI -526.60 to -141.00), but did not decrease serum phosphorus (19 participants: MD -0.10 mg/dL, 95% CI -0.38 to 0.58) or PTH (19 participants: MD 31.60 pg/mL, 95% CI -29.82 to 93.02). AUTHORS' CONCLUSIONS: There was limited low quality evidence to indicate that dietary interventions (calcium-enriched bread or low phosphorus/protein intake) may positively affect CKD-MBD by increasing serum calcium, decreasing serum phosphorus, the calcium × phosphate product and FGF-23. Large and well-designed RCTs are needed to evaluate the effects of various interventions for people with CKD-MBD.

Rationale and design of the Helping Ease Renal failure with Bupi Yishen compared with the Angiotensin II Antagonist Losartan (HERBAAL) trial: a randomized controlled trial in non-diabetes stage 4 chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. Currently, as for advanced CKD populations, medication options limited in angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), which were partially effective. A Chinese herbal compound, Bupi Yishen formula, has showed renal protective potential in experiments and retrospective studies. This study will evaluate the efficacy and safety of Bupi Yishen formula (BYF) in patients with CKD stage 4. DESIGN: In this double blind, double dummy, randomized controlled trial (RCT), there will be 554 non-diabetes stage 4 CKD patients from 16 hospitals included and randomized into two groups: Chinese medicine (CM) group or losartan group. All patients will receive basic conventional therapy. Patients in CM group will be treated with BYF daily while patients in control group will receive losartan 100 mg daily for one year. The primary outcome is the change in estimated glomerular filtration rate (eGFR) over 12 months. Secondary outcomes include the incidence of endpoint events, liver and kidney function, urinary protein creatinine ratio, cardiovascular function and quality of life. DISCUSSION: This study will be the first multi-center, double blind RCT to assess whether BYF, compared with losartan, will have beneficial effects on eGFR for non-diabetes stage 4 CKD patients. The results will help to provide evidence-based recommendations for clinicians. TRIAL REGISTRATION: Chinese Clinical Trial Registry Number: ChiCTR-TRC-10001518 .

Dang shen [Codonopsis pilosula (Franch.) Nannf] herbal formulae for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the efficacy and safety of Dang shen [Codonopsis pilosula (Franch.) Nannf., root] formulae for the treatment of chronic obstructive pulmonary disease (COPD). English and Chinese databases were searched, and 48 randomized controlled trials were included. Dang shen formulae improved lung function forced expiratory volume in 1 s compared with conventional pharmacotherapy (CP) [mean difference (MD) 0.22 L, 95% confidence interval (CI) 0.13-0.31, p < 0.001, I(2) = 5%] and quality of life (St. Georges Respiratory Questionnaire) compared with placebo (MD -7.19, 95% CI -10.82 to -3.56, p < 0.001, I(2) = 0%) and when combined with CP versus CP (MD -9.05, 95% CI -12.72 to -5.38, p < 0.001, I(2) = 89%). Dang shen formulae also increased distance walked in 6 min when combined with CP versus CP alone (MD 51.43 m, 95% CI 30.06-72.80, p < 0.001, I(2) = 27%) and reduced frequency/days with COPD exacerbations. Risk of bias was evaluated using the Cochrane tool. Methodological shortfalls were identified. Adverse events were low and not different between intervention and control groups. Thirty-three events were reported, including gastrointestinal upset, dry mouth, and insomnia. Dang shen formulae appear to improve some aspects of the included COPD outcomes. However, owing to methodological flaws, the current evidence is inadequate to support the routine use of Dang shen formulae outside of Chinese medicine practice. However, these results justify further investigation.

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.

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.

Current status and implementation strategies of patient education in core outcome set development.

OBJECTIVE: Patient participation is essential for Core Outcome Set (COS) development studies. Patient education during participation may help patients better express their views in COS studies. This study aimed to investigate the current status of patient participation and the specified educational information in COS studies. METHODS: We conducted a systematic review of COS development studies. Information on patient participation in COS research, and especially details of patient education, was analyzed. RESULTS: In total, 146 COS development studies were included in this review. Of these, 125 studies (85.6%) mentioned patient participation. Most studies did not provide explicit information on patient participation. Some studies mentioned recruiting patients, but ultimately, none of them responded. Six studies reported conducting patient education through workshops, creating patient forums, or providing videos and slides. However, these studies did not provide details on education. Twenty-three studies used the plain language to explain patient outcomes. CONCLUSION: COS developers are increasingly focusing on patient participation. However, only a few COS studies have explicitly reported conducting measures related to patient education. Further patient education is necessary when they participate in the development of a new Core Outcome Set. PRACTICE IMPLICATION: This article provides implementation strategies related to patient education for future COS development studies.