Specific Immunotherapy and Follow-up Management of Respiratory Allergic Diseases in Children.

Objective: To analyze specific immunotherapy and follow-up management for respiratory allergic diseases in children. Methods: A total of 100 children with allergic bronchial asthma admitted to our hospital from November 2020 to October 2021 were selected. Based on different treatment schemes, they were divided into two groups: the routine treatment group and the immunotherapy group, with 50 cases in each group. The routine treatment group received standard care, while the immunotherapy group underwent specific immunotherapy. Assessment parameters included asthma symptom control score, pulmonary function, immune function, levels of inflammatory factors, clinical efficacy, and adverse reactions. Results: After treatment and during follow-up, the immunotherapy group showed significantly lower scores for daytime and nighttime symptoms compared to the routine treatment group (P < .05). The immunotherapy group also exhibited higher FEV1/FVC and PEF% values compared to the routine therapy group after treatment and at follow-up (P < .05). Furthermore, the immunotherapy group showed higher levels of CD3+, CD4+, and CD4+/CD8+ and lower levels of CD8+ compared to the routine therapy group (P < .05). Additionally, the immunotherapy group demonstrated lower levels of IL-4 and IL-12 compared to the routine therapy group after treatment and during follow-up (P < .05). The total effective rate of the immunotherapy group was higher than that of the routine therapy group (P < .05). The incidence of adverse reactions in the immunotherapy group was similar to that in the routine therapy group (P > .05). Conclusions: Specific immunotherapy is a significantly effective approach to managing children's allergic bronchial asthma. It effectively controls asthma symptoms, improves lung function and immune response, and reduces inflammatory factors. It showed superior clinical efficacy and minimal adverse reactions; specific immunotherapy, therefore, is a safe and beneficial treatment option that warrants further promotion and application.

Effect of Pulmonary Function Training with a Respirator on Functional Recovery and Quality of Life of Patients with Stroke.

A stroke is a sudden onset cerebral blood circulation disorder. It occurs in patients with cerebrovascular disease due to various predisposing factors causing stenosis, occlusion, or rupture of intracerebral arteries, which, in turn, causes acute cerebral blood circulation disturbance and clinically manifests as symptoms and signs of excessive or permanent cerebral dysfunction. It can cause serious harm to patients' physical and mental health. This study aimed to evaluate the effect of Breathe-Link breathing trainers on lung function and the ability to perform activities of daily living in patients with stroke. Sixty patients with stroke were randomly divided into two groups. One group was set as the control group and received routine breathing training. The experimental group received a Breathe-Link trainer based on regular training, with rehabilitation training for 12 weeks as the time node. Respiratory muscle strength, respiratory velocity, respiratory capacity, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and rate in the first second (FEV1/FVC) were used to evaluate the respiratory function of patients, and the Barthel index was used to evaluate the ability to perform activities of daily living. Improvements in respiratory function and daily living ability were compared between the two groups. After 12 weeks of training, respiratory muscle strength, respiratory velocity, respiratory volume, FVC, FEV1, FEV1/FVC, and Barthel index of patients in the two groups improved compared with those before training (P < 0.05), and the improvement in the treatment group was better than that in the control group (P < 0.05). Breathe-Link breathing trainers can improve lung function and the ability to perform activities of daily living in patients with stroke, and its effect is acceptable. It can be recommended for clinical use.

Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening.

Primary cilia dyskinesia (PCD) is a rare genetic disease caused by ciliary structural or functional defects. It causes severe outcomes in patients, including recurrent upper and lower airway infections, progressive lung failure, and randomization of heterotaxy. To date, although 50 genes have been shown to be responsible for PCD, the etiology remains elusive. Meanwhile, owing to the lack of a model mimicking the pathogenesis that can be used as a drug screening platform, thereby slowing the development of related therapies. In the current study, we identified compound mutation of DNAH9 in a patient with PCD with the following clinical features: recurrent respiratory tract infections, low lung function, and ultrastructural defects of the outer dynein arms (ODAs). Bioinformatic analysis, structure simulation assay, and western blot analysis showed that the mutations affected the structure and expression of DNAH9 protein. Dnah9 knock-down (KD) mice recapitulated the patient phenotypes, including low lung function, mucin accumulation, and increased immune cell infiltration. Immunostaining, western blot, and co-immunoprecipitation analyses were performed to clarify that DNAH9 interacted with CCDC114/GAS8 and diminished their protein levels. Furthermore, we constructed an airway organoid of Dnah9 KD mice and discovered that it could mimic the key features of the PCD phenotypes. We then used organoid as a drug screening model to identify mitochondrial-targeting drugs that can partially elevate cilia beating in Dnah9 KD organoid. Collectively, our results demonstrated that Dnah9 KD mice and an organoid model can recapture the clinical features of patients with PCD and provide an excellent drug screening platform for human ciliopathies.

Myocardial Rev-erb-Mediated Diurnal Metabolic Rhythm and Obesity Paradox.

BACKGROUND: The nuclear receptor Rev-erbα/ß, a key component of the circadian clock, emerges as a drug target for heart diseases, but the function of cardiac Rev-erb has not been studied in vivo. Circadian disruption is implicated in heart diseases, but it is unknown whether cardiac molecular clock dysfunction is associated with the progression of any naturally occurring human heart diseases. Obesity paradox refers to the seemingly protective role of obesity for heart failure, but the mechanism is unclear. METHODS: We generated mouse lines with cardiac-specific Rev-erbα/ß knockout (KO), characterized cardiac phenotype, conducted multi-omics (RNA-sequencing, chromatin immunoprecipitation sequencing, proteomics, and metabolomics) analyses, and performed dietary and pharmacological rescue experiments to assess the time-of-the-day effects. We compared the temporal pattern of cardiac clock gene expression with the cardiac dilation severity in failing human hearts. RESULTS: KO mice display progressive dilated cardiomyopathy and lethal heart failure. Inducible ablation of Rev-erbα/ß in adult hearts causes similar phenotypes. Impaired fatty acid oxidation in the KO myocardium, in particular, in the light cycle, precedes contractile dysfunctions with a reciprocal overreliance on carbohydrate utilization, in particular, in the dark cycle. Increasing dietary lipid or sugar supply in the dark cycle does not affect cardiac dysfunctions in KO mice. However, obesity coupled with systemic insulin resistance paradoxically ameliorates cardiac dysfunctions in KO mice, associated with rescued expression of lipid oxidation genes only in the light cycle in phase with increased fatty acid availability from adipose lipolysis. Inhibition of glycolysis in the light cycle and lipid oxidation in the dark cycle, but not vice versa, ameliorate cardiac dysfunctions in KO mice. Altered temporal patterns of cardiac Rev-erb gene expression correlate with the cardiac dilation severity in human hearts with dilated cardiomyopathy. CONCLUSIONS: The study delineates temporal coordination between clock-mediated anticipation and nutrient-induced response in myocardial metabolism at multi-omics levels. The obesity paradox is attributable to increased cardiac lipid supply from adipose lipolysis in the fasting cycle due to systemic insulin resistance and adiposity. Cardiac molecular chronotypes may be involved in human dilated cardiomyopathy. Myocardial bioenergetics downstream of Rev-erb may be a chronotherapy target in treating heart failure and dilated cardiomyopathy.

Capsella bursa-pastoris (L.) Medic. extract alleviate cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Capsella bursa-pastoris (L.) Medic. (CBP) is a cruciferous plant valuable in reducing fever, improving eyesight and calming the liver. This herb was recorded in the Compendium of Materia Medica for cataract treatment. AIM OF THE STUDY: To determine the effects and mechanism of CBP on cataract prevention and treatment using a selenite cataract model. MATERIALS AND METHODS: The main compounds in CBP extract were analyzed by UPLC, 1H-NMR and 13C-NMR spectroscopic techniques. Flavonoids formed a significant proportion of its compounds, thus necessitating an evaluation of their inhibitory effects on the development of cataract using a selenite cataract model. The protective effects of CBP flavonoids (CBPF) against oxidative damage and the modulation of mitochondrial apoptotic pathway were subsequently verified on H2O2-treated SRA01/04 lens epithelial cells. RESULTS: CBPF significantly alleviated the development of cataract by decreasing the MDA level and increasing the GSH-Px and SOD levels in the lens. It also inhibited H2O2-induced apoptosis in SRA01/04 cells, increased the expression of Bcl-2 protein and decreased the expressions of Caspase-3 and Bax proteins. CONCLUSION: CBPF exerts a significant preventive effect on cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells. It is thus a potent traditional Chinese medicine (TCM) whose application should be further developed for the clinical treatment of cataract.

A Tensor-Based Frequency Features Combination Method for Brain-Computer Interfaces.

With the development of the brain-computer interface (BCI) community, motor imagery-based BCI system using electroencephalogram (EEG) has attracted increasing attention because of its portability and low cost. Concerning the multi-channel EEG, the frequency component is one of the most critical features. However, insufficient extraction hinders the development and application of MI-BCIs. To deeply mine the frequency information, we proposed a method called tensor-based frequency feature combination (TFFC). It combined tensor-to-vector projection (TVP), fast fourier transform (FFT), common spatial pattern (CSP) and feature fusion to construct a new feature set. With two datasets, we used different classifiers to compare TFFC with the state-of-the-art feature extraction methods. The experimental results showed that our proposed TFFC could robustly improve the classification accuracy of about 5% ( ). Moreover, visualization analysis implied that the TFFC was a generalization of CSP and Filter Bank CSP (FBCSP). Also, a complementarity between weighted narrowband features (wNBFs) and broadband features (BBFs) was observed from the averaged fusion ratio. This article certificates the importance of frequency information in the MI-BCI system and provides a new direction for designing a feature set of MI-EEG.

Effects of omega-3 polyunsaturated fatty acids supplementation for patients with cardiovascular disease risks: a dose-response meta-analysis.

BACKGROUND: Previous studies assessing the impact of omega-3 polyunsaturated fatty acids (ω-3 PUFA) have shown conflicting results in regard to the cardiovascular mortality. It is likely that higher dose of ω-3 PUFA would have a greater effect on the major adverse cardiovascular events (MACEs). Therefore, we performed a dose-response meta-analysis to explore the potential protective effect of ω-3 PUFA, with the increase of daily intake and extension of the intervention period, on patients with cardiovascular disease risks. Outcomes included major adverse cardiovascular events, cardiovascular and all-cause mortality. METHODS: A systematic literature search of PubMed, Embase and the Cochrane Library from inception to September 31, 2019 was conducted to identify the randomized controlled trails (RCTs) of ω-3 PUFA supplementation, which reported cardiovascular events or deaths and recruited no less than 500 participants. We evaluated the effect of ω-3 PUFA through the pooled relative risks (RR) and 95% confidence intervals (95% CI), and further carried out subgroup analysis and dose-response meta-analysis. RESULTS: Fourteen trials including 87718 individuals were reviewed. By conventional statistical significance, there was no apparent difference between the two groups on major adverse cardiovascular effects (RR 0.94, 95% CI 0.84-1.04) and all-cause mortality (RR 0.96, 95% CI 0.91-1.00), but there was an effect on the cardiovascular mortality (RR 0.93, 95% CI 0.88-0.99). However, with the dose increased and intervention period prolonged (daily dose × intervention period > 8 grams/day × years), subgroup analyses showed a more obvious reduction of MACEs (RR 0.79, 95% CI 0.65-0.95) and all-cause mortality (RR 0.93, 95% CI 0.85-1.03). Furthermore, the dose-response meta-analysis presented a 13.05% reduction of MACEs and 8.99% reduction of all-cause mortality with 10 grams/day × years increments. CONCLUSIONS: Updated with the newly published RCTs, this meta-analysis indicated that large dose and long period of interventions with ω-3 PUFA supplementation produce a close association with MACEs and cardiovascular or all-cause mortality. A dose-response beneficial effect was preliminarily established.

Complementary and Alternative Medicine for Dysmenorrhea Caused by Endometriosis: A Review of Utilization and Mechanism.

Endometriosis (EM) is a common and benign estrogen-dependent gynecological disorder among women of reproductive age, and secondary dysmenorrhea is one of the more severe symptoms. However, the mechanism behind the development of dysmenorrhea is poorly understood, and there is a lack of effective methods for diagnosing and treating EM dysmenorrhea. In this regard, complementary and alternative medicine (CAM) has recently come into widespread use due to its limited adverse reactions and high efficiency. This review updates the progress of CAM in the treatment of EM dysmenorrhea and seeks to identify the therapeutic efficacy as well as the mechanisms behind these effects based on the available clinical and experimental studies. According to the literature, CAM therapy for EM dysmenorrhea, including herbs (herbal prescriptions, extracts, and patents), acupuncture, and Chinese herbal medicine enema (CHM enema), is effective for relieving dysmenorrhea with fewer unpleasant side effects when compared to hormonal and surgical treatments. In addition, we discuss and analyze the existing gaps in the literature. We hope to provide some instructive suggestions for clinical treatment and experimental research in the future.

Efficacy and safety of Xiyanping injection in the treatment of COVID-19: A multicenter, prospective, open-label and randomized controlled trial.

Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID-19). Here, we conducted a prospective, multicenter, open-label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID-19. We consecutively recruited 130 COVID-19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID-19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID-19 patients at different disease stages.

Effects of Different Patterns and Sources of Trace Elements on Laying Performance, Tissue Mineral Deposition, and Fecal Excretion in Laying Hens.

This study was conducted to investigate the effects of different patterns and sources of Zn, Fe, Cu, Mn, and Se on performance, mineral deposition (liver, kidney, pancreas, spleen, pectorals muscle, and tibia), and excretion of laying hens, then to find an optimal dietary supplemental pattern of trace elements in laying hens. A total of 864 healthy laying hens with similar laying rate (Roman, 26-week-old) were randomly divided into nine treatments, with six replications of 16 birds per replication, including a control treatment and four patterns with different element sources (inorganic or organic): (1) Control treatment (basic diet without added extra trace minerals, CT); pattern 1, NRC (1994) recommended level (NRC-L): (2) inorganic minerals of NRC-L pattern (IN), (3) organic minerals of NRC-L pattern (ON); pattern 2, NY/T 33-2004 recommended level (NY/T-L): (4) inorganic minerals of NY/T-L pattern (IY), (5) organic minerals of NY/T-L pattern (OY); pattern 3, 50% NRC (1994) recommended level (50% NRC-L): (6) inorganic minerals of 50% NRC-L pattern (IHN), (7) organic minerals of 50% NRC-L pattern (OHN); pattern 4, the ratio of minerals in blood of laying hens was taken as the supplement proportion of trace elements, and Zn was supplemented depended on NRC recommended level (TLB): (8) inorganic minerals of TLB pattern (IB), (9) organic minerals of TLB pattern (OB). Two weeks were allowed for adjustment to the conditions and then measurements were made over eight weeks. Supplementation of trace elements led to increased daily egg weight (p < 0.05). Patterns of minerals in diets affected the content of liver Mn, pancreas Mn, tibia Mn, and the tissues Se (p < 0.05). Sources of minerals had positive effects on daily egg weight (p < 0.05), the concentrations of liver Fe, kidney Cu, tissues Se (except spleen), and fecal Se (p < 0.05). In conclusion, diet supplemented with the organic trace minerals of 50% NRC-L pattern (OHN) in laying hens promoted optimum laying performance, mineral deposition, and reduced mineral excretion.

The effect of Tai Chi on the pulmonary rehabilitation of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of Tai Chi for chronic obstructive pulmonary disease (COPD) so far is unclear. The present systematic review aimed to determine the influence of Tai Chi among people with COPD. METHODS: We searched six electronic databases for relevant studies in September, 2019. The methods of standard meta-analysis were used for identifying relevant studies, quality appraisal, and synthesis. The primary outcomes were six-minute walking distance (6MWD), percentage predicted forced expiratory flow volume in the first second (%PredFEV1), and St. George's Respiratory Questionnaire (SGRQ) score. RESULTS: A total of 23 studies including 1663 participants were included in the meta-analysis. The pooled data showed that the Tai Chi group was associated with a significant improvement in 6MWD [mean difference (MD) 40.83 m, 95% CI: 32.47 to 49.19], %PredFEV1 (MD 1.67%, 95% CI: 0.41 to 2.93), SGRQ score (MD -6.57, 95% CI: -10.17 to -2.98), and Chronic Respiratory Disease Questionnaire (CRQ) (MD 1.60, 95% CI: 0.89 to 2.30) relative to the blank control population. When compared with breathing exercises, the 6MWD was significantly enhanced with Tai Chi (MD 14.15 m, 95% CI: 3.76 to 24.53). Finally, when compared with breathing and walking exercises, Tai Chi was associated with a significant improvement in 6MWD (MD 7.68 m, 95% CI: 2.28 to 13.09 m) and SGRQ score (MD -6.31, 95% CI: -9.13 to -1.48). CONCLUSIONS: Tai Chi may have the potential to reduce dyspnoea, enhance exercise capacity, and improve the quality of life in COPD patients. People with COPD may obtain benefit from practicing Tai Chi.

The Complementary and Alternative Medicine for Polycystic Ovary Syndrome: A Review of Clinical Application and Mechanism.

As a reproductive endocrine disease, polycystic ovary syndrome (PCOS) has influenced billions of women during childbearing age worldwide. Owing to its complex etiology and ambiguous pathogenesis, there is still not a specific method to cure it. Clinical treatments, such as hormone therapy and surgical treatment, have side effects. Therefore, it is essential and urgent to seek alternative treatment to solve these problems. The satisfactory efficacy of complementary and alternative medicine (CAM), such as traditional Chinese medicine (TCM), immunotherapy, medicinal foods, vitamin therapy, diet therapy, psychotherapy, spa, and oxygen therapy, in treating PCOS, has aroused an increasing number of medical workers' concern and gradually become the mainstream. This paper reviews the application of CAM in the treatment of PCOS, especially from the perspective of TCM. Meanwhile, the limitations of the literature about CAM in the treatment of PCOS are mentioned and analyzed as well.

Washing fresh tea leaves before picking decreases pesticide residues in tea.

BACKGROUND: The use of pesticides during tea plant cultivation helps agricultural production and prevents and controls pests, diseases and weeds. It is of the utmost importance to balance pesticide application with tea quality, safety and consumer health. The uptake of pesticides into plants may lead to the presence of residues that are hazardous to human health, especially for some foliar-applied insecticides. The movability or penetration behavior of a pesticide remains unknown after it has been sprayed on a tea leaf. RESULTS: Two organophosphate (acephate, trichlorfon) and three neonicotinoid pesticides (imidacloprid, thiamethoxam and acetamiprid) were confirmed with respect to their removal from the treated fresh leaves of tea saplings via washing in a phytotron. Four of the targets have little penetrative ability into tea leaves, mainly existing (> 92%) on the tea leaf surface, except for trichlorfon (> 70%), for 30 days. With higher vapor pressures, trichlorfon and acetamiprid had relatively higher penetration ratios of 8.63-29.60% and 0.28-8.03% respectively. Two organophosphate insecticides were found to degrade more quickly, with lower final amounts of residues on and in the whole leaf compared to the neonicotinoid pesticides. In a field test, these residues could be reduced by 45-72% after a pre-harvest interval of 3 days, and by 16-89% after 7 days, when the fresh tea shoots were sprayed with 2 or 4 L m-2 water. CONCLUSION: Pesticides with different structures have different penetration abilities on the tea leaf surface, and some pesticides in commercial tea can be reduced by spraying with water before fresh leaves are picked. © 2020 Society of Chemical Industry.

Effects of Tai Chi training on the physical and mental health status in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Tai Chi is a systematic whole body movement developed in ancient China. It plays an increasingly important role in the field of pulmonary rehabilitation for patients with chronic obstructive pulmonary disease (COPD). Our review aimed to explore the impact of Tai Chi on the physical and mental health of patients with COPD. METHODS: We searched several English and Chinese databases and used the combination of subject words and free words to search for available literature from the establishment of the library until August 28, 2018. Two researchers screened studies and collected the data independently. The study inclusion criteria included: (I) patients diagnosed with COPD; (II) Tai Chi or Tai Chi Qigong as an intervention in addition to routine treatment; (III) routine treatment with or without exercises as control group. The primary outcomes were lung function, exercise capacity and health status; (IV) randomized controlled trials. RESULTS: Sixteen articles were included from 2009 to 2018 (n=1,096). The average time duration of Tai Chi program was 53.4 minutes each session, 4.13 sessions a week for a total of 4.13 months. Comparing with control group, Tai Chi group improved some lung function (forced volume capacity: mean difference =0.12, 95% CI: 0.03-0.21), (forced expiratory volume in 1s: mean difference =0.15, 95% CI: 0.08-0.21), enhanced 6-minute walking distance score (mean difference =30.78, 95% CI: 15.15-46.42), decreased COPD Assessment Test score (mean difference =-5.00, 95% CI: -7.51 to -2.50), decreased St. George's Respiratory Questionnaire score (mean difference =-8.66, 95% CI: -14.60 to -2.72), enhanced Chronic Respiratory Disease Questionnaire score (mean difference =2.16, 95% CI: 1.49-2.83), decreased Hospital Anxiety and Depression Scale score(anxiety: mean difference =-1.04, 95% CI: -1.58 to -0.51; depression: mean difference =-1.25, 95% CI: -1.77 to -0.73). Comparing with exercise group, Tai Chi group statistically enhanced 6-minute walking distance score (mean difference =7.77, 95% CI: 2.63-12.91). CONCLUSIONS: Tai Chi may represent an appropriate alternative or complement to standard rehabilitation programs. However, whether Tai Chi is better than pulmonary rehabilitation exercise has not been determined.

Glutamine Metabolism Is Essential for Stemness of Bone Marrow Mesenchymal Stem Cells and Bone Homeostasis.

Skeleton has emerged as an endocrine organ which is both capable of regulating energy metabolism and being a target for it. Glutamine is the most bountiful and flexible amino acid in the body which provides adenosine 5'-triphosphate (ATP) demands for cells. Emerging evidences support that glutamine which acts as the second metabolic regulator after glucose exerts crucial roles in bone homeostasis at cellular level, including the lineage allocation and proliferation of bone mesenchymal stem cells (BMSCs), the matrix mineralization of osteoblasts, and the biosynthesis in chondrocytes. The integrated mechanism consisting of WNT, mammalian target of rapamycin (mTOR), and reactive oxygen species (ROS) signaling pathway in a glutamine-dependent pattern is responsible to regulate the complex intrinsic biological process, despite more extensive molecules are deserved to be elucidated in glutamine metabolism further. Indeed, dysfunctional glutamine metabolism enhances the development of degenerative bone diseases, such as osteoporosis and osteoarthritis, and glutamine or glutamine progenitor supplementation can partially restore bone defects which may promote treatment of bone diseases, although the mechanisms are not quite clear. In this review, we will summarize and update the latest research findings and clinical trials on the crucial regulatory roles of glutamine metabolism in BMSCs and BMSC-derived bone cells, also followed with the osteoclasts which are important in bone resorption.

Acupuncture and clomiphene for Chinese women with polycystic ovary syndrome (PCOSAct): statistical analysis approach with the revision and explanation.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women. Clomiphene is regarded as the first-line medical treatment for ovulation induction in PCOS patients and acupuncture is often used as an alternative and complementary treatment for fertility issues such as those associated with PCOS. The efficacy of acupuncture alone or combined with clomiphene still lacks strong supporting evidence. Factorial 2 × 2 designs can be used for the evaluations of two treatments within a single study, to test the main effects of acupuncture and clomiphene and their interactions. METHODS: PCOSAct was designed to test the effect of clomiphene and acupuncture by three two-group comparisons in the original protocol. However, the trial was designed as a standard factorial trial and the factorial analysis approach for analyzing the data that were actually obtained during the trial was found to be more appropriate and more powerful than the three two-group comparisons described in the original protocol, so the statistical analysis approach and different datasets of PCOSAct in the primary publication were accordingly changed. DISCUSSION: Although the statistical analysis approach used in the primary publication deviated from the statistical analysis planned in the study protocol, focusing on the main effects of the two interventions and their interactions was a more standard approach to a factorial trial and proved to be more suitable and consistent with the characteristics of the trial data. Statistically, the revision is more powerful and precise and should be more useful to the journal and the readers. TRIAL REGISTRATION: Chinese clinical trial registry, ChiCTR-TRC-12002081 . Registered on 20 March 2012. Clinicaltrials.gov, NCT01573858 . Registered on 4 April 2012.

Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

Herbal medicines for fatty liver diseases.

BACKGROUND: Fatty liver disease is potentially a reversible condition that may lead to end-stage liver disease. Since herbal medicines such as Crataegus pinnatifida and Salvia miltiorrhiza have increasingly been used in the management of fatty liver disease, a systematic review on herbal medicine for fatty liver disease is needed. OBJECTIVES: To assess the beneficial and harmful effects of herbal medicines for people with alcoholic or non-alcoholic fatty liver disease. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2012), MEDLINE, EMBASE, and Science Citation Index Expanded to 1 March 2012. We also searched the Chinese BioMedical Database, Traditional Chinese Medical Literature Analysis and Retrieval System, China National Knowledge Infrastructure, Chinese VIP Information, Chinese Academic Conference Papers Database and Chinese Dissertation Database, and the Allied and Complementary Medicine Database to 2 March 2012. SELECTION CRITERIA: We included randomised clinical trials comparing herbal medicines with placebo, no treatment, a pharmacological intervention, or a non-pharmacological intervention such as diet or lifestyle, or Western interventions in participants with fatty liver disease. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. We used the 'risk of bias' tool to assess the risk of bias of the included trials. We assessed the following domains: random sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other sources of bias. We presented the effects estimates as risk ratios (RR) with 95% confidence intervals (CI) or as mean differences (MD) with 95% CI, depending on the variables of the outcome measures. MAIN RESULTS: We included 77 randomised clinical trials, which included 6753 participants with fatty liver disease. The risks of bias (overestimation of benefits and underestimation of harms) was high in all trials. The mean sample size was 88 participants (ranging from 40 to 200 participants) per trial. Seventy-five different herbal medicine products were tested. Herbal medicines tested in the randomised trials included single-herb products (Gynostemma pentaphyllum, Panax notoginseng, and Prunus armeniaca), proprietary herbal medicines commercially available, and combination formulas prescribed by practitioners. The most commonly used herbs were Crataegus pinnatifida,Salvia miltiorrhiza,Alisma orientalis,Bupleurum Chinense,Cassia obtusifolia, Astragalus membranaceous, and Rheum palmatum. None of the trials reported death, hepatic-related morbidity, quality of life, or costs. A large number of trials reported positive effects on putative surrogate outcomes such as serum aspartate aminotransferase, alanine aminotransferase, glutamyltransferase, alkaline phosphatases, ultrasound, and computed tomography scan. Twenty-seven trials reported adverse effects and found no significant difference between herbal medicines versus control. However, the risk of bias of the included trials was high.The outcomes were ultrasound findings in 22 trials, liver computed tomography findings in eight trials, aspartate aminotransferase levels in 64 trials, alanine aminotransferase activity in 77 trials, and glutamyltransferase activities in 44 trials. Six herbal medicines showed statistically significant beneficial effects on ultrasound, four on liver computed tomography, 42 on aspartate aminotransferase activity, 49 on alanine aminotransferase activity, three on alkaline phosphatases activity, and 32 on glutamyltransferase activity compared with control interventions. AUTHORS' CONCLUSIONS: Some herbal medicines seemed to have positive effects on aspartate aminotransferase, alanine aminotransferase, ultrasound, and computed tomography. We found no significant difference on adverse effects between herbal medicine and control groups. The findings are not conclusive due to the high risk of bias of the included trials and the limited number of trials testing individual herbal medicines. Accordingly, there is also high risk of random errors.

Effects of dietary supplementation with vitamin E and selenium on rat hepatic stellate cell apoptosis.

AIM: To evaluate the effects of dietary supplementation with vitamin E and selenium on proliferation and apoptosis of hepatic stellate cells (HSCs), in acute liver injury induced by CCl(4), and to explore their role in the recovery from hepatic fibrosis phase. METHODS: An acute liver damage model of rats was established by intraperitoneal injection of carbon tetrachloride (0.3 mL/100 g body weight) twice a week, then the rats were killed at 6, 24, 48, and 72 h after the first and third injection, respectively. A liver fibrosis model was established by the same injection for 8 wk. Then three rats were killed at 3, 7, 14, and 28 d after the last injection, respectively. The rats from the intervention group were fed with chow supplemented with vitamin E (250 mg/kg) and selenium (0.2 mg/kg), and the rats in the normal control group and pathological group were given standard chow. Livers were harvested and stained with hematoxylin and eosin, Sirius red. Activated HSCs were determined by alpha-smooth muscle actin immunohistochemistry staining. Apoptotic HSCs were determined by dual staining with the terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL) and alpha-smooth muscle actin immunohistochemistry. Serum alanine aminotransferase and aspartate aminotransferase were also analyzed. RESULTS: In the acute liver damage model, the degree of liver injury was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, while the number of apoptotic HSCs was more in the intervention group than in the pathological group. In the liver fibrosis model, the degree of liver fibrosis was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, and the number of apoptotic HSCs was more in the intervention group than in the pathological group. CONCLUSION: Vitamin E and selenium supplementation at the given level can inhibit CCl(4)-induced activation and proliferation of HSCs and promote the apoptosis of activated HSCs in acute damage phase. Vitamin E and selenium can also effectively decrease the degree of hepatic fibrosis and promote the recovery process.