STUDY QUESTION Does acupuncture improve insulin sensitivity more effectively than metformin or sham acupuncture in women with polycystic ovary syndrome (PCOS) and insulin resistance (IR)? SUMMARY ANSWER Among women with PCOS and IR, acupuncture was not more effective than metformin or sham acupuncture in improving insulin sensitivity. WHAT IS KNOWN ALREADY Uncontrolled trials have shown that acupuncture improved insulin sensitivity with fewer side effects compared with metformin in women with PCOS and IR. However, data from randomized trials between acupuncture and metformin or sham acupuncture are lacking. STUDY DESIGN, SIZE, DURATION This was a three-armed randomized controlled trial enrolling a total of 342 women with PCOS and IR from three hospitals between November 2015 and February 2018, with a 3-month follow-up until October 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged from 18 to 40 years with PCOS and homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.14 were randomly assigned (n = 114 per group) to receive true acupuncture plus placebo (true acupuncture), metformin plus sham acupuncture (metformin, 0.5 g three times daily) or sham acupuncture plus placebo (sham acupuncture) for 4 months, with an additional 3-month follow-up. True or sham acupuncture was given three times per week, and 0.5 g metformin or placebo was given three times daily. The primary outcome was change in HOMA-IR from baseline to 4 months after baseline visit. Secondary outcomes included changes in the glucose AUC during an oral glucose tolerance test, BMI and side effects at 4 months after baseline visit. MAIN RESULTS AND THE ROLE OF CHANCE After 4 months of treatment, the changes of HOMA-IR were –0.5 (decreased 14.7%) in the true acupuncture group, –1.0 (decreased 25.0%) in the metformin group and –0.3 (decreased 8.6%) in the sham acupuncture group, when compared with baseline. True acupuncture is not as effective as metformin in improving HOMA-IR at 4 months after baseline visit (difference, 0.6; 95% CI, 0.1–1.1). No significant difference was found in change in HOMA-IR between true and sham acupuncture groups at 4 months after baseline visit (difference, –0.2; 95% CI, –0.7 to 0.3). During the 4 months of treatment, gastrointestinal side effects were more frequent in the metformin group, including diarrhea, nausea, loss of appetite, fatigue, vomiting and stomach discomfort (31.6%, 13.2%, 11.4%, 8.8%, 14.0% and 8.8%, respectively). Bruising was more common in the true acupuncture group (14.9%). LIMITATIONS, REASONS FOR CAUTION This study might have underestimated the sample size in the true acupuncture group with 4 months of treatment to enable detection of statistically significant changes in HOMA-IR with fixed acupuncture (i.e. a non-personalized protocol). Participants who withdrew because of pregnancy did not have further blood tests and this can introduce bias. WIDER IMPLICATIONS OF THE FINDINGS True acupuncture did not improve insulin sensitivity as effectively as metformin in women with PCOS and IR, but it is better than metformin in improving glucose metabolism (which might reduce the risk of type 2 diabetes) and has less side effects. Metformin had a higher incidence of gastrointestinal adverse effects than acupuncture groups, and thus acupuncture might be a non-pharmacological treatment with low risk for women with PCOS. Further studies are needed to evaluate the effect of acupuncture combined with metformin on insulin sensitivity in these women. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants 2017A020213004 and 2014A020221060 from the Science and Technology Planning Project of Guangdong Province. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER Clinicaltrials.gov number: NCT02491333. TRIAL REGISTRATION DATE 8 July 2015. DATE OF FIRST PATIENT’S ENROLLMENT 11 November 2015.

Constraint-induced movement therapy (CIMT) combined with repetitive transcranial magnetic stimulation (rTMS) have shown great potential in improving function in schoolchildren with unilateral cerebral palsy attributed to perinatal stroke. However, the prospect of application in preschool children with unilateral cerebral palsy (UCP) attributed to various brain disorders remains unclear. In this prospective, assessor-blinded, randomized controlled study, 40 preschool children with UCP (aged 2.5–6 years) were randomized to receive 10 days of CIMT combined with active or sham rTMS. Assessments were performed at baseline, 2 weeks, and 6 months post-intervention to investigate upper limb extremity, social life ability, and perceived changes by parents and motor-evoked potentials. Overall, 35 participants completed the trial. The CIMT plus active stimulation group had greater gains in the affected hand function (range of motion, accuracy, and fluency) than the CIMT plus sham stimulation group (P < 0.05), but there was no significant difference in muscular tone, social life ability, and perceived changes by parents between the two groups (P > 0.05). In addition, there was no significant difference in hand function between children with and without motor-evoked potential (P > 0.05). No participants reported severe adverse events during the study session. In short, the treatment of CIMT combined with rTMS is safe and feasible for preschool children with UCP attributed to various brain disorders. Randomized controlled studies with large samples and long-term effects are warranted.

Ovarian carcinoma (OV) is one of the most lethal gynecological malignancies globally, and the overall 5-year survival rate of OV was 47% in 2018 according to American data. To increase the survival rate of patients with OV, many researchers have sought to identify biomarkers that act as both prognosis-predictive markers and therapy targets. However, most of these have not been suitable for clinical application. The present study aimed at constructing a predictive prognostic nomogram of OV using the genes identified by combining The Cancer Genome Atlas (TCGA) dataset for OV with the immune score calculated by the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm. Firstly, the algorithm was used to calculate the immune score of patients with OV in the TCGA-OV dataset. Secondly, differentially expressed genes (DEGs) between low and high immune score tissues were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis was performed to predict the functions of these DEGs. Thirdly, univariate, multivariate and Lasso Cox's regression analyses were carried out step by step, and six prognosis-related DEGs were identified. Then, Kaplan-Myer survival curves were generated for these genes and validated by comparing their expression levels to further narrow the range of DEGs and to calculate the risk score. Two genes were identified, cell division cycle 20B and patatin-like phospholipase domain containing 5, which were both shown to have higher expression levels in OV tissues and to be significantly associated with the prognosis of OV. Next, a nomogram was created using these two genes and age, and using the receiver operating characteristic (ROC) curve and calibration curve, the effectiveness of the nomogram was validated. Finally, an external validation was conducted for this nomogram. The ROC showed that the areas under the curve (AUCs) of the 3-and 5-year overall survival predictions for the nomogram were 0.678 and 0.62, respectively. Moreover, the ROC of the external validation model showed that the AUCs of the 3-and 5-year were 0.699 and 0.643, respectively, demonstrating the effectiveness of the generated nomogram. In conclusion, the present study has identified two immune-related genes as biomarkers that reliably predict overall survival in OV. These biomarkers might also be potential molecular targets of immune therapy to treat patients with OV.

Background: Traditional Chinese medicine (TCM) usually involves syndrome differentiation and treatment. Acupuncture, one form of TCM, requires the selection of appropriate acupoints and needling techniques, but many clinical trials on acupuncture have used fixed acupuncture protocols without accounting for individual patient differences. We have designed a multicenter randomized controlled trial (RCT) to evaluate whether personalized or fixed acupuncture increases the likelihood of live births in infertile women with polycystic ovary syndrome (PCOS) compared with letrozole or placebo letrozole. We hypothesize that letrozole is more effective than personalized acupuncture, which in turn is more effective than fixed acupuncture, and that placebo letrozole is the least effective intervention. Moreover, we hypothesize that personalized acupuncture is more likely to reduce the miscarriage rate and the risk of pregnancy complications compared with letrozole. Methods/design: The study is designed as an assessor-blinded RCT. A total of 1100 infertile women with PCOS will be recruited from 28 hospitals and randomly allocated to 4 groups: personalized acupuncture, fixed acupuncture, letrozole, or placebo letrozole. They will receive treatment for 16 weeks, and the primary outcome is live birth. Secondary outcomes include ovulation rate, conception rate, pregnancy rate, pregnancy loss rate, changes in hormonal and metabolic parameters, and changes in quality of life scores. Adverse events will be recorded throughout the trial. All statistical analyses will be performed using IBM SPSS Statistics version 21.0 software (IBM Corp., Armonk, NY, USA), and a P value < 0.05 will be considered statistically significant.

Response surface methodology (RSM) was utilized to optimize the ultrasonic-assisted extraction (UAE) of Dioscorea cirrhosa pigment (DCP).

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Background: Nutritional problems are common in children with cerebral palsy (CP), yet the relationship between nutritional status and the severity of CP is unclear.Objective: To describe the nutritional status and characteristics of children with CP, and to explore the relationship between severity of CP and nutritional status in children.Methods: This multicentre cross-sectional study included children with CP in China. Weight and height were measured and converted to z-scores. Gross Motor Function Classification System (GMFCS), Eating and Drinking Ability Classification System (EDACS), Subjective Global Nutritional Assessment (SGNA), social life ability, and blood indicators were tested.Results: All 1,151 participants were given oral-feeding and 50.8% of them demonstrated undernutrition. Compared with those in GMFCS or EDACS levels I–III, the odds of moderate and severe undernutrition were 2.6 and 8.9 times higher in GMFCS levels IV and V, and 4.3 and 12.6 times higher in EDACS levels IV and V, respectively. Except for serum 25-hydroxyvitamin D, no significant differenceswere found in blood indicators among normal, undernourished and overnourished groups.Conclusion: Degrees of undernutrition in children with CP are correlated with the severity of eating and drinking dysfunction and with gross motor impairment. Blood indicators may not reflect nutritional status in children with CP. LAY ABSTRACTCerebral palsy is the most common physical disability in children in the world. Children with cerebral palsy may have a high risk of having malnutrition as a result of the high energy consumption and/or low energy intake. The former is mainly caused by the abnormal muscular tone, and the latter may emerge from the dysphagia and gastrointestinal problems. As for the optimization of nutritional status is integral to the overall health and clinical management of children with cerebral palsy, the nutritional status stands out for its clinical importance in this group. Children with cerebral palsy are affected by different degrees of motor dysfunction, and may also be faced with eating and drinking problems or limited daily life ability, it is not clear whether nutritional status and function are interrelated. What's more, it is believed that the blood tests may indicate the nutritional status, but it is not well understood. In this project we will look at the nutritional status of children with cerebral palsy in China and investigate the relationship between nutritional status and function and blood indicators. This will then allow clinicians and caregivers to formulate future policies to improve nutritional status for this group of children.