Sodium Niobate with a Large Interlayer Spacing: A Fast-Charging, Long-Life, and Low-Temperature Friendly Lithium-Storage Material.

Niobate Li+ -storage anode materials with shear ReO3 crystal structures have attracted intensive attention due to their inherent safety and large capacities. However, they generally suffer from limited rate performance, cyclic stability, and temperature adaptability, which are rooted in their insufficient interlayer spacings. Here, sodium niobate (NaNb13 O33 ) micron-sized particles are developed as a new anode material owning the largest interlayer spacing among the known shear ReO3 -type niobates. The large interlayer spacing of NaNb13 O33 enables very fast Li+ diffusivity, remarkably contributing to its superior rate performance with a 2500 to 125 mA g-1 capacity percentage of 63.2%. Moreover, its large interlayer spacing increases the volume-accommodation capability during lithiation, allowing small unit-cell-volume variations (maximum 6.02%), which leads to its outstanding cyclic stability with 87.9% capacity retention after as long as 5000 cycles at 2500 mA g-1 . Its cyclic stability is the best in the research field of niobate micron-sized particles, and comparable to that of "zero-strain" Li4 Ti5 O12 . At a low temperature of -10 °C, it also exhibits high rate performance with a 1250 to 125 mA g-1 capacity percentage of 65.6%, and even better cyclic stability with 105.4% capacity retention after 5000 cycles at 1250 mA g-1 . These comprehensively good electrochemical results pave the way for the practical application of NaNb13 O33 in high-performance Li+ storage.

[Tiaohe Yinyang acupotomy for knee osteoarthritis: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of Tiaohe Yinyang acupotomy (acupotomy for regulating and harmonizing yin and yang) for knee osteoarthritis (KOA). METHODS: A total of 88 patients with KOA were randomized into a acupotomy group and a sham-acupotomy group, 44 cases in each group. In the acupotomy group, acupotomy was applied at yin side (4-5 high stress points i.e. pes anserinus and terminal of popliteus) and yang side (1-2 high stress points i.e. stimulation point of infrapatellar ligament and suprapatellar bursa) of knee joint. In the sham-acupotomy group, sham-acupotomy was applied at the same points as the acupotomy group. The treatment was given once a week for 2 weeks in the two groups. Before and after treatment, the Western Ontario and McMaster Universities arthritis index (WOMAC) score, visual analogue scale (VAS) score, thickness of medial and lateral collateral ligaments of knee joint, motion range of knee joint and plantar pressure distribution were observed in the two groups. In the follow-up of 3 months after treatment, the WOMAC and VAS scores were recorded in the acupotomy group. RESULTS: After treatment, the sub item scores (pain, stiffness and function) and total scores of WOMAC and VAS scores were decreased in the both groups (P<0.05), pain score, function score and total score of WOMAC and VAS score in the acupotomy group were lower than those in the sham-acupotomy group (P<0.05). Before and after treatment, there were no statistical differences in thickness of medial and lateral collateral ligaments of knee joint and motion range of knee joint between the two groups (P>0.05). After treatment, the plantar medial pressure was increased while the plantar lateral pressure was decreased (P<0.05), and the plantar force line moved medially in the acupotomy group. In the follow-up, the sub item scores and total score of WOMAC and VAS score were lower than those before and after treatment in the acupotomy group (P<0.05). CONCLUSION: Tiaohe Yinyang acupotomy can improve the clinical symptoms of knee joint in patients with KOA by changing the local biological stress.

3 CpG Methylation Biomarkers for the Diagnosis of Polycystic Ovary Syndrome (PCOS) in Blood Samples.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease in women that seriously interferes with patient's metabolic and reproductive functions. The current diagnostic criteria for PCOS are expert-based and still disputed. Previous studies have identified changes in DNA methylation in peripheral blood of women with PCOS, but their diagnostic potential for PCOS remains to be studied. OBJECTIVE: The present study aimed to identify potential methylation biomarkers for the diagnosis of PCOS in blood. METHODS: Methylation profiling of peripheral blood was downloaded from a public database, Gene Expression Omnibus (GEO), including 30 PCOS patients (diagnosed with the revised 2003 Rotterdam consensus criteria) and 30 age-matched healthy women recruited from Centre of Reproductive Medicine, Linyi People's Hospital, Shandong, China. Weighted gene co-expression network analysis (WGCNA) was utilized to identify PCOS-related co-methylation CpG sites (co- MPs). Functional enrichment analysis was performed on the localized genes of PCOS-related co- MPs. The least absolute shrinkage and selection operator (LASSO) regression was used to screen out CpG methylation signatures for PCOS diagnosis, and receiver operating characteristic (ROC) analysis was conducted to evaluate their diagnostic accuracy. To assess the accuracy of the combination of the investigated indicators, multivariate ROC analysis was performed on the predicted probability values obtained using binary logistic regression on the methylation levels of selected CpGs. RESULTS: Seven co-methylation modules were obtained, among which the turquoise module is the most relevant to PCOS, containing 194 co-MPs. The genes that these co-MPs located in were mainly associated with the immune-related pathway. According to LASSO regression, three Co- MPs (cg23464743, cg06834912, cg00103771) were identified as potential diagnostic biomarkers of PCOS. ROC analysis showed an AUC (area under curve) of 0.7556 (sensitivity 60.0%, specificity 83.3%) for cg23464743, 0.7822 (sensitivity 70.0%, specificity 80.0%) for cg06834912, and 0.7611 (sensitivity 63.3%, specificity 83.3%) for cg00103771. The diagnostic accuracy of the combination of these 3 indicators presented to be higher than any single one of them, with the AUC of 0.8378 (sensitivity 73.3%, specificity 93.3%). CONCLUSION: The combination of 3 CpG methylation signatures in blood was identified with a good diagnostic accuracy for PCOS, which may bring new insight into the development of PCOS diagnostic markers in the future.

Effect of acupotomy in knee osteoarthritis patients: study protocol for a randomized controlled trial.

BACKGROUND: Symptomatic knee osteoarthritis (KOA) is common in China. Pharmacological therapy is not the first recommendation because of its safety issues. Nonpharmacological therapy, such as lifestyle adjustments, weight loss, muscle strengthening, and aerobic exercise programs, is strongly recommended for KOA. However, these approaches may fail due to poor patient compliance. There is a lack of high-quality randomized controlled trials of acupotomy, an effective treatment for KOA. This study was designed to investigate the efficacy of acupotomy in patients with KOA. METHODS: A total of 136 patients will be enrolled at the First Affiliated Hospital of Guangzhou University of Chinese Medicine and assigned to the acupotomy group or sham acupotomy group according to the block randomization scheme. Patients in the acupotomy group will receive 2 sessions of acupotomy for 2 weeks (once a week). Patients in the sham group will receive 2 sessions of sham stimulation for 2 weeks (once a week). All patients will use indomethacin cream externally. The primary outcome will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the secondary outcomes will be the visual analog scale (VAS) score, plantar pressure distribution test result, X-ray examination findings, musculoskeletal ultrasound findings, maximum knee circumference, joint mobility, and quality of life. Measurements will be taken at baseline, 1 week after the end of treatment, and at the 3- and 6-month follow-ups. DISCUSSION: To the best of our knowledge, this will be the first single-blind, sham-controlled study of acupotomy. The outcome assessors will also be blinded. The aim of this work is to demonstrate the efficacy of acupotomy in treating KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033047 . Registered on 18 May 2020.

A Comprehensive Network Pharmacology-Based Strategy to Investigate Multiple Mechanisms of HeChan Tablet on Lung Cancer.

BACKGROUND: HeChan tablet (HCT) is a traditional Chinese medicine preparation extensively prescribed to treat lung cancer in China. However, the pharmacological mechanisms of HCT on lung cancer remain to be elucidated. METHODS: A comprehensive network pharmacology-based strategy was conducted to explore underlying mechanisms of HCT on lung cancer. Putative targets and compounds of HCT were retrieved from TCMSP and BATMAN-TCM databases; related genes of lung cancer were retrieved from OMIM and DisGeNET databases; known therapeutic target genes of lung cancer were retrieved from TTD and DrugBank databases; PPI networks among target genes were constructed to filter hub genes by STRING. Furthermore, the pathway and GO enrichment analysis of hub genes was performed by clusterProfiler, and the clinical significance of hub genes was identified by The Cancer Genome Atlas. RESULT: A total of 206 compounds and 2,433 target genes of HCT were obtained. 5,317 related genes of lung cancer and 77 known therapeutic target genes of lung cancer were identified. 507 unique target genes were identified among HCT-related genes of lung cancer and 34 unique target genes were identified among HCT-known therapeutic target genes of lung cancer. By PPI networks, 11 target genes AKT1, TP53, MAPK8, JUN, EGFR, TNF, INS, IL-6, MYC, VEGFA, and MAPK1 were identified as major hub genes. IL-6, JUN, EGFR, and MYC were shown to associate with the survival of lung cancer patients. Five compounds of HCT， quercetin, luteolin, kaempferol, beta-sitosterol, and baicalein were recognized as key compounds of HCT on lung cancer. The gene enrichment analysis implied that HCT probably benefitted patients with lung cancer by modulating the MAPK and PI3K-Akt pathways. CONCLUSION: This study predicted pharmacological and molecular mechanisms of HCT against lung cancer and could pave the way for further experimental research and clinical application of HCT.

Effectiveness and safety of warm needle acupuncture on chronic renal failure: Protocol for a systematic review and meta-analysis.

BACKGROUND: Warm needle acupuncture (WNA) is an integral part of the acupuncture therapy. Chronic renal failure (CRF) is a common disease, which is a type of kidney disease characterized by a slow and progressive decline in renal function. The clinical practice indicates that WNA has a therapeutic effect on CRF. Therefore, we will provide a protocol to explore the effectiveness and safety of WNA for CRF. METHODS: We will search the randomized controlled trials literatures of WNA for CRF in 5 English databases (PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials [Cochrane Library], and World Health Organization International Clinical Trials Registry Platform) and 4 Chinese databases (Chinese national knowledge infrastructure, Chinese Scientific Journal Database Information, Wanfang Database, and Chinese biomedical literature database). The renal function will be considered as the primary outcome and the secondary outcome will include curative effect, security, syndrome according to standards for assessing traditional Chinese medicine, adverse events caused by WNA, such as dizziness, nausea, vomiting, weariness, and so on. We will use EndnoteX7 software to perform the selection of the studies. And all analyses will be conducted by using RevMan software V5.3. RESULT: This study will provide a rational synthesis of current evidences for WNM on CRF. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of WNA on CRF.Registration: PROS-PERO CRD42019144530.

Effectiveness and safety of fire needle on periarthritis of shoulder: Protocol for a systematic review and meta-analysis.

BACKGROUND: Fire needle which is an integral part of the acupuncture therapy. Periarthritis of shoulder (PAS) is a common disease, which brings lots of pain for patients. The clinical practice indicates that fire needle has a therapeutic effect on the PAS. Here, we will provide a protocol to explore the effectiveness and safety of fire needle for the PAS. METHODS: We will search the randomized controlled trails (RCT) literatures of fire needle for the PAS in 9 electronic databases, including 5 English databases (PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials [Cochrane Library], and WHO International Clinical Trials Registry Platform [TCTRP]) and 4 Chinese databases (Chinese National Knowledge Infrastructure [CNKI], Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database [CBM]). We will consider the Ability assessment of daily living activities (ADL) as the primary outcome and the secondary outcome will include visual analogue scale (VAS), shoulder range of motion (ROM) and adverse events incidence caused by fire needle, such as dizziness, nausea, vomiting, weariness, etc. The selection of the studies will be performed by EndnoteX7 software. All analyses will be conducted by using RevMan software V5.3. RESULT: This study will provide a rational synthesis of current evidences for fire needle on PAS. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of fire needle on PAS. REGISTRATION: PROS-PERO CRD42019119686.

Yixinshu capsule combined with conventional treatment for chronic heart failure: Protocol for a systematic review and trial sequential analysis.

BACKGROUND: Yixinshu Capsule is widely utilized in Asia for the treatment of chronic heart failure (CHF) as a conventional drug, but a comprehensive conclusion is lacking. Here, we will provide a protocol to perform a meta-analysis and trial sequential analysis to evaluate the efficacy of Yixinshu Capsule combined with conventional treatment for chronic heart failure. METHODS: We will conduct a thorough search in six databases, PubMed, EMBASE, Cochrane Library Database, Chinese National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP), and Chinese Biomedical and Medical Database (CBM). Inclusion criteria will be randomized control trials (RCTs) with one group receiving Yixinshu Capsule based on conventional treatment and another group receiving conventional treatment alone. Modified Jadad scale and Cochrane's risk of bias assessment will be used to assess methodological quality. Only studies with modified Jadad scale score ≥3 will be included in meta-analysis for efficacy, which will be defined as moderate methodological quality. The total effective rate will be considered as the primary outcome and the secondary outcome will include mortality, rehospitalized rate, left ventricular ejection fraction (LVEF), 6-minute walking distance, E/A, left ventricular end-diastolic diameter (LVEDD), BNP, and NT-proBNP. We will conduct trial sequential analysis to evaluate the reliability of the primary outcome. RESULTS: This study will provide a rational synthesis of current evidences for Yixinshu Capsule on chronic heart failure. CONCLUSION: The conclusion of this study will provide evidence for judging the efficacy of Yixinshu Capsule on chronic heart failure. REGISTRATION: PROS-PERO CRD42019119612.

Effectiveness and safety of warm needle acupuncture on children with cerebral palsy: Protocol for a systematic review and meta-analysis.

BACKGROUND: Warm needle acupuncture (WNA) is an integral part of the acupuncture therapy, which combines acupuncture and moxibustion. Children with cerebral palsy (CP) is a common disease in children, which seriously affects children's growing development, physical and mental health. The clinical practice indicates that WNA has a therapeutic effect on children with CP. Here we will provide a protocol to explore the effectiveness and safety of WNA for children with CP. METHODS: We will search the randomized controlled trails (RCT) literatures of WNA for children with CP in 5 English databases [PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials (Cochrane Library), and WHO International Clinical Trials Registry Platform (ICTRP)] and 4 Chinese databases [Chinese National Knowledge Infrastructure (CNKI), Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database (CBM)]. Activity of Daily Living Scales (ADL) of the patient will be considered as the primary outcome and the secondary outcome will include 88 items of gross motor function scale (GMFM-88), Gesell Growth Table (GGT), Criteria for judging efficacy and adverse events caused by WNA such as dizziness, nausea, vomiting, weariness, etc. The selection of the studies will be performed by EndnoteX7 software. And we will conduct all analyses with RevMan software V5.3. RESULT: This study will provide a rational synthesis of current evidences for WNA on children with CP. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of WNA on children with CP. REGISTRATION: PROS-PERO CRD42019122034.

Oral oxymatrine for hepatitis B cirrhosis: A systematic review protocol.

BACKGROUND: Characterized by diffuse hepatic fibrosis and nodule formation, hepatitis B cirrhosis (HBC), an important result of chronic hepatitis B development, mainly contains compensated and decompensated stage. Compensated cirrhosis can further develop into decompensated stage and hepatocellular carcinoma with serious complications and high mortality. Antiviral therapy using interferon (IFN) or nucleos(t)ide analogs (NUCs) is essential for improving the prognosis of the disease but IFN has large side effects while NUCs often develop drug resistance. Antifibrosis is also an important strategy, but currently there is no effective antifibrosis drug. Pharmacologic studies have demonstrated that oxymatrine (OM) exhibits anti-hepatitis B virus (HBV) and antifibrosis effects. An increasing number of clinical controlled studies also have found that OM combined with conventional therapy could improve the curative effect and reduce adverse events incidence in treating HBC but there is no systematic review of it. Based on the extensive collection of literature, we will use meta-analysis to assess the efficacy and safety of OM for HBC. METHODS: PubMed, MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang data, Chinese Scientific Journals Database (VIP), and China biomedical literature database will be searched to obtain the eligible studies published up to July 15, 2018. The primary outcome will be liver function indexes, liver fibrosis indexes, and Child-Pugh score. The secondary outcome will be hepatitis B virus DNA quantification, HBV DNA seroconversion rate, hepatitis B e antigen (HBeAg) seroconversion rate, and adverse events incidence. Data analysis will be conducted using RevMan 5.3 and Stata V.9.0 software. Trial sequential analysis (TSA) will be performed to assess the risk of random error and the validity of conclusion using TSA program version 0.9 beta. RESULTS: This systematic review will provide a high quality synthesis of OM for HBC from various evaluation aspects including liver function indexes, liver fibrosis indexes and Child-Pugh score, HBV DNA quantification, HBV DNA seroconversion rate, HBeAg seroconversion rate and adverse events incidence. CONCLUSION: The systematic review will provide evidence to assess the efficacy and safety of OM in the treatment of HBC. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018095275.

Berberine Combined with Triple Therapy versus Triple Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the effects and safety of berberine combined with triple therapy on Helicobacter pylori (H. pylori) eradication in adults. METHODS: PubMed, MEDLINE, EMBASE, Cochrane Library, and Chinese databases including China National Knowledge Infrastructure (CNKI), Wanfang data, Chinese Technology Journal Full-text Database (VIP), and China biomedical literature database (CBM) were searched to obtain the eligible studies published up to October 10, 2017. The primary outcome was eradication rate of H. pylori. The secondary outcome was incidence of adverse effects. Data analysis was conducted by RevMan5.2 and Stata V.9.0 software. Trial sequential analysis (TSA) was performed to assess the risk of random error and the validity of conclusion with TSA program version 0.9 beta. RESULTS: The meta-analysis results indicated berberine combined with triple therapy could improve the eradication rates of H. pylori (urea breath test subgroup: RR=1.18, 95%CI=(1.12,1.24), P < 0.00001, biopsy subgroup: RR=1.23, 95%CI=(1.13,1.34), P < 0.00001) and reduce the total occurrence of adverse effects (OR=0.59, 95%CI(0.46, 0.75), P < 0.0001) when compared with only using triple therapy. Besides, the incidence of nausea (OR=0.59, 95%CI(0.41, 0.86), P < 0.05) and diarrhea (OR=0.41, 95%CI(0.24, 0.71) was remarkably lower in experimental group while that of abdominal distention (OR=0.64, 95%CI(0.40,1.04), P > 0.05) and vomiting (OR=0.65, 95%CI(0.37, 1.15), P > 0.05) had no significant change. TSA of H. pylori eradication rates and adverse effects incidence illustrated that the cumulative value of Z-curve went across the conventional boundary value, trial sequential monitoring boundary for benefit, and required information size, suggesting the results were stable. CONCLUSION: Evidence from meta-analysis suggested that berberine combined with triple therapy can be an option for increasing H. pylori eradication rates and reducing overall therapy-related adverse effects incidence, particularly nausea and diarrhea, whereas more randomized controlled trials designed according to CONSORT statement are demanded to support the efficacy in further studies.