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Graphical abstract, The use of herbs to treat various human diseases has been recorded for thousands of years. In Asia's current medical system, numerous herbal formulas have been repeatedly verified to confirm their effectiveness in different periods, which is a great resource for drug innovation and discovery. Through the mining of these clinical effective formulas by network pharmacology and bioinformatics analysis, important biologically active ingredients derived from these natural products might be discovered. As modern medicine requires a combination of multiple drugs for the treatment of complex diseases, previously clinical formulas are also combinations of various herbs according to the main causes and accompanying symptoms. However, the herbs that play a major role in the treatment of diseases are always unclear. Therefore, how to rank each herb's relative importance and determine the core herbs, is the first step to assisting herb selection for active ingredients discovery. To solve this problem, we built the platform FangNet, which ranks all herbs on their relative topological importance using the PageRank algorithm, based on the constructed symptom-herb network from a collection of clinical empirical prescriptions. Three types of herb hidden knowledge, including herb importance rank, herb-herb co-occurrence, and associations to symptoms, were provided in an interactive visualization. Moreover, FangNet has designed role-based permission for teams to store, analyze, and jointly interpret their clinical formulas, in an easy and secure collaboration environment, aiming at creating a central hub for massive symptom-herb connections. FangNet can be accessed at http://fangnet.org or http://fangnet.herb.ac.cn.

Objective. To determine the effectiveness and safety of acupuncture for perimenopausal depression.Methods. We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CNKI, VIP Citation Databases, Wan Fang, and online trial registries such as ClinicalTrials.gov for randomized controlled trials (RCTs) assessing the efficacy and safety of acupuncture for perimenopausal depression. Literature screening, data extraction, and determination of the risk of bias were performed by two researchers independently. The extracted data were pooled and meta-analyzed using RevMan5.3 software.Results. In total, 16 RCTs covering 1311 patients were enrolled. Overall, the results showed that acupuncture was more effective in the treatment of perimenopausal depression than antidepressants (OR = 2.68, 95% CI (1.84, 3.90),P<0.00001). Furthermore, HAMD scores in the manual acupuncture group and electroacupuncture group were lower than those of antidepressants (manual acupuncture vs. antidepressants (MD = −2.35, 95% CI (−2.93, −1.77),P<0.00001) and electroacupuncture vs. antidepressants (MD = −1.2, 95% CI (−1.92, −0.48),P=0.001)). Data analysis revealed that the treatment effect of acupuncture was more stable than that of antidepressants (MD = −2.4, 95% CI (−3.37, −1.43),P<0.00001). Moreover, acupuncture was safer than antidepressants based on the incidence of adverse events (OR = 0.23, 95% CI (0.1, 0.52),P=0.0004). But acupuncture has no effect on estrogen levels (P≥0.05).Conclusions. Acupuncture for perimenopausal depression is safe and effective. Moreover, it has more stable long-term effects than antidepressants and hormone replacement therapy (HRT). We recommend acupuncture as a clinical treatment of perimenopausal depression.

OBJECTIVES This study aimed to explore the efficacy of group reminiscence therapy based on Chinese traditional festival activities (CTFA-GRT) to mediate the loneliness and perceived stress of older adults living alone in rural China. The results can provide a scientific foundation for improving psychological health. METHOD A randomized controlled trial of 64 (aged 65.70 ± 3.69 years) Chinese rural older adults living alone was conducted. They were randomly divided into either an eight-month intervention group or a control group. The perceived stress scale (PSS) and the UCLA loneliness scale (UCLA-LS) evaluated the perceived stress and loneliness of the two groups at three different times. A repeated-measures analysis of variance model was used to compare each outcome measure of the two groups. RESULTS The CTFA-GRT yielded a benefit for the perceived stress and loneliness of rural older adults living alone in the intervention group. Combined with a simple effects test, the PSS and UCLA-LS of those in the intervention groups significantly decreased at eight months after the baseline (F PSS = 23.540, F UCLA-LS = 40.159; all P

Background MicroRNAs (miRNAs) are a class of 21–24 nucleotide endogenous non-coding small RNAs that play important roles in plant development and defense responses to biotic and abiotic stresses. Tobacco curly shoot virus (TbCSV) is a monopartite begomovirus, cause leaf curling and plant stunting symptoms in many Solanaceae plants. The betasatellite of TbCSV (TbCSB) induces more severe symptoms and enhances virus accumulation when co-infect the plants with TbCSV. Methods In this study, miRNAs regulated by TbCSV and TbCSB co-infection in Nicotiana benthamiana were characterized using high-throughput sequencing technology. Results Small RNA sequencing analysis revealed that a total of 13 known miRNAs and 42 novel miRNAs were differentially expressed in TbCSV and TbCSB co-infected N. benthamiana plants. Several potential miRNA-targeted genes were identified through data mining and were involved in both catalytic and metabolic processes, in addition to plant defense mechanisms against virus infections according to Gene Ontology (GO) analyses. In addition, the expressions of several differentially expressed miRNAs and their miRNA-targeted gene were validated through quantitative real time polymerase chain reaction (qRT-PCR) approach. Conclusions A large number of miRNAs are identified, and their target genes, functional annotations also have been explored. Our results provide the information on N. benthamiana miRNAs and would be useful to further understand miRNA regulatory mechanisms after TbCSV and TbCSB co-infection.

Background. Premenstrual syndrome (PMS) is one of the most common gynecological conditions with no standard modern therapeutic schedule. Some studies have reported the effects of acupuncture in treating PMS, but the intervention time varies. This review evaluated the efficacy of acupuncture for patients with PMS and the appropriate time to initiate acupuncture therapy. The review has been registered on the “PROSPERO” website; the registration number is CRD42018109724. Methods. A comprehensive literature search was performed on 9 electronic databases from the time of inception to September 2018. RCTs studies on acupuncture for PMS compared with medication, sham acupuncture, or no treatment were included. Statistical analysis and investigation of heterogeneity source were carried out using RevMan5. 3. Results. A total of 15 studies, comprising of 1103 cases, were included. Overall, acupuncture significantly increased the effective rate of PMS compared with medicine and sham acupuncture. Subgroup analyses showed no significant difference among different intervention time to start acupuncture treatment. Among the acupoints involved in the treatment of PMS, SP6, LR3, and RN4 were the most commonly used. Conclusions. The current meta-analysis reveals that acupuncture leads to better effective rate, but the intervention time has no significant effect on the efficacy of acupuncture treatment for PMS. SP6, LR3, and RN4 are the most commonly used acupoints in treating PMS. However, large-scale, case-control studies with rigorous designs are required to provide more accurate evidence.

To development biomimetic strategy for enhanced cancer therapy, the paclitaxel loaded egg white/sodium alginate nanoparticles were prepared by electronic spray method. Their appearance and particle size were observed by transmission electron microscope and particle size analyzer. The drug release behavior of nanoparticles was determined by high performance liquid chromatography (HPLC). The toxicity, morphology and interaction of nanoparticles to cells were studied by means of MTT, live/dead staining and laser scanning confocal microscopy. The results show that the nanoparticles have good particle size dispersion, regular morphology, good drug release performance, good biocompatibility and in vitro effective inhibition of CT26 colorectal cancer cells. These results demonstrated that the good biocompatibility of egg white coated sodium alginate nanoparticles and PTX loaded these nanoparticles would show potential application for cancer therapy.

Objective: To explore the correlations between five-pattern personality scores and autonomic nervous response indicators in Chinese female college students, to provide a foundation for further exploration of the modern physiological basis of these personality types. Methods: Subjects were asked to fill in “The Five-Pattern Personality Inventory” (revised edition 2008). Taiyang, Shaoyang, yin-yang balance, Taiyin, and Shaoyin personalities were scored. The galvanic skin response and heart rate, and the low frequency (LF), high frequency (HF), and LF/HF ratio of heart rate variability were collected using a 16-channel physiological recorder (BIOPAC MP150). Relationship between the five-pattern personality scores and autonomic nervous response indicators was analyzed using bivariate correlation. Results: The five-pattern personality scores of the subjects were compared with national averages. The Taiyang and Shaoyang personality scores of the subjects were significantly lower than the overall national average, the national female average, and the national female average in the 18–29-year-old age group (all P

Background A previous study indicated that microRNA(miR)-328-3p upregulation might be critical for resveratrol-mediated suppression of metastatic ability in human osteosarcoma, implying its potential role in this malignancy. However, the clinical significance and the biological functions of miR-328-3p in osteosarcoma remain unclear. Methods miR-328-3p expression in 88 pairs of osteosarcoma and matched non-cancerous bone tissues were detected by quantitative real-time PCR. Then, the associations of miR-328-3p expression with various clinicopathological features of osteosarcoma patients were statistically analyzed. Cell Counting Kit-8 and scratch-wound healing were performed to evaluate roles of miR-328-3p in human osteosarcoma cells. After that, luciferase reporter assay, western blot analysis and rescue assay were applied to determine the underlying molecular mechanisms of miR-328-3p in osteosarcoma cells. Results miR-328-3p expression in osteosarcoma tissues was significantly lower than those in non-cancerous bone tissues (P

Background. Increasing attention has been paid to electroacupuncture (EA) for promoting postoperative rehabilitation, but the effectiveness of EA for rehabilitation after total knee arthroplasty (TKA) remains obscure. Objective. To examine the effect of EA on rehabilitation after TKA. Methods. Database searches on PubMed, CINAHL, Embase, and China National Knowledge Infrastructure (CNKI) were carried out to obtain articles, from inception to 15 October 2020. All identified articles were screened, and data from each included study were extracted independently by two investigators. Meta-analysis was conducted to assess the effects of acupuncture on pain, range of knee motion, and postoperative vomiting after TKA. Results. In the current study, a total of ten randomized clinical trials were included according to the inclusion and exclusion criteria. Compared to basic treatment, EA combined with basic treatment showed a significantly greater pain reduction on 3, 7, and 14 days postoperatively after TKA. However, we found that EA had no significant improvement in enhancing the range of knee motion and decreasing the percentage of vomiting. Subgroup analysis suggested that a combination of EA and rehabilitation training was superior to rehabilitation training in pain relief, while EA combined with celecoxib capsules showed no significant difference in improving pain compared to celecoxib capsules alone. Conclusions. In the postacute phase after TKA, EA, as a supplementary treatment, could reduce postoperative pain, but no evidence supported the benefits of EA for improving ROM of knee and decreasing the ratio of vomiting. Additional high-quality and large-scale RCTs are warranted.

Pharmacotranscriptomics has become a powerful approach for evaluating the therapeutic efficacy of drugs and discovering new drug targets. Recently, studies of traditional Chinese medicine (TCM) have increasingly turned to high-throughput transcriptomic screens for molecular effects of herbs/ingredients. And numerous studies have examined gene targets for herbs/ingredients, and link herbs/ingredients to various modern diseases. However, there is currently no systematic database organizing these data for TCM. Therefore, we built HERB, a high-throughput experiment- and reference-guided database of TCM, with its Chinese name as BenCaoZuJian. We re-analyzed 6164 gene expression profiles from 1037 high-throughput experiments evaluating TCM herbs/ingredients, and generated connections between TCM herbs/ingredients and 2837 modern drugs by mapping the comprehensive pharmacotranscriptomics dataset in HERB to CMap, the largest such dataset for modern drugs. Moreover, we manually curated 1241 gene targets and 494 modern diseases for 473 herbs/ingredients from 1966 references published recently, and cross-referenced this novel information to databases containing such data for drugs. Together with database mining and statistical inference, we linked 12 933 targets and 28 212 diseases to 7263 herbs and 49 258 ingredients and provided six pairwise relationships among them in HERB. In summary, HERB will intensively support the modernization of TCM and guide rational modern drug discovery efforts. And it is accessible through http://herb.ac.cn/.

Objective. To determine the effectiveness and safety of acupuncture for chemotherapy-induced peripheral neuropathy. The review has been registered on the “PROSPERO” website; the registration number is CRD42020151654. Methods. A comprehensive literature search was performed on 7 electronic databases from the time of inception to March 2020. RCTs studies on acupuncture for CIPN compared with medication or sham acupuncture were included. Statistical analysis was carried out using RevMan 5.3. Results. In total, 19 RCTs covering 1174 patients were enrolled. The results showed that acupuncture significantly increased the effective rate of CIPN compared with medicine and sham acupuncture. And acupuncture had a good effect on the recovery of nerve conduction velocity and improving pain. Among the acupoints involved in the treatment of CIPN, LI4, LI11, ST36, EX10 (Bafeng), and EX-UE 9 (Baxie) were the most commonly used. Conclusion. The use of acupuncture in the management of CIPN is safe and effective. The most used acupoints for CIPN are LI4, LI11, ST36, EX10 (Bafeng), and EX-UE 9 (Baxie).

W34 is a prodrug of FL118, and it can be converted to FL118 via a hydrolysis reaction. In this report, a highly sensitive LC-MS/MS method using a C18 column was validated and used for the simultaneous determination of W34 and FL118 in rat blood. A stepwise gradient elution with 0.1% formic acid in water and acetonitrile was employed. The assays were linear over a concentration range of 0.50-50.0 ng/ml for both W34 and FL118. The accuracy of the validation method ranged from 89.74 to 98.94% for W34 and from 88.61 to 94.60% for FL118. The precision was within 7.15% for W34 and 9.63% for FL118. Extraction recoveries of W34 were 94.56-100.49 and 87.67-106.32% for FL118. No significant matrix effects for both W34 and FL118 were observed in blood. The assay has been successfully applied to biological samples obtained from a stability and pharmacokinetic study of W34 and FL118.

Inflammation secondary to tissue injuries serves as a double-edged sword that determines the prognosis of tissue repair. As one of the most important enzymes controlling the inflammation process by producing leukotrienes, 5-lipoxygenase (5-LOX, also called 5-LO) has been one of the therapeutic targets in regulating inflammation for a long time. Although a large number of 5-LOX inhibitors have been explored, only a few of them can be applied clinically. Surprisingly, phosphorylation of 5-LOX reveals great significance in regulating the subcellular localization of 5-LOX, which has proven to be an important mechanism underlying the enzymatic activities of 5-LOX. There are at least three phosphorylation sites in 5-LOX jointly to determine the final inflammatory outcomes, and adjustment of phosphorylation of 5-LOX at different phosphorylation sites brings hope to provide an unrecognized means to regulate inflammation. The present review intends to shed more lights into the set-point-like mechanisms of phosphorylation of 5-LOX and its possible clinical application by summarizing the biological properties of 5-LOX, the relationship of 5-LOX with neurodegenerative diseases and brain injuries, the phosphorylation of 5-LOX at different sites, the regulatory effects and mechanisms of phosphorylated 5-LOX upon inflammation, as well as the potential anti-inflammatory application through balancing the phosphorylation-depended set-point.

The modification of 2-amino-6-chloropurine on polyamidoamine was performed to synthesize a derivative, AP-PAMAM, which was then employed as a carrier for p53 gene delivery to achieve anti-tumor efficacy. Using a human prostate tumor cell line PC-3 as a model, enhanced expression level of p53 gene could be detected by RT-PCR, qPCR and western blotting. Based on the successful p53 gene transfection, an obvious anti-proliferative effect could be obtained, which was identified to be associated with the simultaneous induction of cell apoptosis and cell cycle arrest at the G1 phase. The cell apoptosis was elucidated to be triggered by the activation of the mitochondria-dependent apoptotic signaling pathway. In addition, AP-PAMAM/p53 transfection could restrain the migration of tumor cells as demonstrated by wound healing and Transwell migration assays. Notably, AP-PAMAM-mediated p53 delivery exhibited a stronger inhibitory effect on both cell proliferation and migration than the PAMAM/p53 group. In summary, AP-PAMAM/p53 transfection provided a promising route to achieve the p53-based gene therapy.

Objective To explore the effects of joy and sorrow on pulse-graph parameters in healthy subjects and analyze their potential effect to provide preliminary evidence that pulse diagnosis can identify human emotional changes. Design and intervention Forty healthy female college students from Beijing University of Chinese Medicine were recruited. The emotion-evoking experiment was conducted to observe the effects of joy and sorrow on pulse-graph parameters, taking neutral emotion as a control. The experiment included the following criteria. (1) Emotions evoked and evaluated: the same subjects watched three emotional videos which were, respectively, neutral, joyful and sorrowful to evoke the corresponding emotions. They completed the “subjective emotion evaluation form” (SEEF) before watching each video (T0), immediately after watching the video (T1) and 15 min after watching the video (T2) to conduct subjective emotion evaluation. Simultaneously, their heart rate, galvanic skin response and heart rate variability were collected with a 16-lead physiological recorder to conduct an objective evaluation of emotional arousal. (2) Collection of pulse-graph parameters: pulse-graph parameters of the subjects at T0, T1 and T2 were collected with a pulse condition analyzer. Results When watching the joy video, the rapid ejection phase extended significantly, both the left ventricular diastole and the cardiac cycle shortened significantly. When watching the sorrow video, the left ventricular diastole extended significantly, the cardiac cycle showed an upward trend, and heart rate showed a downward trend. Conclusion Joy and sorrow have a certain effect on pulse-graph parameters of the subjects. The mechanisms may be that joy contributes to rapid ejection phase extension and a shortening of the left ventricular diastole and the cardiac cycle, while sorrow extends the left ventricular diastole. According to the theory of Traditional Chinese Medicine (TCM), the visceral functions can be mediated through human qi flow. Moderate joy and sorrow can promote, respectively, the smooth qi flow of the heart and the lung. However, excessive or long-term joy and sorrow can lead to disharmonious qi flow of the two viscera. Therefore, maintaining moderate emotions is beneficial to the physiological functions of the viscera. Great emotional fluctuations may damage the visceral functions. Future studies with effects of other emotions on pulse-graph parameters are warranted to determine the reliability of the association of emotions and pulse diagnosis.

Background: Upper respiratory tract infections (URTIs) is a common disease in children, which is also known as the common cold. Pediatric Tuina is a common treatment that Traditional Chinese Medicine (TCM) doctors commonly use for URTIs. However, there has no relevant systematic review studied on its effects and safety been reported. We plan to perform a systematically reviewing of all the clinical evidence on the effectiveness and safety of Tuina for URTIs in children. Methods: We will conduct the literature searching in the following electronic databases: Pubmed, Embase, Cochrane Library, Web of science, Chinese National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biomedical Literature Database (CBM), Chinese Clinical Trial Registry System. The time limit for retrieving studies is from establishment to July 2019 for each database. All published randomized controlled trials (RTCs) related to this review will be included. Review Manager (V.5.3.5) will be implemented for the assessment of bias risk and data analyses. Subgroup analysis and sensitivity analysis will be performed based on the conditions of included data. Results: A high-quality synthesis of current evidence of Tuina for children with URTIs will be provided in this study. Conclusion: This systematic review will provide evidence of whether Tuina is an effective intervention for children with URTIs. PROSPERO registration number: CRD42019126963.

The begomovirus C4 protein is required for disease symptom development during virus infection in host plants. It can reprogram the cell cycle process for more efficient virus accumulation. In this study, we showed that the Malvastrum yellow vein virus (MaYVV) C4 protein could cause leaf up-ward curling and flower malformation, and increase virus accumulation in plants using PVX-based transient expression technology. We also demonstrated that, in the presence of its cognate betasatellite DNA (MaYVB), a mutant MaYVV, defective in producing the C4 protein (MaYVVΔC4), caused and alleviated infection in Nicotiana benthamiana. Transgenic plants expressing the MaYVV C4 protein showed upward leaf curling and uneven leaf lamina growth. Microscopic analysis showed that the epidermal cells of the C4 transgenic leaves were much smaller than those in the wild type (WT) leaves, and the mesophyll cells size and arrangement of transgenic plants was significantly altered. Inoculation of C4 transgenic plants with MaYVV or MaYVVΔC4 alone or associated with MaYVB showed that the transgenic C4 protein could promote viral and betasatellite accumulation and rescue the accumulation defect of MaYVVΔC4. Other transient expression assays also confirmed that the MaYVV C4 protein could suppress silencing of a GFP gene. In summary, our results indicate that the MaYVV C4 protein is a determinant of disease symptom and viral DNA accumulation. This protein can also function as a suppressor of RNA silencing and alter cell division and expansion.

Background: Primary insomnia is one of the common sleep disorders. Auriculotherapy originated from traditional Chinese medicine, has been thought as a promising treatment for primary insomnia. We aim to evaluate the efficacy and safety of auriculotherapy for patients with primary insomnia through this systematic review. Methods: Five English databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, and CINAHL), 4 Chinese databases (CBM, CNKI, CQVIP, and Wanfang), and 5 clinical trial registration databases (ClinicalTrials.gov, ANZCTR, EU-CTR, ChiCTR, and ICTRP) will be searched from establishment of the database until November 2018. Articles written in English or Chinese languages will be included. The randomized controlled trials of auriculotherapy (auricular acupuncture and auricular acupressure) for patients with primary insomnia will be included. The primary outcome will be assessed according to the Pittsburgh sleep quality index. Meta-analysis will be conducted with the use of RevMan 5.3. The specific process will refer to the Cochrane Handbook 5.1 for Systematic Review. Results: High-quality synthesis of current evidence on the efficacy and safety of auriculotherapy for primary insomnia will be provided in this study. Conclusion: This systematic review aims to present evidence for whether auriculotherapy is an effective intervention which can improve sleep quality in patients suffering primary insomnia. PROSPERO registration number: CRD42019106422.

Background: Depression is one of common disease in the female perimenopausal period. It deprives women of their right to work and live normally, and even destroys the happiness of their families. Acupuncture is a promising treatment for perimenopausal depression. Methods: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Internet (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and on-line trial registries such as ClinicalTrials.gov (ClinicalTrials.gov/), European Medicines Agency (EMA)(www.ema.europa.eu/ema/), WHO International Clinical Trials Registry Platform (www.who.int/ictrp) will be searched from establishment of the database until Oct. 2018. There are no restrictions on the language of publication. The randomized controlled trials of acupuncture (electroacupuncture and manual acupuncture) for perimenopausal depression will be included, and all articles will be screened and collected by 2 reviewers independently. Revman 5.3.5 software will be used for meta-analysis. The specific process will refer to the Cochrane Handbook for Systematic Review. Results: The efficacy and safety of acupuncture for perimenopausal depression will be comprehensively assessed from the outcomes, including the effective rate, HAMD score, estrogen level and incidence of adverse events. Conclusion: This systematic review will provide evidence for whether acupuncture can improve perimenopausal depression. Ethics and dissemination: There is no requirement of ethical approval, and the review will be reported in a peer-reviewed journal.

A large number of genetic variants have been associated with human diseases. However, the lack of a genetic diversification approach has impeded our ability to interrogate functions of genetic variants in mammalian cells. Current screening methods can only be used to disrupt a gene or alter its expression. Here we report the fusion of activation-induced cytidine deaminase (AID) with nuclease-inactive clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (dCas9) for efficient genetic diversification, which enabled high-throughput screening of functional variants. Guided by single guide (sg)RNAs, dCas9-AID-P182X (AIDx) directly changed cytidines or guanines to the other three bases independent of AID hotspot motifs, generating a large repertoire of variants at desired loci. Coupled with a uracil-DNA glycosylase inhibitor, dCas9-AIDx converted targeted cytidines specifically to thymines, creating specific point mutations. By targeting BCR-ABL with dCas9-AIDx, we efficiently identified known and new mutations conferring imatinib resistance in chronic myeloid leukemia cells. Thus, targeted AID-mediated mutagenesis (TAM) provides a forward genetic tool to screen for gain-of-function variants at base resolution.

Background Breast cancer is common among women throughout the world and endocrine therapy is an established part of its treatment. But, unfortunately, this has also resulted in intolerable side effects affecting the quality of life. Acupuncture has been widely used to treat endocrine-related side effects in patients with breast cancer, but how long its effect can be maintained has not been published. The systematic review is designed to evaluate the maintenance efficacy of acupuncture for related side effects after breast cancer endocrine therapy. Methods and analysis We will search for the following databases: PubMed, Embase, Cochrane Library, Web of Science, including China National Knowledge Infrastructure (CNKI), WanFang Data, Technology Periodical Database (VIP), and China Biology Medicine (CBM) from inception to May 2020. Two reviewers will search these databases, collect all articles, and assess the quality of studies separately, and there will be no limitations on language. The primary outcomes will be assessed using acupuncture for endocrine-related hot flashes and joint pain duration (1 month, 3 months, 6 months). Measurement tools include the Kupperman index, Brief Pain Inventory Short Form (BPI-SF), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Brief Pain Inventory-Short (BPI-SF). We will use RevMan V.5.3 for meta-analysis and employ the Grading of Recommendations Assessment, Development and Evaluation System to assess the quality of evidence. Results This systematic review will evaluate the maintenance efficacy of acupuncture on the side effects of breast cancer endocrine therapy. Conclusion This study will provide high-quality current evidence of how long its effect can be maintained after acupuncture for related side effects after breast cancer endocrine therapy. Ethics and dissemination Ethical committee approval is not required for this systematic review as patient data will not be collected. This study will help to inform doctors and researchers on the duration of acupuncture treatment for endocrine-related hot flashes and joint pain. The results will be published in a peer-reviewed journal and will be disseminated in relevant conferences. Inplasy registration number INPLASY202040024.

Background Postoperative nausea and vomiting (PONV) is a condition that commonly following anesthesia and surgery, antiemetics can lead to some side effects in treating PONV. Acupuncture PC6(Neiguan) has been widely used in the prevention and treatment of postoperative nausea and vomiting. However, there still exists controversy towards its effectiveness, appropriate, and effective intervention time. We, therefore, design this meta-analysis to assess the effectiveness and confirm the optimal time of acupuncture PC6 point for PONV. Methods The following electronic databases will be searched from their inception to April 2020, including PubMed, Cochrane Library, EMBASE, Web of Science, WHO International Clinical Trials Registry Platform, Chinese National Knowledge Infrastructure, WanFang Database, Chinese Biomedical Literature Database, the Chongqing VIP Chinese Science, and Technology Periodical Database. All randomized controlled trials in English or Chinese involving acupuncture PC6 for patients with PONV will be included. Two reviewers will independently responsible for the data extraction, study selection, risk of bias assessment and assessment of study quality. The primary outcome was the number of postoperative nausea, postoperative vomiting and PONV during 0 to 6 hours and after 6 hours of the postoperatively. The secondary outcome is the number of people with side effects and the use of rescue therapy. The meta-analysis will be conducted using RevMan V.5.3.5 statistical software. Results This systematic review will evaluate the efficacy and appropriateness time of acupuncture PC6 in the treatment of PONV. Conclusion This study will provide high-quality current evidence of the effectiveness and optimal time of acupuncture PC6 point for the patient with PONV. Ethics and dissemination Ethical approval is not required; this review will not involve individuals' information. The results will be published in a peer-reviewed publication or disseminated in relevant conferences. Inplasy registration number DOI 10.37766/inplasy2020.4.0012.

Background Knee osteoarthritis (KOA) is a disabling joint disease with an increasingly prevalence among the older individuals. Tai Chi, one of the ancient meditative movements, has been recognized to have clinical benefits for KOA. We aim to evaluate the efficacy and safety of Tai Chi for patients with KOA through this systematic review. Methods Five English databases (Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, and CINAHL), 4 Chinese databases (CBM, CNKI, CQVIP, and Wanfang), and 5 clinical trial registration databases (ClinicalTrials.gov, ANZCTR, EU-CTR, ChiCTR, and ICTRP) will be searched from establishment of the database until November 31, 2019. Grey literature will be searched in SIGLE, Grey Net, Microsoft Academic, Google Scholar, Open Aire, World Wide Science.org, and WorldCat. There will be no restrictions on language. The randomized controlled trials of Tai Chi training for patients with KOA will be included. The primary outcome will be assessed according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Meta-analysis will be conducted with the use of RevMan 5.3. The specific process will refer to the Cochrane Handbook 5.1 for Systematic Review. Results High-quality synthesis of current evidence on the efficacy and safety of Tai Chi training for KOA will be provided in this study. Conclusion This systematic review aims to present evidence for whether Tai Chi training is an effective intervention which can improve both physical condition and life quality in patients suffering KOA.

Background: Growing body of scientific researches in recent years have suggested the promising effect of meditation on improving cognitive impairment of Alzheimer disease (AD) and mild cognitive impairment (MCI). This paper aims to provide a protocol for systematic review to evaluate the efficacy of meditation on cognition performance of patient with AD and MCI. Methods: The Cochrane Library, PubMed, EMBASE, Web of Science, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang database, and VIP information database will be searched systematically and electronically from establishment to March 2020. All published randomized controlled trials related will be included. Assessment of bias risk and data analyses will be implemented by Review Manager (V.5.3.5). The strength of the evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation system. Results: A high-quality synthesis of current evidence of meditation for patient with AD and mild cognitive impairment will be provided in this study. Conclusion: This protocol of systematic review will be helpful for providing evidence of whether meditation is an effective and safe intervention for cognitive impairment of patient with AD and MCI. Ethics and dissemination: Ethical approval is unnecessary since this protocol is only for systematic review and does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation. Systematic review registration: PROSPERO CRD42019145932.

Aim The aim of this review is to assess the efficacy and safety of tripterygium wilfordii multiglycosides combined with prednisone in the treatment of idiopathic membranous nephropathy. Background Tripterygium wilfordii multiglycosides, a Chinese patent medicine, is widely in-depth research in China, and is proved to have anti-inflammatory and immunosuppressive effect. It has been extensively used in China for the treatment of autoimmune diseases, such as idiopathic membranous nephropathy (IMN). However, there has no relevant systematic review studied on its effects and safety been reported. We plan to perform a systematically reviewing to assess the efficacy and safety of tripterygium wilfordii multiglycosides combined with hormones in the treatment of IMN. Methods Seven electronic databases will be searched to identify eligible trials. Randomized controlled trials (RCTs) that compared tripterygium wilfordii multiglycosides combined with prednisone versus standard therapy are included. Methodological quality is assessed using the Cochrane Collaboration Risk of Bias tool. A random- or fixed-effect model is used to analyze outcomes that are expressed as risk ratios (RRs) or mean differences (MD), and the I statistic is used to assess heterogeneity. Results A high-quality synthesis of current evidence of tripterygium wilfordii multiglycosides combined with prednisone in the treatment of idiopathic membranous nephropathy will be provided in this study. Conclusion This systematic review will provide evidence of whether tripterygium wilfordii multiglycosides is an effective intervention for idiopathic membranous nephropathy.PROSPERO registration number: No.CRD42018118179.

BACKGROUND A recent study has reported that there are >240 million patients infected with chronic hepatitis B (CHB) worldwide. Once patients with CHB start antiviral treatment, they need to take antiviral drugs for a long period, which may lead to a series of side effects, and the resistance to the antiviral drugs may also emerge. We aim to evaluate the efficacy and safety of kushenin (KS) combined with entecavir (ETV) for chronic hepatitis B. METHODS Randomized controlled trials (RCTs) of KS combined with ETV for CHB will be identified from PubMed, EMBASE, Web of Science, The Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, Chongqing VIP, Wangfang Data. Literature screening and data extraction will be independently performed by 2 researchers. The cochrane collaboration tool for assessing risk of bias will be applied to evaluate the risk of bias of the RCTs included. The extracted data will be analyzed by Rev-man 5.3.0 software. RESULTS A high-quality synthesis of current evidence on the efficacy and safety of KS combined with ETV for CHB will be provided in this study. CONCLUSION This systematic review will aim to evaluate the efficacy and safety of KS combined with ETV for CHB. PROSPERO REGISTRATION NUMBER CRD42019124790.

Chronic diabetic foot ulcer (DFU) is a major cause of disability and mortality in patients with diabetes. Dysfunctional endothelial progenitor cells (EPCs) play important roles in preventing vascular complications in these patients. Our results determined the elevated expression of histone deacetylase 2 (HDAC2) both in patients with DFU and in high glucose (HG) induced EPCs. In this study, HDAC2 siRNA (si-HDAC2) was transfected to investigate the effects of HDAC2 on EPCs. Cell proliferation decreased in HG-induced EPCs, but it was upregulated after si-HDAC2 transfection. Tube formation of EPCs also decreased with HG, which was reversed by si-HDAC2 transfection. Furthermore, inflammatory factors and reactive oxygen species (ROS) in EPCs were detected, showing that HG increased TNF-α, IL-1β, IL-6, and ROS production in EPCs. However, si-HDAC2 reversed these effects. These results indicate that HDAC2 inhibitor may resist HG-induced EPC injury. Finally, reduced expression of HO-1-Sirt1 signaling in HG-induced EPCs also was reversed by HDAC2 siRNA. In conclusion, these findings indicate that HDAC2 inhibitor may prevent impaired cell proliferation, tube formation, inflammation, and ROS production in high-glucose EPCs.

Endothelial progenitor cells (EPCs) are involved in diabetes-associated complications, including diabetic foot ulcer (DFU). Recent reports showed that miR-155 downregulation promotes wound healing in diabetic rats and ameliorates endothelial injury induced by high glucose, but its role in DFU is unknown. We found that miR-155 was overexpressed in EPCs from patients with DFU and in high glucose-induced EPCs from healthy people. Reductions in cell viability, migration, tube formation and nitric oxide production, as well as increases in lactated hydrogenase, cell apoptosis, and reactive oxygen species induced by high glucose, were enhanced by miR-155 overexpression and restrained by miR-155 inhibition. Additionally, dual-luciferase reporter assay demonstrated that miR-155 directly targeted the 3' untranslated region of patched-1 (PTCH1), a receptor of the sonic hedgehog signaling pathway, and downregulated the mRNA and protein expression of PTCH1. qRT-PCR and Western blot results revealed that the PTCH1 was downregulated in EPCs treated with high glucose. Silencing PTCH1 by PTCH1 siRNA alleviated the protective effect of anti-miR-155 on high glucose-induced EPC dysfunction. Our results indicate that miR-155 worsened high glucose-induced EPC function by downregulating PTCH1. These findings suggest that miR-155 may be a potential therapeutic target for DFU.

Pregnancy loss occurs in about 15% of clinically recognized pregnancies, and defective maternal-fetal immune tolerance contributes to more than 50% of these events. We found that signaling by the type I membrane protein T cell immunoglobulin and mucin-containing protein 3 (Tim-3) in natural killer (NK) cells had an essential protective role during early pregnancy. Tim-3 on peripheral NK (pNK) cells was transiently increased in abundance during the first trimester of pregnancy, which depended on interleukin-4 (IL-4)-signal transducer and activator of transcription 6 (STAT6) and progesterone signaling. Tim-3+ pNK cells displayed immunosuppressive activities, including the production of anti-inflammatory cytokines and the induction of regulatory T cells (Tregs) in a transforming growth factor-β1 (TGF-β1)-dependent manner. Tim-3 on pNK cells was stimulated by its ligand galectin-9 (Gal-9), leading to signaling by the kinases c-Jun N-terminal kinase (JNK) and AKT. In recurrent miscarriage (RM) patients, Tim-3 abundance on pNK cells was reduced and the immunosuppressive activity of Tim-3+ pNK cells was impaired. Compared to Tim-3+ pNK cells from donors with normal pregnancies, RM patient Tim-3+ pNK cells exhibited changes in DNA accessibility in certain genetic loci, which were reversed by inhibiting accessible chromatin reader proteins. Furthermore, Tim-3+ pNK cells, but not Tim-3- pNK cells, reduced fetal loss in abortion-prone and NK cell-deficient mice. Together, our findings reveal a critical role for Tim-3-Gal-9 signaling-mediated immunoregulation by pNK cells in maternal-fetal immune tolerance and suggest that Tim-3 abundance on pNK cells is a potential biomarker for RM diagnosis.

Android system versions update and iterate frequently with severe fragmentation. The distribution of the various Android versions’ market share is scattered, making system-level vulnerabilities’ risk extensive and serious. For the limitations of the present research, we design and implement a new comprehensive system-level vulnerability detection system VScanner. For the first time VScanner is based on Lua script engine as the core. It gives priority to dynamic detection by exploiting, and static detection by feature matching is complementary. Vulnerability trigger is developed by the form of plugins, and it bases on vulnerability taxonomy by POCAS, which shows good scalability. For system-level vulnerabilities, we have implemented 18 plugins, which all are system-level vulnerabilities in high risk. By experimental evaluation, VScanner has high efficiency, low false alarm rate, and good effects on vulnerability detection.

This study aims to test the moderation and mediation effects of self-acceptance and self-reported health on self-worth's impact on subjective well-being among elderly Chinese rural empty-nester elderly, and confirm whether self-report health is a moderating variable between self-worth and subjective well-being.This cross-sectional study was performed from May 2017 to April 2018; the participants were 365 empty-nest elderly adults from rural areas of Chifeng City in Inner Mongolia.Data were collected with the General information questionnaire, Self-worth questionnaire for adults, Self-acceptance Questionnaire, and Memorial University of New Found land Scale of Happiness. For the analyses, correlations, regressions, and structural equation models were used. Bootstrapping was performed to confirm the mediation effect. Multiple regression analysis was performed to confirm the moderation effect.Self-worth showed significant correlations with self-acceptance and subjective well-being (all P < .01). Bootstrapping indicated that the mediating role of self-acceptance was statistically significant. And self-reported health moderated the self-worth and subjective well-being association.Self-acceptance partially mediated the relationship between self-worth and subjective well-being of the rural empty-nest elderly and self-reported health moderated self-worth and subjective well-being association. Consequently, to improve the subjective well-being of the rural empty-nest elderly, self-acceptance and personal health should be the focus.

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Igκ locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Igκ 3’ and distal enhancers that was mimicked by depletion of E2A or PU.1, as well as a global decrease in chromatin accessibility at enhancers. Importantly, re-expression of the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation of the Igκ enhancers and restored their chromatin accessibility. Our data suggest that TET proteins and lineage-specific transcription factors cooperate to influence chromatin accessibility and Igκ enhancer function by modulating the modification status of DNA. DOI: http://dx.doi.org/10.7554/eLife.18290.001

Summary Iron deposition is frequently observed in human autoinflammatory diseases, but its functional significance is largely unknown. Here we showed that iron promoted proinflammatory cytokine expression in T cells, including GM-CSF and IL-2, via regulating the stability of an RNA-binding protein PCBP1. Iron depletion or Pcbp1 deficiency in T cells inhibited GM-CSF production by attenuating Csf2 3′ untranslated region (UTR) activity and messenger RNA stability. Pcbp1 deficiency or iron uptake blockade in autoreactive T cells abolished their capacity to induce experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. Mechanistically, intracellular iron protected PCBP1 protein from caspase-mediated proteolysis, and PCBP1 promoted messenger RNA stability of Csf2 and Il2 by recognizing UC-rich elements in the 3′ UTRs. Our study suggests that iron accumulation can precipitate autoimmune diseases by promoting proinflammatory cytokine production. RNA-binding protein-mediated iron sensing may represent a simple yet effective means to adjust the inflammatory response to tissue homeostatic alterations.