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Shuai Gao,1,&ast; Yuanjie Sun,1,&ast; Hangyu Shi,1,2 Jiufei Fang,1 Zhishun Liu1 1Department of Acupuncture, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhishun Liu, Department of Acupuncture, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange Street, Xicheng District, Beijing, People’s Republic of China, Email zhishunjournal@163.comPurpose: Cyclic mastalgia is prevalent among women and negatively impairs their daily life and work. There is still a lack of effective therapies for mastalgia, and acupuncture may be a promising method. We design this multicenter randomized trial to evaluate the efficacy and safety of acupuncture on cyclic mastalgia.Study Design and methods: Sixty participants with moderate-to-severe cyclic breast pain (with a duration of 5– 21 days and the worst pain scoring 5 points or more on Numerical Rating Scale [NRS]) will be recruited at three hospitals in China. They will be randomly assigned to acupuncture group or sham-acupuncture group at 1:1 ratio to receive 16-session treatment during 3 consecutive menstrual cycles, and follow-up for 6 menstrual cycles after treatment. The primary outcome is the change from baseline in the NRS score on the worst breast pain during the third cycle of treatment period. All statistical tests will be two-sided and P value < 0.05 will be considered statistically significant.Keywords: cyclic breast pain, complementary and alternative medicine, RCT, sham acupuncture

This study ascertained to explore the potential contribution of ARRDC3 polymorphisms in the risk and prognosis of glioma. One thousand sixty-one patients and healthy controls were conducted to assess whether ARDC3 polymorphism was associated with glioma risk and prognosis. Four sites in ARRDC3 were selected and genotyped in MassARRAY platform. The calculated odd ratios and 95% confidence intervals from logistic regression were applied for risk assessment. The relationship between ARRDC3 variants and glioma prognosis was evaluated using log-rank test, Kaplan-Meier analysis, and so on. Also, false-positive report probability (FPRP) and statistical power were also assessed. Our findings suggested the negative role of ARRDC3 polymorphisms in the glioma risk. We also found the effect of candidate SNPs in ARRDC3 on the susceptibility to glioma was dependent on the age, gender, and histology of glioma patients. The results suggested that the genetic polymorphisms of ARRDC3 were related to an increased risk of glioma.

Glioma is a common and fatal primary malignant tumor of the central nervous system, and its prognosis is poor. To determine the susceptibility markers of gliomas in Chinese population we conducted a genome-wide association study (GWAS) of glioma in the Han Chinese population, with a total of 485 glioma cases and 485 controls. Genotyping was conducted using the Applied Biosystems Axiom Precision Medicine Diversity Array. Besides, we carried out imputation using IMPUTE 2.0 software, and the 1000 Genomes Phase 3 was used as the reference panel. The logistic regression model was used to analyze the association of each SNP with glioma risk, assuming an additive genetic model, which was implemented in PLINK version 1.9. Odds ratio (OR) and 95% confidence interval (CI) were estimated from logistic regression analysis with adjustment for age and gender. The results revealed that the SNP (rs688755) in the exon region of CYP4F12 at 19p13.12 reached genome-wide significance associated with gliomas (P = 2.35 × 10-8 , OR = 3.55, 95% CI = 2.20-5.74). Our findings provide deeper insight into the genetic contribution to glioma in different populations.

Purpose Genetic factor is a risk factor in glioma occurrence. This study was designed to detect the effect of ADCY9 polymorphisms on glioma risk and prognosis. Methods We performed a case-control study of 1080 participants (584 cases and 496 controls) to assess the relationship of ADCY9 polymorphisms with the risk and prognosis of glioma among the Chinses Han population. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to evaluate the relationship between ADCY9 variants and glioma risk. The correlation of SNPs with survival was analyzed by the Cox regression model. Results Our study showed that rs2230742 and rs2531992 polymorphisms played protective roles in glioma susceptibility (OR 0.65, p = 0.001; OR 0.73, p = 0.038, respectively). While rs2230742 significantly increased the susceptibility of III-V grade glioma patients (OR 1.50, p = 0.036). Haplotype analysis revealed that Crs879620Ars2230742Ars2230741 haplotype was related to a significantly decreased glioma risk (OR 0.65, p = 0.002). Notably, rs2531995 and rs879620 polymorphisms significantly enhanced death risk in high-grade glioma patients (hazard ratio [HR] 1.36, p = 0.041; HR 1.37, p = 0.042; respectively). For rs2230742 and rs2531992 SNPs, glioma patients had a worse prognosis (HR 2.30, p = 0.021; HR 2.30, p = 0.021; respectively). We further observed that age, chemotherapy, and surgical scope can affect the glioma prognosis. Conclusion We firstly studied the association of ADCY9 variants with glioma risk and prognosis, which might give scientific evidence for exploring the molecular mechanism of glioma.

IntroductionPelvic organ prolapse (POP) is downward descent of pelvic organs, which causes symptoms of the lower genital, urinary and gastrointestinal tracts, and undermines women’s daily activities and quality of life. Although studies indicated that electroacupuncture (EA) may be effective in improving the POP symptoms, evidences were not robust. Therefore, this study aims to conduct a randomised controlled trial (RCT) to evaluate the efficacy and safety of electroacupuncture on relieving symptoms of a POP stage II and III among women.Methods and analysisA two-arm, multicentre, patient-blind RCT will be conducted to compare EA with sham electroacupuncture (SEA) for treating symptoms of POP stage II and III among women in six tertiary hospitals in China. One hundred and sixty eligible women will be assigned with a 1:1 ratio to have received either EA or SEA for 24 times in 12 weeks and followed-up for 24 weeks. The primary outcome will be the change on the total score of the Pelvic Floor Distress Inventory-short form 20 at week 12 from baseline, and will be analysed by t-test or multiple regression model. Intention-to-treat analysis will be performed for all outcomes, and a p value of less than 0.05 (two-sided testing) will be considered as statistical significance.Ethics and disseminationThe study protocol has been approved by the Medical Ethical Committee of Guang’ammen Hospital (No. 2019-249-KY-01). Patients will be informed about the details of the study and asked to sign consent form before enrolment. The results of this study are expected to be written and published on peer-reviewed journals.Trial registration numberNCT04589715.

Min Xi,1 Gang Zhang,1 Liang Wang,2 Hu Chen,2 Li Gao,2 Luyi Zhang,1 Zhangkai Yang,1 Hangyu Shi1 1Department of Neurosurgery, Xi’an Children’s Hospital, Xi’an, 710043, People’s Republic of China; 2Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, 710038, People’s Republic of ChinaCorrespondence: Hangyu Shi, Department of Neurosurgery, Xi’an Children’s Hospital, #69, Xijuyuan Lane, Lianhu District, Xi’an, 710043, Shaanxi, People’s Republic of China, Tel/Fax +86-15202910508, Email shihangyu723@aliyun.comBackground: This study aimed to evaluate the relationship between CARMN polymorphisms and glioma risk and prognosis in a Chinese Han population.Methods: Seven single nucleotide polymorphisms (SNPs) in CARMN were genotyped among 592 glioma patients and 502 healthy controls. Log-additive models were used for risk assessment by the odds ratios (ORs) and 95% confidence intervals (CIs). Univariate and multivariate Cox regression analysis was applied to calculate Hazard ratios (HRs) and 95% CIs for prognosis assessment.Results: CARMN rs13177623 was a protective factor for glioma susceptibility (OR = 0.78, p = 0.043). In addition, rs13177623, rs11168100, rs12654195 and rs17796757 were associated with the risk of glioma among the subgroup stratified by age or gender. We also found that G rs13177623G rs12654195 haplotype was related to the decreased risk of glioma (OR = 0.61, p = 0.005). Importantly, rs13177623 [overall survival (OS): HR = 0.83, p = 0.047, and progression free survival (PFS): HR = 0.82, p = 0.031], rs12654195 (OS: HR = 0.64, p = 0.005 and PFS: HR = 0.65, p = 0.007) and rs11168100 (OS: HR = 0.71, p = 0.035) were associated with a better prognosis for glioma, especially in grade I-II glioma. In patients with grade III-IV glioma, rs17796757 polymorphism presented an improved OS.Conclusion: Our results firstly reported the contribution of CARMN variants (rs11168100, rs12654195, rs13177623, and rs17796757) to the susceptibility and prognosis of glioma in a Chinese Han population, which provided a novel insight on the relationship between CARMN gene and glioma tumorigenesis.Keywords: glioma, CARMN variants, susceptibility, prognosis, genetic variations

Hot flashes (HF) are a prevalent symptom associated with menopause affecting up to 85% of women aged 40 to 65 years. Previous studies indicated that acupuncture might relieve the symptom of HF significantly; however, its effectiveness has not been clarified quantitatively. Electro-press needles (EPN) is a novel acupuncture that combines a shallow tiny needle with an electrical transdermal stimulator. Either the needle or the electrical stimulator could function in the treatment. This study aims to evaluate the effectiveness of EPN in comparison with no intervention in relieving HF of perimenopausal and postmenopausal women.This study will be a 2-arm randomized waitlist controlled trial. According to the ratio of 1:1 and block randomization, a total of 122 patients with moderate or severe HF will be randomly allocated to either EPN group or waitlist control group. The EPN group will receive 3 sessions of EPN treatment each week in consecutive 6 weeks, 18 sessions in total. The waitlist control group will get no intervention over the first 6 weeks. All the patients will be followed up in the next 24 weeks. The primary outcome will be the percentage of the participants whose 24-hour mean HF is 50% less than the baseline at Week 6. Secondary outcomes will include HF score, HF frequency, HF severity, the Menopause Rating Scale and Menopause-Specific Quality of Life Questionnaire Score.This study will evaluate the effectiveness and safety of EPN treatment to alleviate HF symptoms in perimenopausal and postmenopausal women, excluding self-healing factors. The limitations of the trial design are its single-center scope, lack of placebo control and impossible to blind the acupuncturists and patients.Trial registration: This clinical trial has been registered in Clinical Trial Registry (registration number: NCT04995107; date of registration: Aug 6, 2021).

Venture capital investment has serious conflicts of interest and information asymmetry. Venture capitalists often make investment decisions on the basis of the passion of entrepreneurs, including enthusiasm and preparedness, in the process of interacting with them. Most of the previous research on relational capital have focused on the cooperative relationship between suppliers and buyers. However, the role of relational capital in the process of partnership between venture capitalists and entrepreneurs has not been revealed. On the basis of signaling theory, we explore the relationship between entrepreneurial passion and venture capitalists’ willingness to invest. We also examine the mediating and moderating roles of relational capital. This study takes 79 projects between venture capitalists and entrepreneurs as samples for empirical analysis to verify our hypothesis. Results show that entrepreneurs’ enthusiasm and preparedness have a significant positive impact on venture capitalists’ willingness to invest. Relational capital plays a mediating role between entrepreneurial passion and venture capitalists’ willingness to invest. Relational capital positively moderates the relationship between preparedness and venture capitalists’ willingness to invest but has no moderating effect between enthusiasm and venture capitalists’ willingness to invest. Results deepen the understanding of the relationship between entrepreneurs’ passion and venture capitalists’ willingness to invest, which has guiding significance for venture capital practice in China.

This study aimed to evaluate the relationship betweenSeven single nucleotide polymorphisms (SNPs) inOur results firstly reported the contribution of

Entrepreneurship research generally focuses more on the entrepreneurial outcomes of entrepreneurs and less on their entrepreneurial process. To a certain extent, well-being reflects how tired entrepreneurs are during entrepreneurship. Based on conservation of resources theory, this study proposes a double-edged sword model of the effect of entrepreneurial identity on subjective well-being, using the two-dimensional structure of work rumination as a mediator. This study also concentrates on the moderating role of entrepreneurial mindfulness. Multiple hierarchical regression methods are used to analyze and test 882 valid samples. Results suggest that the effect of entrepreneurial identity produces distinctly different outcomes. On the one hand, entrepreneurial identity induces entrepreneurs' work-related affective rumination to reduce their subjective well-being through the path of resource depletion. On the other hand, entrepreneurial identity stimulates entrepreneurs' contemplation on work-related problem-solving pondering to enhance their subjective well-being through the path of resource acquisition. In the path of resource depletion, work-related affective rumination produces a “suppressing effect” between an entrepreneur's identity and entrepreneurial subjective well-being. In addition, entrepreneurial mindfulness weakens the resource depletion path. Entrepreneurial mindfulness negatively moderates the relationship between entrepreneurial identity and work-related affective rumination. Entrepreneurial mindfulness also does not strengthen the resource acquisition path. Mindfulness does not positively moderate the relationship between entrepreneurial identity and work-related problem-solving pondering. The findings further extend the research on the influence of entrepreneurial identity on subjective well-being. They also reveal the mechanisms and boundary conditions of the effect of entrepreneurial identity on subjective well-being.

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti-inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute-1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC50 dose was obtained at 30 µM. For further studies, we selected the 30 µM IC50 dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma.

Background: glioma is a highly fatal malignant tumor with a high recurrence rate. We aimed to determine the association between single nucleotide polymorphisms (SNPs) of NDRG1 and glioma risk and prognosis in the Chinese Han population.Methods: 5 candidate SNPs were genotyped by Agena MassARRAY; logistic regression was used to analyze the association between SNPs and glioma risk; We used multi-factor dimensionality reduction to analyze the interaction of ‘SNP-SNP’; the prognosis analysis was performed by log-rank test, Kaplan–Meier analysis and Cox regression model.Results: our results showed that the rs3808599 was associated with the reduction of glioma risk in all participants (p = 0.024) and the participants ≤40 years old (p = 0.020). rs3802251 may reduce glioma risk in all participants (p = 0.008), the male (p = 0.033) or astrocytoma patients (p = 0.023). rs3779941 was associated with poor glioma prognosis in the all participants (p = 0.039) or astrocytoma patients (p = 0.038). We also found that the key factors for glioma prognosis may include surgical operation, radiotherapy and chemotherapy.Conclusion: this study is the first to find that NDRG1 gene polymorphisms may have a certain association with glioma risk or prognosis in the Chinese Han population.

MicroRNAs (miRNAs) play important roles in several human cancers. Although miR-188 has been suggested to function as a tumor repressor in cancers, its precise role in glioma and the molecular mechanism remain unknown. In the present study, we investigated the effect of miR-188 on glioma and explored its relevant mechanisms. We found that the expression of miR-188 is dramatically downregulated in glioma tissues and cell lines. Subsequent investigation revealed that miR-188 expression was inversely correlated with β-catenin expression in glioma tissue samples. Using a luciferase reporter assay, β-catenin was determined to be a direct target of miR-188. Overexpression of miR-188 reduced β-catenin expression at both the mRNA and protein levels, and inhibition of miR-188 increased β-catenin expression. Moreover, we found that overexpression of miR-188 suppressed glioma cell proliferation and cell cycle G1–S transition, whereas inhibition of miR-188 promoted glioma cell proliferation. Importantly, silencing β-catenin recapitulated the cellular and molecular effects seen upon miR-188 overexpression, which included inhibiting glioma cell proliferation and G1–S transition. Taken together, our results demonstrated that miR-188 inhibits glioma cell proliferation by targeting β-catenin, representing an effective therapeutic strategy for glioma.

The Boltzmann equation is an integro-differential equation representing a wide range of transport and radiative transfer problems. In this paper, we propose to use the half boundary method (HBM) in the spherical coordinate system for deriving accurate and robust numerical solutions of the Boltzmann transport equation for neutron transport problem, respectively for vacuum boundary conditions, reflection boundary conditions and multilayer dielectric materials, yielding the recursive equation of the angular neutron flux by discretizing the transport equation's space and angle variables. The relationship between any point and the boundary point is derived and the particle flux distribution is obtained. Compared to traditional discrete ordinate method, the HBM uses no inverse matrix, which increases the degree of discretion, significantly reducing the computation expenses in the solution process. Finally, the HBM results are compared to those of the Monte Carlo method, proving the proposed method's feasibility, high accuracy and applicability.

Circular dichroism (CD) of a stretchable chiral metamaterial with bilayer L-shaped and T-shaped Au patterns on the Polydimethylsiloxane substrate (SCMM-BLT) is investigated theoretically. Due to the excitation of plasmonic hybridization modes, CD effect happens. SCMM-BLT can produce large optical chirality (OC) of 53.6% in mid-infrared region, and we attribute the double bands of CD to the excitation of the bonding and antibonding modes. By stretching SCMM-BLT, the bands of CD shift to longer wavelengths, which prove SCMM-BLT can be a candidate as the tunable chiral metamaterial. Our findings pave a way in designing wearable electronic devices, such as sensors.

Hippocampus has attracted the attention of the neuroscientists for its involvement in a wide spectrum of higher-order brain functions and pathological conditions, especially its persistent neurogenesis in subgranular zone (SGZ). The development of hippocampus was intensively investigated on animals such as rodents. However, in prenatal human hippocampus, little information on the distribution of neural stem/progenitor cells, newly generated neurons and mature neurons is available and the timetable of a series of neurogenesis event is even more obscure. So in the present study, we aim at immunohistochemically providing more information on neurogenesis in prenatal human hippocampus from 9 weeks to 32 weeks of gestation. We found that the ki67-positive cells were always detected in hippocampus from 9 weeks to 32 weeks, with a peak at 9 weeks in cornu ammonis (CA) or 14 weeks in dentate gyrus (DG). At 9 weeks the nestin-expressing cells were distributed throughout the hippocampus, with concentrated immunoreactivity in intermediate zone (IZ), marginal zone (MZ), fimbria, and relatively sparse immunoreactivity in the ventricular zone (VZ) and hippocampal plate (HP). With development, the optical density (OD) and the number of nestin-positive cells decreased gradually. At 32 weeks, there were relatively more nestin-positive cells in DG than that in CA. About DCX-positive cells, they displayed a similar distribution as nestin-positive cells (immunoreactivity concentrated in IZ, MZ, fimbria and HP) and a dramatic decrease of OD or cell number density from 9 weeks on. NeuN-positive cells, with small nuclei, were firstly found in MZ and subplate of hippocampus at 9 weeks. After 14 weeks, many NeuN-positive cells extended from subplate into HP and the density of NeuN-positive cells peaked at 22 weeks. That the immunoreactivity for NeuN was the strongest and the nuclei were the biggest at 32 weeks suggests that the neurons reach maturity gradually. Therefore this study provides an important timetable of neurogenesis in prenatal human hippocampus for the clinicians in neuroscience or pediatrics.

The development of glioma is a complex process which may be influenced by many factors including the epidermal growth factor (EGF) gene polymorphism. Previous studies showed that EGF rs4444903 polymorphism could result in increased risk of tumorigenesis in multiple human cancers, but published data regarding the association between EGF rs4444903 polymorphism and glioma risk were inconsistent. To derive a more precise estimation of the association between EGF rs4444903 polymorphism and glioma risk, we performed a systematic review and meta-analysis of previous published studies. PubMed, Embase, and the Wanfang databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Ten published studies with 1,891 glioma cases and 2,836 controls were finally included into the study. Overall, there was a significant association between EGF rs4444903 polymorphism and glioma risk in all four genetic models (the allele model: OR = 1.25, 95 % CI 1.15–1.37, P

MicroRNA-375 (miR-375) is frequently demonstrated to be frequently dysregulated and functions as a tumor suppressor or an oncogene in different cancer types. However, its roles in human gliomas have not been reported. The aim of this study was to investigate the expression pattern and clinical significance of miR-375 in patients with gliomas.Real-time quantitative RT-PCR assay was performed to detect miR-375 expression in human gliomas and non-neoplastic brain tissues. Then, the association of miR-375 expression with clinicopathological factors and prognosis of glioma patients was also statistically analyzed.miR-375 expression was significantly decreased on average in glioma tissues relative to non-neoplastic brain tissues (P0.0001) with ascending pathological grade. Then, the low miR-375 expression in glioma tissues was significantly associated with advanced pathological grade (P=0.003) and low Karnofsky performance score (KPS, P=0.01). Moreover, both univariate and multivariate Cox regression analyses determined that loss of miR-375 expression effectively predicted the decreased overall survival in patients with gliomas.These findings offer the first convinced evidence that the downregulation of miR-375 expression in human gliomas may play an inhibitory role during the tumor development. This miRNA might function as a candidate unfavorable prognostic marker for human gliomas.