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Lin Lu,1,* Bing Chen,1,* Xueli Zhao,1 Jie Zhai,1 Pan Zhang,2 Zhen Hua1 1Department of Anesthesiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing Chen, Department of Anesthesiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Dahua Road, DongDan, Beijing, 100730, People’s Republic of China, Tel +8613811295927, Email chenbingbjh@163.comPurpose: We designed this trial to compare the recovery time of remimazolam and propofol in elderly patients undergoing painless gastrointestinal endoscopy.Patients and Methods: In this randomized, non-Inferiority trial, 360 patients aged 65 years or older, scheduled for elective outpatient gastrointestinal endoscopy, were randomly assigned to the remimazolam combined with fentanyl (RF) group or the propofol combined with fentanyl (PF) group. The primary outcome was the post-anesthesia care unit (PACU) stay time, defined as the time from the end of the examination to scoring 9 points using the Modified Post-Anesthetic Discharge Scoring System (MPADSS) criteria. Secondary outcomes included sedation-related adverse events, recall, injection pain, as well as postoperative Quality of Recovery-15 (QoR-15) scores and Pittsburgh Sleep Quality Index (PSQI) scores at 1 day, 1 week, and 1 month postoperatively.Results: A total of 351 patients completed the study, with 174 receiving remimazolam and 177 receiving propofol. The PACU stay time in RF group was non-inferior to that in PF group [14 (11, 18) vs 13 (10, 17), mean difference 1 (95% confidence interval 0, 2), P=0.084 for noninferiority]. However, remimazolam was associated with lower rate of hypoxemia [4.7% (8/180) vs 12.4% (22/180), P=0.011], reduced use of vasoactive drugs [1 (0, 1) vs 1 (1, 2), P< 0.001], less injection pain [2 (1.2%) vs 35 (21.3%), P< 0.001], and lower recall [20 (11.8%) vs 36 (20.3%), P=0.034]. There were no differences in the QoR-15 scores and PSQI scores at postoperative 1 day, 1 week, and 1 month between groups.Conclusion: This non-inferiority study revealed that in elderly outpatients undergoing gastrointestinal endoscopy, remimazolam achieved recovery times comparable to propofol, with fewer associated complications.Keywords: remimazolam, postoperative recovery, older patients, gastrointestinal endoscopy

Lu Huang, Yujing Fu, Jinghong Cao, Jianjun Zhai Department of Obstetrics and Gynecology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of ChinaCorrespondence: Jianjun Zhai, Department of Obstetrics and Gynecology, Beijing Tongren Hospital, Capital Medical University, NO.1 of Dongjiaominxiang Street, Dongcheng District, Beijing, 100730, People’s Republic of China, Email jianjunzhai0504@163.comObjective: As a common endocrine and metabolic disorder, polycystic ovary syndrome (PCOS) is mostly associated with an obese phenotype. The present research focuses on the clinical significance of miR-379 in obesity-PCOS and attempts to elucidate its potential mechanisms.Methods: Healthy individuals (n = 46), obesity-PCOS (n = 92), and non-obesity PCOS (n = 31) subjects were enrolled. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the level of serum miR-379. The receiver operating characteristic (ROC) curve and logistic regressions were applied to reveal the diagnostic significance. Dual luciferase reporters were performed to validate the targeting relationships. And cell count kit (CCK-8) assay was used to detect cell proliferation.Results: Serum miR-379 was highly expressed in PCOS patients (P < 0.05), in especially obesity-PCOS patients. Higher miR-379 was associated with greater body mass index (BMI), higher bioavailable testosterone (bT), and greater insulin resistance (IR). Additionally, miR-379 was an independent risk factor for the development of obesity-PCOS. The sensitivity of miR-379 in identifying patients with obesity-PCOS from healthy or non-obesity-PCSO patients was 81.52% and 72.83%, and the specificity was 86.96% and 80.65%. Semaphorin 3 A (SEMA3A) was identified as a target of miR-379 and was reduced in the patients with obesity PCOS (P < 0.05). Inhibition of miR-375 reduced KGN proliferation, but this reduction was partially restored by silencing of SEMA3A (P < 0.05).Conclusion: Elevated miR-379 assists the diagnosis of obesity-PCOS and regulates the proliferation of KGN by targeting SEMA3A engaged in disease development.Keywords: obesity, PCOS, miR-379, diagnostic, SEMA3A

Jing Liu,1,&ast; Tingting Hu,2,3,&ast; Yulan Guan,2,4 Jinguo Zhai2 1Department of Gynecology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510700, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 3Department of Gynecology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 4Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510105, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulan Guan, Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, No. 261 Datong Road, Yuexiu District, Guangzhou, 510105, People’s Republic of China, Tel +8615989117143, Email 15989117143@163.com Jinguo Zhai, Nursing School, Southern Medical University, No. 1023-1063 Sha Tai Nan Road, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +8618620287620, Email helenjxzhai@gmail.comPurpose: To explore the risk and protective factors for developing ovarian cancer and construct a risk prediction model.Methods: Information related to patients diagnosed with ovarian cancer on the electronic medical record data platform of three tertiary hospitals in Guangdong Province from May 2018 to September 2023 was collected as the case group. Patients with non-ovarian cancer who attended the clinic during the same period were included in the control group. Logistic regression analysis was used to screen the independent variables and explore the factors associated with the development of ovarian cancer. An ovarian cancer risk prediction model was constructed using a decision tree C4.5 algorithm. The ROC and calibration curves were plotted, and the model was validated.Results: Logistic regression analysis identified independent risk and protective factors for ovarian cancer. The sample size was divided into training and test sets in a ratio of 7:3 for model construction and validation. The AUC of the training and test sets of the decision tree model were 0.961 (95% CI:0.944– 0.978) and 0.902 (95% CI:0.840– 0.964), respectively, and the optimal cut-off values and their coordinates were 0.532 (0.091, 0.957), and 0.474 (0.159, 0.842) respectively. The accuracies of the training and test sets were 93.3% and 84.2%, respectively, and their sensitivities were 95.7% and 84.2%, respectively.Conclusion: The constructed ovarian cancer risk prediction model has good predictive ability, which is conducive to improving the efficiency of early warning of ovarian cancer in high-risk groups.Keywords: ovarian cancer, incidence factors, decision tree model, risk prediction

Yinci Zhu,1,2 Zhong Zheng,1,2 Bihong Fan,1,2 Yun Sun,1,2 Junyu Zhai,1,2 Yanzhi Du1,2 1Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200135, People’s Republic of China; 2Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, 200135, People’s Republic of ChinaCorrespondence: Junyu Zhai; Yanzhi Du, Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200135, People’s Republic of China, Tel +86-21-20284525; +86-21-20284518, Email zhaijy2007@foxmail.com; duyz@sjtu.edu.cnPurpose: Together with ultrasound measurement of follicle size, serum estradiol (E2) provides guidance for controlled ovarian hyperstimulation (COH). However, during the COH process, some patients experience decreased serum E2 level, especially before human chorionic gonadotropin (hCG) trigger. In order to elucidate the effect of E2 reduction as well as the role of oral contraceptive pretreatment, a retrospective study was performed in our center from 2013 to 2019.Patients and Methods: In total, 333 patients who experienced an E2 decrease prior to hCG administration were recruited as E2 decline group, while 333 patients with continuously E2 increase during COH were considered as control group. Based on pretreatment strategy, the two groups were further categorized into oral contraceptive (OC) and non-OC sub-groups, and IVF and clinical outcomes were compared between paired groups.Results: Number of dominant follicles on hCG day and normally fertilized zygotes were significantly decreased in E2 decline group, and the significantly reduced live birth rate in E2 decline group indicated the close relationship between E2 decline and clinical outcomes. To analyse further, we found that in patients without OC pretreatment, the pregnancy rate and live birth rate of E2 decline group (n = 141) were significantly lower than control group (n = 136) (56.3% versus 68.0%, 50.8% versus 63.5%, respectively). However, for patients with OC pretreatment, no difference was detected between two groups, suggesting a potential effect of OC pretreatment on clinical outcomes.Conclusion: E2 decline prior to hCG-triggering day adversely affects IVF and clinical outcomes in patients without OC pretreatment, especially fertilization rate and live birth rate.Keywords: estradiol decline, controlled ovarian hyperstimulation, oral contraceptive, in vitro fertilization, fertilization rate, live birth rate

Jiajia Zhai,1 Junyan Zhang,2,3 Jingfang He,3 Minzhi Lv,4,5 Bozheng Zhang,6 Guanqun Li,7 Yuanjie Du,1 Guimin Hao1 1Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Shanxi Bethune Hospital, Shanxi Academy Of Medical Sciences, Department of Clinical Epidemiology and Evidence-Based Medicine, Taiyuan, People’s Republic of China; 3Bothwin Clinical Study Consultant, Shanghai, People’s Republic of China; 4Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Center of Evidence-Based Medicine, Fudan University, Shanghai, People’s Republic of China; 6Department of Psychology, College of Arts and Sciences, University of Washington, Seattle, WA, 98053, USA; 7Technoderma Medicines Inc, Shanghai, People’s Republic of ChinaCorrespondence: Guimin Hao, Email haoguimin@163.comObjective: For patients with polycystic ovary syndrome (PCOS) to undergo in vitro fertilization (IVF) and embryo transfer (ET), there has been no consensus regarding which protocol is the most optimal for live birth rate in fresh cycles. We sought to evaluate depot gonadotropin-releasing hormone (GnRH) agonist protocol versus GnRH antagonist protocol in IVF outcomes for PCOS patients in a single fertility center.Methods: In this retrospective cohort, PCOS patients who visited the Second Hospital of Hebei Medical University reproductive center between February 2012 and December 2019 were screened, and 533 PCOS infertility patients were included undergoing their first IVF cycle, with 470 in the depot GnRH agonist group and 63 in the GnRH antagonist group. The primary of this study outcome was the fresh live birth rate (LBR).Results: PCOS women in the depot GnRH agonist group had a higher LBR (49.79%) than those in the GnRH antagonist group (34.92%, p = 0.027). The multivariable logistic regression also confirmed that women in the depot GnRH agonist group had a higher LBR than those in the GnRH antagonist group (OR = 1.83, 95% CI 1.05~3.18, p = 0.032). After propensity score matching (PSM), the LBR in the depot GnRH agonist group was higher (50.32%) than that of the GnRH antagonist group (35.48%), p = 0.033. The ovarian hyperstimulation syndrome (OHSS) rates were similar between the two groups, with 35 in the depot GnRH group and 6 in the GnRH antagonist group (p = 0.561).Conclusions: For PCOS patients in fresh embryo transfer cycles, the depot GnRH agonist protocol may lead to a higher LBR than the antagonist protocol with satisfied lower OHSS rates.Keywords: PCOS, depot gonadotropin-releasing hormone agonist protocol, gonadotropin-releasing hormone antagonist protocol, cumulative live birth rate, live birth rate

Jiajia Zhai,1 Junyan Zhang,2,3 Jingfang He,3 Guanqun Li,4 Guimin Hao1 1Reproductive Center, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Clinical Epidemiology and Evidence-Based Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, Shanxi, People’s Republic of China; 3Bothwin Clinical Study Consultant, Shanghai, People’s Republic of China; 4Technoderma Medicines Inc, Shanghai, People’s Republic of ChinaCorrespondence: Guimin Hao, Email haoguimin@163.comPurpose: This study aims to investigate the impact of the Chinese New Year (CNY) holiday season on the outcomes of In Vitro Fertilization (IVF) fresh embryo transfer cycles.Participants and Methods: This retrospective study analyzed 4688 patients who received their first IVF fresh cycle attempt between January 2017 and October 2021. Of these, 4449 women underwent IVF during non-holiday seasons, while 239 women were treated during the CNY holiday season. The study included women who underwent IVF treatment during the specified time frame. The primary outcome was the live birth rate (LBR).Results: The study found that the LBR of IVF performed during the CNY holiday season was 32.22%, which is significantly lower than that of the non-holiday season (43.38%, p< 0.001). Multivariate logistic regression analysis showed that the CNY holiday season (OR=0.62, 95% CI 0.47– 0.82, p=0.001) was an independent factor associated with the live birth rate. Propensity score matching (PSM) data analysis showed that the LBR in the CNY holiday season group was 31.78% compared to 42.64% in the non-holiday season group (p=0.005). Inverse probability of treatment weighting (IPTW) data also indicated that the CNY holiday season had a lower LBR than the non-holiday season (OR=0.64, 95% CI 0.47– 0.87, p=0.005).Conclusion: IVF performed during the CNY holiday season results in a lower live birth rate, potentially indicating that certain lifestyle adjustments during this period, such as unhealthy dietary, tobacco and alcohol usage, sleep disruption, and emotional stress experienced could have some influence on the outcomes.Keywords: Chinese New Year holiday, live birth rate, culture, stress, smoking, alcohol

Yuntong Yang, Yanhong Luo, Ming Chen, Jie Zhai Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yanhong Luo, Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China, Tel +86-1868 486 0548, Email luoyanhong2006@126.comPurpose: Mobile phone addiction has motivated a widespread concern in recent years. From a developmental perspective, this study explored the predictive relations between life events, boredom proneness (BP), and mobile phone addiction tendency (MPAT) among undergraduate students. It also tested the longitudinal mediation of BP between life events and MPAT.Methods: Five hundred and eighty-four undergraduate students completed the Mobile Phone Addiction Tendency Scale, the Adolescent Self-Rating Life Events Checklist, and the Boredom Proneness Scale-Short Form. A longitudinal mediation analysis based on latent growth modeling was conducted to test the hypothesized relationships among life events, BP and MPAT.Results: Latent growth modeling (LGM) showed that the BP and MPAT of undergraduate students both increased linearly. A longitudinal model based on LGM showed that negative life events both directly and indirectly affected the initial level and the growth rate of the MPAT through the mediating effect of the initial level of BP.Conclusion: These results reveal that negative life events are an indicator of the development of MPAT. It has practical implications for calling for adopting health coping styles when facing negative life events. Supported for reducing college students’ boredom proneness in order to lessen the tendency towards mobile phone addiction to improve their mental health.Keywords: mobile phone addiction, life events, boredom proneness

Qingjuan Zuo,1,2 Guorui Zhang,1,3 Lili He,2 Sai Ma,4 Huijuan Ma,5 Jianlong Zhai,6 Zhongli Wang,7 Tingting Zhang,2 Yan Wang,2 Yifang Guo1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Cardiology, the Third Hospital of Shijiazhuang City Affiliated to Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Internal Medicine, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 5Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 6Department of Cardiology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 7Department of Physical Examination Center, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yifang Guo, Department of Geriatric Cardiology, Hebei General Hospital, No. 348, Heping West Road, Xinhua District, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +86-15100189182, Email guoyifang@hotmail.comPurpose: To investigate the effect of canagliflozin (20 mg/kg) on hepatic steatosis and atherosclerosis, and further to explore its possible mechanism.Methods: Blood glucose, blood lipid, oxidative stress response and inflammatory cytokines were examined by intraperitoneal glucose tolerance test and ELISA assay. HE and Oil Red O staining were used to estimate the extent of hepatic steatosis and atherosclerosis. RNA-seq and qRT-PCR were used to further investigate the potential mechanism. The effects of canagliflozin on autophagy were detected using transmission electron microscopy and Western blotting. The endothelial function-related markers were determined by qRT-PCR.Results: Canagliflozin notably alleviated the elevation in blood glucose and insulin resistance in western diet-fed ApoE-/- mice. In ApoE-/-+Cana group, ApoE-/- mice had lower levels of TG, TC, LDL-C, TNF-α, IL-6, IL-1β, and MCP-1. HE and Oil Red O staining presented that canagliflozin restrained the atherosclerotic plaque development and lipid accumulation. RNA-seq showed that 87 DEGs were relevant to improvement of hepatic steatosis and atherosclerosis by canagliflozin. Among them, CPS1, ASS1, ASL, ARG1, MATLA, GLS2, GOT1, SREBP1, Plin5, Retreg1, and C/EBPβ were verified. KEGG enrichment analysis indicated that DEGs were mainly involved in amino acid metabolism. Besides, we observed that canagliflozin reduced the contents of aspartic acid and citrulline in liver. Western blotting showed that ASS1 and p-AMPK/AMPK was remarkably elevated after administration of canagliflozin. Correspondingly, canagliflozin down-regulated SREBP1, FAS, ACC1, HMGCR, p-mTOR/m-TOR, p-ULK1/ULK1 and p62, but up-regulated CPT1, Beclin 1 and LC3 II/LC3I. TEM showed that canagliflozin reduced the number of lipid droplets and increased the autophagosomes. Moreover, we found that canagliflozin elevated the aortic endothelial function-associated markers including ASS1, ASL and eNOS.Conclusion: Canagliflozin may attenuate hepatic steatosis by improving lipid metabolism, enhancing autophagy, and reducing inflammatory response through ASS1/AMPK pathway. Besides, canagliflozin further effectively improves the aortic endothelial function, thereby suppressing atherosclerosis development.Keywords: canagliflozin, hepatic steatosis, atherosclerosis, RNA-seq, dyslipidemia, inflammatory response, autophagy

Ying Liu,1,&ast; Zhifang Zhong,1,&ast; Zhihong Li,1,&ast; Xin Li,2 Shengkun Zhang,2 Jie Sun,1 Jingfang Zhai,3 Xuekui Liu,4 Min Liu1 1Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 2Department of Obstetrical and Gynecological, Xuzhou Central hospital, Xuzhou, People’s Republic of China; 3Prenatal Diagnosis Center, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 4Department of Endocrinology, Xuzhou Central hospital, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Liu, Department of Ultrasound, Xuzhou Central Hospital, Jiefang Road 199#, Xuzhou, 221009, People’s Republic of China, Email 24187358@qq.com Xuekui Liu, Department of Endocrinology, Xuzhou Central Hospital, Jiefang Road 199#, Xuzhou, 221009, People’s Republic of China, Email liuxuekui314@njmu.edu.cnAim: Exposure to famine in early life has been shown to increase the prevalence of non-alcoholic fatty liver disease (NAFLD). Neutrophil-to-lymphocyte ratio (NLR) is a risk factor for developing NAFLD. However, it is not clear that the association between NLR and NAFLD in individuals who were exposed to famine in early life.Methods: To match for age, we selected two group populations from Xuzhou city, China, on two different occasions, 2013 and 2017. The group recruited in 2013 included participants who were born during a period of great famine in China. Participants in the another group recruited in 2017 were born between 1965 and 1968. Clinical characteristics of individuals as well as serology indexes were examined for all participants. Ultrasonography to diagnose NAFLD was performed by trained doctors. A total of 10,574 participants were included in the final analysis.Results: Individuals born during the famine period have a higher NAFLD prevalence than those who had not been exposed to famine and these findings were similar for both sexes (male: 57.6% vs 48.9%, female: 47.6% vs 40.3%). The prevalence of NAFLD according to NLR quartiles in those exposed to famine was 49.5%, 52.7%, 52.9% and 55.5% for Q1, Q2, Q3 and Q4 NLR, respectively, and was higher than that in non-exposed to famine group. After adjusting for age, BMI, and other metabolic variables, the association between NLR and NAFLD disappeared in the non-famine group. The non-linear relationship between NLR and NAFLD was found in those who had been exposed to famine.Conclusion: Individuals who were exposed to famine in early life have a higher prevalence of NAFLD than those who were not exposed. Compared with lower NLR levels, elevated NLR is a risk factor for developing NAFLD. However, there is a non-linear relationship between NLR and the risk of developing NAFLD.Keywords: non-alcoholic fatty liver disease, famine, neutrophil-to-lymphocyte ratio, non-linear relationship

Tu C Le,1 Jiali Zhai,2 Wei-Hsun Chiu,3 Phong A Tran,3,4 Nhiem Tran21School of Engineering, RMIT University, Melbourne, VIC 3001, Australia; 2School of Science, RMIT University, Melbourne, VIC 3001, Australia; 3School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane, QLD 4000, Australia; 4Interface Science and Materials Engineering group, School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD 4000, AustraliaCorrespondence: Nhiem TranSchool of Science, RMIT University, 124 La Trobe Street, Melbourne VIC 3000, AustraliaTel +61 3 9925 2131Email Nhiem.tran@rmit.edu.auAbstract: Janus particles, which are named after the two-faced Roman god Janus, have two distinct sides with different surface features, structures, and compositions. This asymmetric structure enables the combination of different or even incompatible physical, chemical, and mechanical properties within a single particle. Much effort has been focused on the preparation of Janus particles with high homogeneity, tunable size and shape, combined functionalities, and scalability. With their unique features, Janus particles have attracted attention in a wide range of applications such as in optics, catalysis, and biomedicine. As a biomedical device, Janus particles offer opportunities to incorporate therapeutics, imaging, or sensing modalities in independent compartments of a single particle in a spatially controlled manner. This may result in synergistic actions of combined therapies and multi-level targeting not possible in isotropic systems. In this review, we summarize the latest advances in employing Janus particles as therapeutic delivery carriers, in vivo imaging probes, and biosensors. Challenges and future opportunities for these particles will also be discussed.Keywords: Janus particles, therapeutics, theranostics, imaging, sensing

Xiangyi Kong,1,2,* Kai Zhang,3,* Xiangyu Wang,1,4,* Xue Yang,1,* Yalun Li,5 Jie Zhai,1 Zeyu Xing,1 Yihang Qi,1 Ran Gao,1 Xiaoli Feng,6 Jing Wang,1 Yi Fang11Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, MA 02114-3117, USA; 3Department of Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 4Department of Laboratory Medicine, Mayo Clinic, Rochester, MN 55902, USA; 5Department of Breast Surgery, Yantai Yuhuangding Hospital, Yantai 264000, People’s Republic of China; 6Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China*These authors contributed equally to this workBackground: Trastuzumab is an effective drug for the treatment of Her2-positive breast cancer. But, primary or secondary resistances to trastuzumab have become an important factor influencing the curative effect. The mechanisms of trastuzumab resistance are somewhat complex. The present work aims to explore the mechanism of trastuzumab resistance caused by HER-2 mutation in breast carcinomas.Methods: Firstly, the HER2 wild type (WT) and HER2 mutant (HER2 Q429R, HER2 Q429H and HER2 T798M are the commonest 3 types of mutations) MCF7 cell lines were established. Cell proliferation inhibition was then assessed by the Cell Counting Kit-8 assay and BrdU assay. Transwell invasion assays were also conducted to investigate the metastatic potential influenced by the HER2 mutation. Furthermore, Western blotting and co-immunoprecipitation were conducted to detect protein levels and the physical interaction of HER2 and trastuzumab.Results: The results showed that the mutant MCF7 cells were less sensitive to trastuzumab than the WTMCF7 cells. The mutation of HER2 almost had no influence on the expression of HER2 and the interaction of HER2 and trastuzumab. Finally, the mutation of HER2 weakened the inhibition of trastuzumab in the PI3K/AKT pathways. In addition, the inhibition of PI3K/AKT signaling-pathway increased the trastuzumab-sensitivity of HER2-mutant MCF7 cells.Conclusions: Dysregulation of the PI3K-AKT signaling-pathway was a key mechanism inducing the trastuzumab-resistance to HER2 mutant breast cancer cells.Keywords: HER2, trastuzumab, resistance, PI3K

Environmental sustainability constitutes an important part of the political and educational context in China as it strives to move toward an ecological civilization. However, there is limited literature documenting the ways in which sustainability is embedded in higher education (HE) teaching. This qualitative research involves interviews and focus groups with 30 faculty in Business and Economics disciplines at three high-ranked Chinese Universities and offers an original exploration of how they include environmental sustainability in their teaching, and the opportunities and challenges they encounter. The findings are significant in suggesting that a broad range of sustainability concepts and aligned pedagogies are incorporated but that political and institutional culture, limitations on obtaining research data, constraints on curriculum design, and individual beliefs are significant barriers to implementation. Strategies employed by faculty to embed sustainability are investigated and reviewed in the context of the 'theory of the second best', previously used in UK research.

We report the pulsed-laser deposition of epitaxial double-perovskite Bi2FeCrO6(BFCO) films on the (001)-, (110), and (111)-oriented single-crystal SrTiO3 substrates. All of the BFCO films with various orientations show the 1/2 1/2 1/2 and 3/2 3/2 3/2 superlattice-diffraction peaks. The intensity ratios between the 1/2 1/2 1/2-superlattice and the main 111-diffraction peak can be tailored by simply adjusting the laser repetition rate and substrate temperature, reaching up to 4.4%. However, both optical absorption spectra and magnetic measurements evidence that the strong superlattice peaks are not correlated with the B-site Fe3+/Cr3+ cation ordering. Instead, the epitaxial (111)-oriented Bi2FeCrO6 films show an enhanced remanent polarization of 92 μC/cm2 at 10 K, much larger than the predicted values by density-functional theory calculations. Positive-up-negative-down (PUND) measurements with a time interval of 10 μs further support these observations. Therefore, our experimental results reveal that the strong superlattice peaks may come from A- or B-site cation shifts along the pseudo-cubic [111] direction, which further enhance the ferroelectric polarization of the BFCO thin films.

Shallow meridional overturning circulations are superimposed on the deep circulations that produce precipitation in nearly all monsoon regions, and these shallow circulations transport subtropical, mid-tropospheric dry air into the tropical monsoon precipitation maxima. Here horizontal moisture advection produced by shallow meridional circulations is characterized in the monsoon regions of West Africa, South Asia, Australia, and southern Africa during local summer. Horizontal flow in the upper and lower branches of the shallow meridional circulations consistently dries and moistens air, respectively, in the continental precipitation maxima of each region. The peak drying by horizontal advection occurs at a lower altitude than peak winds in the upper branch of the shallow circulations, consistent with the small scale height of water vapour. Advection of time-mean moisture by time-mean wind dominates horizontal moisture advection in South Asia and West Africa, while most horizontal moisture advection in Australia and southern Africa is produced by transient eddies. Much of the transient eddy advection can be accurately represented as a first-order horizontal diffusion with a constant, globally uniform diffusivity. These results suggest that horizontal moisture advection in theoretical and conceptual models of seasonal mean monsoons can be adequately represented in terms of time-mean winds plus a simple horizontal moisture diffusion. Finally, interannual variations in the summer mean regional averages of monsoon precipitation and horizontal advective drying in the lower free troposphere are shown to be negatively correlated in most regions, consistent with the hypothesis that advective drying by shallow meridional circulations inhibits monsoon precipitation.

Observed nonlinearities in the seasonal evolution of monsoons have been previously explained using theories for Hadley circulations driven by zonally symmetric thermal forcings, even though monsoonal forcings deviate strongly from the assumption of zonal symmetry. Here, an idealized model of a dry, three-dimensional atmosphere is used to compare the response to zonally symmetric and asymmetric off-equatorial thermal forcings. For symmetric forcings, the zonal-mean, cross-equatorial mass flux increases more rapidly with the amplitude of the forcing once the forcing becomes strong enough to reduce the upper-tropospheric absolute vorticity to near zero, consistent with previous studies of the transition to angular momentum-conserving flow. For zonally asymmetric forcings, the zonal-mean cross-equatorial flow exhibits a similar dependence on forcing strength and a similar reduction of the zonal-mean upper-level vorticity, but asymmetric forcings also produce strong zonal overturnings with subsidence west of the heating, as in the well-known linear response to off-equatorial heatings. The mass flux in these zonal overturnings increases linearly with forcing strength until its rate of increase tapers off for the strongest forcings; the total upward mass flux (i.e., the zonal-mean plus zonally asymmetric components) increases linearly with the strength of zonally asymmetric forcings and exhibits no abrupt or nonlinear dependence on forcing amplitude. These results indicate the importance of considering the zonally asymmetric part of the divergent response to off-equatorial forcings and suggest that theories based on zonally symmetric forcings need further examination before they can be assumed to describe observed monsoons.

Decision making ability has been reported to be impaired in schizophrenia patients, but no research has examined the genetic bases of this impairment. This study investigated how decision making was affected by the genetic variants in the serotonin transporter gene (triallelic 5- HTTLPR) and serotonin receptor 1A gene (rs6295) and their interaction in 465 schizophrenia patients and 448 healthy controls. The Iowa Gambling Task (IGT) was used to evaluate decision making under ambiguity (the first 40 trials) and decision making under risk (the last 60 trials). Results showed that, among the patients, the main effects of 5- HTTLPR (F(2) (,16) = 6.54, P = 0.002) and HTR1A rs6295 (F(2) (,16) = 3.87, P = 0.021) polymorphisms and their interaction effect (F(4) (,16) = 3.32, P = 0.005) were significant for the first 40 trials, with the GG genotype of HTR1A rs6295, the L'L' genotype of 5- HTTLPR and the GG-L'L' combination showing poorer IGT performance than their counterparts. Results for the healthy controls showed a similar pattern but did not reach statistical significance. No significant effects were found for the last 60 trials. These results are discussed in terms of their implications for our understanding of the genetic mechanisms of decision making in schizophrenia patients as well as healthy adults.

[Objective] The study aims to investigate the effects of light quality with different red and blue ratios on the growth, photosynthesis, flavonol accumulation, and antioxidant capacity of Ginkgo biloba, select the light quality suitable for the growth and flavonoid accumulation, and provide a theoretical basis for improving the medicinal value of G. biloba leaves. [Methods] Two-year-old G. biloba seedlings were used, and four light quality treatments with red and blue ratios of 1∶1 (1R1B), 1∶3 (1R3B), 1∶5 (1R5B), and white light (W, control) were set up. The growth, photosynthetic physiology, flavonol content, and antioxidant capacity of G. biloba after 20 days of treatment were analyzed. [Results] Different ratios of red and blue light reduced the biomass of G. biloba leaves, which was not conducive to the growth of plant height and ground diameter, but was conducive to the improvement of leaf length, width, and area and photosynthetic gas exchange parameters.1R5B treatment increased the total chlorophyll content of leaves. 1R1B treatment promoted the accumulation of total leaf biomass. The chlorophyll fluorescence parameters, antioxidant capacity, carotenoid, and total flavonol contents of leaves under 1R3B were the highest. [Conclusion] The appropriate proportion of red and blue light had a significant effect on the growth and photosynthetic characteristics of G. biloba, and significantly increased the content of flavonols and antioxidant capacity. 1R3B red and blue light quality was the most conducive to the accumulation of flavonoids.