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The main task in the production of steel in the basic oxygen furnace (BOF) is dephosphorization Therefore, the prediction and control of the end-point phosphorus content of molten steel is of great significance. Four machine learning regression models (Lasso, Random Forest, Xgboost, and Neural Network) were established to predict the end-point phosphorus content of molten steel in the BOF based on raw and auxiliary material data, process parameters, and production quality data. The prediction effect of the four models was further compared, and their prediction results were interpreted based on the interpretability of the models and the permutation importance method. The results showed that compared with linear regression and neural network regression model, two types of ensemble tree model have higher prediction accuracy, better stability with small data sets, and lower data preprocessing requirements. The factors influencing the end-point phosphorus (P) content in BOF were ranked in order of importance as: Tapping temperature > Turning down times > Steel scrap quantity> Operation habits of different working groups > Amount of oxygen injection> Sulfur and phosphorus content of molten iron > Addition amount of lime, limestone, and lightly burnt dolomite in the slag > Slag-splashing amount.

In hemisphere point temperature (Thp) measurement of continuous casting mold flux, the evaporation of volatiles under high temperature will have a strong impact on the results. Based on the comprehensive analysis of hemisphere point method and its influencing factors, the corresponding volatile-containing mold flux and non-volatile mold flux were selected to get Thp with different heating rates. Combined with the Thp measurement and TG-DSC results, the effect of relevant factors during measuring process were analysed and the way to characterize and evaluate the effects were suggested. Furthermore, an improved method of mold flux melting point test was put forward. The results showed that for non-volatile mold flux, the temperature hysteresis had a greater effect than heat transfer delay and fractional melting. As for the mold flux with volatile, the effect of evaporation was greater than other factors. Traditional hemisphere-point method is no longer suitable for the volatile mold flux. In order to get through this problem, improved methods were proposed. One is measuring Thp traditional way, correcting the composition at the Thp, and corresponding Thp with the corrected composition. Another is taking the initial composition, revising the hemispherical point temperature Thp, and matching the revised Thp with the initial composition.

Xianling Feng,1,* Fucheng Tao,2,* Min Ren,3,* Mao Niu4 1School of Medical, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2Department of Stomatology, Shenzhen University General Hospital, Shenzhen, 518055, People’s Republic of China; 3Department of Stomatology, Rizhao Traditional Chinese Medicine Hospital, Rizhao, 276800, People’s Republic of China; 4School of Medical Technology and Nursing, Shenzhen Polytechnic University, Shenzhen, 518055, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao Niu, School of Medical Technology and Nursing, Shenzhen Polytechnic University, 7098 Liuxian Avenue, Nanshan District, Shenzhen, 518055, People’s Republic of China, Tel +86 755 26011160, Fax +86 755 26018477, Email niu1037@szpu.edu.cnObject: The present study intended to evaluate the effect of simvastatin-loaded nanomicelles (SVNs) on promoting new bone formation and reducing alveolar ridge resorption at the tooth extraction sites at the early healing of the extraction sockets.Methods: SVNs were synthesized using a dialysis method. The rabbit tooth extraction model was established, SVNs and simvastatin (SV) were loaded on gelatin sponge and inserted into the extraction socket. CBCT scans were performed at 0, 2, and 4 weeks postoperatively to evaluate bone formation and alveolar ridge absorption in the extraction sockets. And all the animals were sacrificed and the mandibles were harvested. And HE staining and Masson staining were used for histological evaluation of the bone formation in the extraction sockets.Results: Radiographic evaluation showed that compared with the blank control group, at 2 and 4 weeks after extraction, SVNs increased the new bone density in the extraction sockets by 75.7% and 96.5%, and reduced the absorption rate of alveolar ridge length at the extraction sites by 60.8% and 49.1%, respectively. Histological evaluation showed that SVNs significantly improved the maturation of new bone tissue in the extraction sockets.Conclusion: SVNs can significantly accelerate healing and effectively reduce the absorption of alveolar ridge at the extraction sites in the early stage of tooth extraction socket healing.Keywords: alveolar ridge preservation, simvastatin-loaded nanomicelles, tooth extraction sites, bone formation

Mingyuan Ren,1,2,* Yijia He,1,* Jianzhong Zhang,3 Jinfang Zhang,1,2 Guoqiang Zhang1,2 1Department of Dermatology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Hebei Technical Innovation Center for Dermatology and Medical Cosmetology Technology, Shijiazhuang, People’s Republic of China; 3Department of Dermatology, Affiliated Hospital of Hebei University of Engineering, Handan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinfang Zhang; Guoqiang Zhang, Email 58303110@hebmu.edu.cn; 57702800@hebmu.edu.cnAbstract: Tjalma’s syndrome is a benign combination of ascites, pleural effusion, and elevated CA-125 occurring in patients with systemic lupus erythematosus. Reports of Tjalma’s syndrome are scarce. An elevated CA-125 level often suggests the possibility of the presence of a malignant tumor. We report a case of generalised erythema and blisters with pruritus, massive unilateral pleural effusion and elevated CA-125. This patient was finally diagnosed with bullous systemic lupus erythematosus after exclusion of tumour and other maculopapular disorders. We hope that this particular case may provide a more comprehensive and novel diagnostic idea of systemic lupus erythematosus and pleural effusion, avoiding unnecessary anxiety, laboratory tests and surgical interventions.Keywords: systemic lupus erythematosus, bullous systemic lupus erythematosus, pleural effusion, Tjalma’s syndrome, CA-125

Jiwen Fan,1 Meng Ren,2 Binay Kumar Adhikari,3 Haodong Wang,1 Yuquan He1 1Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Medical Oncology, Jilin Provincial Cancer Hospital, Changchun, People’s Republic of China; 3Department of Cardiology, Nepal Armed Police Force (APF) Hospital, Kathmandu, NepalCorrespondence: Yuquan He, Department of Cardiology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Road, Changchun, People’s Republic of China, Tel +86 15604411532, Email heyq@jlu.edu.cnAbstract: Cardiac fibrosis often has adverse cardiovascular effects, including heart failure, sudden death, and malignant arrhythmias. However, there is no targeted therapy for cardiac fibrosis. Inflammation is known to play a crucial role in the disorder, and the NLR pyrin domain-containing-3 (NLRP3) inflammasome is closely associated with innate immunity. Therefore, further understanding the pathophysiological role of the inflammasome in cardiac fibrosis may provide novel strategies for the prevention and treatment of the disorder. The aim of this review was to summarize the present knowledge of NLRP3 inflammasome-related mechanisms underlying cardiac fibrosis and to suggest potential targeted therapy that could be used to treat the condition.Keywords: NLRP3 inflammasome, cardiac fibrosis, AIM2, ASC, caspase-1

Menghao Ren,1 Shengqi Zou,1,2 Shuyu Ding,3 Daoqun Ding1,4 1Department of Psychology, School of Education Science, Hunan Normal University, Changsha, People’s Republic of China; 2Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, People’s Republic of China; 3Department of Education, Shandong Women’s University, Jinan, People’s Republic of China; 4Center for Mind and Brain Sciences, Hunan Normal University, Changsha, People’s Republic of ChinaCorrespondence: Daoqun Ding, Department of Psychology, School of Education Science, Hunan Normal University, 36 Lushan Road, Changsha, Hunan, 410081, People’s Republic of China, Tel +86-731-88872869, Email psychding@hunnu.edu.cnPurpose: Childhood environments have an impact on an individuals’ behavior and cognition. We explored the relationship and possible mechanisms between childhood environmental unpredictability (CEU) and prosocial behavior (PSB) in adults.Participants and Methods: We recruited Chinese college students (N = 1035) and adopted a questionnaire survey and structural equation modeling.Results: The results showed that CEU negatively predicted PSB in adults. Life-history strategy and dark personality chains mediated this relationship. Higher CEU facilitated faster development of life-history strategies in individuals, and dark personalities, via fast life-history strategies, further influenced PSB in adults. The mediating pathways of Machiavellianism, narcissism, and sadism were significant, while psychopathy was not. Women were more prosocial than men, and there was no sex difference in the influence mechanism of CEU on PSB.Conclusion: This study has practical significance as it emphasizes the importance of shaping a stable childhood environment and that individuals’ prosociality can be improved by intervening in the mediation.Keywords: childhood environmental unpredictability, prosocial behavior, life-history strategy, dark personality

Qingen Da,1,2,&ast; Mingming Ren,2,&ast; Lei Huang,2 Jianhua Qu,1 Qiuhua Yang,3 Jiean Xu,4 Qian Ma,4 Xiaoxiao Mao,4 Yongfeng Cai,4 Dingwei Zhao,4 Junhua Luo,5 Zilong Yan,1 Lu Sun,2 Kunfu Ouyang,2 Xiaowei Zhang,6 Zhen Han,2 Jikui Liu,1 Tao Wang2 1Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 2Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 3Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA; 4Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of China; 5Department of Urological Surgery, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 6School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jikui Liu, Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email liu8929@126.com Tao Wang, Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email szwangtao@126.comObjective: We aimed to explore the prognostic patterns of ferroptosis-related genes in papillary renal cell carcinoma (PRCC) and investigate the relationship between ferroptosis-related genes and PRCC tumor immune microenvironment.Methods: We obtained the mRNA expression and corresponding clinical data of PRCC from the public tumor cancer genome atlas database (TCGA). The PRCC patients were randomly divided into two cohort, training cohort and verification cohort, respectively. Univariate Cox regression, LASSO Cox regression, multivariate Cox regression analysis were utilized to construct ferroptosis signature for PRCC patients. And then, risk prognostic model was established and verified. The correlation of ferroptosis-related signature with survival and immune microenvironment was systematically analyzed.Results: A 4-genes ferroptosis signature (CDKN1A, MIOX, PSAT1, and RRM2) was constructed. Multivariate Cox regression assay indicates that the risk score of ferroptosis signature was an independent prognostic indicator (HR=1.391, p< 0.001). The survival curve shows that the high-risk group has a poorer prognosis than the low-risk group (p< 0.001). The risk prognostic model was established based on prognostic factors of clinical-stage, hemoglobin, and risk score. The time-dependent receiver operating characteristic curve (ROC) analysis proves the predictive capacity of the ferroptosis signature, the 3 years area under the curve (AUC) is 0.890, and the 5 years AUC is 0.733. Further analysis suggested that cell cycle, pentose phosphate pathway, P53 signaling pathway were significantly enriched in the high-risk group. The significantly different fractions of dendritic cells resting, macrophage cells, and T cells follicular helper were observed in risk groups.Conclusion: This study implicates a ferroptosis signature which has a good predict capacity of the prognosis in PRCC patients. Ferroptosis-related genes may have a key role in the process of anti-tumor and serve as therapeutic targets for PRCC.Keywords: papillary renal cell carcinoma, ferroptosis, gene signature, prognosis model, tumor immune microenvironment

Jinlu Liu,1,&ast; Ling Yang,1,&ast; Xin Yuan,2,&ast; Meimei Xiong,1 Jiao Zhu,1 Wenbi Wu,1 Min Ren,1 Jianlin Long,3 Xuewen Xu,2 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Plastic and Burn Surgery, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maling GouState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaEmail goumaling@scu.edu.cnXuewen XuDepartment of Plastic and Burn Surgery, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaEmail xxw_0826@163.comIntroduction: β-lactamase (LACTB) is a tumor suppressor gene in various tumors including melanoma. However, it remains challenging to efficiently deliver the LACTB gene into melanoma. Recently, we designed a nonviral nanocarrier iRGD/DOTAP/MPEG-PDLLA (iDPP) that could deliver gene targetedly to melanoma efficiently without obvious adverse effects.Methods: In this study, the tumor-targeted nanoparticle iDPP was prepared to deliver LACTB gene to treat melanoma in vitro and in vivo. First, the expression level of LACTB in 6 clinical specimens of melanoma patients was evaluated. Subsequently, the characteristics of iDPP/LACTB nanocomplexes were studied. Afterwards, the in vitro and in vivo anti-tumor efficacy of the iDPP/LACTB nanocomplexes were explored utilizing the B16-F10 mouse melanoma cell line and the B16-F10 subcutaneous melanoma model.Results: Compared with the normal epithelium, the expression level of LACTB in melanoma tissues was significantly downregulated. In vitro B16-F10 cell tests showed iDPP/LACTB nanocomplexes could increase the mRNA levels of P21, Bid, Bax, Pidd1, and Sival genes and up-regulate the p53 signaling pathway of melanoma cells, thus promoting cell apoptosis and blocking the cell cycle. Injected intravenously, iDPP nanoparticles could deliver DNA to the subcutaneous melanoma targetedly. Based on in vivo mouse xenograft model, iDPP/LACTB nanocomplexes could effectively inhibit tumor proliferation and induce tumor apoptosis, thus significantly inhibiting melanoma growth (tumor inhibition rate is about 68%) in the subcutaneous B16-F10 melanoma model.Conclusion: The downregulated LACTB might be a potential target for melanoma therapy. The iDPP/LACTB nanocomplexes could inhibit the growth of the mouse melanoma without obvious side effects, which provide a new option for melanoma gene therapy research.Keywords: melanoma, LACTB, nanocomplexes, gene therapy

Yingyi Zhang,1 Libin Ren,1 Min Ren,2 Hua Yang,1 Kunmeng Li,1 Hongliang Cong,1 Zhigang Guo3 1Department of Cardiology, Tianjin Chest Hospital, Tianjin, 300222, People’s Republic of China; 2Tianjin Cardiovascular Institute, Tianjin, 300222, People’s Republic of China; 3Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin, 300222, People’s Republic of ChinaCorrespondence: Hongliang CongDepartment of Cardiology, Tianjin Chest Hospital, No. 261 of Taierzhuang South Road, Jinnan District, Tianjin, 300222, People’s Republic of ChinaTel +86 13702102871Email chlcong@163.comZhigang GuoDepartment of Cardiac Surgery, Tianjin Chest Hospital, No. 261 of Taierzhuang South Road, Jinnan District, Tianjin, 300222, People’s Republic of ChinaTel +86 13821002900Email zgguohosp@163.comObjective: This study aims to investigate the correlation between triglyceride–glucose index (TyG) and the risk of cardiovascular disease (CVD).Methods: A total of 102,061 permanent residents of Tianjin, China, aged 35– 75 years were surveyed. A questionnaire, physical examination, and blood tests for biochemical markers were conducted for all subjects. The risk of CVD was judged based on the results, identifying the population with a high risk of CVD. TyG was calculated for all subjects who were then grouped into TyG quartiles. The correlation between TyG and the detection rate of subjects with a high risk of CVD was analyzed using the chi-square test and Pearson’s correlation analysis. The cut-off points and the magnitude of the predictive effect of TyG in determining a high risk of CVD were identified by calculating the TyG through analysis of the receiver operator characteristic (ROC) curve.Results: The surveyed population consisted of 39,598 males (38.8%) and 62,463 females (61.2%). The average age was 55.84 ± 10.27 years. A statistically significant difference in the incidence of a high CVD risk between subjects in the four groups divided by the TyG levels was identified (p < 0.01). Pearson’s correlation analysis showed that TyG was correlated with all risk factors for CVD (p < 0.01). The maximum Youden’s J statistic for determining the high risk of CVD was found at a TyG of 9.04 (specificity 0.575, sensitivity 0.754). The area under the ROC curve was 0.780 (confidence interval [CI]: 0.777, 0.783, p < 0.01).Conclusion: TyG index is closely related to the aggregation of cardiovascular risk factors and is correlated with the judgment results of the screening population’s high risk of CVD, suggesting that more attention should be paid to the identification and control of multiple risk factors in the population with significantly elevated TyG.Keywords: triglyceride–glucose index, cardiovascular disease, risk, insulin resistance

Meteorites represent the only samples available for study on Earth of a number of planetary bodies. The minerals within meteorites therefore hold the key to addressing numerous questions about our solar system. Of particular interest is the Ca-phosphate mineral merrillite, the anhydrous end-member of the merrillite-whitlockite solid solution series. For example, the anhydrous nature of merrillite in Martian meteorites has been interpreted as evidence of water-limited late-stage Martian melts. However, recent research on apatite in the same meteorites suggests higher water content in melts. One complication of using meteorites rather than direct samples is the shock compression all meteorites have experienced, which can alter meteorite mineralogy. Here we show whitlockite transformation into merrillite by shock-compression levels relevant to meteorites, including Martian meteorites. The results open the possibility that at least part of meteoritic merrillite may have originally been H+-bearing whitlockite with implications for interpreting meteorites and the need for future sample return.

A new maternity colony of lesser horseshoe bats (Rhinolophus hipposideros) was found and described in an abandoned building in Aljezur, Portugal. Between June 25 and July 4, 2022, we conducted emergence and juvenile counts, took light intensity measurements during emergence times and evaluated microclimatic conditions inside the roost, namely temperature and relative humidity. Moreover, we took ultrasound recordings in the open and performed transects to locate foraging areas and commuting corridors. We found the colony amounted to at least 501 individuals (371 adults and 130 juveniles), currently the largest known in Portugal and one of the biggest in Europe. Sixteen matching echolocation calls were recorded away from the colony near a water reservoir, a probable foraging area together with the Vale da Telha valley connecting the roost to the water body, which may also serve as a commuting corridor. Considering the threatened conservation status of the lesser horseshoe bat, the large colony size and its lack of protection, we proposed several conservation measures aimed at preserving the colony. We hope our recommendations will be included in the management plan currently being prepared for the Natura 2000 site Costa Sudoeste. Following up on this research, a radio-tracking study would definitively confirm the bats' movements and foraging grounds. [ABSTRACT FROM AUTHOR]

Huan Gao,1 Tao Tian,1 Suoni Li,2 Yinbin Zhang,3 Xiao Fu,1 Xiaoqiang Zheng,1 Na Liu,1 Aimin Jiang,1 Mengdi Ren,1 Xiaoni Zhang,1 Xuan Liang,1 Zhiping Ruan,1 Zhimin Geng,4,* Yu Yao1,* 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Medical Oncology, Tumor Hospital of Shaanxi, Xi’an, People’s Republic of China; 3Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu YaoDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel/Fax +86-29-85323422Email 13572101611@163.comZhimin GengDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel/Fax +86-29-85323893Email gengzhimin@mail.xjtu.edu.cnPurpose: Biliary tract cancers (BTCs) have a poor overall prognosis, as patients who underwent curative surgery frequently experience disease recurrence. At present, there is a paucity of well-documented adjuvant chemotherapy regimen. This study aimed to assess whether gemcitabine plus platinum or S-1 adjuvant chemotherapy have different impact on relapse-free survival (RFS).Patients and Methods: We selected patients undergoing radical biliary tract cancer surgery, pathologically confirmed adenocarcinoma and received gemcitabine plus platinum (cisplatin or oxaliplatin) or S-1 adjuvant chemotherapy from September 2013 to May 2020. The primary study endpoint was RFS. The secondary endpoint was safety.Results: Overall 136 patients were enrolled. The median follow-up was 32.3 months and the median RFS was 17.0 months (95% CI 8.9– 25.1). The median RFS was 14.1 months (95% CI 6.7– 21.5) in gemcitabine plus platinum group and 33.0 months (95% CI 9.3– 56.7) in gemcitabine plus S-1 (GS) group, a non-significant difference both in univariate (P=0.092) and in multivariate analysis (P=0.058). Lymph node status (N- vs N+: HR=0.477, 95% CI 0.285– 0.799; P=0.005) and chemotherapy cycles (< 6 vs 6– 8: HR=1.828, 95% CI 1.117– 2.993; P=0.016) were independent impact factors for RFS. GS group had lower incidence of adverse reactions.Conclusion: Compared with gemcitabine plus platinum, GS regimen has a tendency to obtain longer RFS (although there is no statistically significant difference) and less toxic. GS regimen has the potential to be investigated as a standard regimen for adjuvant chemotherapy.Keywords: biliary tract cancer, adjuvant chemotherapy, gemcitabine, platinum, S-1

Qing Liu,1,2,* Hongwei Xia,2,* Sheng Zhou,1,2 Qiulin Tang,1,2 Jitao Zhou,1 Min Ren,1 Feng Bi1,2 1Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng BiDepartment of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of ChinaTel +86 189 8060 1771Email bifeng@scu.edu.cnBackground: Statins, which are used to lower blood cholesterol levels by inhibiting HMG-CoA reductase, have shown anticancer effects in many cancer cells. However, the role of statins in gastric cancer remains unclear. This study aims to investigate whether the statins could antagonize progression of gastric cancer cells and tried to find the molecule mechanism.Methods: Effects of simvastatin on the morphology, proliferation, migration, apoptosis, and invasion of gastric cancer cells were detected and compared. Western blotting, cell viability assay, fluorescence, and transfection were employed to study the molecule mechanism of the effects and the interaction between YAP and β-catenin signaling.Results: Simvastatin could inhibit proliferation, migration and invasion, and promote the apoptosis in gastric cancer cells. Mechanistic studies showed that simvastatin treatment could inhibit the expression of β-catenin and the activity of YAP and the downstream targets of YAP and β-catenin in gastric cancer cells. Moreover, we found that YAP and β-catenin could form a positive feedback loop in gastric cancer cells. Further investigation revealed that simvastatin mainly acted through by inhibiting the activity of RhoA to inhibit YAP and β-catenin, and the geranylgeranyl pyrophosphate pathway mediated this regulation.Conclusion: Statins represent a promising therapeutic option for gastric cancer by simultaneously targeting YAP and β-catenin signaling.Keywords: gastric cancer, simvastatin, YAP, β-catenin, RhoA

Min Zhang, 1, 2 Jiangrong Wang, 1 Yong Zhang, 1 Pei Zhang, 1 Zhisheng Jia, 2 Manyi Ren, 1 Xiaomeng Jia, 1 Liping Ma, 1 Mei Gao, 1 Yinglong Hou 1 1Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, People’s Republic of China; 2Department of Cardiology, The Fifth People’s Hospital of Jinan, Jinan 250022, Shandong, People’s Republic of ChinaCorrespondence: Mei GaoDepartment of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan 250014, Shandong, People’s Republic of ChinaTel +86-13791126569Fax +86-531 8296 3647Email gaomei0217@163.comYinglong HouDepartment of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan 250014, Shandong, People’s Republic of ChinaTel +86-13791120810Fax +86-531 8296 3647Email houyinglong2010@hotmail.comObjective: This retrospective cohort study is to analyze the impacts of CYP2C19 polymorphism and clopidogrel dosing on in-stent restenosis (ISR) after coronary stenting.Methods: Totally, 111 patients were included, who underwent percutaneous coronary intervention (PCI) with drug-eluting stent. Patients received clopidogrel treatment after the intervention on the background treatment with aspirin, based on the genotypes: 75 mg clopidogrel once each day for subjects without CYP2C19 loss-of-function (LOF) alleles (n=51; EM), 75 mg clopidogrel once each day (n=27; IM75) or twice each day (n=33; IM150) for subjects with one CYP2C19 LOF allele. ISR at 3– 18 months after coronary stenting was assessed.Results: ISR rate was significantly higher in the IM75 group (40.7%) than the EM group (11.8%). ISR rate in the IM150 group was lower than the IM75 group (6.1% vs 40.7%), and comparable to that in the EM group. Multivariate logistic regression showed that both CYP2C19 genotype and clopidogrel dosing were associated with the risk of ISR after adjusting the relevant confounding factors. ISR risk was higher in the IM patients than the EM patients. Patients with clopidogrel dose of 75 mg once each day had significantly higher risk of ISR than those with the dose of 75 mg twice each day.Conclusion: Increased dose of clopidogrel may reduce the risk of ISR after PCI in CYP2C19 LOF allele(s) carriers. The presence of CYP2C19 LOF allele(s) increases the risk of ISR after stenting, which could be counteracted by the increased dose of clopidogrel.Keywords: CYP2C19 polymorphism, in-stent restenosis, ISR, clopidogrel, percutaneous coronary intervention, PCI

Feng Qiu,1,* Kunyu Wang,1,* Tingting Li,2 Dandan Song,3 Zhiwei Wang,1 Hailing Zhang,4 Jianguo Liu,1 Ming Ren,5 Xiaokun Qi1 1Department of Neurology, Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, People’s Republic of China; 2Department of Gastroenterology, Second Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Medicine, Beijing Northern Hospital of China North Industries Group Corporation, Beijing 100089, People’s Republic of China; 4Department of Neurology, Changhai Hospital, Shanghai 200433, People’s Republic of China; 5Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing 100191, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaokun QiDepartment of Neurology, Sixth Medical Center of PLA General Hospital, 6 Fucheng Road, Haidian District, Beijing 100048, People’s Republic of ChinaTel +86 139 1079 7081Email bjqxk@sina.com Ming RenBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, 37 Xueyuan Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86 139 1079 7081Email mren201017@hotmail.comBackground: The differential diagnosis of Parkinson’s disease (PD) with multiple-system atrophy (MSA) is difficult because of their similarity in symptoms and signs. The objective of this study was to investigate the value of external anal-sphincter electromyography (EAS-EMG) and urethral-sphincter electromyography (US-EMG) in differentiating MSA from PD.Methods: A total of 201 patients, — 101 MSA and 100 PD — were recruited in this study. Average duration and amplitude of motor unit potentials (MUPs), percentage of polyphasic MUPs, amplitude during strong contractions, and recruitment patterns during maximal voluntary contractions were recorded and analyzed to assess diagnostic efficiency of EAS-EMG and US-EMG for MSA.Results: Significant differences in average MUP duration and recruitment patterns during maximal voluntary contractions were found between patients with MSA and patients with PD using both EAS-EMG (P

Sheng Zhou,1,2 Meilin Ren,1,2 Huanji Xu,1,2 Hongwei Xia,2 Qiulin Tang,2 Ming Liu1 1Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, People’s Republic of China; 2Laboratory of Molecular Targeted Therapy in Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan Province 610041, People’s Republic of ChinaCorrespondence: Qiulin Tang; Ming Liu Tel +86-28-85164045Fax +86-28-85423203Email tangqiulin1981@163.com; mingliu721@aliyun.comBackground: Colon cancer is one of the most common cancers worldwide. IFN-stimulated gene 15 (ISG15), a ubiquitin-like molecule, is strongly up-regulated by type I interferon as a crucial response to a variety of microbial and cellular stress stimuli. However, the role of ISG15 in colon cancer remains unclear.Methods: The expression of ISG15 in colon cancer tissues and cell lines was detected by using Western blotting and immunohistochemistry. ISG15 expression levels of colon cancer cells treated with trametinib was verified by using the data downloaded from the Gene Expression Omnibus (GEO) databases, quantitative real-time PCR analysis and Western blots assays. ISG15-siRNA was used to silence ISG15 in colon cancer cell line to determine the roles of ISG15 in colon cancer cell proliferation.Results: ISG15 was highly expressed in colon cancer tissues and ISG15 upregulation was closely associated with poor prognoses in colon cancer patients. Enhanced ISG15 expression promoted the migration and proliferation of colon cancer cells in vitro, while ISG15 knockdown decreased cell proliferation and metastasis. In addition, we first found that the mRNA and protein expression of ISG15 were up-regulated following trametinib treatment. Further investigation showed that ISG15 knockdown could enhance the anti-cancer effect of trametinib in colon cancer cells.Conclusion: We proposed an interesting possibility that ISG15 may be a prognostic bio-marker, and the combined targeting of ISG15 and MEK might be a promising therapeutic strategy for colon cancer.Keywords: ISG15, MEK, Trametinib, GEO

This study aimed to compare the efficacy and safety of oral and transdermal estradiol in alleviating menopausal symptoms. A total of 257 recently menopausal women were randomized into two groups. The t-E2 group received transdermal estradiol (2.5 g per day) (n = 128) and the o-E2V group received oral estradiol valerate (2 mg per day) (n = 129) for 24 weeks; both groups received micronized progesterone (200 mg per day). The primary outcome measure is the change in the modified Kupperman Menopausal Index (KMI) after 24 weeks of treatment. Menopausal symptoms were recorded at screening and at 4, 12 and 24 weeks using both the KMI and the Menopause Rating Scale (MRS). Significant amelioration was observed by KMI and MRS scores for both groups after treatment (p < 0.001). The mean KMI scores showed no difference between the two groups. The mean MRS scores were similar between the two groups at baseline and after 4 weeks of treatment. The results showed statistical differences after 12 weeks and 24 weeks of treatment (p = 0.005 and p = 0.011). Both the after-treatment scores minus the baseline scores of KMI and MRS and the incidence of adverse effects showed no difference between the two groups. This study shows that both transdermal and oral estradiol are effective in relieving menopausal symptoms, with little difference in treatment efficacy and safety. ChiCTR2300073146 [ABSTRACT FROM AUTHOR]

Li Qiao1,2, Chunjiang Yu,1 Hongwei Zhang,1 Mingshan Zhang,1 Yanming Qu,1 Ming Ren,1 Chunyu Gu,1 Haoran Wang11Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Gansu Provincial Hospital, Lanzhou, Gansu Province, People’s Republic of ChinaPurpose: The relationship of clinical results and survival analysis of operative patients with petroclival meningioma (PCM) was studied.Patients and methods: Data from a total of 176 PCM patients receiving surgical resection were retrospectively collected. Follow-up was conducted through outpatient review by reexamination telephone calls and letters. Clinical outcomes, survival, and Karnofsky Performance Scale (KPS) data were analyzed.Results: Seventy-two percent of patients (127/176) received only surgery, 8.5% (15/176) received surgery and adjuvant radiation therapy (RT) (surgery + RT), and 19.3% (34/176) received surgery and adjuvant gamma knife surgery (GKS) (surgery + GKS). Gross total resection (GTR) was performed in 34.7% of patients (61/176), subtotal resection (STR) in 58.0% (102/176), and partial resection (PR) in 7.4% (13/176). Recent follow-up KPS was higher than preoperative (80 vs 70, P

Zhongxin Feng,1,2,* Qi Chen,2,* Mingqiang Ren,2 Zuguo Tian,2 Yuping Gong1 1Department of Hematology, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China; 2Department of Hematology, Affiliated Hospital of Zunyi Medical University, Zunyi, China *These authors contributed equally to this work Introduction: Acute myeloid leukemia (AML), the hematological malignant tumor with high mortality, is still difficult to treat. CD40L is a type II transmembrane protein, which has been reported to have the potential to inhibit growth of some cancer cells. Materials and methods: In order to determine the role of CD40L on AML-M5 cell line THP-1, we overexpressed CD40L in the cells using a lentiviral vector system (pHBLV-CMVIE-Zs Green-T2A-puro vector); overexpression was confirmed by the detection of green fluorescent protein and CD40L protein expression. Results: Cellular apoptosis, proliferation, and cycle assays showed that CD40L could promote the apoptosis of, suppress the proliferation of, and stimulate the arrest of the G1/S phase of THP-1 cells. Finally, the protein expression of P53, Bax/Bcl-2, cyclinD1, PCNA, PTEN, and p-Akt illustrated that CD40L may partly influence cell growth of THP-1 cells through those genes, which was confirmed by immunohistochemistry and a PI3K/Akt activator. Conclusion: Taken together, CD40L could inhibit cell growth of THP-1 cells through the PI3K/Akt pathway, indicating that the overexpression of CD40L may be a potential target to treat the AML-M5 disease. Keywords: CD40L, cell proliferation, AML-M5, P53, cyclinD1, PCNA, tumor suppressor, cell apoptosis

Changlin Wang,1,* Gang Wang,1,* Zijian Zhang,1,* Zichun Wang,1 Minghua Ren,1 Xiaoxiong Wang,2 Haoming Li,1 Yipeng Yu,1 Jing Liu,1 Licheng Cai,1 Yong Li,3 Daming Zhang,2 Cheng Zhang1 1Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; 2Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; 3Department of PET/CT, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China *These authors contributed equally to this work Background: Long noncoding RNAs (lncRNAs) have been identified as important factors in cancer biology and are deregulated in many cancers. The present study aimed to determine the expression and roles of lncRNA DHRS4-AS1 in the progression of clear cell renal cell carcinoma (ccRCC). Methods and results: Using high-throughput RNA-sequencing data of ccRCC tumors from the Cancer Genome Atlas project, we identified lncRNA DHRS4-AS1 as significantly associated with ccRCC patients’ overall survival. We confirmed the downregulation of DHRS4-AS1 in ccRCC by assessing its expression levels in a cohort of 52 tumor and paired non-tumor samples. In addition, we found that low DHRS4-AS1 expression was significantly associated with a high tumor node metastasis stage, lymph node metastasis, advanced pathological grade and poor prognosis. Furthermore, DHRS4-AS1 overexpression inhibited the progression of cell cycles of ccRCC in vitro. These data indicate that DHRS4-AS1 functions by preventing the proliferation and invasion, inhibiting the cell cycle progression and promoting the apoptosis of ccRCC cells. Conclusion: Taken together, our findings identify the role of DHRS4-AS1 as a tumor inhibitor in ccRCC for the first time, demonstrating that DHRS4-AS1 is a potential prognostic biomarker that could potentially be applied in ccRCC therapy. Keywords: long noncoding RNAs, DHRS4-AS1, clear cell renal cell carcinoma, prognosis

Yunxia Zhang,1,2 Jing Wang,2 Di Wu,1 Miao Li,1 Fenshu Zhao,1 Mulan Ren,2 Yunlong Cai,2 Jun Dou1 1Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China Background: Epithelial ovarian cancer (EOC) with insidious characteristic manifests no symptoms in its early onset but most patients have advanced and distant cancer metastasis at diagnosis. Innovative early diagnosis and effective treatment of EOC are urgently needed. Methods: In the study, we developed a novel agent of IL-21-secreting human umbilical cord mesenchymal stem cells (hUCMSCs) combined with miR-200c to evaluate its effects on SKOV3 EOC in vitro and in vivo.Results: hUCMSCs-LV-IL-21 combined with miR-200c significantly inhibited the SKOV3 cell mobility and tumorigenesis compared with hUCMSCs-LV-IL-21, hUCMSCs- LV-vector, and hUCMSCs, respectively. These were reflected in decreasing the tumor sizes and elongating the tumor bearing nude mouse survival, accompanied with increasing the serum cytokine levels of IFN-γ, IL-21 and TNF-α as well as the splenocyte cytotoxicity. In addition, the expression of β-catenin, cyclin-D1, Gli1, Gli2, and ZEB1 was decreased but the E-cadherin expression was increased in tumor tissues of mice treated with hUCMSCs-LV-IL-21 plus miR-200c.Conclusion: We demonstrated that the synergistic effect of fighting SKOV3 EOC is attributable to repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in SKOV3 EOC. The findings may provide a new strategy for therapy of EOC. Keywords: epithelial ovarian cancer, umbilical cord mesenchymal stem cells, IL-21, miR-200c, Wnt/β-catenin signaling, epithelial–mesenchymal transition

The failure modes of products gradually show a diversified trend with the precision and complexity of the product structure. The combination of fault tree analysis and generalized grey relational analysis is widely used in the fault diagnosis of complex systems. In this study, we utilize a method that combines fault tree analysis and generalized grey relational analysis. This method is applied to diagnose the Expansion Adhesive Debonding fault of automobile doors. Then, we analyse and compare the differences in actual fault diagnosis results. The comparison involves three analysis methods: Fault Tree Analysis combined with Absolute Grey Relation Analysis (F-AGRA), Fault Tree Analysis combined with Relative Grey Relation Analysis (F-RGRA), and Fault Tree Analysis combined with Comprehensive Grey Relation Analysis (F-CGRA). Subsequently, we compare the findings with actual production results. This comparison allows us to discuss the differences between the three methods in the fault diagnosis of complex systems. We also discuss the application occasions of these methods. This study will provide a new method for fault analysis and fault diagnosis in the actual production of the automobile manufacturing industry. This method can eliminate faults effectively and accurately and improve product quality and productivity. [ABSTRACT FROM AUTHOR]

Heng-Cong Luo,1,2,* Na Li,1,* Li Yan,1 Kai-jin Mai,3 Kan Sun,1 Wei Wang,1 Guo-Juan Lao,1 Chuan Yang,1 Li-Ming Zhang,3 Meng Ren1 1Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Medical Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Endocrinology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3School of Materials Science and Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Several biological barriers must be overcome to achieve efficient nonviral gene delivery. These barriers include target cell uptake, lysosomal degradation, and dissociation from the carrier. In this study, we compared the differences in the uptake mechanism of cationic, star-shaped polymer/MMP-9siRNA complexes (β-CD-(D3)7/MMP-9siRNA complexes: polyplexes) and commercial liposome/MMP-9siRNA complexes (Lipofectamine® 2000/MMP-9siRNA complexes: liposomes). The uptake pathway and transfection efficiency of the polyplexes and liposomes were determined by fluorescence microscopy, flow cytometry, and reverse transcriptase-polymerase chain reaction. The occurrence of intracellular processing was assessed by confocal laser scanning microscopy. Endosomal acidification inhibitors were used to explore the endosomal escape mechanisms of the polyplexes and lysosomes. We concluded that the polyplexes were internalized by non-caveolae- and non-clathrin-mediated pathways, with no lysosomal trafficking, thereby inducing successful transfection, while the majority of liposomes were internalized by clathrin-dependent endocytosis (CDE), caveolae-mediated endocytosis, and macropinocytosis, and only CDE induced successful transfection. Liposomes might escape more quickly than polyplexes, and the digestion effect of acidic organelles on liposomes was faint compared to the polyplexes, although both complexes escaped from endolysosomes via the proton sponge mechanism. This may be the key aspect that leads to the lower transfection efficiency of the β-CD-(D3)7/MMP-9siRNA complexes. The present study may offer some insights for the rational design of novel delivery systems with increased transfection efficiency but decreased toxicity. Keywords: β-CD-(D3)7, liposome, endocytosis, endolysosomal escape, intracellular trafficking