Search

Tingting Wang,1 Juntao Tan,2 Tiantian Wang,2 Shoushu Xiang,2 Yang Zhang,1 Chang Jian,1 Jie Jian,1 Wenlong Zhao1,3 1College of Medical Informatics, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Operation Management Office, Affiliated Banan Hospital of Chongqing Medical University, Chongqing, 401320, People’s Republic of China; 3Medical Data Science Academy, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Wenlong Zhao, College of Medical Informatics, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-13883163651, Email cqzhaowl@163.comPurpose: Hospitalized hypertensive patients rely on blood pressure medication, yet there is limited research on the sole use of amlodipine, despite its proven efficacy in protecting target organs and reducing mortality. This study aims to identify key indicators influencing the efficacy of amlodipine, thereby enhancing treatment outcomes.Patients and Methods: In this multicenter retrospective study, 870 hospitalized patients with primary hypertension exclusively received amlodipine for the first 5 days after admission, and their medical records contained comprehensive blood pressure records. They were categorized into success (n=479) and failure (n=391) groups based on average blood pressure control efficacy. Predictive models were constructed using six machine learning algorithms. Evaluation metrics encompassed the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). SHapley Additive exPlanations (SHAP) analysis assessed feature contributions to efficacy.Results: All six machine learning models demonstrated superior predictive performance. Following variable reduction, the model predicting amlodipine efficacy was reconstructed using these algorithms, with the light gradient boosting machine (LightGBM) model achieving the highest overall performance (AUC = 0.803). Notably, amlodipine showed enhanced efficacy in patients with low platelet distribution width (PDW) values, as well as high hematocrit (HCT) and thrombin time (TT) values.Conclusion: This study utilized machine learning to predict amlodipine’s effectiveness in hypertension treatment, pinpointing key factors: HCT, PDW, and TT levels. Lower PDW, along with higher HCT and TT, correlated with enhanced treatment outcomes. This facilitates personalized treatment, particularly for hospitalized hypertensive patients undergoing amlodipine monotherapy.Keywords: anti-hypertensive drugs, hypertension, machine learning, shapley additive explanations

Jingjing Zhu, Shuhui Xiang, Yan Li Shanghai Institute of Early Childhood Education, Shanghai Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Yan Li, Shanghai Institute of Early Childhood Education, Shanghai Normal University, No. 100 Guilin Road, Shanghai, 200234, People’s Republic of China, Email liyan@shnu.edu.cnIntroduction: Problem behaviors in preschoolers signals social adjustment challenges. This study investigates the mediating role of parenting stress in the relationship between co-parenting and these behaviors, and examines how family resilience impacts this dynamic.Methods: A detailed survey was conducted with 1279 mothers of 3-6-year-olds in Shanghai, China, focusing on co-parenting, family resilience, parenting stress, and children’s behaviors. We employed SPSS 26 for initial tests and the Hayes PROCESS macro in SPSS 23.0 for advanced analysis, using bootstrap methods to assess mediation and moderation effects.Results: The analysis revealed that maternal parenting stress mediates the relationship between co-parenting and children’s problem behaviors. Specifically, unsupportive co-parenting or low levels of supportive co-parenting heightened maternal stress, which in turn increased children’s problem behaviors. Family resilience was found to moderate this relationship, buffering the impact of unsupportive co-parenting on maternal stress. High family resilience levels were associated with lower parenting stress, regardless of co-parenting quality.Conclusion: These findings highlight the importance of enhancing family resilience and supportive co-parenting to mitigate parenting stress and reduce problem behaviors in children. It has practical implications for developing family-centred interventions and policies to strengthen family resilience and co-parenting skills.Keywords: co-parenting relationships, family resilience, parenting stress, problem behaviors, preschool children

Zhenghui Xu,1,* Junli Zhang,1,* Shoukui Xiang,1,* Fei Hua,1 Lu Chen1,2 1Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China; 2Department of Clinical Nutrition, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Hua, Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China, Tel +86 0519-68870000, Email huafei1970@suda.edu.cn Lu Chen, Department of Clinical Nutrition, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China, Tel +86 0519-68870424, Email cl2324@czfph.comPurpose: To explore the association between the water distribution in the human body and 25-hydroxyvitamin D among patients with type 2 diabetes mellitus (T2DM), and to analyze whether water distribution is a mediator between vitamin D and T2DM complications.Patients and Methods: In total, 533 T2DM inpatients were included from August 1, 2016 to April 1, 2023. Water distribution indicators, whether from the whole body, arms, trunk, or legs, were measured to calculate the association with vitamin D using linear regression analysis. Subgroups based on age, sex, body mass index, and macrovascular complications were established to clarify changes in the association between vitamin D and water distribution in different populations. Mediation analysis was applied to evaluate the correlation between vitamin D, water distribution, and T2DM complications.Results: There was a negative correlation between 25-hydroxyvitamin D and the ratio of extracellular water (ECW)/total body water (TBW) both in the whole body (P=0.045, β=− 0.008) and in certain parts. A U-shaped restricted cubic spline curve further presented an inflection point (approximately 23 ng/mL 25-hydroxyvitamin D) in the relationship between 25-hydroxyvitamin D and the ECW/TBW of the whole body. A negative correlation was observed between ECW/TBW and vitamin D in the obese subgroup (P=0.015, β=− 0.038). In the total effect of vitamin D on diabetic nephropathy (DN), the mediation effect of ECW/TBW accounted for 15.44%.Conclusion: A correlation between vitamin D and water distribution was observed, and a high ECW/TBW was one of the pathways through which low vitamin D levels might affect DN.Keywords: 25-hydroxyvitamin D, ECW/TBW, type 2 diabetes mellitus, diabetic nephropathy

Qi Lou,1,* Lu Pan,1,* Shengjin Xiang,1,2,* Yueting Li,1 Jiahui Jin,1 Jingyang Tan,1 Baoshan Huang,1,2 Kaihui Nan,1,2 Sen Lin1,2 1National Engineering Research Center of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 2State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kaihui Nan; Sen Lin, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Tel +86-577-88067962, Email lin_sen@wmu.edu.cn; nankh@l63.comIntroduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED).Methods: The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael’s addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction.Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission.Conclusion: NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.Keywords: melatonin liposome, dry eye disease, benzalkonium chloride, pyroptosis, NLRP3/Caspase-1/GSDMD signaling axis

Zhixuan Fei,1,2 Zian Zhang,1 Yingzhen Wang,1 Haining Zhang,1 Shuai Xiang1 1Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Qingdao University, Medical Department, Qingdao, People’s Republic of ChinaCorrespondence: Shuai Xiang, Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email 15169093669@163.comPurpose: Two-stage revision is the most common treatment for periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). Few studies have compared the clinical efficacy of different articulating spacers. This study compared the outcomes of all-cement articulating spacers and sterilized replanted metal-polyethylene articulating spacers for PJI following TKA.Patients and Methods: In this retrospective observational study, 47 patients who received two-stage revision for PJI following TKA between 2006 and 2020 in our hospital were included. Patients were categorized as receiving an all-cement articulating spacer or a sterilized replanted metal-polyethylene articulating spacer in exclusion. Data on demographics, surgical information, and outcomes were collected in 2021.Results: Forty-seven spacers were identified: all-cement spacer was noted in 23 patients and sterilized replanted spacer in 24. Patients in the all-cement spacer group had shorter operation time (155.87 ± 33.12 vs 189.79 ± 51.21 min; P = 0.0102) and less blood loss (845.22 ± 525.92 vs 1114.50 ± 547.81 mL; P = 0.0427) in exclusion. Patients in the sterilized replanted spacer group had superior interval range of motion (ROM; 61.00 ± 31.94° vs 31.75 ± 33.38°; P = 0.0072), postoperative ROM (85.00 ± 11.11° vs 77.37 ± 9.18°; P = 0.0329) as compared to all-cement spacers, but there was no difference in infection control between 2 groups.Conclusion: The two types of spacers had no difference in the reinfection rate, indicating that both articulating spacers are safe and effective for 2-stage revision. Considering ROM of knee joint, bone loss and cost, sterilized replanted metal-polyethylene spacers are preferred in the treatment of PJI.Keywords: total knee arthroplasty, periprosthetic joint infection, articulating spacer

Zhibo Chen,1 Dewei Xie,1 Yun Li,1 Zebin Dai,2 Saina Xiang,2 Zhiyuan Chen,2 Weiqian Zhu1 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2College of the First Clinical Medical Sciences of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Weiqian ZhuDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People’s Republic of ChinaTel +86 577 55579372Fax +86 577 55579318Email zhuwqfyxy@aliyun.comObjective: The novel biomarker, neutrophil percentage-to-albumin ratio (NPAR), as a prognostic tool for inflammation in relation to all-cause mortality for patients afflicted by strokes has yet to be explored.Methods: Data sets associated with patient files stored within the MIMIC-III V1.4 database were obtained. Data files from 940-patients were obtained for this retrospective analysis. Clinical endpoints were determined to represent a month (30-), three months (90-) and year (365-) all-cause mortality in stroke patients were determined. In order to determine NPAR and clinical endpoint relationships, Cox proportional hazards models were utilized.Results: For all-cause mortality within a 30-day period, in an unadjusted model, the HR (95% CIs) in group B (NPAR 20.5– 25.0) and C (NPAR > 25.0) was 1.17 (0.85, 1.63) and 1.55 (1.13, 2.11) compared with group A (NPAR < 20.5). Proceeding adjustment for more confounding factors, higher NPAR still obtained significant predictive power for 30-day all-cause mortality (HR= 1.45, 95% CI: 1.05, 2.00). Statistical significance (P = 0.0196) was also observed for the other time-based subgroupings for all-cause mortality.Conclusion: A strong correlation was present between increased levels of the novel biomarker NPAR and increased risk of mortality in stroke patients.Keywords: neutrophil-albumin ratio, mortality, stroke, biomarker

Shihao Xiang, 1,* Kan Chen, 2,* Ling Xu, 3 Ting Wang, 3 Chuanyong Guo 1, 2 1Medical College of Soochow University, Suzhou, 215006, People’s Republic of China; 2Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China; 3Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuanyong Guo Email guochuanyong@hotmail.comObjective: Hepatic ischemia reperfusion (IR) limits the development of liver transplantation technology. The aim of this study was to explore the protective effects of Bergenin on hepatic IR, particularly the elimination of reactive oxygen species (ROS) and activation of the peroxisome proliferators activated receptor γ (PPAR-γ) pathway.Methods: Initial experiments were performed to confirm the non-toxicity of Bergenin. Mice were randomly divided into sham, IR, and IR + Bergenin (10, 20 and 40 mg/kg) groups, and serum and tissue samples were obtained at 2, 8 and 24 h for detection of liver enzymes (ALT and AST), inflammatory factors (TNF-α, IL-6 and IL-1β), ROS, cell death markers (Bcl-2, Bax, Beclin-1 and LC3) and related important pathways (PPAR-γ, P38 MAPK, NF-κB p65 and JAK2/STAT1).Results: Bergenin reduced the release of ROS, down-regulated inflammatory factors, and inhibited apoptosis and autophagy. Additionally, expression of PPAR-γ-related genes was increased and phosphorylation of P38 MAPK, NF-κB p65 and JAK2/STAT1-related proteins was decreased in Bergenin pre-treatment groups in a dose-dependent manner.Conclusion: Bergenin exerts hepatic protection by eliminating ROS, affecting the release of inflammatory factors, and influencing apoptosis- and autophagy-related genes via the PPAR-γ pathway in this model of hepatic IR injury.Keywords: hepatic ischemia reperfusion, Bergenin, reactive oxygen species, apoptosis, autophagy

Zhenlang Guo,1 Yuliang Wang,2 Songtao Xiang,3 Shusheng Wang,3 Franky Leung Chan21The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, People’s Republic of China; 3Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaBackground: The prognostic value of chromogranin-A (CHGA) as a biomarker of prostate cancer (PCa) has been evaluated extensively. However, to date the results still remain controversial. This study aims to perform a meta-analysis on previous studies in order to determine whether CHGA would be a biomarker for survival in PCa patients.Methods: MEDLINE, Embase, Web of Science, and Cochrane Library databases were searched to identify eligible studies published before September 2018, regarding the association of CHGA gene expression with survival outcomes in patients with PCa. Multivariate adjusted HRs and associated 95% CIs were calculated using random effects models.Results: Ten cohort studies involving 3,172 patients were finally included. According to the included studies, circulating CHGA levels were tested in serum, plasma, and tissues. The results showed an association between high CHGA expression and worse overall survival (OS) (HR=1.24, 95% CI: 1.07–1.44; P=0.004; I2,=77.6%) in PCa patients. However, no significant association was observed between increasing CHGA expression and shorter progression-free survival (HR=1.73, 95% CI: 0.92–3.28; P=0.090; I2,=73.9%). The results of sensitivity analysis validated the rationality and reliability of our analysis.Conclusion: Current evidence indicates that high CHGA expression is a potential marker for poor OS in PCa. Future studies are needed to explore tailored treatments that directly target CHGA for the improvement of survival in men with PCa.Keywords: prostate cancer, chromogranin-A, prognosis, survival, meta-analysis

Shiyun Yuan,1 Lin Li,1 Shili Xiang,2 Hexun Jia,3 Tao Luo11Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 3Office of academic, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaBackground: The cadherin-11 (CDH11, OB-cadherin) gene is a member of the cadherin family and is located on chromosome 16q22.1. Previous studies have revealed that cadherins play significant roles in the development of many human malignancies. Increasing evidence has identified CDH11 as a functional tumour suppressor, which is commonly silenced by promoter methylation, but the functions of this gene in colorectal cancer (CRC) have been unclear.Methods: The CDH11 expression in primary CRC tissues and cell lines was investigated by qRT-PCR, RT-PCR and immunohistochemistry. The promoter methylation status of CDH11 was measured by methylation-specific PCR (MSP). Cell proliferation assay, colony formation assay, flow cytometry analysis, wound-healing assay, transwell assay and in vivo experiments were used to investigate the function of CDH11 in CRC. The mechanisms of CDH11 also were explored by western blots.Results: Our study suggests that CDH11 downregulation in CRC due to its promoter methylation and induced cell cycle arrest in G0/G1 phase and apoptosis, suppressing tumor cell proliferation, colony formation, migration and invasion by affecting the NF-kB signaling pathway.Conclusion: Overall, CDH11 may be considered as a functional tumour suppressor gene (TSG) in CRC, CDH11 has the potential to serve as a valuable prognostic marker for colorectal cancer.Keywords: cadherin 11, colorectal cancer, methylation, NF-kB, tumour suppressor

Machine learning (ML) has been used to build high-performance prediction models in the past without considering race. African Americans (AA) are vulnerable to acute kidney injury (AKI) at a higher eGFR level than Caucasians. AKI increases mortality, length of hospital stays, and incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD). We aimed to establish an ML-based prediction model for the early identification of AKI in hospitalized AA patients by utilizing patient-specific factors in an ML algorithm to create a predictor tool. This is a single-center, retrospective chart review. We included participants 18 years or older and admitted to an urban academic medical center. Two hundred participants were included in the study. Our ML training set provided a result of 77% accuracy for the prediction of AKI given the attributes collected. For the test set, AKI was accurately predicted in 71% of participants. The clinical significance of this model can lead to great advancements in the care of AA patients and provide practitioners avenues to optimize their therapy of choice in AAs when given AKI risk ahead of time.

Farooq Naeem,1 Tariq Munshi,1 Shuo Xiang,1 Megan Yang,1 Farhad Shokraneh,2 Yumeen Syed,3 Muhammad Ayub,1 Clive E Adams,4 Saeed Farooq5 1Department of Psychiatry, Queens University, Kingston, ON, Canada; 2Institute of Mental Health, Nottingham, UK; 3Trenlogic, Toronto, ON, Canada; 4Nottingham University, Nottingham, 5Keele University, Stafford, UK Background: Randomized trials evaluating electronic Media (eMedia) delivery of interventions are increasingly frequent in mental health. Although a number of reviews have reported efficacy of these interventions, none has reviewed the type of eMedia interventions and quality of their description. We therefore decided to conduct a survey of eMedia-delivered interventions for schizophrenia.Methods: We surveyed all relevant trials reliably identified in the Cochrane Schizophrenia Group’s comprehensive register of trials by authors working independently. Data were extracted regarding the size of the trial, interventions, outcomes and how well the intervention was described.Results: eMedia delivery of interventions is increasingly frequent in trials relevant to the care of people with schizophrenia. The trials varied considerably in sample sizes (mean =123, median =87, range =20–507), and interventions were diverse, rarely evaluating the same approaches and were poorly reported. This makes replication impossible. Outcomes in these studies are limited, have not been noted to be chosen by end users and seem unlikely to be easy to apply in routine care. No study reported on potential adverse effects or cost, end users satisfaction or ease of use. None of the papers mentioned the use of CONSORT eHealth guidelines.Conclusion: There is a need to improve reporting and testing of psychosocial interventions delivered by eMedia. New trials should comply with CONSORT eHealth guidance on design, conduct and reporting, and existing CONSORT should be updated regularly, as the field is constantly evolving. Keywords: randomized trials, survey, eMedia, information technology, schizophrenia, methodology

Abstract Gastric cancer (GC) is a highly heterogenic disease, and it is the second leading cause of cancer death in the world. Common chemotherapies are not very effective for GC, which often presents as an advanced or metastatic disease at diagnosis. Treatment options are limited, and the prognosis for advanced GCs is poor. The landscape of genomic alterations in GCs has recently been characterized by several international cancer genome programs, including studies that focused exclusively on GCs in Asians. These studies identified major recurrent driver mutations and provided new insights into the mutational heterogeneity and genetic profiles of GCs. An analysis of gene expression data by the Asian Cancer Research Group (ACRG) further uncovered four distinct molecular subtypes with well-defined clinical features and their intersections with actionable genetic alterations to which targeted therapeutic agents are either already available or under clinical development. In this article, we review the ACRG GC project. We also discuss the implications of the genetic and molecular findings from various GC genomic studies with respect to developing more precise diagnoses and treatment approaches for GCs.

The effects of Flavomycin, Bacillus licheniformis and Enramycin on broiler performance, nutrient digestibility, gut morphology and the intestinal microflora were studied in a 42-d experiment. A total of 288, one-day-old, male, Arbor Acres broilers were randomly assigned to 1 of 4 dietary treatments with 12 pens per treatment and 6 birds per pen. The treatments were comprised of a control diet without supplementation, a diet supplemented with 5 ppm Flavomycin, a diet supplemented with the combination of 5 ppm Flavomycin and 1.35×109 CFU/kg Bacillus licheniformis, as well as a diet supplemented with 5 ppm Enramycin. The average daily gain (ADG) and feed conversion ratio (FCR) of birds fed the diet with Flavomycin combined with Bacillus licheniformis and the Enramycin diet were improved (P

Zhang F, Li M, Wu X, et al. Drug Des Devel Ther. 2015;9:3969–3987. On page 3976, Figure 3B should be presented as follows: Following a review of the data post-publication, the authors found two identical cell cycle images in two different groups were placed for 200μM and 400μM. We have replaced the image for 400μM in this corrigendum. The authors confirmed that this error does not affect any statistical results or any relevant conclusions about Figure 3B. The authors apologize for this oversight. Read the original article here

Fei Zhang,* Maolan Li,* Xiangsong Wu,* Yunping Hu, Yang Cao, Xu’an Wang, Shanshan Xiang, Huaifeng Li, Lin Jiang, Zhujun Tan, Wei Lu, Hao Weng, Yijun Shu, Wei Gong, Xuefeng Wang, Yong Zhang, Weibin Shi, Ping Dong,# Jun Gu,# Yingbin Liu#Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work #These authors jointly directed this work Abstract: Gallbladder cancer (GBC), the most frequent malignancy of the biliary tract, is associated with high mortality and extremely poor prognosis. 20(S)-ginsenoside Rg3 (20(S)-Rg3) is a steroidal saponin with high pharmacological activity. However, the anticancer effect of 20(S)-Rg3 in human GBC has not yet been determined. In this study, we primarily found that 20(S)-Rg3 exposure suppressed the survival of both NOZ and GBC-SD cell lines in a concentration-dependent manner. Moreover, induction of cellular senescence and G0/G1 arrest by 20(S)-Rg3 were accompanied by a large accumulation of p53 and p21 as a result of murine double minute 2 (MDM2) inhibition. 20(S)-Rg3 also caused a remarkable increase in apoptosis via the activation of the mitochondrial-mediated intrinsic caspase pathway. Furthermore, intraperitoneal injection of 20(S)-Rg3 (20 or 40 mg/kg) for 3 weeks markedly inhibited the growth of xenografts in nude mice. Our results demonstrated that 20(S)-Rg3 potently inhibited growth and survival of GBC cells both in vitro and in vivo. 20(S)-Rg3 attenuated GBC growth probably via activation of the p53 pathway, and subsequent induction of cellular senescence and mitochondrial-dependent apoptosis. Therefore, 20(S)-Rg3 may be a potential chemotherapeutic agent for GBC therapy.Keywords: gallbladder cancer, 20(S)-ginsenoside Rg3, senescence, apoptosis, p53 pathway

Mixtures of factor analyzers (MFAs) have been popularly used to cluster the high-dimensional data. However, the traditional estimation method is based on the normality assumptions of random terms and thus is sensitive to outliers. In this article, we introduce a robust estimation procedure of MFAs using the trimmed likelihood estimator. We use a simulation study and a real data application to demonstrate the robustness of the trimmed estimation procedure and compare it with the traditional normality-based maximum likelihood estimate.

Dormancy in barley has been thoroughly studied and shown to negatively impact malt quality, resulting in selection against dormancy. However, reduced dormancy coincides with increased preharvest sprout (PHS) risk, thus sparking a new interest in integrating dormancy back into American barley lines if the negative effects of dormancy on malt quality can be overcome. We evaluated the dormancy and hydration index (HYI) in a biparental mapping population to determine the genotypes that would protect against PHS but have good malt quality. We found 4 HYI QTLs and 4 dormancy QTLs, one of which was near the well‐described SD2 QTL. The HYI QTLs were pleiotropically related to seed size (1H), dormancy (5H) and malt quality (2H). Lines with dormancy (5H) and increased HYI (2H and 3H) had malt quality similar to nondormant lines while maintaining PHS resistance, suggesting improvements in HYI could be the key to overcoming the negative effects of dormancy in malting. [ABSTRACT FROM AUTHOR]

In this paper, we investigate a robust estimation of the number of components in the mixture of regression models using trimmed information criteria. Compared to the traditional information criteria, the trimmed criteria are robust and not sensitive to outliers. The superiority of the trimmed methods in comparison with the traditional information criterion methods is illustrated through a simulation study. Two real data applications are also used to illustrate the effectiveness of the trimmed model selection methods.

ObjectivesThe aim of this study was to identify socio-economic and acculturation factors associated with hepatitis C (HCV) screening and infection among US Vietnamese Americans.MethodsParticipants were recruited from 7 Vietnamese community-based organizations in Pennsylvania and New Jersey. The analysis ultimately included 309 participants who participated in a HCV education intervention program.ResultsOverall, 82.5% (255 of 309) intervention participants completed HCV screening over the 6 months prior to the post-intervention assessment. In multivariate-adjusted analysis, participants who lived in Vietnam for 40 years versus 20 years were more likely to receive HCV screening; unemployed individuals were less likely to receive HCV screening than employed people. Among screened participants, 7.5% had HCV infection.ConclusionsThese findings will guide future culturally and linguistically appropriate interventions to reduce HCV infection and HCV-related liver cancer.

OBJECTIVE: Ovarian cancer (OC) ranks among the most prevalent gynecological malignancies, with surgery, chemotherapy, and immunotherapy constituting primary treatment modalities. However, despite advancements, immunotherapy, particularly immune checkpoint inhibitors, has yielded suboptimal outcomes. The pressing need to identify biomarkers predictive of clinical prognosis underscores our objective. We aim to discern gene signatures and establish prognostic subgroups, specifically in the context of immunotherapy and chemotherapy, guiding clinical decision-making. MATERIALS AND METHODS: We used the Tumor Immunotherapy Gene Expression Resource (TIGER) and The Cancer Genome Atlas (TCGA) databases to extract signature genes of prognostic significance. Unsupervised consensus clustering was employed to classify patients based on these signature genes. The Tumor Immune Estimation Resource (TIMER) database, along with the R packages "maftools" and "ESTIMATE" facilitated immune infiltration estimation. Gene set variation analysis (GSVA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were implemented to probe immune-related cell signaling pathways among distinct subtypes. The Tumor Immune Dysfunction and Exclusion (TIDE) database was used to assess immunotherapy effects, while the R package "OncoPredict" evaluated drug sensitivity differences among subtypes. RESULTS: We identified five prognostically influential genes in ovarian cancer: IGFBP7, JCHAIN, CCDC80, VSIG4, and MS4A1. Utilizing these signature genes, we categorized TCGA-OV patients into five clusters, each associated with varying clinical prognoses. Notably, 2 clusters exhibited superior prognoses, accompanied by enhanced immune cell infiltration. KEGG enrichment analysis revealed their heightened enrichment in cellular immunity and immune cell interaction pathways. Given the elevated expression levels of multiple immune checkpoint molecules, these clusters may substantially benefit from immune checkpoint inhibitor therapy. Additionally, chemotherapy sensitivity analysis indicated their favorable responses to first or second- line chemotherapy regimens. CONCLUSIONS: We subclustered ovarian cancer patients by 5 signature genes obtained from the Single-cell RNA sequencing (scRNAseq) dataset, which demonstrated a good typing effect. Patients in the two molecular subtypes showed better survival, higher immune cell infiltration, and higher drug sensitivity. This meticulous typing may help clinicians to quickly assess the prognosis of patients and the response to immunotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]