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Development and validation of prognostic nomogram based on log odds of positive lymph nodes for patients with gastric signet ring cell carcinoma

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Chinese Journal of Cancer Research 2020年第6期32卷 778-793页

作者： Zijie Xu Jing Jing Guiliang Ma Department of General Surgery Qingdao Municipal HospitalQingdao UniversityQingdao 266071China Department of Endocrinology Qingdao Municipal HospitalQingdao UniversityQingdao 266071China

Objective: Our aims were to establish novel nomogram models, which directly targeted patients with signet ring cell carcinoma(SRC), for individualized prediction of overall survival(OS) rate and cancer-specific survival(CSS).Methods: We selected 1,365 SRC patients diagnosed from 2010 to 2015 from Surveillance, Epidemiology and End Results(SEER) database, and then randomly partitioned them into a training cohort and a validation *** predicted indicators, which were identified by using univariate testing and multivariate analyses, were used to construct our prognostic nomogram models. Three methods, Harrell concordance index(C-index), receiver operating characteristics(ROC) curve and calibration curve, were used to assess the ability of discrimination and predictive accuracy. Integrated discrimination improvement(IDI), net reclassification improvement(NRI) and decision curve analysis(DCA) were used to assess clinical utility of our nomogram ***: Six independent predicted indicators, age, race, log odds of positive lymph nodes(LODDS), T stage, M stage and tumor size, were associated with OS rate. Nevertheless, only five independent predicted indicators were associated with CSS except race. The developed nomograms based on those independent predicted factors showed reliable discrimination. C-index of our nomogram for OS and CSS was 0.760 and 0.763, which were higher than American Joint Committee on Cancer(AJCC) 8 th edition tumor-node-metastasis(TNM) staging system(0.734 and 0.741, respectively). C-index of validation cohort for OS was 0.757 and for CSS was 0.773. The calibration curves also performed good consistency. IDI, NRI and DCA showed the nomograms for both OS and CSS had a comparable clinical utility than the TNM staging ***: The novel nomogram models based on LODDS provided satisfying predictive ability of SRC both in OS and CSS than AJCC 8 th edition TNM staging system alone.

关键词： Log odds of positive lymph nodes nomograms prognosis signet ring cell

Patients with MMAF induced by novel biallelic CFAP43 mutations have good fertility outcomes after intracytoplasmic sperm injection

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Asian Journal of Andrology 2023年第5期25卷 564-571页

作者： Jing Ma Shun-Hua Long Hai-Bing Yu Ye-Zhou Xiang Xiang-Rong Tang Jia-Xun Li Wei-Wei Liu Wei Han Rong Jin Guo-Ning Huang Ting-Ting Lin Center for Reproductive Medicine Women and Children's Hospital of Chongqing Medical UniversityChongqing 400010China Chongqing Health Center for women and children Chongqing 400010China Chongqing Key Laboratory of Human Embryo Engineering Chongqing 400010China

As a specific type of asthenoteratozoospermia,multiple morphological abnormalities of the sperm flagella(MMAF)is characterized by composite abnormalities,including absent,short,coiled,angulation,and irregular-caliber *** in cilia-and flagella-associated protein 43(CFAP43)are one of the main causative factors of MMAF established to *** identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations,we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing *** systematic analysis,seven mutations in CFAP43,including five novel mutations and two previously reported mutations,were identified from four families and related to MMAF in an autosomal recessive *** staining,immunofluorescence,and electronic microscopy further clarified the semen characteristics a nd abnormal sperm morphologies,including disorganized axonemal and peri-axonemal structures,of the CFAP43-deficient *** female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection,and one of them successfully gave birth to a healthy *** study significantly expands the mutant spectrum of CFAP43,and together with the available information regarding male infertility and MMAF,provides new information for the genetic diagnosis and counseling of MMAF in the future.

关键词： asthenoteratozoospermia CFAP43 intracytoplasmic sperm injection MMAF

Functions and mechanisms of protein lysine butyrylation(Kbu):Therapeutic implications in human diseases

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Genes & Diseases 2023年第6期10卷 2479-2490页

作者： Qianqian Xue Yanyan Yang Hong Li Xiaoxin Li Lu Zou Tianxiang Li Huibo Ma Hongzhao Qi Jianxun Wang Tao Yu Institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266000China Department of Immunology School of Basic MedicineQingdao UniversityQingdaoShandong 266021China Clinical Laboratory Central Laboratory.The Affiliated Qingdao Hiser Hospital of Qingdao UniversityQingdaoShandong 266000China Department of Vascular Surgery The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266000China Department of Cardiac Ultrasound The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266000China

Post-translational modifications(PTM)are covalent modifications of proteins or peptides caused by proteolytic cleavage or the attachment of moieties to one or more amino *** play essential roles in biological function and regulation and have been linked with several *** of protein acylation(Kac),a type of PTM,are known to induce epigenetic regulatory processes that promote various ***,an increasing number of studies focusing on acylation modifications are being ***(Kbu)is a new acylation process found in animals and *** has been recently linked to the onset and progression of several diseases,such as cancer,cardiovascular diseases,diabetes,and vascular ***,the mode of action of certain drugs used in the treatment of lymphoma and colon cancer is based on the regulation of butyrylation levels,suggesting that butyrylation may play a therapeutic role in these *** addition,butyrylation is also commonly involved in rice gene expression and thus plays an important role in the growth,development,and metabolism of *** tools and analytical methods that could be utilized for the prediction and detection of lysine butyrylation have also been *** study reviews the potential role of histone Kbu,as well as the mechanisms underlying this *** also summarizes various enzymes and analytical methods associated with Kbu,with the goal of providing new insights into the role of Kbu in gene regulation and diseases.

关键词： Butyrylation Gene regulation Histone Post-translational modification Target treatment

Skeletal muscle-specific Bambi deletion induces hypertrophy and oxidative switching coupling with adipocyte thermogenesis against metabolic disorders

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Science China Life Sciences 2025年

作者： Xiangping Yao Xudong Mai Ye Tian Yifan Liu Guanghui Jin Ze Li Shujie Chen Xiaoshuang Dai Liujing Huang Zijing Fan Guihua Pan Xiaohan Pan Xiangmin Li Michael C Yu Jia Sun Jingxing Ou Hong Chen Liwei Xie College of Life and Health Sciences Guangdong Industry Polytechnic Department of Endocrinology and Metabolism Zhujiang Hospital Southern Medical University State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied MicrobiologyInstitute of Microbiology Guangdong Academy of Sciences Institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics School of Medical Technology Guangdong Medical University Department of Hepatic Surgery and Liver transplantation Center of the Third Affiliated hospital Organ Transplantation Institute Sun Yat-sen University Organ Transplantation Research Center of Guangdong ProvinceGuangdong province engineering laboratory for transplantation medicine Guangdong Provincial Key Laboratory of Liver Disease Research School of Public Health Xinxiang Medical University BGI Institute of Applied Agriculture BGI-Shenzhen Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University Department of Biological Sciences State University of New York at Buffalo Department of Internal Medicine Shunde Women and Children's Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan) Guangdong Medical University

Skeletal muscle plays a significant role in both local and systemic energy metabolism. The current investigation aims to explore the role of the Bambi gene in skeletal muscle, focusing on its implications for muscle hypertrophy and systemic metabolism. We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy, improves metabolic performance, and activates thermogenic adipocytes via the reprogramming of progenitor of i WAT, offering potential therapeutic strategies for metabolic syndromes. Leveraging the Chromatin immunoprecipitation(ChIP)-seq and bioinformatics analysis, Bambi gene is shown to be a direct target of HIF2α, which is further confirmed by ChIP-qPCR and promoter luciferase assay. Skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters, even under high-fat diet conditions. This deletion induced metabolic reprogramming of stromal vascular fractions(SVFs) into thermogenic adipocytes, contributing to systemic metabolic improvements, potentially through the secretory ***, mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders, highlighting a potential therapeutic pathway for metabolic syndrome management. Thus, skeletal muscle-specific deletion of Bambi triggers muscle growth, enhances metabolic performance, and activates thermogenic adipocytes. These findings suggest Bambi as a novel therapeutic target for metabolic syndromes, providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement. The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism, offering a novel perspective on treating metabolic disorders.

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Binary prodrug nanoassemblies combining chemotherapy and ferroptosis activation for efficient triple-negative breast cancer therapy

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Chinese Chemical Letters 2024年第10期35卷 348-352页

作者： Lin Li Bingjun Sun jin Sun Lin Chen Zhonggui He Department of Pharmacy Women and Children's Hospital of Chongqing Medical University/Chongqing Health Center for Women and ChildrenChongqing 401147China Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China

Chemotherapy has been recommended as the standard protocol for triple-negative breast cancer(TNBC)at the advanced ***,the current treatment is unsatisfactory due to inefficient drug accumulation and rapid ***,rational design of advanced drug delivery systems that can induce multiple cell death pathways is a promising strategy to combat *** is a powerful non-apoptotic cell death modality,showing potential in tumor ***,we propose a binary prodrug nanoassemblies that combines chemotherapy with ferroptosis for TNBC *** this system,paclitaxel is linked with paracetamol(ferroptosis activator)by a disulfide linkage to construct self-assembly ***,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-methyl(polyethylene glycol)-2000-tyrosine(DSPE-PEG2k-tyrosine)is applied for large neutral amino acid transporter 1(LAT1)targeting,which is highly expressed in *** prodrug nanoassemblies exhibit good stability and a glutathione(GSH)-responsive release ***,the LAT1-targeted nanoassemblies show stronger cytotoxicity,higher cellular uptake,and more obvious ferroptosis activation than non-decorated *** a TNBC mice model,the prodrug nanoassemblies demonstrate strong anti-tumor *** application of ferroptosis-assisting chemotherapy may provide a promising strategy for TNBC therapy.

关键词： Prodrug nanoassemblies Paclitaxel Ferroptosis LAT1 Triple-negative breast cancer

Association of GCKR Gene Polymorphisms with the Risk of Nonalcoholic Fatty Liver Disease and Coronary Artery Disease in a Chinese Northern Han Population

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Journal of Clinical and Translational Hepatology 2019年第4期7卷 297-303页

作者： Hui Gao Shousheng Liu Zhenzhen Zhao Xinjuan Yu Qun Liu Yongning Xin Shiying Xuan Department of Infectious Disease Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Central Laboratories Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Department of Gastroenterology Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Digestive Disease Key Laboratory of qingdao QingdaoShandongChina

Background and Aims: Accumulated studies have eval-uated the effects of glucokinase regulatory protein(GCKR)gene polymorphisms on the risk of nonalcoholic fatty liver disease(NAFLD)and coronary artery disease(CAD),but the association of GCKR polymorphisms with the risk of NAFLD and CAD in the Chinese Han population have remained *** aim of this study was to investigate the association between GCKR gene polymorphisms(rs780094 and rs1260326)and the risk of NAFLD and CAD in NAFLD patients in a Chinese Northern Han ***: GCKR rs780094 and rs1260326 gene polymorphisms were geno-typed by polymerase chain reaction sequencing for B-type ultrasonography-proven NAFLD patients with(n = 82)or without(n = 142)CAD,and in healthy controls(n = 152).Serum lipid profiles'levels were determined using biochemi-cal *** analyses were conducted using SPSS 22.0 statistical ***: As the results showed,sig-nificant differences in the serum lipid profiles existed between each *** significant differences were observed in the distributions of genotypes and alleles of GCKR rs780094 and rs1260326 in each *** GCKR rs780094 T and rs1260326 T allele carriers possessed decreased body mass index value,and serum fasting plasma glucose and TG levels in the overall subjects,*** addition,the GCKR rs780094 T allele carriers possessed decreased serum fasting plasma glucose level in the controls and NAFLD+CAD ***: GCKR rs780094 and rs1260326 poly-morphisms were found to be not associated with the risk of NAFLD nor of CAD in NAFLD patients in this Chinese Northern Han *** rs780094 T and rs1260326 T alleles could affect the body mass index value and serum fasting plasma glucose and triglyceride levels.

关键词： Non-alcoholic fatty liver disease Glucokinase regulatory protein gene Polymorphism Coronary artery disease

Clinicopathological and prognostic significance of aberrant Arpin expression in gastric cancer

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World Journal of Gastroenterology 2017年第8期23卷 1450-1457页

作者： Tao Li Hong-Mei Zheng Nai-Mei Deng Ying-Jian Jiang Jiang Wang Dian-Liang Zhang Center of Colon and Rectum Qingdao Municipal HospitalQingdao University Infection Department Qingdao Municipal Hospital

AIM To detect the expression of Arpin, and determine its correlation with clinicopathological characteristics and the prognosis of gastric cancer (GC) patients. METHODS A total of 176 GC patients were enrolled as study subjects and classified into groups according to different clinicopathological variables. GC mucosal tissues were obtained via surgery. Another 43 paraffin-embedded tissue blocks of normal gastric epithelium (> 5 cm away from the edge of the tumor) were included in the control group. Immunohistochemistry (IHC) for the Arpin and Arp3 proteins was performed on the formalin-fixed, paraffin-embedded GC tissues. Additionally, expression of the Arpin protein in 43 normal gastric tissues was also determined using IHC. RESULTS Expression of the Arpin protein in GC was lower than that in normal gastric mucosa (30.68% vs 60.47%, P < 0.001). A chi(2) test of the 176 GC samples used for IHC showed that decreased Arpin expression was associated with advanced TNM stage (P < 0.01) and the presence or absence of lymph node metastasis (80.92% vs 35.56%, P < 0.001). Additionally, a significant correlation was observed between the expression of Arpin and the presence of the Arp2/3 complex in GC tissues (chi(2) = 30.535, P < 0.001). Moreover, a multivariate Cox regression analysis revealed that Arpin expression [hazard ratio (HR) = 0.551, P = 0.029] and TNM stage (HR = 5.344, P = 0.001) were independent prognostic markers for overall survival of GC patients. Regarding the 3-year disease-free survival (DFS), the recurrence rate of GC patients with low Arpin expression levels (median DFS 19 mo) was higher than that in the high-Arpin-expression group (median DFS 34 mo, P = 0.022). CONCLUSION Low Arpin levels are associated with clinicopathological variables and a poor prognosis in GC patients. Arpin may be regarded as a potential prognostic indicator in GC.

关键词： clinicopathological characteristics Gastric cancer Arpin Arp2/3 complex Prognosis

Primary resistance to crizotinib treatment in a non-small cell lung cancer patient with an EML4-ALK rearrangement:a case report

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Cancer Biology & Medicine 2018年第2期15卷 178-181页

作者： Ling Zhang Yunxia Li Shaohong Zhang Chen Gao Keke Nie Youxin Ji Department of Oncology Qingdao Cancer Hospital Department of Medicine Laixi Meihuashan Hospital Department of Oncology Affiliated Qingdao Central Hospital of Qingdao University

Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)*** gene point mutation is the primary mechanism of acquired crizotinib resistance;however,the intrinsic mechanism is not fully ***,we report a patient with a low mutant allele fraction(MAF)of EML4-ALK rearrangement,who experienced primary resistance to crizotinib *** patient was a 66-year-old Chinese man,who had a history of metastatic lung cancer and was treated with first-and third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs).After 14 months of osimertinib treatment,his disease progressed,and next-generation sequencing was performed from a liquid biopsy of the patient’s *** EML4-ALK rearrangement was found and crizotinib was *** patient’s lung lesions continued to progress after one month of crizotinib treatment,and pemetrexed-bevacizumab was *** two cycles of chemotherapy,the metastatic cancers shrunk,and the patient maintained stable disease at his last ***4-ALK rearrangements can happen in patients with EGFR-positive NSCLC,after acquired resistance to EGFR TKI *** EGFR T790M and C797G mutations occur in cis is a critical mechanism of resistance to osimertinib *** MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.

关键词： Non-small cell lung cancer EML4-ALK target therapy crizotinib

Newborn screening with targeted sequencing:a multicenter investigation and a pilot clinical study in China

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Journal of Genetics and Genomics 2022年第1期49卷 13-19页

作者： Chanjuan Hao Ruolan Guo Xuyun Hu Zhan Qi Qi Guo Xuanshi Liu Yuanhu Liu Yanhua Sun Xiaofen Zhang Feng Jin Xiujie Wu Ren Cai Dingyuan Zeng Xijiang Hu Xiaohua Wang Xiaoping Ji Wenjie Li Quansheng Xing Lanfang Mu Xiulian Jiang Xue Yang Weimin Yang Yan Zhang Qianli Yin Xin Ni Wei Li Beijing Key Laboratory for Genetics of Birth Defects Beijing Pediatric Research InstituteBeijing 100045China MOE Key Laboratory of Major Diseases in children Beijing 100045China Rare Disease Center National Center for Children’s HealthBeijing 100045China Beijing children’s hospital Capital Medical UniversityBeijing 100045China Shunyi women and children’s Healthcare hospital of Beijing children’s hospital Beijing 101300China Liuzhou Maternal and Child Healthcare hospital LiuzhouGuangxi 545001China Wuhan Maternal and Child Healthcare hospital Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanHubei 430016China Inner Mongolia Maternity and Child Healthcare hospital HohhotInner Mongolia Autonomous Region 010020China qingdao women and children’s hospital QingdaoShandong 266012China Qinghai Maternal and Child Health hospital XiningQinghai 810007China Guiyang Maternity and Child Healthcare hospital GuiyangGuizhou 550003China Urumqi First People’s hospital UrumqiXinjiang 830011China

Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 women and children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.

关键词： Newborn screening Next-generation sequencing Targeted sequencing Monogenic disorders Clinical practice