1.PDZ-binding kinase as a prognostic biomarker for pancreatic cancer: a pan-cancer analysis and validation in pancreatic adenocarcinoma cells.
Jinguo WANG ; Yang MA ; Zhaoxin LI ; Lifei HE ; Yingze HUANG ; Xiaoming FAN
Journal of Southern Medical University 2025;45(10):2210-2222
OBJECTIVES:
To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer.
METHODS:
PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting.
RESULTS:
PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2.
CONCLUSIONS
PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans
;
Pancreatic Neoplasms/genetics*
;
Prognosis
;
Biomarkers, Tumor/genetics*
;
Cell Line, Tumor
;
Cell Proliferation
;
Adenocarcinoma/metabolism*
;
Tumor Microenvironment
;
Cell Movement
;
Mitogen-Activated Protein Kinase Kinases
2.An association study between ALOX15 gene polymorphisms and non-cardia gastric carcinogenesis
Ning Chu ; Wenjie Dong ; Fang Gao ; Yingze Li ; Yaru Chen ; Bin Zhang ; Yanbin Jia
Acta Universitatis Medicinalis Anhui 2025;60(10):1865-1873
Objective:
To explore the association between single nucleotide polymorphism(SNP) in the arachidonate 15-lipoxygenase(ALOX15) gene and Helicobacter pylori(H. pylori) infection as well as the risk of non-cardia gastric cancer in Baotou Han population, and to provide experimental evidence and data support for the screening of susceptible population for non-cardia gastric cancer.
Methods:
A total of 458 cases with non-cardia gastric cancer and 460 healthy examination people were collected. The 14C urea breath test(UBT) and enzyme-linked immunosorbent assay(ELISA) were used to detect H. pylori infection in the 460 healthy individuals. The genotypes of ALOX15 rs2619112, rs2619118, rs2664593, rs7220870 were detected by polymerase chain reaction-restriction fragment length polymorphism, and the association of SNP with H. pylori infection as well as the risk of non-cardia gastric cancer was statistically analyzed.
Results:
The positive rate of H. pylori infection was 42.4%. ALOX15 rs2619112, rs2619118, rs2664593, and rs7220870 had no association with H. pylori infection. ALOX15 rs2619112, rs2664593, and rs7220870 were not associated with the risk of non-cardia gastric cancer. Compared with the carriers of(CC + CT) genotype, the carriers of rs2619118 TT genotype had an increased onset risk of non-cardia gastric cancer [OR(95%CI)=1.512(1.110-2.060)]. The haplotype ACCC constructed by ALOX15 rs2619112, rs2619118, rs2664593, and rs7220870 could reduce the onset risk of non-cardia gastric cancer. The second-order interaction of ALOX15 rs2619112 and rs2619118 was associated with the risk of non-cardia gastric cancer ( P < 0. 05 ) .
Conclusion
ALOX15 rs2619112 , rs2619118 , rs2664593 , rs7220870 may not play a major role in H. pylori infection. ALOX15 rs2619118 TT genotype is a risk factor for the development of non⁃cardia gastric cancer. The haplotype ACCC constructed by ALOX15 rs2619112 , rs2619118 , rs2664593 , and rs7220870 reduces the onset risk of non⁃cardia gastric cancer. The interaction of ALOX15 rs2619112 and rs2619118 has a synergistic effect in the development of non⁃cardia gastric cancer.
3.Distal dynamic locking and distal static locking of proximal femoral bionic intramedullary nails: a biomechanical finite element analysis
Yuchuan WANG ; Xiaodong CHENG ; Yanbin ZHU ; Yonglong LI ; Zhongzheng WANG ; Yanjiang YANG ; Wei CHEN ; Yingze ZHANG
Chinese Journal of Orthopaedic Trauma 2024;26(2):138-142
Objective:To characterize the biomechanics of distal dynamic locking and distal static locking of proximal femur bionic nails (PFBN) in fixation of intertrochanteric fractures by a finite element analysis.Methods:The CT image data from the hip to the upper tibia from an adult male volunteer were used to establish a three-dimensional model of the femur by Mimics 20.0 and Geomagic 2013 which was processed further into a model of Evans type I intertrochanteric fracture by software NX 12.0. With reference to the internal fixation parameters commonly used, 4 models of PFBN fixation were established: distal single transverse nail dynamic locking (model A), single oblique nail dynamic locking (model B), single nail static locking (model C) and double nail dynamic locking (model D). Abaqus 6.14 software was used to load and analyze the internal fixation stresses and displacements of fracture ends.Results:Under a 2100N loading, the peak stress was located upon the main nail in the 4 models. The smallest peak stress upon the main nail was in Model D (161.9 MPa), decreased by 15.9% compared with model A (192.5 MPa), by 15.6% compared with model B (191.9 MPa), and by 0.9% compared with model C (163.3 MPa). The peak stress upon the fixation screw was the largest in model A (95.3 MPa), the smallest in model B (91.5 MPa), and 91.5 MPa and 92.2 MPa in models C and D, respectively. The overall displacements of the implants, in a descending order, were 10.14 mm in model A, 10.10 mm in model B, 10.09 mm in model C, and 10.05 mm in model D. Similarly, the displacements of fracture ends were 0.125 mm in model A, 0.121 mm in model B, 0.110 mm in model C, and 0.098 mm in model D.Conclusion:Compared with dynamic locking, distal static locking of PFBN provides a better mechanical stability and reduces stress concentration upon internal fixation.
4.Clinical guidelines for indications, techniques, and complications of autogenous bone grafting.
Jianzheng ZHANG ; Shaoguang LI ; Hongying HE ; Li HAN ; Simeng ZHANG ; Lin YANG ; Wenxing HAN ; Xiaowei WANG ; Jie GAO ; Jianwen ZHAO ; Weidong SHI ; Zhuo WU ; Hao WANG ; Zhicheng ZHANG ; Licheng ZHANG ; Wei CHEN ; Qingtang ZHU ; Tiansheng SUN ; Peifu TANG ; Yingze ZHANG
Chinese Medical Journal 2024;137(1):5-7
5.Association study between mammalian sterile 20-like kinase 1 SNPs and colorectal cancer
Licong MA ; Xiaoxia YAN ; Fang GAO ; Wenjie DONG ; Yingze LI ; Yanbin JIA
Acta Universitatis Medicinalis Anhui 2024;59(3):547-553
Objective To explore the association between mammalian sterile 20-like kinase 1(MST1)gene poly-morphism and haplotype and the risk of colorectal cancer,rectal cancer,and colon cancer in the Han population in Baotou area by case-control association study.Methods A total of 390 patients with colorectal cancer diagnosed by pathology and 413 normal physical examination population were collected,and 2 ml of peripheral blood was taken for subsequent gene genotyping.Single nucleotide polymorphisms(SNPs)of MST1 gene were screened according to the genetic polymorphism data of Chinese Han population provided by the National Center for Biotechnology In-formation-Haplotype Mapping database.Gene genotyping was performed by Taqman method.Logistic regression was used to calculate the association between each SNP and the risk of colorectal cancer,colon cancer,and rectal cancer under codominant,dominant,overdominant,and recessive genetic models.Results Four SNPs of MST1 gene were screened,namely rs8000,rs2234197,rs2267853,and rs6073629.Among them,SNP rs2234197 was associated with the risk of rectal cancer.Compared with the GG+AA genotype,the AG genotype could reduce the risk of rectal cancer,OR[95%confidence interval(CI)]=0.657(0.442-0.976).SNP rs8000 was associated with the risk of colon cancer.Compared with the TT+GT genotype,the GG genotype could reduce the risk of colon cancer[OR(95%CI)=0.425(0.182-0.992)].Conclusion MST1 gene SNP rs2234197 AG genotype and SNP rs8000 GG genotype may be protective factors for rectal cancer and colon cancer,respectively.
6.Survey on status of perioperative aspirin use in thoracic surgery in China
Yingze NING ; Weijie ZHU ; Yang HAO ; Dong LI ; Huayu HE ; Jizheng TANG ; Songlei OU ; Chaoyang LIANG ; Guangliang QIANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(11):680-684
Objective:To understand the current status of the use of aspirin in perioperative period of thoracic surgery in China and the awareness of thoracic surgeons on the prevention and treatment of arterial thromboembolic diseases during the perioperative period.Methods:A survey was conducted among thoracic surgeons nationwide using an electronic questionnaire through a software platform from January 20, 2024 to February 29, 2024. The questionnaire mainly included three parts: basic information, aspirin use, and awareness of arterial thromboembolic diseases, with a total of 27 questions.Results:A total of 1318 valid questionnaires were collected, covering all 33 provincial administrative regions except Taiwan. 69.7%(919/1 318) of thoracic surgeons stopped using aspirin for all patients before surgery; differences could be found in the timing of aspirin withdrawal before surgery and resumption after surgery. 65.1%(858/1 318) of surgeons made perioperative medication decisions based on domestic guidelines or consensus, while 20.9%(276/1 318) of surgeons based their decisions on departmental or personal experience. 87.9%(1 159/1 318) of surgeons believed that it is necessary to develop guidelines for the prevention of arterial thromboembolic diseases in the perioperative period of thoracic surgery.Conclusion:The current use strategy of aspirin in the perioperative period of thoracic surgery in China shows a high degree of inconsistency, and there are also significant differences in the awareness of arterial thromboembolic diseases. It is necessary to establish guidelines for the prevention and treatment of arterial thromboembolic diseases in the perioperative period.
7.Surgical methods and treatment effects of the adult anterior dislocation of the sacroiliac joint
Shicai FAN ; Zhiyong HOU ; Yan ZHUANG ; Gang LYU ; Shuquan GUO ; Kangshuai XU ; Qiguang MAI ; Tao LI ; Yuhui CHEN ; Zhenhua ZHU ; Yingze ZHANG
Chinese Journal of Orthopaedics 2023;43(8):477-483
Objective:To explore the surgical methods and treatment effects of adult anterior dislocation of the sacroiliac joint (AADSJ).Methods:A multi-center retrospective case series study was conducted to analyze the clinical data of 25 cases admitted in 5 clinical centers (affiliations of authors in this article) from January 2016 to January 2021. There were 18 males and 7 females, aged 38.8±15.5 years (range, 18-83 years). The AADSJ clinical classification system was formulated based on the radiographic morphology of anterior dislocation of the sacroiliac joint, which includes two types. Type I: complete anterior dislocation of the sacroiliac joint, and displacement of the entire iliac auricular surface to the front of the sacrum. Type II: fracture of the sacroiliac joint combined with anterior dislocation, subdivided into 3 subtypes. Type IIa: iliac fracture involves the anterior 1/3 of the sacroiliac joint, and dislocation of the ilium anterior to the sacrum. Type IIb: iliac fracture involves the posterior 2/3 of the sacroiliac joint, and dislocation of the ilium anterior to the sacrum. Type IIc: iliac fracture involves the posterior 2/3 of the sacroiliac joint, and dislocation of the ilium anteromedial to the sacrum. The reliability and repeatability of the clinical classification, Tile classification and Young-Burgess classification were performed based on the results of two-phase assessments in four observers. The operations were performed by the lateral-rectus approach and the ilioinguinal approach. The operation time and intraoperative bleeding were recorded. Pelvic X-ray and CT scan were rechecked after the operation. The quality of fracture reduction was evaluated according to Matta score. The postoperative functional rehabilitation was evaluated according to the Majeed rehabilitation standard at one-year follow-up.Results:Among 25 cases in this study, there were 3 cases of Type I, 5 cases of Type IIa, 9 cases of Type IIb and 8 cases of Type IIc according to the clinical classification system. The Kappa values of reliability tests for the clinical classification, Tile classification and Young-Burgess classification were 0.681, 0.328 and 0.383, respectively. The Kappa values of repeatability tests for the clinical classification, Tile classification and Young-Burgess classification were 0.690, 0.221 and 0.395, respectively. The reliability and repeatability of the AADSJ clinical classification were significantly better than other classifications. There were 14 cases underwent lateral rectus abdominis approach and 11 cases underwent ilioinguinal approach. The operative time for managing anterior dislocation of the sacroiliac joint was 122.0±50.7 min (range, 65-148 min) through the lateral rectus abdominis approach, and through the ilioinguinal approach was 178.0±49.9 min (range, 110-270 min), with a significant difference ( t=2.76, P=0.011). The amount of intraoperative blood loss through the lateral rectus approach was 680±330 ml (range, 350-2,120 ml), which was significantly less than that through the ilioinguinal approach (1,660±968 ml, 680-3,300 ml), with a significant difference ( t=3.55, P=0.002). The follow-up period was 1-3 years. At one week after surgery, the quality of fracture reduction evaluated by Matta score showed that the excellent and good reduction rate of the lateral-rectus approach was 79% (11/14), and that of the ilioinguinal approach was 73% (11/14), with no statistically significant difference ( P=1.000). At a one-year follow-up, according to Majeed's criteria, the overall excellent and good rate of the lateral-rectus approach was 64% (9/14), which is similar to 64% (7/11) of that of the ilioinguinal approach. No fracture reduction loss or internal fixation loosening failure occurred. Conclusion:The AADSJ clinical classification system can accurately describe the imaging features and clinical manifestations of AADSJ, with high reliability and repeatability. The AADSJ can be treated by the lateral-rectus approach or the ilioinguinal approach, with similar therapeutic effects but the former having less trauma.
8.Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair (version 2023)
Junchao XING ; Long BI ; Li CHEN ; Shiwu DONG ; Liangbin GAO ; Tianyong HOU ; Zhiyong HOU ; Wei HUANG ; Huiyong JIN ; Yan LI ; Zhonghai LI ; Peng LIU ; Ximing LIU ; Fei LUO ; Feng MA ; Jie SHEN ; Jinlin SONG ; Peifu TANG ; Xinbao WU ; Baoshan XU ; Jianzhong XU ; Yongqing XU ; Bin YAN ; Peng YANG ; Qing YE ; Guoyong YIN ; Tengbo YU ; Jiancheng ZENG ; Changqing ZHANG ; Yingze ZHANG ; Zehua ZHANG ; Feng ZHAO ; Yue ZHOU ; Yun ZHU ; Jun ZOU
Chinese Journal of Trauma 2023;39(1):10-22
Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.
9.An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique (version 2023)
Jie SHEN ; Lin CHEN ; Shiwu DONG ; Jingshu FU ; Jianzhong GUAN ; Hongbo HE ; Chunli HOU ; Zhiyong HOU ; Gang LI ; Hang LI ; Fengxiang LIU ; Lei LIU ; Feng MA ; Tao NIE ; Chenghe QIN ; Jian SHI ; Hengsheng SHU ; Dong SUN ; Li SUN ; Guanglin WANG ; Xiaohua WANG ; Zhiqiang WANG ; Hongri WU ; Junchao XING ; Jianzhong XU ; Yongqing XU ; Dawei YANG ; Tengbo YU ; Zhi YUAN ; Wenming ZHANG ; Feng ZHAO ; Jiazhuang ZHENG ; Dapeng ZHOU ; Chen ZHU ; Yueliang ZHU ; Zhao XIE ; Xinbao WU ; Changqing ZHANG ; Peifu TANG ; Yingze ZHANG ; Fei LUO
Chinese Journal of Trauma 2023;39(2):107-120
Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.
10.Clinical guideline for diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture (version 2023)
Jianan ZHANG ; Bohua CHEN ; Tongwei CHU ; Yirui CHEN ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Yong HAI ; Lijun HE ; Yuan HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Dechun LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Wei MEI ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Honghui SUN ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Yongming XI ; Hong XIA ; Jinglong YAN ; Liang YAN ; Wen YUAN ; Gang ZHAO ; Jie ZHAO ; Jianguo ZHANG ; Xiaozhong ZHOU ; Yue ZHU ; Yingze ZHANG ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2023;39(3):204-213
Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.


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