1.Loss of histone H3K27me3 up-regulates SLC7A11 in diffuse gastric cancer cells
Yuanfeng REN ; Wenkang LIU ; Zhaole CHU ; Biying LIU ; Yongying HOU ; Linyu WU ; Xianfeng LI ; Dongfeng CHEN ; Tao WANG ; Bin WANG ; Min YANG
Journal of Army Medical University 2025;47(1):71-81
Objective To map the genome-wide distribution profile of histone H3K27me3 modification in diffuse gastric cancer tissues,identify target genes regulated by H3K27me3,and primarily explore the potential mechanism of its modification reprogramming in the occurrence and development of the tumor.Methods Normal gastric mucosal tissues and diffuse gastric cancer tissues were harvested from the patients who underwent examinations or treatments in the departments of gastroenterology and gastrointestinal surgery of our medical center between 2021 and 2023.There were 14 patients in the normal group(6 males and 8 females,average age of 46 years)and 14 patients in the gastric cancer group(8 males and 6 females,average age of 63 years).Cleavage under target and tagmentation(CUT&Tag)technology was employed to capture genomic regions modified by H3K27me3,and analyze the reprogramming characteristics of these modifications.RNA sequencing data,data from high-throughput chromosome conformation capture(Hi-C)technology,and publicly available single-cell data were integrated to investigate the target genes regulated by the reprogramming of H3K27me3 modifications in diffuse gastric cancer cells.Results The quality of the CUT&Tag and RNA sequencing data met the standards required for subsequent analysis.Histone H3K27me3 modifications in normal gastric mucosa and diffuse gastric cancer tissues were primarily distributed in distal intergenic regions and intronic regions.In gastric cancer tissues,compared to normal tissues,there was significant reprogramming of H3K27me3 modifications,characterized by a marked reduction in overall H3K27me3 signal intensity.The loss of 2 912 H3K27me3 signal peaks might lead to the up-regulation of 822 tumor-associated genes.Among them,56 genes displayed the most significant up-regulation(fold change in signal intensity≥2,P<0.05),with notable enrichment in the mammalian target of rapamycin complex 1(mTORC1)signaling pathway.Specifically,the methionine transporter SLC7A5 and the cystine transporter SLC7A11 were found to have the highest expression levels in gastric cancer tissues.Single-cell data revealed that the abnormal overexpression of SLC7A11 in diffuse gastric cancer was primarily observed in tumor epithelial cells.Further validation using public data and immunohistochemical experiments confirmed the elevated expression of SLC7A11 in diffuse gastric cancer,which is associated with poor prognosis in gastric cancer patients.Conclusion The reprogramming of histone H3K27me3 modification is an important epigenetic characteristic in diffuse gastric cancer.Loss of H3K27me3 signal peaks may up-regulate the expression of SLC7A11 in diffuse gastric cancer cells,and thereby promote tumor progression.
2.Enhancer remodeling characteristics in diffuse-type gastric cancer and role in upregulating GDF15 expression and promoting cancer cachexia
Yuting TAN ; Linyu WU ; Yuwei PAN ; Shiyin PENG ; Rui XUE ; Xianfeng LI ; Zhaole CHU ; Biying LIU ; Ke LI ; Xuan ZHANG ; Bin WANG
Journal of Army Medical University 2025;47(11):1165-1176
Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6~8 weeks old,weighing 18~21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.
3.Drug Resistance and Prognosis of 150 Cases of Peritoneal Dialysis-associated Peritonitis
Yueyuan WU ; Xiaohua DAI ; Jie XU ; Xianfeng ZHANG ; Deyu XU ; Kun HU ; Lei SHEN ; Guoyuan LU ; Qiang HAN ; Yongfu HANG
Herald of Medicine 2024;43(2):287-291
Objective To analyze the pathogenic bacteria and drug resistance of peritoneal dialysis-associated peritonitis(PDAP),and provide a clinical reference for the rational use of antibiotics.Methods The demographic data of PDAP patients admitted to the peritoneal dialysis(PD)Center of the First Affiliated Hospital of Soochow University from July 1,2015 to December 30,2021 were collected,and the pathogens,drug resistance and prognosis were retrospectively analyzed.Results A total of 150 episodes of PDAP occurred in 92 patients.The positive rate of PD fluid culture was 61.33%,including 65 cases(70.65%)of Gram-positive(G+)bacteria,mainly Staphylococcus and Streptococcus.Gram-negative(G-)bacteria were in 16 cases(17.39%),mainly Escherichia coli and Enterobacter cloacae.There were 11 cases(11.96%)of multiple infections,including 5 cases of combined fungal infection.From 2016 to 2021,the incidence of G+bacteria-related PDAP decreased from 14 to 8 cases.G+strains were resistant to methicillin(35.00%),and were sensitive to linezolid(100.00%),teicoplanin(100.00%)and rifampicin(100.00%).The sensitivity rate to vancomycin was 98.59%.G-strains were sensitive to ceftazidime(86.36%),ceftizoxime(88.89%)and amikacin(100.00%).The MIC of vancomycin against Staphylococcus showed an upward trend in 2019-2021.The overall cure rate of PDAP was 81.33%in patients who responded to antibiotic treatment,and the cure rate of G+bacteria was higher than that of multiple infections(89.23%vs.36.36%,P<0.01).The outcome of patients with multiple infections,especially those with concurrent fungal infection was poor.Conclusion The incidence of PDAP in the PD center has shown a decreasing trend in recent years.G+bacteria are still the main pathogenic bacteria causing PDAP,and they are highly resistant to methicillin,so vancomycin should be used as empirical therapy.For G-bacteria,cefotaxime and amikacin can be chosen as empirical therapy.There is a drift in the MIC values of vancomycin against Staphylococcus in the study period,so it is necessary to monitor the MIC of vancomycin against Staphylococcus and its changing trend.
4.Identification of novel biomarkers for varicocele using iTRAQ LC-MS/MS technology.
Xianfeng LU ; Na LI ; Lufang LI ; Yongai WU ; Xuefeng LYU ; Yingli CAO ; Jianrong LIU ; Qin QIN
Chinese Medical Journal 2024;137(3):371-372
5.Construction and application of physical restraint reduction scheme for adult patients after cardiac surgery based on eCASH concept
Shanshan LYU ; Jing ZHENG ; Xianfeng LIU ; Xuying GUO ; Chuanni WU ; Huihui WANG
Chinese Critical Care Medicine 2024;36(10):1102-1107
Objective:To construct a physical restraint reduction scheme based on eCASH concept (that is early Comfort using Analgesia, minimal Sedatives and maximal Human care for adult patients after cardiac surgery, and intervene, and to evaluate its effectiveness.Methods:A non-synchronous case-control study was conducted. A total of 486 patients after cardiac surgery admitted to the cardiac surgery intensive care Unit (ICU) of Shandong Provincial Hospital Affiliated to Shandong First Medical University from July to October 2022 were enrolled as subjects. According to the implementation time node of the physical restraint reduction scheme, 250 patients admitted from July to August were served as the control group, and 236 patients admitted from September to October were served as the observation group. The control group adopted the routine physical restraint nursing process, including selecting the appropriate restraint device according to the patient's condition and consciousness and following the doctor's advice, and checking on time to prevent adverse reactions. The observation group implemented the physical restraint reduction scheme based on eCASH concept, including preoperative visit, postoperative assessment of whether patients needed physical restraint according to the restraint decision wheel and the physical restraint flow, and adopted personalized nursing programs. The restraint rate, restraint duration, incidence of restraint-related complication (edema of the limbs, redness and swelling of the skin in the restricted area, skin rupture, etc.), restraint device application standard rate, delirium rate and incidence of unplanned extubation event were compared between the two groups.Results:There was no significant difference in age, gender, cardiopulmonary bypass, endotracheal catheter retention duration and operation type between the two groups with comparability. The restraint rate in the observation group was significantly lower than that in the control group [16.95% (40/236) vs. 84.40% (211/250), P < 0.01], and the restraint duration was significantly shorter than that in the control group [hours: 0 (0, 1.0) vs. 7.0 (5.5, 10.0), P < 0.01], the incidence of restraint-related complication and delirium were significantly lower than those in the control group [restraint-related complication: 0.85% (2/236) vs. 1.60% (4/250), delirium: 0% (0/236) vs. 2.80% (7/250), both P < 0.05], and the restraint device application standard rate was significantly higher than that in the control group [100.00% (40/40) vs. 90.52% (191/211), P < 0.05]. No unplanned extubation event occurred in both groups. Conclusion:The physical restraint reduction scheme based on eCASH concept in adult patients after cardiac surgery can effectively reduce the restraint rate and the incidence of restraint-related complication, shorten the restraint duration, reduce the incidence of delirium, improve the standardization of restraint device application, without increasing the incidence of unplanned extubation events.
6.Intratumoral and peritumoral magnetic resonance imaging radiomics combined with clinical characteristics to predict lymphovascular space invasion in cervical cancer
Baojin LIN ; Zhaoxia WU ; Shi WANG ; Xianfeng LONG ; Lili LIANG ; Disheng LI ; Chaohua ZHU
Chinese Journal of Medical Physics 2024;41(7):851-857
Objective To investigate the value of a nomogram model constructed from intratumoral and peritumoral magnetic resonance imaging radiomics combined with clinical characteristics in predicting the status of lymphovascular space invasion(LVSI)in cervical cancer.Methods A retrospective analysis was conducted on 178 cervical cancer patients confirmed by postoperative pathology,with 70 cases of LVSI(+)and 108 cases of LVSI(-).The patients were divided into a training set[142 cases,including 54 cases of LVSI(+)and 88 cases of LVSI(-)]and a test set[36 cases,including 16 cases of LVSI(+)and 20 cases of LVSI(-)]at a ratio of 8:2.All underwent magnetic resonance imaging before surgery,and regions of interest were manually delineated layer by layer on the T2WI sequence,with the peritumoral region being uniformly expanded outward.Univariate logistic analysis was performed on clinical factors to select independent factors for cervical cancer LVSI(+).Radiomic features were extracted separately from the intratumoral region,the peritumoral region,and the intratumoral-peritumoral region to construct radiomics models,and the differences between the peritumoral and the intratumoral-peritumoral models were compared.A combined model was established based on the radiomics scores of the optimal intratumoral-peritumoral model and clinical independent predictive factors,and a nomogram was plotted.Receiver operating characteristic curves were used to evaluate the diagnostic performance of each model,and decision curve analysis was used to assess the clinical value of the models.Results The combined model demonstrated the best performance among the various models,with AUC of 0.970 in the training set and 0.803 in the test set.Conclusion Intratumoral and peritumoral magnetic resonance imaging radiomics combined with clinical characteristics can effectively predict LVSI in cervical cancer.
7.Ultra-fast scanning scheme based on deep learning reconstruction for cervical MR examination
Xianfeng RAO ; Shuwen YANG ; Jing CHEN ; Zhengwen KANG ; Jianwei CHEN ; Zetao WU ; Tong WANG ; Bo WANG ; Qiusheng ZHANG
Chinese Journal of Medical Imaging Technology 2024;40(6):843-847
Objective To explore the feasibility and diagnostic value of ultra-fast scanning scheme based on deep learning-based reconstruction(DLR)for cervical MR examination.Methods Thirty-six subjects were prospectively enrolled and underwent both conventional scheme(scan time:6 min 14 s)and ultra-fast scheme(2 min)cervical spine MR scanning to acquire encompassing sagittal T1WI,sagittal adipose suppression T2WI and axial T2WI.The ultra-fast MRI were reconstructed using DLR method.The subjective and objective evaluations on imaging qualities of different MRIs were compared,along with the inter-observer agreement for diagnosing intervertebral disc degeneration and herniation.Results Compared with conventional MRI,artifacts in ultra-fast DLR images significantly reduced(P<0.05).The subjective evaluation results of MRI had good agreement(all Kappa≥0.60).Compared with conventional MRI,the sagittal T1WI,T2WI and axial T2WI obtained with ultra-fast DLR showed significantly improved signal-to-noise ratio(SNR)of the spinal cord,cerebrospinal fluid(CSF)and vertebral body,as well as the spinal cord/CSF contrast(all P<0.001).The Kappa value of 2 physicians for diagnosing intervertebral disc degeneration based on ultra-fast DLR and conventional scheme images was 0.94 and 1.00,respectively,of intervertebral disc herniation was 0.96 and 0.98,respectively.Conclusion Compared with conventional scanning scheme,using ultra-fast DLR scheme in cervical MR examination could shorten scanning time while achieve similar image quality and diagnostic accuracy.
8.Cannulated screws for the treatment of Hauck type Ⅱ ulnar styloid process fracture
Zhiwei WANG ; Xianfeng LAN ; Xuejun WU
Chinese Journal of Primary Medicine and Pharmacy 2024;31(7):1013-1016
Objective:To investigate the application value of cannulated screws in the treatment of Hauck type Ⅱ ulnar styloid process fracture.Methods:The clinical data of 93 patients with Hauck type Ⅱ ulnar styloid process fracture who received treatment at Fuzhou Second Hospital Affiliated to Xiamen University from December 2020 to February 2023 were retrospectively analyzed for a case-control study. Among these patients, 38 patients did not undergo surgical fixation and 55 patients underwent surgical fixation. Twenty-seven patients underwent surgical fixation with cannulated screws and twenty-eight patients underwent surgical fixation with Kirschner wires. The fracture healing, postoperative rehabilitation, and functional recovery of the wrist were compared among groups.Results:The fracture healing rate and the incidence of distal radioulnar joint instability in the surgical fixation group were 100.00% (55/55) and 5.45% (3/55), respectively. These were significantly higher and lower respectively compared with the non-surgical fixation group [57.89% (22/38), 50.00% (19/38), χ 2 = 27.66, 24.69, both P < 0.001]. The wrist function recovery in the surgical fixation group was significantly superior to that in the non-surgical fixation group ( Z = -5.18, P < 0.001). There were no statistically significant differences in operative time and intraoperative blood loss between the cannulated screw group and the Kirschner wire group [(21.41 ± 5.15) minutes vs. (20.93 ± 5.71) minutes, (2.11 ± 0.97) mL vs. (2.07 ± 0.90) mL, t = 0.32, 0.15, both P > 0.05]. The fracture healing time and rehabilitation intervention time in the cannulated screw group were shorter than those in the Kirschner wire group [(6.48 ± 1.05) weeks vs. (9.14 ± 1.24) weeks, (2.11 ± 0.32) weeks vs. (3.11 ± 0.57) weeks, t = 8.57, 7.98, both P < 0.001]. The postoperative wrist function scores in the cannulated screw group were superior to those in the Kirschner wire group ( Z = -2.21, P < 0.05). Conclusion:For patients with Hauck type Ⅱ ulnar styloid process fracture, surgical fixation can promote the recovery of wrist function after surgery, and cannulated screw fixation is an effective method for the treatment of Hauck type Ⅱ ulnar styloid process fracture.
9.Construction of a skill training practice system for port health quarantine
Ming XIAO ; Xianfeng WU ; Haibin ZOU ; Caixian LI
Chinese Journal of Medical Education Research 2023;22(8):1127-1132
Based on cognitive psychology, the business attributes of port health quarantine, the requirements for team building, the current status of skill training. This article proposes to strengthen the training of port health quarantine skills. Under the guidance of medical licensing examination for public health, it is recommended to enhance the construction of a standardized skill training practice system, establish a basic skill training center and a field operation training site, develop new skill training courses, innovate skills training and teaching methods, and build a team of high-quality skill training teachers, thereby constructing a standardized skill training and practice system for port health quarantine. The preliminary establishment of the skill training system for port health quarantine at Huangpu Customs shows the feasibility and effectiveness of the construction of skill training and practice system.
10.Exploration of the relationship between the storage time of leukodepleted red blood cell and transfusion adverse reactions
Liu HE ; Jian LIU ; Gang WU ; En WANG ; Fayan YI ; Xingshun TAN ; Shiyu ZHU ; Rui YU ; Guanghui LU ; Yan LIU ; Mei ZHAI ; Qing XIANG ; Ping LIU ; Yanhua LIAO ; Zhizhen FU ; Maolin LI ; Rong HUANG
Chinese Journal of Blood Transfusion 2023;36(10):889-891
【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

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