1.RNF8 promotes DNA damage response through the ATM/CHK2 axis and affects cisplatin resistance in endometrial cancer cells
Cai Feifei ; Yang Tingting ; Shao Yang ; Ma Xin ; Qiang Ping ; Zhao Fang ; Xi Xingshu
Chinese Journal of Cancer Biotherapy 2026;33(8):830-839
[摘 要] 目的:探讨环指蛋白8(RNF8)对子宫内膜癌(EC)细胞顺铂(CDDP)敏感性的影响及可能机制。方法:基于在线数据库分析RNF8在EC组织中的表达及拷贝数变异;采用慢病毒介导shRNA稳定敲低Ishikawa细胞中RNF8表达并进行CDDP处理,按sh-NC+溶剂对照、sh-RNF8+溶剂对照、sh-NC + CDDP、sh-RNF8 + CDDP分组处理,并设置sh-RNF8 + CDDP + KU60019抑制实验。采用CCK-8、克隆形成、Annexin V-FITC/PI流式细胞术、Hoechst 33258/PI染色、WB及γ-H2AX免疫荧光检测细胞活力、克隆形成、凋亡、DNA损伤累积及ATM/CHK2通路相关蛋白表达。结果:RNF8在EC组织和细胞中表达升高。RNF8敲低降低细胞存活率和IC50,抑制克隆形成,并进一步增强CDDP诱导的凋亡;同时BAX、Cleaved-Caspase-3和γ-H2AX表达升高,BCL-2、p-ATM、p-CHK2和RAD21表达降低。KU60019处理进一步促进DNA损伤累积和细胞凋亡,并降低细胞活力。结论:RNF8可能通过ATM/CHK2轴促进DNA损伤应答并降低EC细胞对CDDP的敏感性;敲低RNF8可增加DNA损伤累积并增强CDDP敏感性。
2.Xianglian Huazhuo Prescription Regulates GP73/PERK/ATF4 Signaling Pathway to Influence Endoplasmic Reticulum Stress and Ameliorate Chronic Atrophic Gastritis
Pengli DU ; Yuxi GUO ; Yican WANG ; Ziqi JIN ; Xin KANG ; Xuemei JIA ; Weichao XU ; Yanru CAI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):19-28
ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis (CAG) through regulating the Golgi protein 73 (GP73)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway and modulating endoplasmic reticulum stress (ERS). MethodA mouse model of CAG was induced by multiple factors, including ranitidine, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and irregular feeding. The CAG mice were randomized into five groups: model, Morodan (2.0 g·kg-1), and high-dose, medium-dose, and low-dose (7.6, 3.8, 1.9 g·kg-1, respectively) Xianglian Huazhuo prescription, with 10 mice in each group. At the same time, 10 mice in normal group were set up. The mice in the Morodan group and the high-dose, medium-dose, and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage, and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration, the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (G-17), and GP73 were determined by enzyme-linked immunosorbent assay (ELISA). The pepsinogen ratio (PGR, PGⅠ/PGⅡ) was calculated. The protein levels of GP73, PERK, phosphorylated (p)-PERK, glucose-regulated protein 78 (GRP78), ATF4, CCAAT enhancer-binding protein homologous protein (CHOP), cysteinyl aspartate-specific protease-12 (Caspase-12), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence (IF) assay, and the location of Bcl-2 and Bax by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands, declined serum levels of PGI, PGR, G-17, and GP73 (P<0.01). downregulated protein levels of GP73, p-PERK, ATF4, GRP78, CHOP, Caspase-12, and Bax in the gastric tissue, and upregulated protein level of Bcl-2 (P<0.01). Compared with the model group, the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds, alleviated pathological damage, swelling endoplasmic reticulum, elevated serum levels of PGI, G-17, and GP73 (P<0.05, P<0.01), and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue (P<0.05, P<0.01). The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR (P<0.05, P<0.01) and upregulated protein levels of GP73, p-PERK, ATF4, GRP78, and CHOP in the gastric tissue (P<0.05, P<0.01). ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa, thereby demonstrating a protective effect against CAG in mice.
3.Xianglian Huazhuo Prescription Regulates GP73/PERK/ATF4 Signaling Pathway to Influence Endoplasmic Reticulum Stress and Ameliorate Chronic Atrophic Gastritis
Pengli DU ; Yuxi GUO ; Yican WANG ; Ziqi JIN ; Xin KANG ; Xuemei JIA ; Weichao XU ; Yanru CAI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):19-28
ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis (CAG) through regulating the Golgi protein 73 (GP73)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway and modulating endoplasmic reticulum stress (ERS). MethodA mouse model of CAG was induced by multiple factors, including ranitidine, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and irregular feeding. The CAG mice were randomized into five groups: model, Morodan (2.0 g·kg-1), and high-dose, medium-dose, and low-dose (7.6, 3.8, 1.9 g·kg-1, respectively) Xianglian Huazhuo prescription, with 10 mice in each group. At the same time, 10 mice in normal group were set up. The mice in the Morodan group and the high-dose, medium-dose, and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage, and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration, the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (G-17), and GP73 were determined by enzyme-linked immunosorbent assay (ELISA). The pepsinogen ratio (PGR, PGⅠ/PGⅡ) was calculated. The protein levels of GP73, PERK, phosphorylated (p)-PERK, glucose-regulated protein 78 (GRP78), ATF4, CCAAT enhancer-binding protein homologous protein (CHOP), cysteinyl aspartate-specific protease-12 (Caspase-12), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence (IF) assay, and the location of Bcl-2 and Bax by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands, declined serum levels of PGI, PGR, G-17, and GP73 (P<0.01). downregulated protein levels of GP73, p-PERK, ATF4, GRP78, CHOP, Caspase-12, and Bax in the gastric tissue, and upregulated protein level of Bcl-2 (P<0.01). Compared with the model group, the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds, alleviated pathological damage, swelling endoplasmic reticulum, elevated serum levels of PGI, G-17, and GP73 (P<0.05, P<0.01), and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue (P<0.05, P<0.01). The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR (P<0.05, P<0.01) and upregulated protein levels of GP73, p-PERK, ATF4, GRP78, and CHOP in the gastric tissue (P<0.05, P<0.01). ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa, thereby demonstrating a protective effect against CAG in mice.
4.Expert consensus on visualized tele-round and quality control management based on the improvement of clinical practice ability
Wanhong YIN ; Xiaoting WANG ; Ran ZHOU ; Dawei LIU ; Yan KANG ; Yaoqing TANG ; Xiaochun MA ; Jianguo LI ; Zhenjie HU ; Haitao ZHANG ; Wei HE ; Lixia LIU ; Wenjin CHEN ; Ran ZHU ; Jun WU ; Hongmin ZHANG ; Lina ZHANG ; Wenzhao CHAI ; Shihong ZHU ; Wangbin XU ; Rongqing SUN ; Xiangyou YU ; Tianjiao SONG ; Ying ZHU ; Hong REN ; Ai SHANMU ; Qing ZHANG ; Wei FANG ; Xiuling SHANG ; Liwen LYU ; Shuhan CAI ; Xin DING ; Heng ZHANG ; Guang FENG ; Lipeng ZHANG ; Bo HU ; Dong ZHANG ; Weidong WU ; Feng SHEN ; Xiaojun YANG ; Zhenguo ZENG ; Qibing HUANG ; Xueying ZENG ; Tongjuan ZOU ; Milin PENG ; Yulong YAO ; Mingming CHEN ; Hui LIAN ; Jingmei WANG ; Yong LI ; Feng QU ; Gang YE ; Rongli YANG ; Xiukai CHEN ; Suwei LI ; Juxiang WANG ; Yangong CHAO
Chinese Journal of Internal Medicine 2025;64(2):101-109
Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.
5.Kangliu Zengxiao Jiandu Prescription in Enhancing Cisplatin Chemotherapy for Lung Cancer:A Network Pharmacology and Experimental Study
Wenjie WANG ; Xin LIU ; Jia YANG ; Xiaojie FU ; Xinhong WU ; Yuejiao CAI ; Zhenye XU ; Zhongqi WANG ; Haibin DENG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):38-45
Objective To explore the mechanism of Kangliu Zengxiao Jiandu Prescription(KLJD)in enhancing the efficacy of cisplatin chemotherapy in non-small cell lung cancer(NSCLC)through network pharmacology and in vivo/in vitro experiments.Methods Components of KLJD were screened via the TCMSP database to identify active components and potential targets.Lung cancer-related genes were obtained from the GeneCards and OMIM databases.GO and KEGG pathway enrichment analysis was performed on drug-disease intersection targets using the Metascape database;molecular docking was performed between core target proteins and main active components.A Lewis lung cancer mouse model was established,and intervened with KLJD and cisplatin.Organ indexes and tumor inhibition rate were counted,and Western blot and RT-PCR were used to detect the expressions of key pathway target proteins and mRNA;A549 and H1299 cells were intervened with KLJD,and Western blot was used to detect key target protein expressions.Results Network pharmacology identified 74 active components and 20 key targets of KLJD,primarily involved in biological processes such as cell proliferation and inflammatory response,and pathways in cancer and PI3K/AKT signaling pathway;molecular docking revealed stable binding between EGFR and major compounds.Animal experiments demonstrated that,compared with the model group,the KLJD group showed significantly higher tumor inhibition rate(P<0.01)and downregulation of EGFR,AKT and PI3K protein and mRNA expression in tumor tissues(P<0.05).Compared with the cisplatin group,the combination group exhibited significantly enhanced tumor inhibition rate(P<0.01),elevated thymic and splenic indices(P<0.01),and decreased EGFR,PI3K and AKT protein and mRNA expressions(P<0.01).Cell experiments showed that KLJD concentration-dependently inhibited A549 and H1299 cell proliferation(IC50:14.72 mg/mL and 14.68 mg/mL,respectively).Combined with cisplatin,KLJD synergistically down-regulated EGFR PI3K and AKT protein expressions(P<0.01).Conclusion KLJD effectively enhances cisplatin's chemotherapeutic efficacy in NSCLC by inhibiting the EGFR/PI3K/AKT pathway while improving immune organ function.Its mechanism likely involves multi-target regulation,including suppression of tumor proliferation,promotion of apoptosis,and modulation of the immune microenvironment.
6.Epidemiological characteristics analysis of monkey injury cases caused in Qianlingshan Park, Guiyang City, Guizhou Province
Cai YANG ; Yun CHEN ; Yu CHANG ; Li LI ; Qiying PAN ; Tingting LU ; Dan CHEN ; Chengxian HE ; Mei HUANG ; Liusong YANG ; Tingqin RAO ; Su GUO ; Chong LUO ; Lihong ZHOU ; Xin MU ; Li LIU ; Yayu YANG ; Yuandong HU
Chinese Journal of Preventive Medicine 2025;59(10):1685-1690
Objective:To analyze the epidemiological characteristics of cases involving monkey injuries at medical institutions surrounding Qianlingshan Park in Guiyang City, and to provide a reference basis for preventive measures to reduce monkey injuries and standardized post-exposure treatment.Methods:A retrospective cross-sectional study was conducted, collecting 1 900 cases of monkey-induced injuries in Qianlingshan Park treated at the outpatient clinic of Guizhou Provincial Center for Disease Control and Prevention and the Department of Surgery at Qianling Hospital, Guiyang City, from 2021 to 2024. Statistical analysis was performed using Pearson′s chi-square test.Results:Total of 1 900 cases of monkey-related injuries in Qianlingshan Park were collected from 2021 to 2024. The exposure time distribution exhibited significant seasonality, with 48.58% of cases occurring during July and August, totaling 923 cases, indicating a peak in the summer. There were 774 male patients and 1 126 female patients, with a ratio of 1∶1.45.and significant differences were observed between different age groups and genders (χ2=195.00, P<0.001), with the highest number of cases occurring in the 0-9 and 20-29 age groups, accounting for 22.05%(419 cases) and 21.79%(414 cases), respectively. The upper limbs were the most common injury site, accounting for 50.84% of the total cases(966 cases in total), with significant differences between gender and injury location (χ2=22.00, P<0.001), Among females, the proportion of injuries to the upper and lower limbs (30.11% and 16.47%, respectively) was higher than that among males (20.74% and 8.63%, respectively). The majority of injuries were classified as Grade Ⅲ, making up 57.38% of cases(1 069 cases in total). Self-treatment after exposure was the most common approach(60.44%), with significant differences observed between wound severity and treatment method (χ2=6.90, P=0.032), Patients with Grade Ⅱ and Grade Ⅲ wounds were more likely to choose self-management (26.84% and 33.23%, respectively) than outpatient management (15.14% and 24.15%). Approximately 98.05% (1 863 cases) of monkey-injured patients had received rabies vaccinations. Conclusions:This study analyzes monkey-related injuries in Qianlingshan Park from 2021 to 2024, clarifying the temporal distribution of injuries, demographic characteristics, injury sites, and treatment methods. The findings provide references for optimizing human-monkey conflict management and the prevention and control of zoonotic diseases in urban ecological parks.
7.Effects of Yiqi Juanbi Formula on chondrocyte pyroptosis in collagen-induced arthritic rats via NF-κB/NLRP3/Caspase-1 signaling pathway
Xin-yu CUI ; Hao-lin LI ; Wei-qing LI ; Hui-qin KANG ; Wei-gang CHENG ; Pei-xin HE ; Cai-hong YANG ; Ping CHEN ; Hai-dong WANG
Chinese Traditional Patent Medicine 2025;47(9):2880-2887
AIM To investigate the effects of Yiqi Juanbi Formula on chondrocyte pyroptosis in rat models of collagen-induced arthritis(CIA).METHODS Fifty rats were subcutaneously injected at the tail base with an emulsion containing equal volumes of bovine type Ⅱ collagen and incomplete Freund's adjuvant(IFA)to establish the CIA models.These rats were then randomly assigned to the model group,the methotrexate group(0.35 mg/kg),and the low-dose,medium-dose,and high-dose Yiqi Juanbi Formula groups(9.4,18.7,37.4 g/kg),in contrast to the ten intact rats serving in the normal control group.Following four weeks of intragastric administration,the rats had their general conditions observed;their joint swelling and arthritis indices measured;their ankle joint pathology assessed by HE staining;their serum levels of IL-1β,IL-18 and TNF-ɑ detected by ELISA;their mRNA expressions of NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ in ankle cartilage quantified by RT-qPCR;their protein expressions of NF-κB,NLRP3 and Caspase-1 in ankle cartilage analyzed by Western blot;and their NLRP3 and GSDMD positive expressions in ankle cartilage examined by immunohistochemistry.RESULTS Compared to the control group,the model group showed significantly increased joint swelling and arthritis indices(P<0.01);elevated serum levels of IL-1 β,IL-18 and TNF-ɑ(P<0.01);pathological changes including cartilage surface defects,reduced cell count,altered cellular morphology,irregular cell arrangement,and significant inflammatory cell infiltration in synovial tissue;upregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P<0.01)and increased protein expressions of NF-κB,NLRP3 and Caspase-1(P<0.01)in ankle cartilage;enhanced positive expressions of NLRP3 and GSDMD in ankle cartilage(P<0.01).Compared to the model group,the groups intervened with methotrexate or medium-or high-dose Yiqi Juanbi Formula exhibited reduced joint swelling and arthritis indices(P<0.01);alleviated pathological damage in ankle joints;decreased serum levels of IL-1β,IL-18 and TNF-ɑ(P<0.01);downregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P<0.05,P<0.01),and reduced protein expressions of NF-κB,NLRP3 and Caspase-1(P<0.05,P<0.01)in ankle cartilage;and diminished positive expressions of NLRP3 and GSDMD in ankle cartilage(P<0.01).CONCLUSION Yiqi Juanbi Formula alleviates inflammation in CIA rats,potentially by inhibiting the activation of the NF-κB/NLRP3/Caspase-1 signaling pathway,thereby suppressing chondrocyte pyroptosis.
8.Risk factors and their diagnostic efficacy of perioperative lower limb deep venous thrombosis in polytrauma patients with predominant severe limb trauma
Xiao YANG ; Jimin CAI ; Xin GE ; Yan WANG ; Weiya ZHOU ; Yongjun RUI
Chinese Journal of Trauma 2025;41(8):764-772
Objective:To investigate the risk factors and their diagnostic efficacy of perioperative lower limb deep vein thrombosis (DVT) in polytrauma patients with predominant severe limb trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 155 polytrauma patients with predominant severe trauma who were admitted to Wuxi Ninth People′s Hospital from January 2021 to December 2024, including 64 males and 91 females, aged 13-95 years [(52.1±16.9)years]. Abbreviated injury scale (AIS) was 5-15 points [(7.4±2.1)points] and injury severity score (ISS) was 17-59 points [(21.3±6.5)points]. Based on the occurrence of DVT in the perioperative period, the patients were divided into preoperative DVT group with 17 patients (11.0%) and non-preoperative DVT group with 138 patients (89.0%) as well as postoperative DVT group with 24 patients (15.5%) and non-postoperative DVT group with 131 patients (84.5%). Basic clinical data were collected, including gender, age, body mass index (BMI), underlying diseases (hypertension, diabetes mellitus), hemoglobin level (Hb), platelet count (PLT), D-dimer, ISS, trauma site [cranial and brain trauma, thoracic and abdominal trauma, upper limb trauma, lower limb trauma (femoral fracture, patellar fracture, tibial or fibular fracture, foot fracture, vascular injury), and pelvic fracture], preoperative waiting time for surgery, surgical site (pelvis and lower limb, other areas), surgical protocols (pelvic and lower limb internal fixation, external fixation of lower limb, lower limb amputation), operation duration less or more than 2 hours, amount of intraoperative blood loss, intraoperative blood transfusion requirement, venous thromboembolism (VTE) prophylaxis (pharmacological and mechanical modalities) and length of hospital stay. Univariate analysis and multivariate binary Logistic regression analysis were conducted to investigate the correlation between the aforementioned indicators and incidence of perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma and determine the independent risk factors. Receiver operating characteristic (ROC) curve and area under the curve (AUC) of the relevant risk factors were analyzed to evaluate and compare the diagnostic efficacy of the risk factors for perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma.Results:Univariate analysis results showed that age, history of hypertension, D-dimer, thoracic and abdominal trauma, pelvic fracture, preoperative waiting time for surgery, and length of hospital stay were significantly correlated with preoperative of DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), pelvic fracture ( OR=5.03, 95% CI 1.09, 23.20, P<0.05), preoperative waiting time for surgery ( OR=1.10, 95% CI 1.00, 1.22, P<0.05) and length of hospital stay ( OR=0.89,95% CI 0.81,0.98, P<0.05) were highly correlated with preoperative DVT of the lower limbs in the patients ( P<0.05). Univariate analysis results showed that age, D-dimer, ISS, foot fracture, and length of hospital stay were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.01, 1.08, P<0.01), D-dimer ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), ISS ( OR=1.09, 95% CI 1.01, 1.17, P<0.05), and foot fracture ( OR=3.51 , 95% CI 1.25 , 9.87 , P<0.05) were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of the ROC curve analysis indicated that preoperative waiting time for surgery (AUC=0.83, 95% CI 0.75, 0.91) had the highest diagnostic efficacy for preoperative DVT of the lower limbs in the patients, with the diagnostic efficacies of pelvic fracture (AUC=0.75, 95% CI 0.65, 0.85) and age (AUC=0.70, 95% CI 0.59, 0.82) decreasing successively. For postoperative DVT of the lower limbs in the patients, D-dimer (AUC=0.71, 95% CI 0.61, 0.81) exhibited the highest diagnostic efficacy, followed by age (AUC=0.70, 95% CI 0.59, 0.81), ISS (AUC=0.64, 95% CI 0.51, 0.76) and foot fracture (AUC=0.62, 95% CI 0.49, 0.74), with diagnostic efficacy decreased successively. Conclusions:For polytrauma patients with predominant severe limb trauma, age, pelvic fracture and preoperative waiting time for surgery are independent risk factors for preoperative DVT, while age, D-dimer, ISS and foot fracture are independent risk factors for postoperative DVT. Additionally, preoperative waiting time for surgery has the best diagnostic efficacy for preoperative DVT, followed by pelvic fracture and age. D-dimer has the best diagnostic efficacy for postoperative DVT, followed by age, ISS and foot fracture.
9.Therapeutic efficacy and mechanism of artesunate for mouse model of polycystic ovary syndrome
Xueling WANG ; Peiling ZHONG ; Zhipeng ZHAO ; Fei CHEN ; Xin LIU ; Sijia LIU ; Lie YUAN ; Lu FANG ; Qianyi YAO ; Xiong YANG ; Chao LIU ; Jiakun CHENG ; Yongqing CAI ; Xiaoli LI ; Weihong LI
Journal of Army Medical University 2025;47(3):193-204
Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P<0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P<0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P<0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P<0.05),and reduced HOMA-IR,TC and TG levels(P<0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P<0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.
10.Clinical Characteristics and Prognostic Analysis of Newly Diagnosed Acute Myeloid Leukemia Patients with NRAS and KRAS Gene Mutations.
Zhang-Yu YU ; Bo CAI ; Yi WANG ; Yang-Yang LEI ; Bing-Xia LI ; Yu-Fang LI ; Yan-Ping SHI ; Jia-Xin CHEN ; Shu-Hong LIU ; Chang-Lin YU ; Mei GUO
Journal of Experimental Hematology 2025;33(3):682-690
OBJECTIVE:
To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis.
METHODS:
The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed.
RESULTS:
Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037).
CONCLUSION
In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans
;
Leukemia, Myeloid, Acute/diagnosis*
;
Mutation
;
Prognosis
;
Proto-Oncogene Proteins p21(ras)/genetics*
;
GTP Phosphohydrolases/genetics*
;
Retrospective Studies
;
Membrane Proteins/genetics*
;
Female
;
Male
;
Middle Aged
;
Adult
;
Aged

Result Analysis
Print
Save
E-mail