1.Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6.
Yifeng SHI ; Sunlong LI ; Shuhao ZHANG ; Caiyu YU ; Jiansen MIAO ; Shu YANG ; Yan CHEN ; Yuxuan ZHU ; Xiaoxiao HUANG ; Chencheng ZHOU ; Hongwei OUYANG ; Xiaolei ZHANG ; Xiangyang WANG
Journal of Pharmaceutical Analysis 2025;15(5):101092-101092
Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.
2.Epidemiological and clinical characteristics of infectious diseases of the central nervous system: a national multicenter cross-sectional study
Jiahua ZHAO ; Jun GUO ; Xiaoyan ZHANG ; Wei LI ; Wen HUANG ; Xiaofei ZHU ; Jianxin YE ; Xiaoling WANG ; Juan DU ; Min LI ; Juan DU ; Zegang YIN ; Jinli FENG ; Chaohui WANG ; Xiaowei MAO ; Jing CHEN ; Xiaowei XING ; Yuheng SHAN ; Yuying CEN ; Xiaojiao XU ; Ruishu TAN ; Jiatang ZHANG
Chinese Journal of Neurology 2025;58(5):485-493
Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.
3.Advances in short stature induced by ACAN gene variation in children
Yuying ZHU ; Bo BAN ; Qianqian ZHAO ; Mei ZHANG
International Journal of Pediatrics 2025;52(2):107-111
Bone growth and development is a major determinant of height.Height development in children is the result of the proliferation and endochondral ossification of growth plate chondrocytes located at the ends of long bones and vertebrae.Short stature,also known as dwarfism,means that a child's height is less than two standard deviations of the normal interval for children of the same race,region,and sex,or below the 3rd percentile of the normal child growth curve,which is a common problem in pediatric endocrinology.A variety of physiological regulatory pathways involving growth plate and long bone development have been reported,and related gene defects may be the key mechanisms leading to growth disorders and abnormal skeletal development in children.The ACAN gene,which is associated with osteochondral dysplasia,has garnered widespread attention from numerous scholars in recent years.This article reviews the genetic etiology,clinical phenotype,treatment and management of short stature caused by ACAN gene mutation in children.
4.Mechanism of spasmolytic polypeptide-expressing metaplasia in gastric mucosa induced by Helicobacter pylori infection
Hainuo WANG ; Yufan LI ; Yuying WANG ; Qianying SHEN ; Jinxia ZHU ; Lifei ZHENG
Basic & Clinical Medicine 2025;45(1):130-134
Helicobacter pylori(H.pylori)infection triggers gastric mucosal inflammatory responses and spasmolytic polypeptide-expressing metaplasia(SPEM).These pathological conditions can escalate the severity of chronic gas-tritis,gastric ulcers and even cause gastric cancer.SPEM is frequently viewed as an early sign of gastric mucosal injury and the onset of carcinogenesis.A comprehensive analysis of the genesis and molecular regulation of SPEM cells in the context of H.pylori infection further has enlightened the pathogenesis of gastric mucosal diseases and provide new ideas and targets for diagnosing and treatment of H.pylori-related gastric mucosal diseases.This paper reviews a variety of molecular biomarkers associated with SPEM,encompassing TFF2,CD44v9,and AQP5,and delineates their pivotal regulatory functions in H.pylori infection and SPEM.This paper also reviews the origination of SPEM cells and pertinent molecular regulatory mechanisms.
5.Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6
Yifeng SHI ; Sunlong LI ; Shuhao ZHANG ; Caiyu YU ; Jiansen MIAO ; Shu YANG ; Yan CHEN ; Yuxuan ZHU ; Xiaoxiao HUANG ; Chencheng ZHOU ; Hongwei OUYANG ; Xiaolei ZHANG ; Xiangyang WANG
Journal of Pharmaceutical Analysis 2025;15(5):1033-1047
Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.
6.Safety analysis of Yttrium-90 resin microsphere selective internal radiation therapy on malignant liver tumors
Jia CAI ; Shiwei TANG ; Rongli LI ; Mingxin KONG ; Hongyan DING ; Xiaofeng YUAN ; Yuying HU ; Ruimei LIU ; Xiaoyan ZHU ; Wenjun LI ; Haibin ZHANG ; Guanwu WANG
Chinese Journal of Clinical Medicine 2025;32(1):24-29
Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (90Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent 90Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of 90Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (99mTc-MAA) perfusion test and received the 90Y-SIRT; one patient received 90Y-SIRT after the second 99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of 90Y-SIRT for treating malignant liver tumors are mild, indicating good safety.
7.Correlation of SERPINC1 and SERPINE1 gene polymorphisms with venous thromboembolism in patients with malignant tumors
Zihui ZHU ; Man HE ; Xueping HOU ; Yuying WANG ; Jianan LIN ; Lizhong WANG ; Weihua JIANG
Cancer Research and Clinic 2025;37(1):14-18
Objective:To investigate the correlation of SERPINC1 and SERPINE1 gene polymorphisms with venous thromboembolism (VTE) in patients with malignant tumors.Methods:A retrospective case-control study was conducted. A total of 227 patients with malignant tumors in the Cancer Hospital Affiliated to Xinjiang Medical University from November 2023 to February 2024 were selected, of which 47 cases developed VTE (VTE group) and 180 cases did not develop VTE (non-VTE group). The patients' venous blood was collected, and D-dimer level was analyzed by using fully automatic coagulation analyzer; fluorescence staining was performed by using digoxin staining solution, and SERPINC1 rs2227589 locus and SERPINE1 rs1799762 locus were used as candidate genes, and fluorescence sequencing was performed by using multichannel fluorescence quantitative analyzer, and the frequencies of C, T, 4G and 5G genes were calculated.Results:There were no statistically significant differences in the age, gender, smoking, alcohol consumption, anticoagulant use, diabetes mellitus, hypertension, coronary artery disease, surgical treatment, intravenous cannulae, radiotherapy, chemotherapy, and targeted therapy between the 2 groups (all P > 0.05). The level of D-dimer in the VTE group was higher than that in the non-VTE group [(8.7±6.9) kg/m 2vs. (2.8±1.0) kg/m 2], and the difference was statistically significant ( t = 5.15, P < 0.001). The differences in C and T genotypes and gene frequencies at the SERPINC1 rs2227589 locus between the VTE group and the non-VTE group were not statistically significant (all P > 0.05). The differences in 4G and 5G genotypes and gene frequencies at the SERPINE1 rs1799762 locus between the VTE group and the non-VTE group were statistically significant (all P < 0.05), and 4G allele frequency in the VTE group was higher than that in the non-VTE group (52.13% vs. 39.72%), and the difference was statistically significant ( χ2 = 4.70, P = 0.030). Conclusions:The elevated expression of 4G allele at the SERPINE1 rs1799762 locus in patients with malignant tumors is associated with development of VTE.
8.Summary of the best evidence for preoperative pre-rehabilitation in elderly patients with hip fracture
Weining LI ; Hailing DI ; Dan YU ; Shuhan LI ; Yuying LI ; Jiaxuan ZHU ; Xiuguo ZHANG
Modern Clinical Nursing 2025;24(5):73-82
Objective To search,evaluate and summarise the best evidence on pre-rehabilitation before surgery for elderly patients with hip fracture so as to provide an evidence-based basis for further standardisation in clinical practice.Methods Based on the"6S Pyramid"evidence model,desktop searches were conducted across databases and websites including Medlive,BMJ Best Practice,UpToDate,the World Health Organization,the Guidelines International Network(GIN),British National Institute for Health and Care Excellence(NICE),American National Guideline Clearinghouse(NGC),Canadian Medical Association:Clinical Practice Guidelines Infobase(CMA),Scottish Intercollegiate Guidelines Network(SIGN),the Registered Nurses'Association of Ontario(RNAO),American College of Sports Medicine(ACSM),American Academy of Orthopaedic Surgeons(AAOS),European Society for Clinical Nutrition and Metabolism(ESPEN),American Society for Parenteral and Enteral Nutrition(ASPEN),the Enhanced Recovery After Surgery Society(ERASS),Cochrane Library,Joanna Briggs Institute,PubMed,CINAHL,Web of Science,Embase,Scopus,Science Direct,CNKI,Wanfang Data,Vip,and SinoMed.The research targeted evidence on pre-rehabilitation in elderly patients with hip-fracture before surgery,encompassing clinical decisions,guidelines,evidence summaries,best practices,expert consensus,systematic reviews and randomized controlled trials(RCTs).The search items spanned from the inception of database to 31st December,2023.Two researchers trained with evidence-based knowledge evaluated the quality of the included literature and extracted and summarised the evidence.Results A total of 14 documents were included,consisting of 2 clinical decisions,4 guidelines,1 best practice,4 expert consensus and 3 systematic reviews.Evidence was summarised into 7 domains from 25 pieces of evidence:multidisciplinary management,preoperative assessment,preoperative health education,multi-modal analgesia,nutritional management,exercise intervention and assessment and prevention of complication risks.Conclusion The best evidence summarised in this study provides a basis for pre-rehabilitation in elderly patients with hip fracture before surgery.Nurses should adapt the findings to specific contexts,standardise the preoperative rehabilitation procedures,and improve clinical outcomes for the patients.
9.The incidence and influencing factors of axillary reticular syndrome after breast cancer surgery:a systematic review
Yuying SUN ; Yeting WANG ; Xiaojuan QIAO ; Yu XU ; Bei YANG ; Qiuyue SONG ; Yaofeng ZHU
Modern Clinical Nursing 2025;24(2):31-39
Objective To systematically evaluate the incidence and influencing factors of axillary web syndrome(AWS)in postoperative breast cancer patients,and to provide evidence for reducing the incidence of axillary web syndrome.Methods A computer search was performed in China National Knowledge Infrastructure(CNKI),VIP,Wanfang,SinoMed,PubMed,Medline,Scopus,The Cochrane Library,Web of Science,Embase,searched for articles on AWS influencing factors of breast cancer published from the establishment of the database to January 6th,2025.The articles were screened according to the inclusion and exclusion criteria.Revman5.4 and Stata17.0 were used for systematic review.Results Fifteen studies involving 3979 breast cancer patients and 1 156 patients with AWS were included.The results of the Meta-analysis showed that there was significant statistical heterogeneity among the included studies(I2=97.0%,P<0.0001).Using the random effects model,the incidence of AWS was 32.2%[95%CI(0.24,0.40),P<0.0001].The influencing factors for AWS after breast cancer surgery are age,body mass index(BMI),total mastectomy,lymph node metastasis,and neoadjuvant chemotherapy.NAC),axillary lymph node dissection(ALND),and the number of harvested axillary lymph nodes.Conclusion The incidence of AWS after breast cancer surgery was high.Clinicians should give early nursing to the influencing factors,reduce the incidence of AWS and improve patients'quality of life after surgery.
10.The incidence and influencing factors of axillary reticular syndrome after breast cancer surgery:a systematic review
Yuying SUN ; Yeting WANG ; Xiaojuan QIAO ; Yu XU ; Bei YANG ; Qiuyue SONG ; Yaofeng ZHU
Modern Clinical Nursing 2025;24(2):31-39
Objective To systematically evaluate the incidence and influencing factors of axillary web syndrome(AWS)in postoperative breast cancer patients,and to provide evidence for reducing the incidence of axillary web syndrome.Methods A computer search was performed in China National Knowledge Infrastructure(CNKI),VIP,Wanfang,SinoMed,PubMed,Medline,Scopus,The Cochrane Library,Web of Science,Embase,searched for articles on AWS influencing factors of breast cancer published from the establishment of the database to January 6th,2025.The articles were screened according to the inclusion and exclusion criteria.Revman5.4 and Stata17.0 were used for systematic review.Results Fifteen studies involving 3979 breast cancer patients and 1 156 patients with AWS were included.The results of the Meta-analysis showed that there was significant statistical heterogeneity among the included studies(I2=97.0%,P<0.0001).Using the random effects model,the incidence of AWS was 32.2%[95%CI(0.24,0.40),P<0.0001].The influencing factors for AWS after breast cancer surgery are age,body mass index(BMI),total mastectomy,lymph node metastasis,and neoadjuvant chemotherapy.NAC),axillary lymph node dissection(ALND),and the number of harvested axillary lymph nodes.Conclusion The incidence of AWS after breast cancer surgery was high.Clinicians should give early nursing to the influencing factors,reduce the incidence of AWS and improve patients'quality of life after surgery.

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