1.Mechanism of action of the fat mass and obesity-associated gene in the development and progression of metabolic dysfunction-associated fatty liver disease and related targeted therapies
Zhaoquan PAN ; Xudong LIU ; Weiqiang TAN ; Xiaoke RAN ; Yuan YUAN ; Xinfeng LOU
Journal of Clinical Hepatology 2025;41(6):1167-1173
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic liver disease with the pathological feature of lipid accumulation in the liver, and it is closely associated with liver metabolic disorders. The latest research has shown that the pathogenesis of MAFLD is associated with the abnormal expression of specific genes, especially the fat mass and obesity-associated (FTO) gene. The abnormal activity of the FTO gene may lead to an imbalance in liver lipid metabolism, which manifests as the increase in fatty acid synthesis and the reduction in fatty acid oxidation, thereby promoting liver fat deposition and inflammatory response. Therefore, regulating the expression or activity of the FTO gene is considered one of the potential strategies for the treatment of MAFLD. At present, drug research targeting the function of the FTO gene has achieved preliminary results, and inhibition of the activity of the FTO gene can help to regulate liver lipid metabolism and alleviate liver inflammatory injury. This article reviews the mechanism of action of the FTO gene in the development and progression of MAFLD, summarizes the advances in drug research on the FTO gene and related metabolic pathways in recent years, and analyzes their application prospect in research and treatment.
2. Establishment and biological characterization of drug-resistant cells and identification of multidrug resistance in small-cell lung cancer
Yong-Qing HAN ; Zheng-Yuan WANG ; Xiu-Fen DAI ; Zi-Ran WANG ; Jing LI ; Xin QI ; Jing LI
Chinese Pharmacological Bulletin 2024;40(2):279-284
Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q
3.Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors
Yue LI ; Guo-qing LI ; Yuan-yuan TIAN ; Cong-ran LI ; Xin-yi YANG ; Kai-hu YAO ; Xue-fu YOU
Acta Pharmaceutica Sinica 2024;59(2):279-288
The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non
4.Research on the application of evaluation and warning system based on Shewhart control chart in medical device related pressure injury
Litian LIU ; Feifei ZHANG ; Zheng YUAN ; Xiaolin ZHENG ; Ran WANG ; Lei ZHANG ; Yingxiao LI ; Xiaojiao WU
China Medical Equipment 2024;21(1):205-208
Objective:To explore the effectiveness of the Shewhart control chart-based assessment and early warning system in prevention of medical device-related pressure injury(MDRPI).Methods:152 critically ill patients admitted to Hebei Central Hospital from January 2020 to December 2021 were selected and divided into a control group and an observation group based on different methods of assessing MDRPI risk,with 76 cases in each group.The control group adopted the Braden scale to assess the risk of MDRPI.The observation group adopted a safety early warning system based on Shewhart control charts to assess the risk of MDRPI in patients.Nursing measures were undertaken according to MDRPI risk grade in both groups.The occurrence of adverse events of MDRPI,nursing safety quality and nursing comprehensive quality were compared between the two groups.Results:The incidence rate of head,neck and face adverse events of MDRPI and the total incidence of adverse events of MDRPI of the patients in the observation group were lower than those in the control group(x2=4.802,5.758,P<0.05).The safety quality and comprehensive quality of nursing of 20 nurses in the observation group were higher than those in the control group(t=6.654,7.172,P<0.05).Conclusion:The application of assessment and early warning system based on Shewhart control chart in clinical nursing management can effectively reduce the incidence of MDRPI adverse events and improve the quality of nursing safety and comprehensive nursing.
5.Mid to long-term clinical outcomes improvement through dual antiplatelet therapy after coronary artery bypass grafting: Interpretation of DACAB-FE trial
Jianyu QU ; Si CHEN ; Zhijian WANG ; Kang ZHOU ; Yuan ZHAO ; Ran DONG ; Dongmei SHI ; Nianguo DONG ; Zhe ZHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(08):1096-1100
Coronary artery bypass grafting (CABG) is one of the most effective revascularization treatments for coronary heart disease. Secondary prevention strategies, which rely on antiplatelet and lipid-lowering drugs, are crucial after CABG to ensure the durability of revascularization treatment effects and prevent adverse cardiovascular and cerebrovascular events in the medium to long term. Previous research conducted by Professor Zhao Qiang's team from Ruijin Hospital of Shanghai Jiao Tong University, known as the DACAB study, indicated that dual antiplatelet therapy (DAPT, specifically ticagrelor+aspirin) after CABG can enhance venous graft patency. However, it remains uncertain whether DAPT can further improve the medium to long-term clinical outcomes of CABG patients. Recently, the team reported the medium to long-term follow-up results of the DACAB study, termed the DACAB-FE study, finding that DAPT administered after CABG can reduce the incidence of major cardiovascular events over five years and improve patients' medium to long-term clinical outcomes. This article will interpret the methodological highlights and significant clinical implications of the DACAB-FE study.
6.Role and mechanism of CXCL5/CXCR2/VEGF pathway in angiogenesis of HBV-related hepatocellular carcinoma
RAN Xiaoke1 ; LIU Xudong2 ; TAN Weiqiang1 ; PANG Huazhen2 ; YUAN Yuan1 ; LOU Xinfeng1 ; WU Tiexiong1 ; PAN Zhaoquan1
Chinese Journal of Cancer Biotherapy 2024;31(11):1123-1130
[摘 要] 目的:探讨CXCL5/CXCR2/VEGF通路在HBV相关肝癌血管生成过程中的作用及其机制。方法:收集2022年10月至2022年12月间在广西中医药大学附属瑞康医院入院的10例HBV-DNA阳性患者的外周血标本[其中5例肝细胞癌(HCC)和5例肝硬化(LC)],用高通量RNA测序技术检测并筛选差异表达mRNA,用GO富集和KEGG通路分析这些差异表达基因的生物学功能和相关信号通路。常规培养HCC细胞HepG2,用转染试剂将C-X-C基序趋化因子配体5(CXCL5)过表达质粒和对照质粒转染至HepG2细胞中,分为对照组,空载组,250 ng/mL和520 ng/mL CXCL5过表达质粒组。用CCK-8法、ELISA、血管生成实验、qPCR法、WB法和免疫荧光染色技术分别检测过表达CXCL5对HepG2细胞增殖能力、VEGF分泌、成管能力、CXCL5、CXCR2、VEGF mRNA及其蛋白表达,以及VEGF表达的影响。结果:RNA测序结果显示,HCC和LC患者外周血中 mRNA表达存在显著差异。GO富集分析发现,这些差异mRNA的相关基因主要参与细胞发育过程的调控、G蛋白偶联受体活性、细胞外区域的组成和信号受体结合。KEGG通路分析发现,这些异表达基因可能参与细胞因子与受体相互作用通路、cAMP信号通路等与癌症作用机制相关的通路、神经活性配体与受体相关作用的通路、钙相关信号通路。过表达CXCL5可明显促进HepG2细胞的增殖能力(P < 0.05)、VEGF的分泌(P < 0.05)、人脐静脉内皮细胞(HUVEC)的成管能力(P < 0.05)、CXCL5、CXCR2和VEGF mRNA和蛋白的表达(P < 0.05或P < 0.01),以及增强HepG2细胞中VEGF的表达。结论:CXCL5可能通过CXCL5/CXCR2/VEGF轴促进HepG2细胞的增殖和HUVEC的成管能力。
7.Research status of the correlation between ferroptosis and renal fibrosis
Li-Juan LIANG ; En-Lai DAI ; Jun-Yuan BAI ; Can LIU ; Zhao-Ran DING ; Jie ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2278-2282
Renal fibrosis is a common pathological manifestation of all chronic kidney diseases.Ferroptosis is closely related to the pathogenesis of renal fibrosis and can influence the onset of renal fibrosis,and it is the most critical step in the development of renal fibrosis.The paper describes the relationship between ferroptosis and renal fibrosis,discusses the research progress of ferroptosis on renal fibrosis,and further summarizes,analyzes,and describes the effective and highly targeted natural active ingredients of traditional Chinese medicines against ferroptosis,and concludes that the reversal of renal fibrosis is achieved through the regulation of the key targets of ferroptosis,with a view to providing a broad new direction for its prospects in the field of renal fibrotic disease prevention and treatment;and to provide a scientific guide for clinical treatment and basis for clinical treatment.
8.Study on treatment course of determining caffeine for treating apnea of prematurity with oxygen discontinuation as target orientation
Jianhui WANG ; Wenhui DONG ; Ying FAN ; Lihong RAN ; Yuan SHI
Chongqing Medicine 2024;53(15):2334-2338
Objective To evaluate the clinical benefit of caffeine treatment regimen determined based on oxygen discontinuation as target orientation for oxygen-dependent preterm infants.Methods A total of 219 preterm infants admitted to the neonatal department of this hospital from October 2021 to September 2023 were selected and divided into the intervention group (caffeine treatment targeting weaning oxygen,n=108) and the control group (routine caffeine treatment,n=111).The differences in the apnea recurrence,reuse of caffeine,time of caffeine discontinuation,duration of using oxygen and hospitalization duration were compared between the two groups.Results Compared with the control group,the correcting fetal age by stopping caffe-ine in the intervention group was greater[(35.9±1.7)weeks vs.(34.4±1.5)weeks],hospitalization dura-tion was longer[(64.62±20.60)d vs.(57.96±17.68)d],and the differences were statistically significant (P<0.05).The apnea recurrence rate,reuse rate of caffeine,duration of oxygen use,incidence rate of moder-ate to severe bronchopulmonary dysplasia,mechanical ventilation use rate,hospitalization expenses,≥grade Ⅱ necrotizing enterocolitis,feeding intolerance,tachycardia incidence rate and body weight increase velocity had no statistical differences between the two groups (P>0.05).Conclusion Determining the caffeine treatment course regimen by oxygen discontinuation as target orientation could not reduce the recurrent risk of preterm infants apnea recurrence risk,which could prolong the hospitalization duration.
9.Distribution of Traditional Chinese Medicine Syndromes and Related Risk Factors in Children with Mycoplasma Pneumoniae Pneumonia:An Analysis of 420 Cases
Tian-Zhu CHEN ; Yuan-Yuan SONG ; Ran LI ; Chuan-Ying LIU ; Ya-Bin CHEN ; Hua LIU ; Hua XU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2704-2712
Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes and related risk factors in children with mycoplasma pneumoniae pneumonia(MPP).Methods The clinical data of 420 children with MPP admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine were collected.The clinical data included gender,age,history of respiratory tract diseases,TCM syndromes,MPP classification,cough duration,fever duration,fever peak value,laboratory indicators of C-reactive protein(CRP),procalcitonin(PCT)and lactate dehydrogenase(LDH),and the complication of infection.SPSS 26.0 software was used for data statistics,and then the distribution of TCM syndromes in children with MPP and its correlation with various clinical data,as well as the related risk factors of MPP with different classification and various TCM syndromes were explored.Results(1)Among the 420 children with MPP,there were 283 cases(67.4%)of mild MPP,76 cases(18.1%)of refractory MPP,and 61 cases(14.5%)of severe MPP.For the distribution of TCM syndromes,there were 152 cases(36.2%)of wind-heat obstructing the lung syndrome,141 cases(33.6%)of phlegm-heat obstructing the lung syndrome,77 cases(18.3%)of damp-heat obstructing the lung syndrome,25 cases(6.0%)of toxin-heat obstructing the lung syndrome,16 cases(3.8%)of lung-spleen qi deficiency syndrome,and 9 cases(2.1%)of yin deficiency and lung heat syndrome.For the classification of infection,there were 295 cases(70.2%)of simple mycoplasma pneumoniae(MP)infection and 125 cases(29.8%)of mixed infection.(2)There were statistically significant differences in age stratification and visit season among MPP children with different TCM syndromes(P<0.01),while no significant differences were shown in the gender,history of respiratory tract diseases,and the complication of infection(P>0.05).(3)There were statistically significant differences in the visit season,history of respiratory tract diseases,and the complication of infection among the children with various MPP types(P<0.05),while no significant differences were shown in the gender and age stratification(P>0.05).(4)There were statistically significant differences in laboratory indicators of CRP and PCT and in the symptoms of cough duration,fever duration and fever peak among MPP children with different TCM syndromes(P<0.05 or P<0.01).(5)Significant differences were presented in laboratory indicators of PCT and LDH and in the symptoms of cough duration,fever duration and fever peak value among the children with different MPP types(P<0.05 or P<0.01).(6)Multivariate logistic regression analysis showed that CRP level ≥10.5 mg/L and wind-heat obstructing the lung syndrome were the independent risk factors for mild MPP(P<0.05 or P<0.01);fever duration≥7 days,cough duration ≥ 12 days and phlegm-heat obstructing the lung syndrome were the independent risk factors for refractory MPP(P<0.05 or P<0.01);cough duration ≥ 12 days,mixed infection and toxin-heat obstructing the lung syndrome were the independent risk factors for severe MPP(P<0.01).Conclusion The results indicated that the classification MPP in children is predominated by mild MPP,and their TCM syndrome types is predominated by wind-heat obstructing the lung syndrome.The proportions of refractory MPP and damp-heat obstructing the lung syndrome increase significantly in autumn,which may be related to the characteristics of regional environment and circuit qi.The increase of CRP level and fever peak may be related to phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome.In clinic,attention should be paid to the early use of heat-clearing and phlegm-resolving drugs or heat-clearing and toxin-removing drugs;children with the history of respiratory tract diseases and mixed infections are more likely to develop into severe MPP,and the physicians should be alert clinically.Wind-heat obstructing the lung syndrome,phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome are the independent risk factor separately for mild MPP,refractory MPP and severe MPP,which requires timely intervention to prevent mild MPP from developing into refractory MPP or severe MPP in clinic.
10.Bibliometric Analysis of Traditional Chinese Medicine Regulating Wnt Signaling Pathway
Licheng RAN ; Yi YUAN ; Hui SHANG ; Lirong CHEN ; Tong YANG ; Lei LI ; Yajun WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(5):1361-1369
Objective To analyze the research status,hot directions and frontier trends of traditional Chinese medicine in the prevention and treatment of diseases by regulating Wnt signaling pathway based on bibliometrics.Methods Based on Citespace and Vosviewer bibliometric software,the literature on the regulation of Wnt signaling pathway by traditional Chinese medicine in CNKI and WoSCC was visually analyzed.Results As of April 2023,607 and 257 related literatures were published in Chinese and English respectively.Since 2008,the number of literatures published in this field has shown a fluctuating increasing trend.China is the country with the most publications;guangzhou University of Traditional Chinese Medicine and Hunan University of Traditional Chinese Medicine were the institutions with the most publications in the Chinese database,and Shanghai University of Traditional Chinese Medicine was the institution with the most publications in the English literature database.Combined with the research direction of each research team and keyword clustering and burst analysis,the research hotspots of traditional Chinese medicine regulating Wnt signaling pathway are focused on osteoporosis,osteoarthritis and renal fibrosis.Diseases such as gastric cancer and breast cancer have become emerging research directions in recent years.Electroacupuncture therapy to promote stem cell proliferation and treat neurological diseases is one of the frontier research trends in this field.The mechanism of traditional Chinese medicine regulating the interaction between Wnt and NF-kappaB signaling pathway to prevent and treat diseases has great research potential.Conclusion In recent years,the prevention and treatment of diseases by traditional Chinese medicine targeting Wnt signaling pathway has developed rapidly.Various expert teams have obtained rich research results,and the research hotspots show a diversified trend.In-depth exploration of this can provide strong evidence for the molecular mechanism of traditional Chinese medicine in the treatment of various diseases.

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