1.Pathogenesis and Syndrome Differentiation Treatment of Heart Failure Based on "Spleen-mitochondria" and Theory of "Dampness, Turbidity, Phlegm, and Fluid-related Diseases"
Rui ZHANG ; Fuyun JIA ; Jingshun YAN ; Xuan LIU ; Yadong WANG ; Yinan MA ; Yan LIU ; Qiang XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):265-274
Guided by Academician Zhang Boli's theory of "dampness, turbidity, phlegm, and fluid-related diseases",this paper elaborated on the pathogenesis and syndrome differentiation treatment of heart failure from the perspective of the "spleen-mitochondria". It analyzed the essential similarities between "spleen-mitochondria" and "dampness, turbidity, phlegm, and fluid-related diseases", as well as their close association with the onset of heart failure. Furthermore,it explored the connection between spleen function and mitochondrial function in traditional Chinese medicine (TCM),positing that the spleen's role in transportation and transformation is analogous to mitochondrial material metabolism and energy conversion,with spleen deficiency closely related to mitochondrial dysfunction. It thus concluded that mitochondrial material metabolism and energy conversion represent the microscopic essence of the spleen's role in transportation and transformation,and mitochondrial dysfunction is a contributing factor to pathological products like dampness and turbid phlegm,which are closely associated with the occurrence of heart failure. The four elements of dampness,turbidity,phlegm,and fluid are a series of related symptoms resulting from abnormal fluid transportation and transformation,serving as both factors in the onset of heart failure and the core pathological basis for its deterioration. Therefore,during the treatment of heart failure,it is essential to regulate mitochondrial function. Early intervention should focus on eliminating dampness and turbidity to improve mitochondrial function and restore normal energy metabolism. In the middle and late stages,emphasis should be placed on resolving phlegm,promoting blood circulation,warming Yang,and reducing water retention to alleviate mitochondrial damage and improve cardiac function. Supporting Qi and strengthening the spleen should be a continuous approach,and treatment should be adjusted to enhance mitochondrial function and stabilize the condition,thereby improving prognosis. This paper discussed the role of the spleen and mitochondria in the pathogenesis of heart failure,examined the evolution of heart failure mechanisms from the perspective of dampness, turbidity, phlegm, and fluid-related diseases,and proposed a phased treatment strategy. It enriched the theory of dampness, turbidity, phlegm, and fluid-related diseases and offered new strategies for heart failure treatment. However,in practical application,TCM strategies for treating heart failure need to be integrated with modern medical approaches to provide a more solid scientific foundation for treatment.
2.Correlation of life events with depression, anxiety and somatic symptoms in graduate students: a study based on network analysis
Weili DENG ; Jia CAI ; Qiuyue LYV ; Qianshu MA ; Yupeng LUO ; Min XIE ; Qiang WANG
Sichuan Mental Health 2025;38(4):364-373
BackgroundGraduate students frequently face life events, many of which may adversely affect their mental well-being. However, the interaction between life events and the development of depression, anxiety, and somatic symptoms remains unclear. ObjectiveTo explore the relationship between life events and the development of depressive, anxiety and somatic symptoms in graduate students, thereby informing prevention strategies for these conditions. MethodsA sample of 6 722 newly enrolled graduate students at a comprehensive university in Southwest China from September to November 2018 was selected. The assessment was conducted using the Adolescent Self-rating Life Events Checklist (ASLEC), the 7-item Generalized Anxiety Disorder scale-7 item (GAD-7), the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Patient Health Questionnaire-15 (PHQ-15). Network analysis was implemented by using the bootnet and qgraph packages in the R software (version 4.2.3), with centrality indices calculated to identify core and bridge symptoms within the network. ResultsThe study encompassed a total of 6 171 graduate students, representing 91.80% of the target population. The prevalence rates of anxiety, depressive, and somatic symptoms among graduate students were 12.59% (777/6 171), 16.63% (1 026/6 171), and 27.66% (1 707/6 171), respectively. Network analysis revealed that 'academic stress' was the core symptom with the highest strength and expected influence (both values=1.207), while 'feeling down, depressed, or hopeless' was the bridge symptom with the highest bridge strength and bridge expected influence (both values=0.454). There was no significant difference in global network strength and edge weight between women and men (P>0.05). ConclusionAcademic stress, emerging as the core symptom, assumes a dominant position within the symptom network and exhibits strong interactions with other negative affective states. There was no gender difference in the network structure.
3.Treatment of Diabetic Cardiomyopathy with Shengmaisan-like Formulae: A Review
Yinan MA ; Fuyun JIA ; Rui ZHANG ; Zhengwei ZHANG ; Hanwen CUI ; Qiang XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):291-298
Diabetic cardiomyopathy (DCM), a cardiovascular complication caused by diabetes mellitus, is a major cause of heart failure and even sudden cardiac death in diabetic patients. Traditional Chinese medicine (TCM) posits that the core pathogenesis of DCM lies in internal deficiency and superficial excess, characterized by deficiency of both Qi and Yin combined with phlegm and blood stasis. Modern medical treatments for DCM primarily focus on blood glucose control and symptom alleviation yet lack targeted therapeutic strategies. In contrast, TCM offers a wealth of practical experience and a complete theoretical system, demonstrating definite clinical efficacy and high medication safety in DCM management. As a classic formula for tonifying Qi and nourishing Yin, Shengmaisan comprises Ginseng Radix et Rhizoma, Ophiopogonis Radix, and Schisandrae Chinensis Fructus. It contains multiple bioactive components, including ginsenosides, ophiopogonin, schisandrins, and homoisoflavonoids, which exhibit cardioprotective properties. The therapeutic mechanisms of Shengmaisan-like formulae for DCM involve enhancing myocardial contractility, attenuating myocardial fibrosis, modulating mitochondrial quality control, regulating glucose metabolism, mitigating oxidative stress, and suppressing inflammatory responses. Clinically, Shengmaisan-like formulae not only manage hyperglycemic status but also ameliorate cardiac structural and functional impairments and enhance exercise tolerance in DCM patients, playing a vital role in the prevention, treatment, and rehabilitation of DCM. This paper analyzes the feasibility of Shengmaisan-like formulae in DCM management and synthesizes current research achievements regarding their chemical components, mechanisms of action, and clinical applications, aiming to provide a scientific foundation for the use of such formulae in the treatment of DCM.
4.Improvement of Colonic Mucosa Inflammatory Response in Mice with Ulcerative Colitis by Xiezhuo Jiedu Recipe Through miRNA-155-5p/JAK2/STAT3 Pathway
Chaodi SUN ; Mengmeng ZHAO ; Xiaomeng LANG ; Jie REN ; Xin KANG ; Jiancong CUI ; Sujie JIA ; Yujing MA ; Yue LIU ; Qiang CHUAI ; Wenjing ZHAI ; Jianping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):174-182
ObjectiveThe differential expression of microRNAs (miRNAs) between the active stage and the remission stage of ulcerative colitis (UC) was analyzed by bioinformatics method, and the regulatory relationship was constructed by screening the differentially expressed genes (DEGs). The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database (GEO), and the most differentially expressed miRNAs were screened by GEO2R, Excel, and other tools as research objects. TargetScan, miRTarbase, miRDB, STRING, TRRUST, and Matescape databases were used to screen key DEGs, predict downstream transcription factors (TFs), gene ontology (GO), and conduct Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor (SOCS1), phosphorylated transcriptional signal transductor and activator 3 (p-STAT3), phosphorylated Janus kinase 2 (p-JAK2), and retinoic acid-associated orphan receptor-γt (ROR-γt). The expression levels of transforming growth factor-β (TGF-β), interleukin-17 (IL-17), interleukin-6 (IL-6), and interleukin-10 (IL-10) in serum were detected by enzyme linked immunosorbent assay (ELISA). ResultThe GSE48957 dataset was screened from the GEO database, and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation, as well as signaling pathways such as stem cell signaling pathway, IL-17 signaling pathway, and helper T cell 17 (Th17) cell differentiation. The Matescape database was used to screen out 10 key DEGs, among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3, p-JAK2, and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice, up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10, increase the level of anti-inflammatory factors, and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice, inhibit the phosphorylation of STAT3, inhibit the differentiation of CD4+ T cells into Th17 cells, reduce the levels of pro-inflammatory factors (IL-17 and IL-6), and increase the levels of anti-inflammatory factors (TGF-β and IL-10). As a result, the inflammation of colon mucosa in UC mice was alleviated.
5.Role of Hedgehog signaling pathway in muscle bone symbiosis in osteo-sarcopenia
Yan-Dong LIU ; Qiang DENG ; Zhong-Feng LI ; Ran-Dong PENG ; Yu-Rong WANG ; Jia-Ming LI ; Ping-Yi MA ; Jian-Qiang DU
The Chinese Journal of Clinical Pharmacology 2024;40(16):2433-2437
This article elaborates on the complex cross-talk and close relationship between muscles and bones involved in this disease,as well as its pathogenesis.It also summarizes that the difficulty of its treatment lies in the need to simultaneously consider both muscles and bones.And elaborated on the key role of the Hedgehog signaling pathway in embryonic development,tissue morphology establishment,and human tissue regeneration and repair.Investigated the remodeling effect of the Hedgehog signaling pathway on skeletal muscle from three aspects:Proliferation and differentiation of muscle stem cells,precursor cell and muscle fiber generation,inhibition of inflammation,and regulation of immunity;this article elucidates the role of the Hedgehog signaling pathway in bone reconstruction from two aspects.
6.Rapid On-Site Screening of Six Kinds of Pesticide Residues in Cosmetics Containing Plant Extracts by Fan-shaped Paper Spray Ionization and Miniature Mass Spectrometry
Yue-Guang LYU ; Jia-Yu ZHAO ; Hong-Yu XUE ; Qiang MA
Chinese Journal of Analytical Chemistry 2024;52(6):838-845
Cosmetics containing plant extracts may pose health risks to consumers due to inadequate control over the quality of plant raw materials,which may lead to residues of pesticides such as carbendazim in cosmetics. Developing rapid detection methods is of paramount importance for regulating product quality and safeguarding human health. A rapid on-site analytical method was developed for the screening of six kinds of pesticide residues in plant extract-based cosmetics using fan-shaped paper spray ionization with chromatographic enrichment functionality coupled with a miniature mass spectrometer. Cosmetic samples were directly loaded onto the fan-shaped paper substrate drop by drop,followed by chromatographic enrichment,paper spray ionization,and the miniature mass spectrometry analysis. The entire analysis time for a single run was less than 1 min. By loading samples in a dropwise manner,significantly improved chromatographic enrichment on the tip and 6 to 32-fold signal enhancement were achieved on the fan-shaped paper substrate compared to traditional triangle-shaped paper substrate. The limits of detection (LODs) and quantitation (LOQs) for the six kinds of pesticides were 0.02-0.05 mg/kg and 0.05-0.10 mg/kg,respectively. The recoveries were 82.6%-101.8% with relative standard deviations of 8.3%-16.5%. The established method was convenient,sensitive,and suitable for rapid,on-site screening of pesticide residues in plant extract-based cosmetics.
7.Models of adenoviral transfection and hypoxia/reoxygenation-induced injury in AMCMs of adult mouse cardiomyocytes
Xiaoru LI ; Xinye YAO ; Jia LIU ; Xiaoyu ZHANG ; Yiman ZHANG ; Baochang LAI ; Qiang MA ; Yidong WANG ; Hongyan TIAN ; Qian YIN
Acta Laboratorium Animalis Scientia Sinica 2024;32(4):435-443
Objective To construct models of viral transfection and hypoxia/reoxygenation induced cellular injury in adult mouse cardiomyocytes(AMCMs)isolated using a non-Langendorff method.Methods AMCMs were isolated,extracted,sedimented,and plated using a non-Langendorff method.The morphology and survival rate of the isolated cells were evaluated 2,24,48 and 72 h after plating,and their integrity was observed by immunofluorescence staining for α-actinin.The isolated AMCMs were infected with adenoviruses carrying an RFP-expressing vector and fluorescence images were obtained at 36 and 48 h post-infection and used to calculate transfection efficiency.The cells were cultured under hypoxic conditions for 45 min,reoxygenated for 24 h,and then stained with propidium iodide(PI)to verify establishment of the hypoxia/reoxygenation injury model.Results The survival rates of AMCMs at 2,24 and 48 h after plating were comparable,but survival was significantly reduced at 72 h.The integrity of the AMCMs was good and>80%of the cells were transfected with adenovirus at 48 h.After hypoxia/reoxygenation treatment,42%of cells were stained by PI,suggesting successful establishment of the AMCM injury model.Conclusions In this study,we developed a non-Langendorff method for the fast and easy isolation of AMCMs with high cell viability.The isolated cells can be efficiently infected with adenovirus and respond to hypoxia/reoxygenation injury.These findings provide a systematic method for isolating AMCMs and for applying gene modification and hypoxia/reoxygenation injury in these cells.
8.Correlation analysis of T lymphocyte subsets and neutrophil/lymphocyte ratio with the severity of sepsis
Miaomiao PENG ; Shuang MA ; Qiang ZHANG ; Meiling ZHAO ; Meng YUAN ; Rumin ZHANG ; Haibo TAN ; Qiuhong MA ; Meijun JIA
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(1):24-27
Objective To analyze the correlation between T lymphocyte subsets,neutrophil/lymphocyte ratio(NLR),procalcitonin(PCT)and the severity of sepsis.Methods A prospective research method was adopted.A total of 78 sepsis patients admitted to the department of intensive care medicine of Zibo Central Hospital from January 2021 to December 2022 were selected as the research subjects.Patients were divided into a septic shock group(37 cases)and a sepsis group(41 cases)based on the severity of their condition,with 40 healthy examinees from our hospital as the healthy control group.Using flow cytometry to measure the levels of CD4+ T lymphocytes count(CD4+ T)and CD8+ T lymphocytes count(CD8+ T)in three groups of subjects,calculate the CD4+ T/CD8+ T lymphocyte ratio(CD4+ T/CD8+ T)and NLR.The levels of PCT and interleukin-6(IL-6)were measured using electrochemiluminescence immunoassay,and the levels of C-reactive protein(CRP)were measured using immunoassay turbidimetry.Acute physiology and chronic health evaluationⅡ(APACHEⅡ)score within 24 hours was recorded for the two groups of patients,and the differences in lymphocyte subsets and various inflammatory indicators were compared between the groups.Pearson correlation analysis was used to analyze the correlation between various indicators and APACHEⅡscore.Results The CD4+ T,CD8+ T,and CD4+T/CD8+T levels in the septic shock and sepsis groups were significantly lower than those in the healthy control group[CD4+ T(×106/L):168.27±76.68,266.08±131.57 vs.789.60±173.78,CD8+ T(×106/L):156.50±68.37,205.81±75.60 vs.636.42±90.59,CD4+ T/CD8+ T:1.09±0.39,1.27±0.34 vs.1.44±0.38,all P<0.01],NLR,PCT,CRP and IL-6 were significantly higher than those in the healthy control group[NLR:25.85±11.62,15.94±8.72 vs.2.68±1.31,PCT(μg/L):21.82±15.28,9.09±4.96 vs.0.13±0.10,CRP(mg/L):158.65±62.33,106.97±51.49 vs.6.48±2.08,IL-6(ng/L):1 344.64±899.21,245.31±176.99 vs.3.25±1.83,all P<0.01].The APACHEⅡscore in the septic shock group was significantly higher than that in the sepsis group(32.00±1.00 vs.22.01±1.09,P<0.05).Correlation analysis showed that the levels of CD4+ T,CD8+ T,CD4+ T/CD8+ T in two groups of sepsis patients were negatively correlated with the APACHEⅡscore(r values were-0.571,-0.506,and-0.555,respectively,all P<0.01),while the levels of NLR,PCT,CRP,and IL-6 were positively correlated with the APACHEⅡscore(r values were 0.711,0.709,0.777,and 0.707,respectively,all P<0.01).Conclusions As the levels of T lymphocyte subsets decrease,inflammatory indicators like NLR and PCT rise,indicating a more severe sepsis condition.Therefore,T lymphocyte subsets and levels of various inflammatory indicators can serve as markers for evaluating the severity of sepsis.
9.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
10.Mechanism of benzyl isothiocyanate in the treatment of undifferentiated thyroid cancer
Chunmei MA ; Duo HAN ; Huiying ZHANG ; Lei YANG ; Dihua LI ; Qicheng ZHANG ; Yan WANG ; Ke XU ; Qiang JIA ; Wei ZHENG ; Jian TAN ; Zhaowei MENG
Chinese Journal of Endocrinology and Metabolism 2024;40(11):966-977
Objective:To investigate the mechanism of benzyl isothiocyanate(BITC) in the treatment of anaplastic thyroid cancer(ATC).Methods:Using network pharmacological analysis, key targets of BITC and ATC were screened, followed by GO and KEGG enrichment analysis. In order to validate the findings, AutoDock software was used to dock BITC and ATC key targets. BITC was applied to two ATC cell lines(8505C and CAL-62). Flow cytometry was used to analyze cell apoptosis. Autophagy inhibitors hydroxychloroquine sulfate(HCQ) and 3-methyladenine(3MA) were used in combination with BITC. Real-time quantitative PCR was conducted to detect the gene level of LC3B, while Western blotting was utilized to examine the expression of NF-κB, LC3B Ⅱ, Beclin-1, and Bcl-2. In animal experiments, a mouse tumor model was constructed using CAL-62 cells, treated with intraperitoneal injections of BITC(100 mg/kg) and normal saline respectively, administered every other day for a total of 21 days. Immunoblotting of tumor tissue was performed to detect the expression of LC3B Ⅱ, Bcl-2, Beclin-1, and NF-κB.Results:A total of 10 key targets with binding energies≤-4.0 kcal/mol were identified. KEGG analysis showed that these genes are mainly involved in NF-κB signaling pathway and apoptosis. BITC inhibited ATC cells with IC50 values of 27.56 μmol/L for 8505C and 28.30 μmol/L for CAL-62. The expression levels of NF-κB, Beclin-1, and Bcl-2 decreased, while LC3B Ⅱ and LC3B gene expression increased. Combining 3MA with BITC enhanced cell inhibition LC3B Ⅱ expression. HCQ increased LC3B Ⅱ expression without enhancing cell and viability inhibition. In the mouse tumor model, compared to the control group, the treatment group had higher LC3B Ⅱ and lower Bcl-2, Beclin-1, and NF-κB levels.Conclusion:BITC could inhibit the growth of ATC cells in vitro and in vivo, disrupt the autophagy degradation, and inhibit the NF-κB pathway.

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