Granulomatous lobular mastitis (GLM) is a chronic, refractory inflammatory condition of the breast with an unclear etiology. Emerging evidence suggests a potential role of pyroptosis in the pathogenesis of GLM. This study investigated the therapeutic effects of Tuolitounong Decoction (TLTND) on pyroptosis in both in vitro and in vivo models of GLM. An in vitro GLM model was established using MCF10A mammary epithelial cells exposed to tissue homogenates derived from GLM-affected human breast tissue. Cells were treated with TLTND at varying concentrations, with or without the pyroptosis inhibitor necrosulfonamide. Pyroptosis-associated proteins, including caspase-1, gasdermin D (GSDMD), lipopolysaccharide-binding protein (LBP), and NLR family pyrin domain containing 3 (NLRP3), were assessed using immunofluorescence and western blotting. Cell viability was evaluated using the Cell Counting Kit-8 (CCK-8) assay. For in vivo analysis, a rat GLM model was induced by injecting a combination of human GLM tissue homogenate supernatant and Freund’s complete adjuvant into the third and fourth pairs of mammary glands in female Sprague Dawley rats. TLTND was administered via daily oral gavage for 21 days. Post-treatment evaluations included histopathological assessment, expression of estrogen receptor (ER) and progesterone receptor (PR), and pyroptosis-related biomarkers in mammary gland tissue. Exposure to GLM homogenate successfully induced pyroptosis-related pathological features in MCF10A cells, whereas serotonin (5-HT) inhibition showed no significant effect. TLTND treatment demonstrated dose- and time-dependent effects, with enhanced therapeutic efficacy at 10 mg/mL after 48 h (P = 0.009). Of note, TLTND significantly reduced the protein expression levels of key pyroptosis markers (cleaved caspase-1, n-GSDMD, cleaved IL-18 and cleaved IL-1β) by 52.6

IntroductionAnthracycline-induced cardiotoxicity is a major concern in cancer treatment, as it can lead to various arrhythmias, with frequent premature ventricular contractions (PVCs) being one of the most common types. Sheng Mai Yin (SMY), a widely used Chinese herbal compound in China, has shown potential in treating anthracycline-induced cardiac dysfunction and arrhythmias. However, the evidence supporting its efficacy is limited due to methodological flaws in prior studies. Therefore, high-quality trials are essential to rigorously evaluate the efficacy and safety of SMY.MethodsThis multicenter, randomized, double-blind, placebo-controlled trial will assess the efficacy and safety of SMY in treating frequent PVCs induced by anthracycline chemotherapy. A total of 212 patients with breast cancer or malignant lymphoma undergoing anthracycline-based chemotherapy, who have been diagnosed with new-onset frequent PVCs and Qi and Yin deficiency syndrome, will be enrolled. Participants will be randomly assigned to receive either SMY or a placebo for 8 weeks, alongside standard medications. The primary outcome is the reduction rate in PVC frequency. Secondary outcomes include PVC symptom scores, Traditional Chinese Medicine syndrome scores, cardiac dysfunction biomarkers, and major adverse cardiovascular events.DiscussionThe results of this trial are expected to provide robust evidence regarding the efficacy and safety of SMY in the treatment of anthracycline-induced frequent PVCs.Trial registrationhttp://itmctr.ccebtcm.org.cn. Registration number: ITMCTR2024000858.

Breast cancer (BC) remains the most prevalent malignancy among women. Clinical evidence indicates that genetic variations related to circadian rhythms, as well as the timing of therapeutic interventions, influence the response to radiation therapy and the toxicity of pharmacological treatments in women with BC. This study aimed to identify key circadian rhythm-related genes (CRGs) using bioinformatics and machine learning, and construct a prognostic model to predict clinical outcomes. Transcriptome data for BC were retrieved from The Cancer Genome Atlas database. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to develop a prognostic model based on CRGs. The predictive performance of the risk score model was evaluated. Univariate and multivariate Cox regression analyses were applied to construct the prognostic model and stratify patients into high-risk and low-risk groups. Additionally, differences in immune microenvironment, immunotherapy efficacy, and tumor mutation burden were assessed between risk groups. A prognostic risk score model comprising 17 CRGs was developed. The areas under the receiver operating characteristic curve for overall survival at 1, 3, 5, and 7 years exceeded 0.6, indicating acceptable predictive performance. Calibration plots and decision curve analyses demonstrated the use of the model in prognostic prediction. Significant differences in immune microenvironment, immunotherapy efficacy, and tumor mutation burden were identified between the low-risk and high-risk groups. The circadian rhythm-based gene model, effectively predicted the prognosis of individuals with BC, highlighting its potential to inform personalized therapeutic strategies and improve patient outcomes.

Granulomatous lobular mastitis (GLM) is an idiopathic inflammatory breast disease that tends to recur on the same side. With the accumulation of clinical cases, it has been observed that GLM can also occur contralaterally. Currently, most studies on GLM focus on treatment methods and risk factors for ipsilateral recurrence, and there are few reports on bilateral GLM. The study aimed to summarize the clinical characteristics of patients with bilateral GLM by reviewing their clinical data, and to discuss the risk factors affecting the occurrence of bilateral GLM. A retrospective study of the medical records database of patients with GLM admitted between May 2019 and August 2022 was performed. Patients were divided into bilateral GLM group (bilateral GLM group) and unilateral GLM patients (unilateral GLM group). Demographic and clinical characteristics, treatment, and follow-up were collected and analyzed. In this study, by reviewing the clinical data of 59 cases of bilateral GLM, we found that the median time between the onset of bilateral GLM on both sides was 6.63 (0-18) months. Additionally, because of the simultaneous or interval onset on both sides, the duration of the disease was longer compared to unilateral cases. Regarding the history of external hospital treatment, it was found that about 57.63% of patients with bilateral GLM received 2 or more treatment modalities, with a higher involvement of herbal medicine. Meanwhile, by counting the clinical data of the 2 groups of patients with bilateral GLM and unilateral GLM, it was shown by univariate analysis that fertility, nipple development, absolute CD4 value, and CD4/CD8 ratio were associated with contralateral onset of GLM in both groups, with inverted nipple being an independent risk factor.

Background: Mammary duct fistula is an abnormal tract formed between the wall of a breast duct and the adjacent tissue or skin, typically resulting from a rupture of the duct wall. This condition is characterized by inflammation due to the leakage of fluid from the surrounding breast tissue. Infection of the sinus tract can lead to the infection of adjacent lactiferous ducts or recurrence in the same sinus tract, ultimately resulting in abscess formation and a prolonged healing process. In severe cases, this condition may be accompanied by breast deformity and other complications. Case Presentation: A patient with a mammary duct fistula from the General Surgery Department of Dongzhimen Hospital, affiliated with the Beijing University of Chinese Medicine, underwent a modified surgical procedure. Post-surgery, the patient's nipple inversion was fully corrected with no recurrence observed. Conclusion: The novel modified surgical procedure demonstrates effectiveness in preventing local recurrence, shortening the clinical course, and addressing pathogenic factors such as nipple inversion. This approach has the potential to improve the cure rate of mammary duct fistulas and is worthy of clinical promotion.

BACKGROUND:Breast cancer is one of the most common type of cancers worldwide and remains a critical health issue. Although there are numerous treatment options for advanced metastatic breast cancer, the results are not satisfactory, particularly for triple-negative breast cancer. New treatment modalities need to be explored. CASE PRESENTATION:We present the case of a breast cancer patient with multiple metastases who achieved a good response and tolerance to the combination treatment of utidelone plus capecitabine. After being treated with 10 cycles of combined treatment, the patient is now in a good general condition with a progression-free survival time of 10 months. CONCLUSION:To our knowledge, this is the first report of utidelone plus capecitabine successfully treating a patient with heavily pretreated metastatic breast cancer. This combined treatment offers a new option for patients with multi-drug resistant breast cancer.

目的:观察紫草阳和汤外敷联合地塞米松软膏治疗肿块期肉芽肿性小叶性乳腺炎的临床效果及对细胞焦亡相关蛋白的影响.方法:将40例肉芽肿性小叶性乳腺炎患者随机分为观察组20例和对照组20例.两组均给地塞米松软膏治疗,观察组在对照组基础上外敷紫草阳和汤治疗.比较两组乳腺肿块体积变化、乳房疼痛及成脓症状、病理组织学及免疫组织化学、细胞焦亡相关指标表达.结果:治疗后,观察组肿块体积差明显大于对照组,对照组为16.7±21.5,实验组为32.9±27.4,两组差异有统计学意义(P<0.05);观察组患者的客观缓解率(ORR=85%)明显高于治疗组(ORR=50%,P<0.05).在成脓率及疼痛程度上,治疗2、3周后观察组乳房疼痛评分明显低于对照组(P<0.05);观察组成脓率为30%,对照组成脓率为20%,差异无统计学意义(P>0.05).观察组caspase-1及GSDMD免疫组化表达水平均明显低于对照组(P<0.05);而在细胞焦亡相关指标表达方面,与对照组比较,观察组GSDMD、caspase-1、NLRP3 表达明显降低(P<0.05).结论:紫草阳和汤外敷联合地塞米松软膏治疗肿块期肉芽肿性小叶性乳腺炎疗效显著,可有效减轻乳房疼痛,缩小肿块体积,降低细胞焦亡相关性指标表达,具有良好的抗炎作用.

Background There is growing emphasis on the cardiotoxicity research over the past 12 years. To look for the hotspots evolution and to explore the emerging trends in the field of cardiotoxicity, publications related to cardiotoxicity were acquired from the Web of Science Core Collection on August 2, 2022. Methods We used the CiteSpace 5.8 R3 and VOSviewer 1.6.18 to perform bibliometric and knowledge-map analysis. Results A total of 8,074 studies by 39,071 authors from 6,530 institutions in 124 countries or regions were published in different academic journals. The most productive country was absolutely the United States, and the University of Texas MD Anderson Cancer Center was the institution with the largest output. Zhang, Yun published the most articles, and the author who had the most frequent co-citations was Moslehi, Javid. New England Journal of Medicine was the most frequently cited journals in this field. Mechanisms of cardiotoxicity have received the most attention and was the main research directions in the field. The disease of cardiotoxicity together with the related risk factors are potential research hotspots. Immune checkpoint inhibitor and myocarditis are two recently discussed and rapidly expanding research topic in the areas of cardiotoxicity. Conclusions This bibliometric analysis provided a thorough analysis of the cardiotoxicity, which would provide crucial sources of information and concepts for academics studying this area. As a rapidly expanding field in cardiology, the related field of cardiotoxicity will continue to be a focus of research.

Objective:To investigate the effects of alkannin on the apoptosis and phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway in malignant breast cell lines MDA-MB-231 and MCF-7.Methods:MDA-MB-231 and MCF-7 cells were cultured in the complete media containing different concentrations of alkannin（0,0.2,0.4,0.8,and 1.0 mg/mL）.The cell viability, apoptosis, and PI3K/Akt expression were determined by CCK-8 assay, Annexin V-FTIC/PI staining-flow cytometry, and western blotting, respectively.Results:Compared with the blank control group（0 mg/mL）,alkannin at a concentration of 0.8 mg/mL and higher significantly inhibited the growth of MDA-MB-231 and MCF-7 cells, and that of 1.0 mg/L demonstrated the best performance.The apoptosis of MDA-MB-231 and MCF-7 cells increased with the rise in alkannin concentration（P＜0.05）.Compared with the blank control group, alkannin down-regulated the expression of PI3K in MDA-MB-231 and MCF-7 cells（P＜0.05）.Conclusion:Alkannin may exert the anti-tumor effects on MDA-MB-231 and MCF-7 cells by inhibiting the PI3K/Akt signaling pathway.

目的 通过动物体内实验探讨托里透脓汤对肉芽肿小叶性乳腺炎caspase-1/GSDMD信号通路的影响与机制.方法 雌性有孕产史SD大鼠20只,使用人肉芽肿小叶性乳腺炎组织匀浆注射法诱导肉芽肿小叶性乳腺炎模型,分组为空白组、模型组、西药组(糖皮质激素组)、托里透脓汤组,其中西药组给药剂量为10 mg/(kg·d),托里透脓汤组给药剂量为20 mg/d,连续给药4周后取材,酶联免疫吸附测定(enzyme linked immunosorbent assay,Elisa)法检测血清白细胞介素(interleukin,IL)-18浓度,蛋白免疫印迹法(Western blot,WB)检测大鼠乳腺组织半胱胺蛋白酶-1(caspase-1)、消皮素-D(gasdermin-D,GSDMD)、IL-1β、IL-18表达水平,HE染色评估乳腺组织情况,免疫组化法测定乳腺组织雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)水平.结果 与模型组相比,西药组及托里透脓汤组的血清IL-18、组织活化的caspase-1、GSDMD-n、活化的IL-1β均表达降低(P<0.05),免疫组化显示托里透脓汤组的ER、PR表达均增高(P<0.05),HE染色可见西药组可见乳腺小叶结构存在,炎细胞浸润不明显;托里透脓汤组可见脓肿边界清晰,脓肿内主要成分为多核巨细胞,脓肿外较模型组炎症细胞浸润较少.结论 托里透脓汤对肉芽肿小叶性乳腺炎具有治疗作用,其作用机制可能与类雌激素作用与抗细胞焦亡作用有关.

A 19-year-old female patient received risperidone 3 mg twice daily for schizophrenia. She did not have nipple discharge before taking the drug. After taking the drug, nipple discharge occurred intermittently. One year later, a mass with pain in the right breast was found, which could not be alleviated after treatments with Rupi Sanjie capsules (乳癖散结胶囊), cefdinir, ibuprofen, rifampicin, and isoniazid and continued to increase, accompanied by bilateral knee pain, nodular erythema and tenderness of lower limbs. Laboratory tests showed white blood cell count 18.4×10 9/L and serum prolactin 37.42 μg/L. Ultrasonography of the right breast showed a 13.2 cm×11.0 cm×3.0 cm area low echo with unclear boundary, local fluidity, and abundant blood flow signals around. Granulomatous lobular mastitis of right breast (abscess stage) and hyperprolactiemia was diagnosed. After excluding physiological and pathological reasons, it was considered that risperidone caused hyperprolactinemia, which then induced granulomatous mastitis. However, risperidone could not be stopped without the guidance of a specialist, so only abscess incision, drainage, debridement, anti-infection, and anti-inflammatory were given. Purulent secretions gradually decreased, pain alleviated, and erythema of lower limbs partially subsided. Then risperidone dose was adjusted to 2 mg twice daily under the guidance of her psychiatrist. The serum prolactin level decreased (28.36 μg/L). At 1 year of follow-up, granulomatous mastitis did not recur.

目的 探讨紫草阳和汤对肉芽肿小叶性乳腺炎大鼠的疗效及炎症指标、细胞焦亡相关蛋白及雌孕激素受体的作用.方法 将20只SPF级雌性SD大鼠随机分为空白对照组、模型组、西药组、紫草阳和汤组,每组各5只,对模型组、西药组及紫草阳和汤组大鼠进行肉芽肿小叶性乳腺炎造模,并于次日开始,予西药组1次/d,10 mg/kg醋酸泼尼松,予紫草阳和汤组1次/d,1.85 g/kg紫草阳和汤,21 d后处死取材.乳腺组织进行病理染色、免疫组化染色法测定雌激素受体(Estrogen receptors,ER)、孕激素受体(Progesterone receptors,PR)表达强度、Elisa法测定各组大鼠血清IL-18表达、Western Blot法测定乳腺组织细胞焦亡有关蛋白[全长消皮素D(GasderminD-fulllenth,GSDMD-fl)、消皮素D-N端蛋白(GasderminD-N,GSDMD-N)、全长天冬氨酸蛋白水解酶1(Cysteinyl aspartate specific proteinase-1 fulllenth,caspase1-fl)、活化的天冬氨酸蛋白水解酶1(Cleavedcysteinyl aspartate spe-cific proteinase 1,cleaved caspase-1)、活化的白细胞介素1β(Cleaved-interleukin 1β,cleaved IL-1β)]表达,测量大鼠第3、4对乳腺直径及大鼠体重.结果 (1)与模型组比较,紫草阳和汤组与西药组均出现了炎性细胞浸润,紫草阳和汤组PR表达明显下降(P<0.05),而ER表达差异无统计学意义;(2)与模型组比较,紫草阳和汤组IL-18明显下降(P<0.05);(3)与模型组比较:紫草阳和汤组cleaved caspase-1及cleaved IL-1β表达水平降低(P<0.05),GSDMD-N明显降低(P<0.001);西药组cleaved caspase-1表达水平明显降低(P<0.05),GSDMD-N明显降低(P<0.001);(4)与模型组比较,紫草阳和汤组与西药组出现了乳房直径下降.结论 紫草阳和汤对肉芽肿小叶性乳腺炎大鼠具有一定疗效,主要表现为对IL-18、IL-1β、cleaved caspase-1及GSDMD-N的影响,并可下调PR的表达.

目的 探讨槐耳颗粒对三阴性乳腺癌MDA-MB-231细胞磷脂酰肌醇3-蛋白激酶B-哺乳动物雷帕霉素靶蛋白信号通路表达的影响.方法 将三阴性乳腺癌MDA-MB-231细胞用含不同浓度的槐耳颗粒的DMEM高糖培养基(分组为0、2、4、8 mg/mL)进行培养,采用细胞计数试剂法检测24小时、48小时、72小时的细胞活性,原位末端转移酶标记技术法细胞爬片染色检测干预48小时后的细胞凋亡情况,蛋白免疫印迹法测定细胞内磷脂酰肌醇3、蛋白激酶B、哺乳动物雷帕霉素靶蛋白表达情况.结果 (1)与空白对照组(0 mg/mL)相比,槐耳颗粒(2、4、8 mg/mL)组的MDA-MB-231 细胞均出现活力下降,且呈时间及浓度依赖性,具有统计学意义(P＜0.05);(2)与空白对照组相比,槐耳颗粒组的MDA-MB-231细胞凋亡增高,呈浓度依赖,且具有统计学意义(P＜0.05);(3)与空白对照组相比,经槐耳颗粒处理的MDA-MB-231细胞磷脂酰肌醇3、蛋白激酶B、哺乳动物雷帕霉素靶蛋白的表达均出现不同程度下降,具有统计学意义(P＜0.05).结论 槐耳颗粒具有针对三阴性乳腺癌MDA-MB-231细胞的抗肿瘤作用,且具浓度及时间依赖性,其机制可能与对磷脂酰肌醇3-蛋白激酶B-哺乳动物雷帕霉素靶蛋白信号通路的抑制有关.

目的:以HE染色及免疫组织化学为途径探讨肉芽肿性小叶性乳腺炎的临床病理特征,并为手术术式选择提供合理依据.方法:对北京中医药大学东直门医院病理诊断为肉芽肿性小叶性乳腺炎患者的病灶及阴性切缘行HE染色及天冬氨酸蛋白水解酶-1(caspase-1)/消皮素-D(gasdermin D,GSDMD)/雌激素受体(estrogen receptor,ER)/孕激素受体(progesterone receptor,PR)免疫组织化学染色,并分析患者的临床资料.结果:40例经乳腺导管探查+乳房再造+乳头乳晕成形术患者均治愈,至2020年11月无同侧复发;6例免疫组织化学可见阴性切缘组织的caspase-1、GSDMD、PR表达均低于病灶组,组间对比差异有统计学意义(P<0.05).结论:肉芽肿小叶性乳腺炎的组织病理学独特,其诊断仍旧依靠病理诊断,经免疫组织化学分析乳腺终末导管外组织病变可能为乳腺导管诱发的继发改变,故肉芽肿小叶性乳腺炎根治手术的术式应包含针对乳腺小叶导管的探查,以避免疾病的反复发作.

ObjectiveIn this study, an animal model of granulomatous lobular mastitis was constructed using human granulomatous lobular mastitis specimen homogenates and a suspension of complete Freund's adjuvant.MethodsTwenty-five rats with a history of maternity were randomly divided into five groups with five rats each: a blank control group, Freund's adjuvant group, normal mammary homogenate group, low-dose lesion homogenate group, and high-dose lesion homogenate group. In the lesion homogenization groups, rats were injected with complete Freund's adjuvant homogenate prepared from granulomatous mastitis patient tissues, and the third and fourth pair of mammary gland injections were administered to the rats at 0.2 mL in the high-dose group and 0.1 mL in the low-dose group. The normal mammary gland homogenate group was injected with normal mammary gland tissue homogenate from patients with granulomatous mastitis. The blank control group was injected with saline. The Freund's adjuvant group was injected with complete Freund's adjuvant. The histomorphological and pathophysiological characteristics of the mammary tissues were observed for 14 days after the completion of modeling, and the effects of the granulomatous lobular mastitis model were compared.ResultsThe morphological changes and physiopathological characteristics of granulomatous lobular mastitis in the high- and low-dose groups were significantly different when compared with the blank control, Freund's adjuvant, and normal breast homogenate groups (P < 0.001).ConclusionHuman granulomatous lobular mastitis specimen homogenates and suspensions of complete Freund's adjuvant for granulomatous lobular mastitis can successfully establish an animal model of the disease and lead to insights and new ideas for the etiology of the disease.

目的:观察乳宁颗粒治疗肿块期肝郁痰凝型乳腺导管扩张症的临床疗效。方法:前瞻性选取2015年5月至2019年4月北京中医药大学东直门医院收治的80例肿块期肝郁痰凝型乳腺导管扩张症患者，按随机数字表法分为观察组和对照组各40例，两组均外敷如意金黄膏7 d，观察组加服乳宁颗粒，3个月为一疗程，经期停用。比较两组临床疗效及治疗前后的肿块长径、乳导管直径、VAS评分和肝郁痰凝证中医症候积分，记录不良反应和肿块复发情况。结果:观察组临床总有效率为92.5%(37/40)，明显高于对照组的75.0%(30/40， P<0.05)。治疗后，两组肿块长径、乳导管直径、VAS评分及肝郁痰凝证中医症候积分均明显下降( P<0.05)，且观察组低于对照组( P<0.05)。观察组肿块复发率和手术引流率分别为7.5%(3/40)和0，均低于对照组的25.0%(10/40)和12.5%(5/40)( P<0.05)。 结论:乳宁颗粒联合如意金黄膏外敷对肿块期肝郁痰凝型乳腺导管扩张症有良好治疗作用。

目的:探讨托里透脓外治法联合封闭负压引流(VSD)治疗脓肿期肉芽肿性小叶性乳腺炎(GLM)的临床治疗意义.方法:将40例入组患者分为VSD联合托里透脓外治法(观察组)和单用VSD治疗(对照组),观察组患者的住院时间、术后至切口愈合期间的换药次数、切口愈合时间、乳房疼痛情况、超声下脓肿范围变化、创面肉芽组织生长情况、切口纵径变化及治疗前后的血清IgG4+、CD4+、CD8+、RF、C1q水平.结果:与对照组相比,VSD联合托里透脓外治法可明显减少住院时间,降低换药换药次数,缩短切口愈合时间,有效改善乳房疼痛,加速脓肿缩小,改善创面肉芽组织生长,加速切口纵径缩小,降低血清IgG4+、CD4+、CD8+、C1q水平.差异有统计学意义(P<0.01).结论:托里透脓外治法联合VSD治疗成脓期GLM疗效可靠,能明显缩短切口愈合时间,改善乳房炎症预后.

目的 比较3D解剖结合动物实体模型与传统解剖在外科教学中的教学效果,建立一种新的有效的外科培养模式.方法 选择北京中医药大学2015届和2016届外科研究生作为培养对象,随机分为两组,采用传统外科教学模式为A组,采用3D解剖教学为B组,通过调查问卷观察学生对教学模式认可度及学习兴趣,学期结束,进行理论考试及实践技能考核,观察两组学生成绩,并通过带教老师评分分析评价两组教学模式的学生课堂学习兴趣及教学效果.结果 3D解剖结合动物实体模型教学组的学生理论及实践技能考核成绩分别为(89.25±6.71)分和(93.00±5.42)分,传统外科教学组成绩分别(74.95±8.96)分和(89.25±6.71)分,P＜0.05,差异有统计学意义.结论 3D解剖结合动物实体模型教学模式较传统教学模式可以有效提高学生的学习兴趣、有较高的学生认可度,取得较好的教学效果.

李乃卿教授发现女性患者乳腺、甲状腺、性腺的增生性疾病及黄褐斑四种疾病常呈两者、三者甚至四者联合或相继发生病变,四者发病存在密切关联性,李乃卿主任在前期"肝系病证"基础上将此表现称为"四联效应"."四联效应"的疾病虽然分属于不同系统,但病因病机以及临床表现具有高度的相似性,发病机理同时符合情志为病和脏腑学说理论.李乃卿教授从中医整体学说、经络辨证及异病同治理论出发,从肝论治"四联效应"取得了显著的临床效果.

Progression of hepatocellular carcinoma involves multiple genetic and epigenetic alterations that promote cancer invasion and metastasis. Our recent study revealed that hyperphosphorylation of ezrin promotes intrahepatic metastasis in vivo and cell migration in vitro. Celastrol is a natural product from traditional Chinese medicine which has been used in treating liver cancer. However, the mechanism of action underlying celastrol treatment was less clear. Here we show that ROCK2 is a novel target of celastrol and inhibition of ROCK2 suppresses elicited ezrin activation and liver cancer cell migration. Using cell monolayer wound healing, we carried out a phenotype-based screen of natural products and discovered the efficacy of celastrol in inhibiting cell migration. The molecular target of celastrol was identified as ROCK2 using celastrol affinity pull-down assay. Our molecular docking analyses indicated celastrol binds to the active site of ROCK2 kinase. Mechanistically, celastrol inhibits the ROCK2-mediated phosphorylation of ezrin at Thr567 which harnesses liver cancer cell migration. Our findings suggest that targeting ROCK2-ezrin signaling is a potential therapeutic niche for celastrol-based intervention of cancer progression in hepatocellular carcinoma.