1.EZH2 promotes malignant biological behavior in esophageal squamous cell carcinoma via EMT.
Yuying JING ; Kaige YANG ; Yiting CHENG ; Tianping HUANG ; Sufang CHEN ; Kai CHEN ; Jianming HU
Journal of Central South University(Medical Sciences) 2025;50(2):155-166
OBJECTIVES:
Esophageal squamous cell carcinoma (ESCC) is characterized by complex pathogenesis and poor prognosis. In recent years, epithelial-mesenchymal transition (EMT) in tumor initiation and progression has attracted increasing attention. Enhancer of zeste homolog 2 (EZH2), which is aberrantly expressed in various tumors, may be closely related to the EMT process. This study aims to examine the expression and correlation of EZH2 and EMT markers in ESCC cells and tissues, evaluate the effects of EZH2 knockdown on ESCC cell proliferation, invasion, and migration, and explore how EZH2 contributes to the malignant biological behavior of ESCC.
METHODS:
Bioinformatics analyses were used to assess EZH2 expression levels in ESCC. Small interfering RNA was used to knock down EZH2 in ESCC cell lines EC109 and EC9706. Cell proliferation, invasion, and migration were evaluated using cell counting kit-8 (CCK-8), wound healing, and Transwell assays. Protein and mRNA expression levels of EZH2, E-cadherin (E-cad), and vimentin (Vim) were detected by Western blotting and real time fluorogenic quantitative PCR (RT-qPCR), respectively. Immunohistochemical (IHC) staining was performed on 70 ESCC tissue samples and 40 paired adjacent normal tissues collected from the First Affiliated Hospital of Shihezi University between 2010 and 2016 to assess the expression of EZH2, E-cad, and Vim, and to analyze their associations with clinicopathological feature and patient prognosis.
RESULTS:
Bioinformatics analysis showed that EZH2 was highly expressed in ESCC (P<0.001), and high EZH2 expression was associated with worse prognosis (P<0.001). CCK-8, wound healing, and Transwell assays demonstrated that EZH2 knockdown significantly suppressed the proliferation, invasion, and migration of ESCC cells (P<0.001). In addition, Vim expression was significantly reduced, while E-cad expression was significantly increased at both protein and mRNA levels in EZH2-silenced cells (all P<0.05). IHC staining analysis revealed higher expression of EZH2 and Vim and lower expression of E-cad in ESCC tissues compared to adjacent normal tissues. Kaplan-Meier survival analysis showed that low expression of EZH2 and Vim and high expression of E-cad were associated with longer survival (all P<0.05).
CONCLUSIONS
EZH2 promotes malignant biological behavior in ESCC by mediating EMT. Elevated EZH2 expression is associated with poor prognosis in ESCC patients.
Humans
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Enhancer of Zeste Homolog 2 Protein/physiology*
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Esophageal Squamous Cell Carcinoma/pathology*
;
Epithelial-Mesenchymal Transition/genetics*
;
Esophageal Neoplasms/metabolism*
;
Cell Proliferation
;
Cell Line, Tumor
;
Cell Movement
;
Cadherins/genetics*
;
Vimentin/genetics*
;
Male
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Female
;
Middle Aged
;
Neoplasm Invasiveness
;
Prognosis
;
RNA, Small Interfering/genetics*
;
Gene Expression Regulation, Neoplastic
2.Oxymatrine, a novel TLR2 agonist, promotes megakaryopoiesis and thrombopoiesis through the STING/NF-κB pathway.
Chengyang NI ; Ling ZHOU ; Shuo YANG ; Mei RAN ; Jiesi LUO ; Kui CHENG ; Feihong HUANG ; Xiaoqin TANG ; Xiang XIE ; Dalian QIN ; Qibing MEI ; Long WANG ; Juan XIAO ; Jianming WU
Journal of Pharmaceutical Analysis 2025;15(1):101054-101054
Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.
3.Intrahepatic cholangiocarcinoma tumor size classification based on prognostic analysis: a retrospective multicenter study
Jiaqian CHEN ; Hongzhi LIU ; Lingtian MENG ; Weiping ZHOU ; Zhangjun CHEN ; Jianying LOU ; Shuguo ZHENG ; Xinyu BI ; Jianming WANG ; Wei GUO ; Fuyu LI ; Jian WANG ; Yamin ZHENG ; Jingdong LI ; Shi CHENG
Journal of Surgery Concepts & Practice 2025;30(4):332-338
Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.
4.Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in anterior mediastinal masses
Junmin ZHU ; Junjie WANG ; Jianming YUE ; Yixin SUN ; Yichen LIU ; Lei WANG ; Lin LIN ; Jie LI ; Jinlan ZHAO ; Xuehua TU ; Ningying DING ; Jianrong HU ; Chunmei HE ; Leilei TIAN ; Hongtao TANG ; Jiasheng ZHAO ; Cheng CHEN ; Yongxiang SONG ; Yunwei TIAN ; Yong XIAO ; Kaidi LI ; Lin MA ; Yun WANG ; Longqi CHEN ; Dong TIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1603-1609
Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.
5.Screening of effective parts for acute and chronic pain relief of Shaoyao gancao decoction and analysis of its blood components
Yuxin XIE ; Zhengqing YANG ; Lianlian XIAO ; Yubo ZHU ; Mian ZHAO ; Yang HU ; Taoshi LIU ; Jianming CHENG
China Pharmacy 2024;35(15):1825-1830
OBJECTIVE To study the pharmacological substance basis of Shaoyao gancao decoction for relieving acute and chronic pain. METHODS The antispasmodic effect of Shaoyao gancao decoction, ethyl acetate extract of Shaoyao gancao decoction and its effluent part of macroporous resin and 90% ethanol elution part of macroporous resin (the concentration of 4 drugs was 13.44 g/mL according to crude drug) was observed by in vitro small intestine tension test in rats. The acetic acid writhing test was conducted in mice to evaluate the analgesic effects of macroporous resin efflux site and macroporous resin 90% ethanol elution site (the dosage of 2.4 g/kg according to crude drug). The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL- 1β), prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) in serum of mice were detected. The serum prototype and metabolites of mice after intragastric administration of macroporous resin 90% ethanol elution site were identified by high performance liquid chromatogre-time-of-flight mass spectrometry. RESULTS In vitro experiment showed that 90% ethanol eluting part of macroporous resin represented the best antispasmodic effect, and the inhibitory rate of small intestine tension was significantly higher than macroporous resin efflux site of Shaoyao gancao decoction (P<0.05) without statistical significance, compared with Shaoyao gancao decoction (P>0.05). In the acetic acid writhing experiment, compared with model group, the writhing times of mice in the macroporous resin 90% ethanol elution part group were reduced significantly (P<0.05), the writhing latency was prolonged significantly (P<0.05), and the levels of COX-2, IL-1β, PGE2 and TNF-α in serum were decreased significantly (P<0.05). Ten kinds of protoproducts including paeoniflorin and glycyrrhizic acid were identified from serum of mice, and twenty-two kinds of metabolites including hydroxylated glycyrrhizin and glucosylated liquiritin were identified. CONCLUSIONS The effective part of Shaoyao gancao decoction for relieving acute and chronic pain is 90% ethanol elution part prepared by macroporous resin from the ethyl acetate extract. Ten components, including glycyrrhetinic acid and paeoniflorin, may be the basis of its pharmacological substances.
6.Study on the Anti-Fatigue and Intestinal Flora Improvement Effects of Fructan Products Isolated from Polygonatum Cyrtone-ma Hua
Na WANG ; Tao LIU ; Chang MA ; Xiaoxian YU ; Jing JI ; Lingchong WANG ; Jianming CHENG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(5):494-502
OBJECTIVE To study the structural characteristics of purified polysaccharide isolated from Polygonatum cyrtonema Hua and explore its anti-fatigue and intestinal bacteria improvement effects,so as to provide theoretical basis for the development of products using this polysaccharide as functional ingredients.METHODS PMP pre-column derivatization-high performance liquid chromatography,trimethylsilyl ether derivatization-gas chromatography and other methods were used to chemically characterize the pu-rified polysaccharide;the mouse weight-loading swimming test and biochemical indicators were used to evaluate its anti-fatigue effect;16S rRNA intestinal flora sequencing was adopted to study the effect of the purified product in improving intestinal bacteria.RESULTS The obtained polysaccharide was a fructan product and contained small amounts of glucose(Glc),galactose(Gal),arabinose(Ara),mannose(Man),rhamnose(Rha)and galacturonic acid(GalA),which had a relative molecular mass in the range of 0.4-285 kDa,and the molecular weight of the main component was around 3 kDa.Compared with the model group,the high-dose polysaccha-ride group could significantly prolong the exhaustive swimming time of mice(P<0.01),reduce the levels of BUN and UA in serum and the LA(P<0.01)and MDA levels(P<0.05)in muscle tissue,and enhance SOD(P<0.01),GSH-Px(P<0.001)and CAT(P<0.05)levels in liver tissue.Compared with the blank control group,the low-dose polysaccharide group could increase the relative a-bundance of probiotics Eggerthelaceae(g_unclassified_f_Eggerthelaceae)and Weissella(g_Weissella)in the fecal microorganisms of mice(P<0.05).CONCLUSION The chemical composition of purified polysaccharide isolated from Polygonatum cyrtonema Hua is determined,and it is proven that the polysaccharide has a good anti-fatigue effect and can promote the growth of probiotics in the intes-tine,which provides a basis for product development using this polysaccharide as a functional ingredient.
7.Risk factors and prediction model of acute respiratory failure in patients with hypertriglyceridemic acute pancreatitis
Yaobing LIANG ; Zhenhua FU ; Ziyue ZHAO ; Jianming LUO ; Dongyu CHENG ; Haixing JIANG ; Shanyu QIN
Tianjin Medical Journal 2024;52(11):1183-1187
Objective To analyze risk factors of acute respiratory failure(ARF)in patients with hypertriglyceridemia acute pancreatitis(HTG-AP)and construct a risk prediction model.Methods A total of 222 HTG-AP patients were included in this study and divided into the non-ARF group(176 cases)and the ARF group(46 cases)according to diagnostic guidelines for ARF.Clinical data of the two groups were compared and the predictive factors were screened.These selected factors were then utilized in a multivariate Logistic regression analysis to construct a Logistic regression model.Subsequent evaluation of the model′s predictive ability,accuracy and clinical utility was conducted through ROC,curve analysis,calibration plot examination and decision curve analysis(DCA),respectively.Results Compared with the non-ARF group,the levels of high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL)-C and albumin(ALB)were decreased in the ARF group(P<0.05),while the levels of creatinine(Cr),urea nitrogen(BUN),aspartate aminotransferase(AST)and C-reactive protein(CRP)were increased,and the incidence of pleural fluid and ascites was also increased(P<0.05).Multivariate Logistic regression analysis showed that higher levels of Cr and AST,lower levels of ALB,HDL-C and ascites were independent risk factors for HTG-AP complicated ARF(P<0.05).Based on these results,a column-line prediction model for HTG-AP complicated ARF was established.After internal verification,the area under curve(AUC)of receiver operating characteristic(ROC)curve of the nomogram model was 0.952(95%CI:0.923-0.981),the Youden index was 0.808 and the sensitivity and specificity were 93.33%and 87.43%,respectively.The calibration curve showed that the probability of HTG-AP concurrent ARF predicted by the model was in good agreement with the actual probability.The DCA curve showed that the model had certain clinical value.Conclusion The nomogram prediction model combined could provide a scheme for the clinical prevention of HTG-AP complicated with ARF.
8.Clinical diagnosis and treatment of peripelvic cysts
Wenyao LIN ; Yangyang PANG ; Jie CHENG ; Haili WANG ; Hang WANG ; Jianming GUO
Chinese Journal of Clinical Medicine 2024;31(4):633-638
Objective To explore the diagnosis and treatment method of peripelvic cysts.Methods A retrospective analysis was conducted on 65 patients with peripelvic cysts admitted to the Department of Urology at Shanghai Xuhui Central Hospital from January 2019 to January 2023.The diagnostic value of ultrasound,intravenous urography(IVU),and computed tomography urography(CTU)for peripelvic cysts was compared,and the efficacy of different surgical treatments for peripelvic cysts was further evaluated.Results All 65 patients underwent ultrasound examination,which indicated cystic lesions at the renal hilum.55 patients underwent IVU examination,but no cyst enhancement was found.Among them,7 patients underwent retrograde pyelography due to poor imaging of the affected renal pelvis.All 53 patients who underwent CTU examination,which clearly showed the renal pelvis and cysts.Among the 65 patients,5 did not undergo surgical treatment and were followed up,while 60 underwent surgery.Four patients were considered for radical nephrectomy due to suspected malignancy.56 cases underwent renal cysts decompression surgery,including 11 open surgeries,37 laparoscopic surgeries,and 8 Da Vinci robot-assisted laparoscopic surgeries.The operative time in the open surgery group was significantly shorter than that in the laparoscopic surgery group and robot-assisted laparoscopic surgery group.Compared with the open surgery group and laparoscopic surgery group,the robot-assisted laparoscopic surgery group had less intraoperative blood loss,lower postoperative analgesic use,shorter time to first ambulation after surgery,and shorter hospital stay.Conclusions Ultrasound,IVU,and CTU are commonly used effective diagnostic tools for peripelvic cysts.Ultrasound can be used as a routine examination,while CTU is more accurate and has a higher diagnostic accuracy than IVU for this condition.Compared with open surgery,laparoscopic and robot-assisted laparoscopic cyst decompression surgery for peripelvic cysts result in less intraoperative blood loss and faster postoperative recovery.
9.Different transplantation models of hepatocellular carcinoma in mice
Rui PAN ; Kun YU ; Hailiang ZHANG ; Yongren ZHENG ; Xiaoyu ZHAO ; Junze TANG ; Jianming WU ; Xin CHENG
Acta Laboratorium Animalis Scientia Sinica 2024;32(3):329-336
Objective To explore the otherness of orthotopic injection of cell suspensions and transplantation of tumor tissue blocks to establish orthotopic implantation models of hepatocellular carcinoma in mice,and to provide a technical reference for the establishment of an orthotopic implantation model.Methods Healthy KM mice were divided into four groups:group A,direct injection of H22 cells;group B,direct injection of H22 ascitic cells;group C,transplantation of tissues;and group D,direct injection of saline.Activity and weight changes were observed regularly in each group and survival times were recorded.Liver tumor formation,tumor size,abdominal organ adhesion degree,and metastasis were observed in all groups.B-ultrasound imaging was performed,concentrations of alpha fetoprotein(AFP)and abnormal prothrombin(DCP)were detected,and liver histopathological changes were detected by hematoxylin and eosin staining.Results Mice molding operation time in groups A,B,and C were(3.36±0.44)min,(3.30±0.41)min,and(5.68±0.65)min,respectively.After modeling for 25 days,the rates of model formation in groups A,B,and C were all 100.0%.Severe abdominal adhesions occurred in 40.0%of mice in group A and 60.0%in group B,but in no mice in group C or D.Ascites occurred in 40.0%,100.0%,and 0.0%and abdominal wall tumors in 30.0%,60.0%,and 0.0%of mice in groups A,B,and C,respectively,while 40.0%of mice in group B also had liver metastasis.B-ultrasound imaging,detection of serum AFP and DCP levels,and histopathological result showed smooth liver margins,uneven echo and slightly lower echo mass,maintained high AFP and DCP secretion,and large numbers of inflammatory cells and tumor cells in mice in groups A,B,and C.Conclusions At day 25,all three methods can thus be used to establish orthotopic transplantation models of HCC.Among these,inj ection of cell suspensions demonstrated the advantage of simplicity in operation and the presence of multiple metastatic nodules within the liver,compared to transplantation of tumor tissue.Conversely,transplantation of tumor tissue showed the advantage of causing less impact on the abdomen and other organs when compared to inj ection of cell suspensions.
10.Application of TSPV 4-step teaching in skill training of gynecologic laparoscopic surgery
Cheng LIU ; Ying WANG ; Li HONG ; Jianming TANG ; Shasha HONG ; Bingshu LI
Chinese Journal of Medical Education Research 2023;22(2):272-275
Objective:To explore the application and teaching effect of TSPV (short for theoretical teaching, simulated surgical skills training, practical surgery training, and video-based review) 4-step teaching in skill training of gynecologic laparoscopic surgery.Methods:A total of 30 trainees who participated in gynecologic laparoscopic surgery training were randomly divided into two groups, with 15 in each group. The experimental group received TSPV 4-step teaching, while the control group adopted traditional teaching and completed training and assessment in stages. The general data, training assessment results, teaching feedback and satisfaction survey of the two groups were compared and analyzed. SPSS 20.0 was used for t-test and Chi-square test. Results:There was no statistical difference in age, gender distribution, education background, clinical working experiences and other general data between the two groups. There was no significant difference in the theoretical examination scores between the two groups [(85.3±4.6) vs. (83.4±4.3), P=0.252]. The scores of simulated operation assessment [(91.7±5.2) vs. [(72.4±5.9), P<0.001] and clinical practice assessment [(88.5±4.8) vs. (82.7±6.7), P=0.011] in the experimental group were better that those in the control group. In addition, the experimental group had a better overall evaluation of teaching satisfaction. Conclusion:TSPV 4-step teaching is a more optimized and popular gynecologic laparoscopic training mode, which is recommended to further promote the validation in teaching.

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