1.Exploring the Mechanism of Anti-Colorectal Cancer Action of Fushao Diqin Decoction Based on the Nrf2/SLC7A11/GPX4 Signaling Pathway
Mingyue ZHENG ; Hongguang ZHOU ; Yupei ZHUANG ; Hongli ZHOU ; Yuwei LIANG ; Haibin CHEN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(5):457-468
OBJECTIVE To explore the mechanism of action of Fushao Diqin Decoction in the treatment of colorectal cancer.METHODS In vitro cell experiments were conducted using Fushao Diqin Decoction to treat colorectal cancer CT-26 cells,and the cell proliferation and migration abilities were detected.Flow cytometry was used to detect the levels of reactive oxygen species(ROS)in colorectal cancer CT-26 cells,as well as the levels of iron ions(Fe2+),malondialdehyde(MDA),and the activity of su-peroxide dismutase(SOD).PCR Array and Western blot methods were used to analyze and verify the differential gene expression of ferroptosis.Balb/c mice were randomly divided into a blank control group,a model group,an oxaliplatin group(1.5 mg·kg-1·d-1),a low-dose group of Fushao Diqin Decoction(4.49 g·kg-1·d-1),a medium dose group of Fushao Diqin Decoction(8.97 g·kg-1·d-1),and a high-dose group of Fushao Diqin Decoction(17.94 g·kg-1·d-1)for in vivo animal experi-ments.The effects of Fushao Diqin Decoction on Fe2+,ROS,MDA levels,SOD activity,and Nrf2,Keap1,SLC7A11 and GPX4 ex-pression levels in mouse tumor tissues were tested.RESULTS In vitro cell experiments showed that compared with the blank control group,Fushao Diqin Decoction significantly inhibited the proliferation and migration of colorectal cancer CT-26 cells in a dose-de-pendent manner.Fushao Diqin Decoction could increase the Fe2+content(P<0.05)and ROS level(P<0.01)in colorectal cancer CT-26 cells,increase the MDA level in CT-26 cells of colorectal cancer(P<0.01)and significantly reduce SOD activity(P<0.01).Iron death PCR array analysis found that compared with the blank control group,after intervention with Fushao Diqin Decoc-tion,the expression of genes GPX4 and SLC7A11 was significantly downregulated,while the expression of GSTA1,HMOX1,Ca9,Chac1,Keap1,Sqstm1,NOX1,FTH1,Tfr1,SAT2,Pparg,and Hamp was significantly upregulated.Western blot analysis revealed that after intervention with Fushao Diqin Decoction,the expression of Keap1 protein was upregulated(P<0.01),while the expression of Nrf2,SLC7A11,and GPX4 proteins was downregulated(P<0.01)in colorectal cancer CT-26 cells.The results of in vivo animal experiments showed that Fushao Diqin Decoction significantly inhibited the growth of subcutaneous transplanted tumors in mice(P<0.05),increased the degree of tumor tissue necrosis,and levels of Fe2+,ROS,and MDA(P<0.05,P<0.01),decreased SOD ac-tivity(P<0.01)and upregulated Keap1 protein expression(P<0.01),while downregulated Nrf2,SLC7A11,and GPX4 protein ex-pression(P<0.01).CONCLUSION Fushao Diqin Decoction has an anti-colorectal cancer effect and may promote ferroptosis in colorectal cancer cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway to exert its anti-colorectal cancer effect.
2.Experimental study of apoptosis induced by Talniflumate in breast cancer cells
Danqing HUANG ; Hongguang LIU ; Yongsheng CHEN ; Guopei ZHENG ; Yixue GU
Journal of Chinese Physician 2022;24(4):531-537
Objective:To explore the effect of the mucin modulator Talniflumate (Tal) on breast cancer cells and its synergistic effect after combined with the chemotherapy drug paclitaxel (PTX).Methods:The breast cancer cells were cultured in vitro. Lymphocyte proliferation activity assay (MTS) was used to detect the effects of different concentrations of Talniflumate alone and paclitaxel on the survival rate of breast cancer cells. The effects of the above drugs on the apoptosis of breast cancer cells were detected by flow cytometry. Western blot was used to detect the expression of glucosamine transferase (GCNT3) (the target of Talniflumate) in breast cancer cells before and after the treatment with Talniflumate. Transcriptome sequencing clarified the changes in related signaling pathways after treatment with Talniflumate. Results:Talniflumate promoted the apoptosis of breast cancer cells MCF7 and MDA-MB-231 cells in a concentration-dependent manner. The combination of Talniflumate and paclitaxel had a significant synergistic killing effect in MCF7 cells but not MDA-MB-231 cells. Western blot indicated that GCNT3 was highly expressed in MCF7 cells, while almost no expression in MDA-MB-231 cells; Talniflumate could reduce the expression of GCNT3 in MCF7 cells and after combined with paclitaxel, the expression of GCNT3 was downregulated more significantly. Transcriptome sequencing suggested that Talniflumate can regulate the expression of multiple signaling pathways such as TNF, p53, and SNARE.Conclusions:Talniflumate could induce apoptosis of breast cancer cell. Talniflumate combined with paclitaxel has a significant synergistic effect in killing tumor cells in breast cancer cells with high GCNT3 expression such as MCF7. The mechanism of Talniflumate induce apoptosis of breast cancer cells may be related to multiple signaling pathways such as TNF, p53, and SNARE.
3.Characteristics of obstructive sleep apnea in children with allergic rhinitis
Xiao HUANG ; Qin YANG ; Ailiang LIU ; Congcong WANG ; Jiahui LI ; Yanmin BAO ; Wenjian WANG ; Yuejie ZHENG ; Hongguang PAN
Chinese Pediatric Emergency Medicine 2022;29(8):622-625
Objective:To analyze the characteristics of sleep disordered breathing (SDB) in children with allergic rhinitis (AR), and improve the diagnosis and treatment at AR combined with obstructive sleep apnea (OSA).Methods:The clinical data of 120 patients with AR and OSA (AR and OSA group) admitted to the respiratory department at Shenzhen Children′s Hospital from May 2019 to December 2020 were retrospectively analyzed.A total of 120 children diagnosed with OSA and excluded AR during the same period were selected as control group.The SDB day and night symptoms, sleep structure characteristics and sleep breathing events were compared between two groups.Results:The average course of disease in children with AR and OSA was significantly longer than that in control group ( P=0.030). The main manifestations of children in AR and OSA group were mouth breathing (100.0%), snoring (99.2%), nasal obstruction (88.5%), and restless sleep (68.0%). There was no significant difference in sleep structure between two groups ( P>0.05), but the sleep efficiency of AR and OSA group was significantly lower than that of control group ( P=0.028). The respiratory events apnea hypopnea index, obstructive apnea index, obstructive apnea hypopnea index, hypopnea index and oxygen desaturation index of each sleep period in AR and OSA group were significantly higher than those in control group ( P<0.05). Among the children in AR and OSA group, moderate and severe OSA were the main manifestations, and the difference between two groups was statistically significant ( P<0.001). Conclusion:The combination of AR delayed the course of OSA in children.The main characteristics of sleep disordered breathing in children with AR are mouth opening, restless sleep, snoring and nasal obstruction.The sleep efficiency is decreased.Obstructive hypopnea and apnea are the most common respiratory events, and oxygen deficiency often occurs in rapid eye movement phase.Children with AR are more likely to have moderate or severe obstructive sleep apnea.
4.Application of skeletonized bilateral internal mammary artery to coronary artery bypass grafting
Jianfeng HOU ; Zhaoji ZHONG ; Haojie LI ; Kai CHEN ; Hongguang FAN ; Yi CHANG ; Ge GAO ; Zhe ZHENG ; Xiaoqi WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(09):1059-1062
Objective To evaluate short-term clinical outcomes of skeletonized bilateral internal mammary artery (sBIMA) in coronary artery bypass grafting (CABG). Methods The clinical data of 62 patients (54 males and 8 females with an average age of 56.8±6.0 years) undergoing isolated CABG using sBIMA in our hospital from October 2016 to May 2017 were retrospectively analyzed. The coronary graft flow, perioperative clinical outcomes and CT results were reviewed. Results All the operations were carried out under extracorporeal circulation. Anastomosis of 124 internal mammary arteries was performed and 116 great saphenous veins were used simultaneously with an average anastomosis site of 4.5±0.8 for each patient. The cardiopulmonary bypass time was 116.4±22.9 min, aortic clamping time was 83.0±18.3 min, mechanical ventilation time was 20.8±21.3 h and ICU stay was 2.7±1.7 d. The graft flow of left internal mammary artery (LIMA), right internal mammary artery (RIMA) and great saphenous vein were 28.8±12.4 mL/min, 32.8±13.8 mL/min and 41.5±21.5 mL/min, respectively. There was no significant difference in the graft flow between LIMA and RIMA (P=0.112). There was no perioperative mortality, myocardial infarction or cerebrovascular accident. Only one male patient suffered sternal complication and poor wound healing and then received debridement as well as suturing. Coronary CT angiography showed that distal anastomosis of 7 vein grafts and 5 artery grafts was demonstrated shallow and 1 vein graft was undemonstrated, suggesting occlusion. Conclusion CABG with sBIMA is a safe and reliable technique with excellent early results.
5.The current situation of Sino-Vietnam traditional medicine communication and strategy for traditional Chinese medicine development in Vietnam
Jieru YANG ; Hongguang YANG ; Jiayao WAN ; Xinyang SONG ; Linyun ZHENG ; Yexin LU
International Journal of Traditional Chinese Medicine 2019;41(8):797-801
Vietnam,as an important country along the "one belt and one road",is closely related to China.Chinese traditional medicine has entered Vietnam and gained strong support from policy and public recognition.It has a good foundation for development and a bright future.Based on the current situation of traditional Chinese medicine exchanges between China and Vietnam and Vietnam's basic national conditions,the author puts forward that exploring new cooperative models through multi-level cooperative projects,which relys on the role of the Chinese Chamber of Commerce,and adheres to the complementary promotion between trade in services and trade in goods.They are the feasible ways for Chinese medicine to develop in Vietnam.The development of Chinese medicine in Vietnam needs the adherance to the four principles of bidirectional positioning,suiting measures to local conditions,standardizing standards and risk prevention.
6.Hybrid surgical and interventional ablation versus video-assisted thoracoscopic surgical ablation for persistent atrial fibrillation: A case control study
LI Haojie ; ZHENG Zhe ; MENG Ying ; GAO Ge ; WANG Xiaoqi ; FAN Hongguang ; LI Linlin ; ZHONG Zhaoji
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2018;25(10):844-848
Objective To verify whether hybrid surgical and interventional ablation(HA) for the treatment of persistent atrial fibrillation (AF) is superior to video-assisted thoracoscopic surgical radiofrequency ablation (VATS-RA). Methods From September 2010 to December 2017, 79 consecutive patients with persistent AF underwent VATS-RA or HA in Fuwai Hospital. VATS-RA was performed in sixty patients (a stand-alone surgical group, 48 males and 12 females, at average age of 56.0±7.6 years, and HA was performed in nineteen patients (a hybrid group, 14 males and 5 females, at average age of 58.0±7.3 years). Follow-up was completed at 3 months, 6 months, 1 year and annually thereafter. Postoperative sinus rhythm was defined as sinus rhythm recorded in 24-hour or 7-day Holter during follow-up, without exhibited rapid atrial tachyarrhythmia≥30 s including AF, atrial flutter, or atrial tachycardia. Results Seventy-eight patients (98.7%) completed the follow-up. Although the preoperative left atrial diameter (49.1±5.3 mm) in the hybrid group was significantly greater than that in the stand-alone surgical group (41.7±6.2 mm, P<0.001). Overall sinus rhythm maintenance rate in the hybrid group was significantly greater than that in the stand-alone surgical group (94.7% versus 64.4%, P=0.011). And sinus rhythm maintenance rate free from anti-arrhythmic drugs (AADs) and catheter ablation in the hybrid group was significantly greater than that in the stand-alone surgical group (84.2% versus 50.8%, P=0.010). Conclusion HA is superior to VATS-RA in the treatment of persistent AF, but a larger sample size is needed for further validation in prospective randomized studies.
7.Outcome of video-assisted thoracoscopic bipolar epicardial radiofrequency ablation for paroxysmal atrial fibrillation
Haojie LI ; Zhe ZHENG ; Hanning LIU ; Zhengxi XU ; Ying MENG ; Xiaoqi WANG ; Ge GAO ; Linlin LI ; Hongguang FAN ; Zhaoji ZHONG
Chinese Journal of Thoracic and Cardiovascular Surgery 2018;34(4):206-209
Objective This study aimed to evaluate the safety and efficacy of video-assisted thoracoscopic bipolar radio-frequency ablation in the treatment of isolated paroxysmal atrial fibrillation.Methods From September 2010 to December 2016,Seventy-two consecutive patients with paroxysmal atrial fibrillation underwent video-assisted thoracoscopic bipolar radio-frequency ablation at Fuwai Hospital.There were 50 males and 22 females with an average age of(56.5 ± 10.5) years and duration of atrial fibrillation with (6.5 ± 4.8) years.45 patients had previous catheter ablation.The patients were followed up at postoperative 3 months,6 months,1 year and annually.Success of ablation was defined as sinus rhythm and no duration of ≥30 s for rapid atrial arrhythmias,including atrial fibrillation,atrial flutter or atrial tachycardia in 24 h Holter examination.Univariate and multivariate logistic regression models were used to analyze the risk factors for atrial fibrillation recurrence.Results One patient converted to sternotomy due to bleeding on operation.All patients were successfully discharged.69 patients completed follow-up,with an average follow-up of(28 ± 18)months(3-60 months).The overall success rate was 73.9%,and the success rate without antiarrhythmic drug was 62.3%.Subgroup analysis showed that the success rate was 80% when left atrial anterior and posterior diameter(LAD) ≤40 mm,and 57.9% when LAD > 40 mm (P =0.035).Multivariate logistic regression analysis showed that LAD >40 mm was an independent risk factor for postoperative recurrence of atrial fibrillation.Conclusion Video-assisted thoracoscopic bipolar radiofrequency ablation is a safe and effective method for the treatment of paroxysmal atrial fibrillation,especially in patients with LAD≤40 mm.
8.Routine use of bilateral internal mammary artery grafts for myocardial revascularization in diabetic patients: a propensity score matched study
ZHONG Zhaoji ; ZHENG Zhe ; WANG Xiaoqi ; GAO Ge ; LI Linlin ; FAN Hongguang ; LI Haojie
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2018;25(12):1038-1042
Objective To evaluate the influence of diabetes on coronary artery bypass graft (CABG) surgery using bilateral internal mammary artery (BIMA). Methods From December 2015 to August 2017, 182 patients (153 males, 29 females, age of 56.5±6.8 years) underwent CABG using BIMA. The propensity score was used to create matched diabetes (n=66) and non-diabetes (n=66) cohorts. The operative data, post-operative outcomes and coronary computed tomographic angiography (CTA) of the diabetes group (53 males, 13 females, age of 57.8±7.2 years) and the non-diabetes group (56 males, 10 females, age of 56.3±6.0 years) were analyzed retrospectively. Results There was no peri-operative mortality. There was no difference in operative sternal wound complication (P=0.466), or graft patency (P=0.730 for internal mammary arteries and 0.684 for saphenous vein grafts) between the matched diabetes and the non-diabetes groups. However, patients with elevated glycated hemoglobin (HbA1c) (n=54) had more sternal wound complications (P=0.006). The level of Hb1Ac of the patients with sternal wound complication was significantly higher than that of the patients without sternal wound complication. Conclusion BIMA grafting may be performed routinely even in diabetic patients, without increased complications. However, elevated HbA1c level should be avoided to reduce sternal wound complication.
9.Skeletonized versus pedicled harvesting of bilateral internal mammary artery in coronary artery bypass graft: A case control study
ZHONG Zhaoji ; HOU Jianfeng ; FAN Hongguang ; LI Haojie ; XIE Yanbo ; WANG Xiaoqi ; ZHENG Zhe ; GAO Ge
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2018;25(2):128-132
Objective To evaluate the safety and efficacy of skeletonized and pedicled harvesting of bilateral internal mammary artery (BIMA) in coronary artery bypass graft (CABG) surgery. Methods From December 2015 to May 2017, 152 patients (128 males, 24 females, age of 56.5±6.8 years) underwent CABG using either skeletonized BIMA (s-BIMA group, n=73) or pedicled BIMA(p-BIMA group, n=79). The operative data and post-operative outcomes were analyzed in the s-BIMA group (61 males, 12 females, age of 56.6±7.0 years) and the p-BIMA group (67 males, 12 females, age of 56.3±6.7 years). Results There was no peri-operative mortality. There was no statistical difference in operative time, cardiopulmonary bypass time, aortic cross-clamp time or internal mammary artery graft flow between the two groups. One patient(1.4%) in the s-BIMA group suffered from severe sternal wound complication, which was major sternal wound complication. Five patients (6.3%) in the p-BIMA group suffered from sternal wound complications, including 1(1.3%) with severe complication and 4(5.1%) with minor complication. One(1.4%) patient in the s-BIMA group and 7 (8.9%) patients in the p-BIMA group suffered from chylothorax. The chest tube drainage significantly reduced in the s-BIMA group, both in postoperative day 1(P=0.000) and postoperative day 1-3 (P=0.001). CT angiography showed no stenosis of BIMA in both groups. Conclusion The use of skeletonized BIMA for CABG is safe and efficacious, with less sternal wound complications, chylothorax and chest tube drainage. Skeletonization should be suggested if BIMA is harvested in CABG.
10.Expression of AMP-activated protein kinase in subcultured rat endplate chondrocytes
Quanlai ZHAO ; Quan ZHENG ; Hongguang XU ; Xiang SHEN ; Hong WANG ; Ping LIU ; Lingting WANG ; Xiaoming YANG ; Xuewu CHEN ; Yu ZHANG ; Yifeng LI ; Hongxing YU
Chinese Journal of Tissue Engineering Research 2016;20(29):4297-4302
BACKGROUND:Endplate cartilage degeneration initiates intervertebral disc degeneration. AMP-activated protein kinase (AMPK) regulates the formation and degradation of cartilage. OBJECTIVE:To explore the role of AMPK in an in vitro natural degeneration model of chondrocytes derived from endplate of rat intervertebral discs. METHODS:Morphology of in vitro subcultured endplate chondrocytes of rat intervertebral discs at passages 0, 2, and 5 were observed under an inverted microscope fol owing cytoskeleton staining. Chondrocyte phenotype, proliferation, and the cartilage marker genes (type II col agen, proteoglycan, SOX-9, matrix metal oproteinase-3 and-13), and AMPK phosphorylation were determined by toluidine blue staining, MTT assay, real-time PCR analysis, and western blot assay, respectively. RESULTS AND CONCLUSION:The altered morphology, decreased proliferation ability, and phenotype loss were observed in chondrocytes with increased passage number. Gene expression of type II col agen, proteoglycan, SOX-9 was significantly decreased;while gene expression of matrix metal oproteinase-3 and-13 was significantly increased in endplate chondrocytes at passage 5 compared with those at passages 0 and 2. AMPK phosphorylation in endplate chondrocytes at passage 5 was significantly decreased. These findings indicate that AMPK phosphorylation is involved in in vitro natural degeneration of chondrocytes derived from the endplate of rat intervertebral discs, and the degeneration of endplate chondrocytes and intervertebral discs can be inhibited through the regulation of AMPK activity.


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