2.Plumbagin Induces Ferroptosis Through Nrf-2/Keap1 Signaling Pathway in Bladder Cancer Cells
Moran JIA ; Yiqun SHAO ; Dongya SHENG ; Mingyang WANG ; Qiang ZHANG ; Rongliang TUN ; Wenjing ZHU ; Yu PENG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(20):39-44
		                        		
		                        			
		                        			ObjectiveTo explore the mechanism of plumbagin as a novel ferroptosis inducer in bladder cancer inhibition. MethodBladder cancer T24 cells were used in this study. The effect of different concentrations of plumbagin (0.1, 1, 2, 3, 6, 12, 24, 48 μmol·L-1) on the viability of T24 cells was detected by cell counting kit-8 (CCK-8). The effect of different concentrations of plumbagin (1.5, 3, 6 μmol·L-1) on the apoptosis of T24 cells was detected by annexin V-fluorescein isothiocyanate (Annexin V FITC)/PI apoptosis kit. Different inhibitors (ferroptosis inhibitor Fer-1, apoptosis inhibitor VAD, and necroptosis inhibitor Nec-1) were used in combination with plumbagin (6 μmol·L-1). Reactive oxygen species (ROS) fluorescent probe (DCFH-DA), malonaldehyde (MDA), and glutathione (GSH) kits were used to detect the effects of different concentrations of plumbagin (1.5, 3, 6 μmol·L-1) on the level of ROS and the content of MDA and GSH in T24 cells, respectively. The effect of different concentrations of plumbagin (1.5, 3, 6 μmol·L-1) on peroxide levels in T24 cells was detected by C11-BODIPY fluorescent probe. Western blot was used to detect the effect of different concentrations of plumbagin (1.5, 3, 6 μmol·L-1) on the protein expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor-2 (Nrf-2), and Kelch-like ECH-associated protein 1 (Keap1). ResultCompared with the blank group, plumbagin could inhibit the activity of T24 cells (P<0.05) with IC50 of 3.52 μmol·L-1. At the concentrations of 1.5, 3, 6 μmol·L-1, plumbagin significantly promoted the apoptosis of T24 cells (P<0.05) as compared with the blank group. Compared with the plumbagin group at 6 μmol·L-1, the ferroptosis inhibitor and apoptosis inhibitor groups could reverse the inhibitory effect of 6 μmol·L-1 plumbagin on the proliferation of T24 cells (P<0.05). Compared with the blank group, the plumbagin groups at 1.5, 3, 6 μmol·L-1 showed increased content of ROS, MDA, and lipid peroxides in T24 cells, decreased GSH level, and reduced SLC7A11, GPX4, and Nrf-2/Keap1 (P<0.05). Conclusionplumbagin can induce ferroptosis, and its mechanism is related to the Nrf-2/Keap1 signaling pathway. 
		                        		
		                        		
		                        		
		                        	
3.Gene expression profile in human cervical epithelial cells infected with Chlamydia trachomatis
Ru JIA ; Chenli SI ; Mingyang LI ; Jia YANG ; Xinlei WU ; Shanli ZHU
Chinese Journal of Microbiology and Immunology 2023;43(2):93-101
		                        		
		                        			
		                        			Objective:To compare gene expression profiles in normal human cervical epithelial cells (HcerEpic) before and after Chlamydia trachomatis ( Ct) infection. Methods:HcerEpic cells that were pretreated with DEAE-D were infected with Ct serotype E standard strain and then cultured for 44 h. Uninfected HcerEpic cells were used as the control group. Total RNA was extracted from the cells in each group and reverse transcribed to construct a cDNA library. Differences in gene expression profiles between the two groups were analyzed by high-throughput sequencing and the representative genes were selected for verification by qPCR. Results:A total of 23 997 genes were detected, including 125 differentially expressed genes. Among the 125 genes, 119 were up-regulated and six were down-regulated. GO analysis showed that the differentially expressed genes were enriched in several biological processes including defense response to virus, typeⅠinterferon signaling pathway and cellular responses to typeⅠinterferons. KEGG enrichment analysis showed the differentially expressed genes were mainly enriched in the pathways related to virus infections, such as influenza A virus, herpes simplex virus, EB virus and HPV, and NOD-like receptor pathway.Conclusions:There were significant differences in transcriptome profiles of HcerEpic cells before and after Ct infection. The differentially expressed genes were mainly enriched in the interferon pathway, which was closely related to the antiviral processes in cells. qPCR verified the differentially expressed genes and the genes closely related to the interferon pathway, such as ISG15, IFIT2, OASL and UBE2L6.
		                        		
		                        		
		                        		
		                        	
4.Butorphanol affects the proliferation, migration and invasion of osteosarcoma MG-63 cells via Hippo/YAP signaling pathway
DU Jianguo ; ZHANG Xun ; ZONG Shilan ; ZHANG Mingyang ; JIA Wanghua ; LIU Zhidong
Chinese Journal of Cancer Biotherapy 2023;30(9):797-803
		                        		
		                        			
		                        			[摘  要]  目的:探讨布托啡诺(BPH)对骨肉瘤(OS)细胞增殖、迁移和侵袭的影响及其相关的作用机制。方法:将MG-63细胞分为对照组、YAP抑制剂组(维替泊芬组)和BPH低、中、高浓度组,MTT法、克隆形成实验、FCM术、划痕愈合实验、Transwell实验、qPCR法、WB法和移植瘤实验分别检测处理后各组细胞的增殖活性、克隆形成数、细胞凋亡率、划痕愈合率,以及上皮钙黏蛋白(E-cadherin)、神经钙黏蛋白(N-cadherin)、波形蛋白(vimentin)mRNA的表达和YAP、TAZ蛋白的表达,同时观察BPH和维替泊芬对移植瘤生长的影响。结果:与对照组相比,维替泊芬组和BPH低、中、高浓度组细胞增殖活性、克隆数、划痕愈合率、侵袭细胞数,以及N-cadherin和vimentin mRNA水平、YAP和TAZ蛋白表达及移植瘤体积均显著降低(均P<0.05),细胞凋亡率、E-cadherin mRNA水平及对移植瘤的抑瘤率均升高(均P<0.05),且BPH高浓度组与维替泊芬组之间各项指标均无明显差异(均P>0.05)。结论:BPH可能通过抑制Hippo/YAP信号通路来抑制OS细胞MG-63增殖、迁移和侵袭。
		                        		
		                        		
		                        		
		                        	
5.Survival efficacy of MDS/AML patients with TP53 abnormal received allogeneic hematopoietic stem cell transplantation
Dan FENG ; Mingyang WANG ; Jia LIU ; Haixiao ZHANG ; Xin CHEN ; Rongli ZHANG ; Weihua ZHAI ; Qiaoling MA ; Aiming PANG ; Donglin YANG ; Jialin WEI ; Yi HE ; Sizhou FENG ; Mingzhe HAN ; Erlie JIANG
Chinese Journal of Hematology 2023;44(3):222-229
		                        		
		                        			
		                        			Objective:TP53-abnormal MDS/acute myeloid leukemia (AML) patients’ allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment’s effectiveness and influencing factors should be studied.Methods:42 patients with TP53 gene status change MDS/AML who underwent allo-HSCT from 2014.8.1 to 2021.7.31 at the Hematology Hospital of the Chinese Academy of Medical Sciences were the subject of a retrospective analysis. The 42 patients were divided into three groups: the TP53 deletion group (group A) , TP53 mono-alle mutation group (group B) , and TP53 multi-hit group (group C) . The differences in clinical features and prognostic factors after transplantation were analyzed.Results:There were 42 MDS/AML patients, including 21 patients with MDS, and 21 patients with AML. The median follow-up period was 34.0 (7.5-75.0) months and the median patient age at the time of transplantation was 41.5 (18-63) years old. The total OS was 66.3% (95% CI 53.4%-82.4%) in 3 years after transplantation, and EFS was 61.0% (95% CI 47.7%-78.0%) in 3 years. For 3 years after receiving hematopoietic stem cell transplantation, there were no statistically significant differences in 3-year OS and EFS in groups A, B, and C ( P≥0.05) . The 3 years OS was 82.5% (95% CI 63.1%-100.0%) in group A, 60.6% (95% CI 43.5%-84.4%) in group B, and 57.1% (95% CI 30.1%-100.0%) in group C. Univariate analysis revealed that the number of co-mutant genes, pre-HSCT treatment, and disease type did not affect prognosis, while age, karyotype, co-mutation, positive blast cell before transplantation, and positive blast cell after transplantation were common prognostic factors for OS and EFS ( P<0.1) . MRD levels before transplantation were found to be independent risk factors for OS ( P=0.037, HR=33.40, 95% CI 1.24-901.17) in a multivariate analysis. Conclusion:Patients with MDS/AML who have TP53 mutations can benefit from allo-HSCT, but patients with complex karyotypes have a worse prognosis. Meanwhile, the final flow cytometry (FCM) monitoring blast cell test before HSCT has a certain guiding significance for prognostic assessment.
		                        		
		                        		
		                        		
		                        	
6.Effect evaluation of PBL and LBL combined teaching method in teaching the skeletal motor system diseases
Xue JIA ; Yuangang WU ; Mingyang LI ; Limin WU ; Kaibo SUN ; Quan CHEN ; Ping QING
Chinese Journal of Medical Education Research 2022;21(8):1012-1015
		                        		
		                        			
		                        			Objective:To explore the effect of combined problem-based learning (PBL) and lecture-based learning (LBL) on the teaching of skeletal motor system diseases for eight-year clinical medicine program students.Methods:The clinical eight-year medical students from Batch 2014 and 2015 participating in the teaching of "osteoarthritis" in the course of Skeletal Motor System Diseases in West China Clinical Medical College of Sichuan University were divided into control group (60 students) and experimental group (82 students). The control group was taught by LBL teaching method, while the experimental group was taught by PBL+LBL teaching method. A questionnaire survey was conducted to retrospectively analyze the teaching effects, including learning enthusiasm, knowledge understanding, thinking ability, teamwork ability, practical ability, self-learning ability and teacher-student relationship, as well as the evaluation of teaching satisfaction. The SPSS 22.0 software was used for t test and chi-square test. Results:The survey results showed that students in the experimental group were significantly superior to those in the control group in such aspects as learning enthusiasm (8.00±1.61 vs. 7.28±1.98), knowledge understanding (8.02±1.59 vs. 7.33±1.79), thinking ability (8.34±1.66 vs. 7.42±1.90), teamwork ability (8.32±1.76 vs. 6.60±2.79), practical ability (7.70±1.69 vs. 6.87 ± 2.57), self-learning ability (8.05±1.65 vs. 7.35±2.48) and teacher-student relationship (7.96±1.75 vs. 7.25±2.10), with statistically significant differences ( P<0.05). Meanwhile, the PBL+LBL group was more satisfied with the teaching mode than the LBL group, and the difference was statistically significant ( P<0.05). Conclusion:The application of PBL+LBL teaching method in clinical medicine eight-year program course teaching of "osteoarthritis" in Skeletal Motor System Diseases can effectively improve the learning enthusiasm of students, improve the quality of education, and obtain good teaching effect.
		                        		
		                        		
		                        		
		                        	
7.Optimization strategy for anesthesia in patients with moyamoya disease undergoing revascularization: scalp nerve block combined with general anesthesia
Guoshuang LI ; Jia JIA ; Beibei ZHANG ; Liming ZHAO ; Mingyang SUN ; Weijia ZHANG ; Sizhe DU ; Chaoyue LI ; Jiaqiang ZHANG
Chinese Journal of Anesthesiology 2022;42(11):1289-1292
		                        		
		                        			
		                        			Objective:To evaluate the efficacy of scalp nerve block combined with general anesthesia in optimizing anesthesia in the patients with moyamoya disease undergoing revascularization.Methods:A total of 154 patients with moyamoya disease, aged 18-64 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective revascularization, were divided into 2 groups ( n=77 each) using a random nunber table method: scalp nerve block combined with general anesthesia group (GN group) and general anaesthesia group (G group). Anesthesia was induced with intravenous midazolam 0.05 mg/kg, sufentanil 0.5-1.0 μg/kg, rocuronium 0.6 mg/kg and etomidate 0.2-0.3 mg/kg.After the patients were tracheally intubated after anesthesia induction, ipsilateral scalp nerve block (2 ml for supraorbital nerve block, 2 ml for supratrochlear nerve block; 3 ml for auriculotemporal nerve block, 3 ml for greater occipital nerve block, 3 ml for less occipital nerve block) was performed with 0.5% ropivacaine in GN group.The equal volume of normal saline was locally injected in G group.Anesthesia was maintained by inhalation of sevoflurane and intravenous infusion of remifentanil 0.05-0.10 μg·kg -1·min -1 and cisatracurium 0.1 mg·kg -1·h -1.The consumption of intraoperative remifentanil, requirement for postoperative rescue analgesia, nausea and vomiting, length of postoperative hospital stay, and early neurological complications were recorded.The modified Rankin Scale scores were evaluated before operation, at discharge and at 6 months after operation. Results:Compared with G group, the consumption of intraoperative remifentanil and requirement for postoperative rescue analgesia were significantly decreased ( P<0.05), and no significant change was found in the incidence of postoperative nausea and vomiting, incidence of neurological complications, length of postoperative hospital stay, and modified Rankin Scale scores at each time point in GN group ( P>0.05). Conclusions:Scalp nerve block combined with general anesthesia can increase the perioperative analgesic efficacy and is helpful in achieving a low-opioid anesthesia mode when used in the patients with moyamoya disease undergoing revascularization.
		                        		
		                        		
		                        		
		                        	
8.Application of FLASH radiotherapy with an ultra-high dose rate in malignant tumor
Hui LUO ; Mingyang YAN ; Xuechao JIA ; Ran ZHAO ; Xiaohui WANG ; Ronghu MAO ; Leijie MA ; Hongchang LEI ; Hong GE
Chinese Journal of Radiological Medicine and Protection 2021;41(8):636-640
		                        		
		                        			
		                        			As a method for local treatment, radiotherapy plays a key role in the management of tumors. In the past few decades, great progress has been made in radiotherapy technology, with improvements in conformity, homogeneity, and radiotherapy efficiency, and the results are encouraging. Nevertheless, the maximum tolerated dose of normal tissue has limited the further increase in radiotherapy dose in the tumor area. If radiation-induced toxicities can be reduced, a higher radiotherapy dose can be delivered to tumor tissue, so as to achieve a better treatment response. In recent years, the unique FLASH effect of ultra-high-dose-rate radiotherapy (FLASH-RT) is capable of maintaining a consistent tumor response whilst reducing radiation-induced toxicities in normal tissue, and therefore, FLASH-RT has become a research hotspot in the field of radiotherapy across the world. At present, some scholars tend to explain the FLASH effect using the theory of acute oxygen depletion, but the protective effect of FLASH-RT on normal tissue remains to be clarified. In addition, preliminary clinical studies have been conducted for FLASH-RT, and the results are promising. Based on existing evidence, this article elaborates on the research advances in FLASH-RT in the treatment of malignant tumor, so as to provide a reference for the translation and application of this new technique.
		                        		
		                        		
		                        		
		                        	
9.Doctor visit, rehabilitation and foster care of children with autism spectrum disorders in Heilongjiang Province
LIU Xiaocui, WANG Jia, SUN Caihong, ZOU Mingyang, MA Yongjuan, WANG Lin, WU Lijie
Chinese Journal of School Health 2019;40(4):503-506
		                        		
		                        			Objective:
		                        			To understand the status of doctor visit, rehabilitation and foster care of children with autism spectrum disorders in Heilongjiang Province, and to provide a scientific reference for improving ASD rehabitation education system and making the related policies.
		                        		
		                        			Methods:
		                        			Eight autism rehabilitation institutions were selected in Heilongjiang Province by stratified cluster sampling, 357 primary caregivers of ASD children participated in the survey by using the questionnaire "ASD Children’s Rehabilitation Education Status and Needs".
		                        		
		                        			Results:
		                        			The average age of abnormal behavior found of ASD children was (31.08±12.96)months, and the average age of first doctor visit was (35.88±13.20) months, the average age of diagnose was (38.64±13.20) months, and initial rehabilitation was (43.56±16.08)months. The proportion of children who had been diagnosed and have trained in the rehabilitation institutions before the age of 3 years was only 39.0% and 32.0%, respectively. The proportion of rehabilitation out of home town was 47.3%, and rehabilitation >20 hours per week was 73.4%. The proportion of fathers’ and mothers’ work lives affected was 34.5% and 67.8%, respectively, the differences were of statistical signficance(χ2=226.32, P<0.01). About 41.2% of ASD families received government financial support.
		                        		
		                        			Conclusion
		                        			The average age of diagnose is late prolonged, and the proportion of children diagnosed and training before the age of 3 years was relatively low. There were obvious regional differences of rehabilitation education resources distributions of ASD in Heilongjiang Province. The results also demonstrate the need to sustain and enhance the coverage rate of the government financial support.
		                        		
		                        		
		                        		
		                        	
10.Anesthetic management of pediatric patients with Kasabach-Merritt phenomenon undergoing radical resection for huge hemangioma of head and neck
Mingyang SUN ; Ningtao LI ; Xiaoguo RUAN ; Enqiang CHANG ; Jia JIA ; Wei ZHANG ; Jiaqiang ZHANG
Chinese Journal of Anesthesiology 2018;38(4):462-465
		                        		
		                        			
		                        			Nine pediatric patients (4 females,5 males) with huge hemangioma of head and neck complicated with Kasabach-Merritt phenomenon,aged 15-135 days,undergoing elective radical resection for huge hemangioma of head and neck,were selected from June 2012 to June 2016 in our hospital.Two pediatric patients were sensitive to preoperative hormone treatment,the platelet count almost increased to the normal value,7 pediatric patients were not sensitive to preoperative hormone treatment,and the increase in platelet count was not obvious.When the platelet count < 40× 109/L,platelet was infused at 12 h before operation until the platelet count > 100× 109/L.Two pediatric patients with larger haemangioma in maxillofacial region kept spontaneous breathing,and anesthesia was induced by inhaling high-concentration of sevoflurane.Anesthesia was induced with intravenous midazolam,sufentanil and cisatracurium in the other seven pediatric patients.Pediatric patients were mechanically ventilated in pressure-controlled mode after endotracheal intubation with airway pressure of 9-12 cmH2O.All pediatric patients inhaled sevoflurane,and anesthesia was maintained by infusing remifentanil.Heart rate and systolic blood pressure were maintained within the normal range during operation.Fluid and blood products were infused according to the blood loss,urine volume,physiological requirement and central venous pressure,etc.Pediatric patients were transferred to pediatric intensive care unit (PICU) at the end of operation,and the endotracheal tube was removed after the patients were completely awake.One pediatric patient developed pulmonary infection after operation,was discharged from PICU on day 7 after operation,then cured and discharged from hospital after healing on day 20 after operation.The other eight pediatric patients were discharged from PICU on day 2 after operation,then cured and discharged from hospital on days 5-10 after operation.After a followup period of 1 yr,the pediatric patients recovered well,the platelet count was normal,and the tumor recurrence was not found.
		                        		
		                        		
		                        		
		                        	
            

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