1.The Mechanism of BPTF Mediating SLC40A1 in Regulating Ferroptosis and Promoting Glioma Growth,Invasion and Metastasis
Zhiren LIN ; Yanling PAN ; Yanxing ZHU
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(4):507-512,534
Objective To verify the mechanism of bromodomain PHD finger transcription factor(BPTF)affecting develop-ment of glioma and ferroptosis by regulating the expression of solute carrier family 40 member 1(SLC40A1)in glioma cells by in v itro and invivo experiments.Methods U87MG cells were divided into sh-NC group,sh-BPTF group,sh-BPTF+ov-NC group and sh-BPTF+ov-SLC40A1 group.Cell lines were stably transfected by lentivirus,and the transfection efficiency was verified by qRT-PCR and Western blotting.Cell proliferation ability was detected by CCK-8 and plate clone formation test.Cell migra-tion and invasion ability were detected by Transwell.Cells were injected subcutaneously into nude mice to detect the tumor growth.To evaluate theferroptosis of cells,the reactive oxygen species(ROS)level,iron content,malondialdehyde(MDA)con-tent and reduced glutathione/oxidized glutathione(GSH/GSSG)ratio in cells were detected by corresponding kits.Co-immuno-precipitation(Co-IP)experiment was used to verify the interaction between BPTF and c-Myc protein.Chromatin immunoprecipi-tation(ChIP)experiment was used to verify that BPTF and c-Myc combined with SLC40A1 promoter.Double luciferase reporter gene experiment was used to verify theeffect of BPTF on SLC40A1 transcription.Results After BPTF knockdown,theexpres-sion of SLC40A1 in glioma cell was decreased,cell proliferation,migration,invasion in vitro,and tumor growth in vivo were in-hibited,iron content,ROS level and MDA content in cells were increased,and GSH/GSSG ratio in cell was de-creased.Overexpression of SLC40A1 reversed the inhibitory effect of BPTF on the proliferation,migration,invasion and tumor grow th in vivo,decreased the iron content,ROS level and MDA content in cells,and increased the GSH/GSSG ratio in cells.There was an interaction between BPTF and c-Myc proteins in gliomacells.A potential binding site of c-Mycin SLC40A1 promoter was verified,BPTF and c-Myc protein bound to SLC40A1 promoter.BPTF knockdown reduced the transcriptional ac-tivity of SLC40A1 promoter,and BPTF knockdown after binding site mutation did not affect the transcriptional activity of SLC40A1 promoter.Conclusion BPTF may upregulate the expression of its downstream target gene SLC40A1 by interacting with c-Myc,thereby inhibiting ferroptosis in glioma cells and promoting glioma progression.
2.The Mechanism of BPTF Mediating SLC40A1 in Regulating Ferroptosis and Promoting Glioma Growth,Invasion and Metastasis
Zhiren LIN ; Yanling PAN ; Yanxing ZHU
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(4):507-512,534
Objective To verify the mechanism of bromodomain PHD finger transcription factor(BPTF)affecting develop-ment of glioma and ferroptosis by regulating the expression of solute carrier family 40 member 1(SLC40A1)in glioma cells by in v itro and invivo experiments.Methods U87MG cells were divided into sh-NC group,sh-BPTF group,sh-BPTF+ov-NC group and sh-BPTF+ov-SLC40A1 group.Cell lines were stably transfected by lentivirus,and the transfection efficiency was verified by qRT-PCR and Western blotting.Cell proliferation ability was detected by CCK-8 and plate clone formation test.Cell migra-tion and invasion ability were detected by Transwell.Cells were injected subcutaneously into nude mice to detect the tumor growth.To evaluate theferroptosis of cells,the reactive oxygen species(ROS)level,iron content,malondialdehyde(MDA)con-tent and reduced glutathione/oxidized glutathione(GSH/GSSG)ratio in cells were detected by corresponding kits.Co-immuno-precipitation(Co-IP)experiment was used to verify the interaction between BPTF and c-Myc protein.Chromatin immunoprecipi-tation(ChIP)experiment was used to verify that BPTF and c-Myc combined with SLC40A1 promoter.Double luciferase reporter gene experiment was used to verify theeffect of BPTF on SLC40A1 transcription.Results After BPTF knockdown,theexpres-sion of SLC40A1 in glioma cell was decreased,cell proliferation,migration,invasion in vitro,and tumor growth in vivo were in-hibited,iron content,ROS level and MDA content in cells were increased,and GSH/GSSG ratio in cell was de-creased.Overexpression of SLC40A1 reversed the inhibitory effect of BPTF on the proliferation,migration,invasion and tumor grow th in vivo,decreased the iron content,ROS level and MDA content in cells,and increased the GSH/GSSG ratio in cells.There was an interaction between BPTF and c-Myc proteins in gliomacells.A potential binding site of c-Mycin SLC40A1 promoter was verified,BPTF and c-Myc protein bound to SLC40A1 promoter.BPTF knockdown reduced the transcriptional ac-tivity of SLC40A1 promoter,and BPTF knockdown after binding site mutation did not affect the transcriptional activity of SLC40A1 promoter.Conclusion BPTF may upregulate the expression of its downstream target gene SLC40A1 by interacting with c-Myc,thereby inhibiting ferroptosis in glioma cells and promoting glioma progression.
3.Effect of Anchang Decoction on intestinal flora and fecal calcitonin in rats with severe ulcerative colitis
Xuan YU ; Sihua LAI ; Dan GAO ; Zhiren ZHU ; Zebin TANG ; Linguang SI ; Pinghao NONG ; Pingliang SUN
International Journal of Traditional Chinese Medicine 2023;45(6):714-718
Objective:To investigate the effects of Anchang Decoction on intestinal microflora and faecal calprotectin (FC) in rats with severe ulcerative colitis based on probiotics.Methods:Totally 50 rats were taken to prepare a model of severe ulcerative colitis. The rats who successfully modeled were divided into model group, Anchang Decoction low-, medium-, high-dosage groups, Lizhu Changle group, and mesalazine group, with 5 rats in each group. Another 6 rats were set and the blank group. Lizhu Changle group received Lizhu Changle suspension (containing 50 million live bacteria/ml) for gavage; Anchang Decoction low-, medium-, high-dosage groups received Anchang Decoction 1, 5, 10 ml/(kg·d) for gavage; Mesalazine group received Mesalazine suspension (10.5 mg/100 g) for gavage. Rats in the blank group and model group were gavaged with the same volume of normal saline for 7 days. Body mass and disease activity index (DAI) before and after administration were measured. 16s rDNA of lactobacillus and bifidobacterium in feces of rats was detected. FC content of rats was detected by ELISA.Results:Compared with the model group, the weight of rats in each administration group increased ( P<0.05), DAI score decreased ( P<0.05), and the level of calprotectin in feces decreased ( P<0.05), and there was no significant difference in the levels of lactobacillus and bifidobacterium in each administration group ( P>0.05). Conclusion:Anchang Decoction can improve the intestinal micro-ecology by regulating the level of calprotectin in rats with severe ulcerative colitis, thereby playing a therapeutic role.
4.Construction of the "Internet + " PICC home nursing service quality evaluation index system
Chunbo LIU ; Qingwen SU ; Simeng WANG ; Qian XU ; Fengwei ZHU ; Haiping YANG ; Wenmin SU ; Zhiren SHENG
Chinese Journal of Modern Nursing 2023;29(33):4507-4514
Objective:To construct the "Internet +" peripherally inserted central catheter (PICC) home nursing service quality evaluation index system, so as to provide objective basis for standardizing the "Internet +" PICC home nursing service quality evaluation.Methods:Based on the three-dimensional quality structure model of "structure-process-outcome", combined with literature research, semi-structured interviews, group discussions and Delphi method, 20 experts who were engaged in intravenous therapy nursing and had management or practical experience in "Internet + nursing services" were selected for two rounds of consultation to determine the "Internet?+" PICC home nursing service quality evaluation index system. The positive coefficient of experts was expressed by the effective response rate of the questionnaire and the rate of expert opinion submission. The degree of expert authority was expressed by the expert authority coefficient. The coordination degree of expert opinions was represented by the Kendall harmony coefficient. The concentration degree of expert opinions was usually expressed in terms of the importance assigned to the indicator, the coefficient of variation, and the full score rate (%) .Results:The effective response rates of the two rounds of consultation questionnaires were all 100%, with expert authority coefficients of 0.793 and 0.848 respectively. The Kendall coordination coefficients of expert opinions were 0.202-0.216 and 0.222-0.270 respectively ( P<0.05). After the second round of expert consultation, the mean importance assigned to all indicators was greater than 4.0, the coefficient of variation was less than 0.2, and the full score rate was greater than 20%. The final "Internet +"PICC home nursing service quality evaluation index system included 3 first-level indicators, 12 second-level indicators and 64 third-level indicators. Conclusions:The "Internet + " PICC home nursing service quality evaluation index system constructed is scientific, reliable and practical, and reflects the specialty characteristics. It can effectively evaluate the "Internet + " PICC home nursing service quality and provide guidance for continuous improvement.
5.The clinical effect of computerized cognitive remediation therapy in schizophrenic patients with different levels of cognitive impairment
Jie ZHANG ; Hongzhen FAN ; Xiaolin ZHU ; Yunhui WANG ; Yunlong TAN ; Fude YANG ; Zhiren WANG ; Yanli ZHAO ; Fengmei FAN ; Junhua GUO ; Zhanjiang LI ; Wenxiang QUAN ; Xiangqun WANG ; Dongfeng ZHOU ; Yizhuang ZOU ; Shuping TAN
Chinese Journal of Psychiatry 2020;53(4):328-334
Objective:To explore the improvement rate of the cognitive function of computerized cognitive remediation therapy (CCRT) on patients with schizophrenia and the clinical effect of CCRT in patients with different levels of cognitive impairment.Methods:A random number table was used to divide 311 patients with schizophrenia into CCRT group ( n=196) and work and amusement therapy (WAT) group ( n=115). The independently developed CCRT and operational music and dance therapy were given for 12 weeks to two treatment groups respectively. All patients were assessed using the MATRICS Consensus Cognitive Battery (MCCB) before and after treatment. According to the total score of MCCB at baseline, the patient′s cognition function was divided into 4 levels: severe cognitive impairment, moderate cognitive impairment, mild cognitive impairment and normal cognitive function. According to the change of MCCB total score, the efficacy of the treatment was divided into 3 levels: no improvement (≤0 points), improvement (0-9.57 points), superior improvement (>9.57 points). The improvement rate of cognitive function between two treatment groups was compared. Results:In the CCRT group, there were 19 cases with superior improvement, 105 cases with improvement, and 46 cases with no improvement. In the WAT group, there were 7 cases with superior improvement, 39 cases with improvement, and 41 cases with no improvement. The improvement of cognitive function of CCRT group was better than that of WAT group, and the difference was statistically significant ( Z=2.978, P=0.003). The patients with serious cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group ( Z=1.860, P=0.032). The patients with moderate cognitive impairment in the CCRT group had a lower no improvement rate than those in the WAT ( Z=-1.817, P=0.035).The patients with mild cognitive impairment in the CCRT group had a lower no improvement rate ( Z=-3.294, P=0.001) and higher improvement rate and superior improvement rate ( Z=2.084, P=0.019; Z=1.969, P=0.025) than those in the WAT group. There was no statistically significant difference in improvement rate between patients with normal cognitive function in the CCRT group and in the WAT group ( P>0.05).The patients with improvement and superior improvement of cognition were combined as responder, and the two treatment groups were compared. The patients with mild cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group (77.2%(44/57) vs. 41.4%(12/29),χ2=10.853, P=0.001). However, for patients with serious and moderate cognitive impairment or with normal cognitive function at baseline, rates of improvement after treatment did not differ significantly between CCRT group and WAT group. According to Cohen′s d, the level of effect size in cognition improvement after CCRT treatment in patients with different cognitive dysfunction level was: mild cognitive impairment (0.59)>moderate cognitive impairment (0.48)>normal cognitive function (-0.12)>serious cognitive impairment (-0.24). Conclusions:Schizophrenic patients treated with CCRT had a higher improvement rate of cognitive function than those with WAT, and the improvement rate of cognitive function is higher in patients with mild cognitive impairment after CCRT treatment.
6.The clinical effect of computerized cognitive remediation therapy in schizophrenic patients with different levels of cognitive impairment
Jie ZHANG ; Hongzhen FAN ; Xiaolin ZHU ; Yunhui WANG ; Yunlong TAN ; Fude YANG ; Zhiren WANG ; Yanli ZHAO ; Fengmei FAN ; Junhua GUO ; Zhanjiang LI ; Wenxiang QUAN ; Xiangqun WANG ; Dongfeng ZHOU ; Yizhuang ZOU ; Shuping TAN
Chinese Journal of Psychiatry 2020;53(4):328-334
Objective:To explore the improvement rate of the cognitive function of computerized cognitive remediation therapy (CCRT) on patients with schizophrenia and the clinical effect of CCRT in patients with different levels of cognitive impairment.Methods:A random number table was used to divide 311 patients with schizophrenia into CCRT group ( n=196) and work and amusement therapy (WAT) group ( n=115). The independently developed CCRT and operational music and dance therapy were given for 12 weeks to two treatment groups respectively. All patients were assessed using the MATRICS Consensus Cognitive Battery (MCCB) before and after treatment. According to the total score of MCCB at baseline, the patient′s cognition function was divided into 4 levels: severe cognitive impairment, moderate cognitive impairment, mild cognitive impairment and normal cognitive function. According to the change of MCCB total score, the efficacy of the treatment was divided into 3 levels: no improvement (≤0 points), improvement (0-9.57 points), superior improvement (>9.57 points). The improvement rate of cognitive function between two treatment groups was compared. Results:In the CCRT group, there were 19 cases with superior improvement, 105 cases with improvement, and 46 cases with no improvement. In the WAT group, there were 7 cases with superior improvement, 39 cases with improvement, and 41 cases with no improvement. The improvement of cognitive function of CCRT group was better than that of WAT group, and the difference was statistically significant ( Z=2.978, P=0.003). The patients with serious cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group ( Z=1.860, P=0.032). The patients with moderate cognitive impairment in the CCRT group had a lower no improvement rate than those in the WAT ( Z=-1.817, P=0.035).The patients with mild cognitive impairment in the CCRT group had a lower no improvement rate ( Z=-3.294, P=0.001) and higher improvement rate and superior improvement rate ( Z=2.084, P=0.019; Z=1.969, P=0.025) than those in the WAT group. There was no statistically significant difference in improvement rate between patients with normal cognitive function in the CCRT group and in the WAT group ( P>0.05).The patients with improvement and superior improvement of cognition were combined as responder, and the two treatment groups were compared. The patients with mild cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group (77.2%(44/57) vs. 41.4%(12/29),χ2=10.853, P=0.001). However, for patients with serious and moderate cognitive impairment or with normal cognitive function at baseline, rates of improvement after treatment did not differ significantly between CCRT group and WAT group. According to Cohen′s d, the level of effect size in cognition improvement after CCRT treatment in patients with different cognitive dysfunction level was: mild cognitive impairment (0.59)>moderate cognitive impairment (0.48)>normal cognitive function (-0.12)>serious cognitive impairment (-0.24). Conclusions:Schizophrenic patients treated with CCRT had a higher improvement rate of cognitive function than those with WAT, and the improvement rate of cognitive function is higher in patients with mild cognitive impairment after CCRT treatment.
7. The relationship between serum high density lipoprotein levels and cognitive function in patients with bipolar disorder
Hongliang ZHU ; Jie CHEN ; Xuyuan YIN ; Baohua ZHANG ; Zhiren WANG ; Qiufang JIA ; Ke ZHENG ; Xiaoli YIN ; Li HUI
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(9):806-810
Objective:
To explore the correlation between serum high density lipoprotein (HDL) levels and cognitive function in patients with bipolar disorder.
Methods:
A total of 99 patients with bipolar disorder were enrolled from the inpatient of Suzhou Guangji Hospital.Serum HDL levels were measured by enzymatic colourimetry.Cognitive function was assessed by the repeatable battery for the assessment of neuropsychological status (RBANS). The relationship between serum high density lipoprotein and cognitive function was analyzed by correlation analysis and stepwise multiple regression analysis.
Results:
Serum HDL levels ((1.39±0.55)mmol/L)were positively correlated with the RBANS total score (68.92±12.48)(
8.Analysis of the influencing factors for the cognitive deficits in schizophrenic patients with diabetes
Baohua ZHANG ; Xiaole HAN ; Zhiren WANG ; Shurong JIANG ; Xiaoyu ZHU ; Limin XIN ; Yun BIAN ; Xingjie YANG ; Qingyan YANG ; Fude YANG ; Yunlong TAN
Chinese Journal of Behavioral Medicine and Brain Science 2018;27(3):246-251
Objective To investigate the influencing factors of the cognitive deficits in schizophrenic patients with diabetes.Methods 578 inpatients with schizophrenia and 400 healthy adults were collected.578 schizophrenic patients were divided into schizophrenia group with type 2 diabetes (combined group,n=277) and schizophrenia without type 2 diabetes (single disease group,n=301).The cognitive function of all subjects were examined by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).The clinical symptoms of patients with schizophrenia were measured with the Positive and Negative Syndrome Scale (PANSS).Fasting glucose,lipids,hemoglobin A1c (HbA1c) and insulin levels were measured.Results The total score and factor scores of RBANS in the combined group were lower than those in the healthy control group (total score (70.51 ± 14.43) vs (80.04 ± 15.14),immediate memory (62.65 ± 16.81) vs (75.66± 17.33),visual span(83.60±20.81) vs (87.61 ± 15.61),verbal function(85.58± 14.64) vs (93.88± 13.10),attention function (73.66± 17.52) vs (87.42±20.37),delayed memory(75.27± 17.80) vs (86.27± 15.27),all P<0.05).The total score of RBANS,immediate memory and attention function factor were lower in the combined group than that in the single disease group ((70.51±14.43) vs (75.02±15.25),(62.65±16.81) vs (67.37±19.12),(73.66±17.52) vs (84.17±15.22),all P<0.05).Multiple linear stepwise regression analysis showed that education,negative symptoms,positive symptoms,BMI,HbAc 1,course of disease and antipsychotic type were the influencing factors of cognitive impairment in schizophrenic patients with diabetes.Conclusion The cognitive impairment of schizophrenic patients with diabetes is more serious and affected by many factors.Targeted early intervention can help reduce cognitive impairment.
9.Therapeutic effect of cannabidiol on methionine-choline deficient diet-induced nonalcoholic steatohepatitis in rats and its mechanism
Rui CHEN ; Xiaogang GAO ; Lei ZHANG ; Xiaomin SHI ; Wenyuan GUO ; Youhua ZHU ; Zhiren FU
Medical Journal of Chinese People's Liberation Army 2017;42(6):515-519
Objective To observe whether treatment with cannabidiol (CBD) affect nonalcoholic steatohepatitis (NASH) induced by methionine choline-deficient diet (MCD) in rats and investigate the underlying molecular mechanism. Methods Sixty-three adult male SD rats were randomly divided in to three groups as follows: Control group (rats fed with normal diet), MCD group (rats fed with MCD and MCD+CBD group [rats fed with MCD and treated with cannabidiol, 2mg/(kg.d), i.p.]. Ten weeks later, steatohepatitis and fibrosis were evaluated by hematoxylin-eosin and Masson staining, respectively. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured by using an automatic biochemical analyzer and hepatic levels of cholesterol and triacylglycerol were determined with kits. Autophagic flux in livers was evaluated by Western blotting. Results Treatment with cannabidiol reduced ratio of liver/body weightratio (4.2%±0.6% versus 3.1%±0.6%, P<0.05), histological scores (4.7±1.1 versus 2.2±0.5, P<0.05) and fibrosis (1.4%±0.4% versus 0.8%±0.3%, P<0.05) in rat livers, lowered levels of ALT (214.5±54.1U/L versus 92.1±36.0U/L, P<0.05) and AST (175.9±55.2U/L versus 70.8±24.9U/L, P<0.05) in serum, attenuated hepatic fat accumulation (cholesterol, 182.4±42.7mmol/mg protein versus 101.0±33.8mmol/mg protein, P<0.05; triglyceride, 71.4±12.5mmol/mg protein versus 38.7±11.1mmol/mg protein, P<0.05), and down-regulated mRNA expression of Col1A1 (2.9±0.4 versus 1.6±0.3, P<0.05) in livers of rats fed with MCD. Furthermore, cannabidiol led to the LC3 turnover (LC3-Ⅱ/LC3-I, 37.1±10.8 versus 71.2±17.1, P<0.05) and p62 decrease (202.4±40.9 versus 125.8±32.7, P<0.05) in the livers of MCD-fed rats. Conclusion Treatment with cannabidiol could relieve MCD-induced NASH in rats, at least in part, by autophagic flux promotion.
10.Optimum extraction of polysaccharides from ophiopogon japonicus by response surface methodology
Jingwen ZHAO ; Min WANG ; Chuanjian LU ; Zhiren WANG ; Wei ZHU
International Journal of Traditional Chinese Medicine 2015;37(10):914-919
Objective To optimize the extraction of polysaccharides from Ophiopogon japonicus by the use of response surface methodology.Method According to the design principle of Box-Behnken, effects of extraction temperature, extraction time , extraction times and solid-liquid ratio on the extraction yield of Ophiopogon japonicus polysaccharides were studied by response surface methodology,meanwhile regression analysis of these experimental data was used by Design-Expert 8.05b software.Results The optimum extraction conditions from Ophiopogon japonicus were concluded as follows: the extraction temperature was 93℃, extraction time was 2 h, extraction times was 3 times, and solid-liquid ratio was 1:15 g/ml.Conclusion Under these conditions, the extraction yield of Ophiopogon japonicus polysaccharides is up to 5.440%, and the relative error is 7.328%.

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