1.Effect of Icariin Regulating mTOR/Akt/CREB Pathway on High Glucose Induced Autophagy and Apoptosis in Podocytes
Mingxia LI ; Qian YANG ; Haixia QIAO ; Xiaoling WANG ; Liyuan JIA ; Limei HU ; Weidong REN
Herald of Medicine 2024;43(1):19-25
		                        		
		                        			
		                        			Objective To investigate the effects of icariin on high glucose-induced autophagy and apoptosis of podocytes,and the regulating effects on mammalian target of rapamycin(mTOR)/serine-threonine kinase(Akt)/cyclic adenosine monophosphate response element binding protein(CREB)pathway.Methods The mouse podocytes MPC5 were taken and divided into five groups:normal control group(5.5 mmol·L-1 glucose),high glucose group(30 mmol·L-1 glucose),icariin group(30 mmol·L-1glucose+5 μmol·L-1icariin),GDC-0349 group(30 mmol·L-1glucose+50 μmol·L-1 GDC-0349),icariin+GDC-0349 group(30 mmol·L-1 glucose+5 μmol·L-1 icariin+50 μmol·L-1 GDC-0349).Cultured for 48 hours,the tetramethylazozolium salt method was used to detect the viability of MPC5 cells;acridine orange staining was used to observe the autophagy of MPC5 cells;apoptosis of MPC5 cells was detected by flow cytometry;Western blotting was used to detect the expression of autophagy[microtubule associated protein one light chain 3(LC3)II,LC3Ⅰ,autophagy-related protein(Beclin-1)],apoptosis[Bcl-2 related X protein(Bax),B cell lymphoma-2(Bcl-2)]and mTOR/Akt/CREB pathway-related proteins of MPC5 cells.Results Compared with the normal control group,the cell viability,expression levels of Bcl-2,phosphorylated mTOR(p-mTOR)/mTOR,phosphorylated Akt(p-Akt)/Akt,phosphorylated CREB(p-CREB)/CREB protein of MPC5 cells in the high glucose group were significantly decreased(P<0.05),the autophagy ability was enhanced,the autophagosome showed orange fluorescence,and the apoptosis rate,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bax protein expression levels were significantly increased(P<0.05).Compared with the high glucose group,the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt,p-CREB/CREB protein expression levels of MPC5 cells in icariin group were significantly increased,the autophagy ability was further enhanced,the number of autophagosomes was increased,the autophagosomes showed brick red fluorescence(P<0.05),the apoptosis rate and Bax protein expression level were significantly decreased(P<0.05),and the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt and p-CREB/CREB proteins expression levels of MPC5 cells in GDC-0349 group were significantly decreased,the autophagy ability was weakened,the number of autophagosomes was reduced,the autophagosomes showed orange fluorescence(P<0.05),and the apoptosis rate and Bax protein expression level were significantly increased(P<0.05);icariin+GDC-0349 could reverse the effect of icariin on high glucose induced MPC5 cells(P<0.05).Conclusion Icariin promotes elevated glucose-induced podocyte autophagy and inhibits apoptosis by activating the mTOR/Akt/CREB pathway.
		                        		
		                        		
		                        		
		                        	
2.Research progress in astrocyte dysfunction and depression
Yongxing QIAO ; Wei DAI ; Haixia WU ; Shuoyu HAN ; Liming ZHANG
Chinese Journal of Pharmacology and Toxicology 2024;38(2):137-143
		                        		
		                        			
		                        			Most of the current research on depression focuses on neuronal regulation,while the astrocytic mechanism of depression is far from explored.Astrocytes are the most numerous and widely distributed glial cells in the central nervous system.With a complex structural morphology,astrocytes play an important role in a variety of neuropsychiatric disorders by interacting with neuronal synapses,vasculature and other glial cells.Recent studies have shown that astrocytes may be involved in depression by regulating monoamine transmitters,glutamate cycle,synaptic plasticity,energy metabo-lism,and neuroinflammation.This review is intended to inspire new ideas for the treatment of depres-sion and the development of novel drugs based on astrocyte regulation.
		                        		
		                        		
		                        		
		                        	
3.The association between RABL6 gene methylation in peripheral blood and early lung cancer in Chinese population
Haixia Huang ; Rong Qiao ; Mengxia Li ; Wanjian Gu ; Baohui Han ; Rongxi Yang
Acta Universitatis Medicinalis Anhui 2023;58(6):1030-1036
		                        		
		                        			Objective    :
		                        			 To explore the relationship between the methylation level of RABL6 in peripheral blood and early lung cancer  (LC) with a case-control study in the Chinese population.
		                        		
		                        			Methods    :
		                        			The methylation levels of 7 CpG sites in RABL6 gene in peripheral blood of samples from 275 LC patients  (81.5%  at  stage  I) ,and  age- and gender-matched 185 benign lung nodule cases and 267 matched healthy controls were measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.Multinomial  Logistic regression  adjusted for  covariates was used to analyze the association between the RABL6 methylation and LC.Mann-Whitney U test was applied for the comparisons of RABL6 methylation levels between clinical characteristics subgroups of LC. 
		                        		
		                        			Results    :
		                        			Compared to the healthy controls,the methylation of RABL6 _CpG_ 17 was inversely associated with LC in females  ( per  -  10%  methylation : OR = 2. 47,95%  CI = 1. 19-5. 13,P = 0. 016) ,but positively  associated with  LC  in males  (per - 10%  methylation : OR = 0. 52,95%  CI = 0. 29-0. 94,P = 0. 030) .In addition,hypermethylation of RABL6_CpG _2 and RABL6_CpG_5 was significantly associated with LC in the subjects older than 55 years  (for RABL6_CpG_ 2 : per -10%  methylation : OR = 0. 77,95%  CI = 0. 60-0. 99,P = 0. 038 ; for  RABL6_CpG_5 : OR = 0. 58,95% CI = 0. 34-0. 97,P = 0. 038) .
		                        		
		                        			Conclusion    
		                        			The  study reveals an association between peripheral blood-based RABL6 methylation levels and early LC,providing a new clue for developing peripheral blood-based DNA methylation as a potential marker for the evaluation of LC risk.
		                        		
		                        		
		                        		
		                        	
4.Cockroach as a Vector of Blastocystis sp. is Risk for Golden Monkeys in Zoo
Lei MA ; Yongbin ZHANG ; Haixia QIAO ; Shuai LI ; Heqin WANG ; Ningning ZHANG ; Xiao ZHANG
The Korean Journal of Parasitology 2020;58(5):583-587
		                        		
		                        			
		                        			 Blastocystis sp. is a kind of protozoa living in the intestinal tract of human and animals, which will cause intestinal diseases such as diarrhea, abdominal distension and vomiting. This paper was aimed to understand the infection of Blastocystis sp. In golden monkeys and the transmission path in North China. Thirty-seven feces samples from golden monkeys and 116 cockroach samples from Shijiazhuang Zoo were collected from July to October 2019 for PCR analysis of Blastocystis sp. Genetic diversity analysis was further conducted on the samples with positive PCR results. The results showed that the infection rate was 48.7% (18/37) in golden monkeys and 82.8% (96/116) in cockroaches, respectively. The genetic evolution analysis based on small subunit ribosomal RNA demonstrated that three subtypes (ST) of Blastocystis sp. including ST1, ST2, and ST3 existed in the intestinal tract of golden monkeys, while only ST2 was detected in the intestinal tract of cockroaches. This paper may provide supports for the quarantine and control of Blastocystis sp. for the zoo in Northern China. 
		                        		
		                        		
		                        		
		                        	
5.The phenotypes and genotypes in 314 patients with isolated methylmalonic acidemia
Lulu KANG ; Yupeng LIU ; Ming SHEN ; Zhehui CHEN ; Jinqing SONG ; Ruxuan HE ; Yi LIU ; Yao ZHANG ; Hui DONG ; Mengqiu LI ; Ying JIN ; Hong ZHENG ; Qiao WANG ; Yuan DING ; Xiyuan LI ; Dongxiao LI ; Haixia LI ; Xueqin LIU ; Huijie XIAO ; Yuwu JIANG ; Hui XIONG ; Chunyan ZHANG ; Zhaoxia WANG ; Yun YUAN ; Desheng LIANG ; Yaping TIAN ; Yanling YANG
Chinese Journal of Pediatrics 2020;58(6):468-475
		                        		
		                        			
		                        			Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.
		                        		
		                        		
		                        		
		                        	
6.Association of dietary patterns and diabetes risk level among adult residents in Datong city of Shanxi Province
Qian SUN ; Hui WANG ; Nan QIAO ; Haixia ZHANG ; Yan CUI ; Jianjun HUANG ; Tong WANG
Chinese Journal of Preventive Medicine 2020;54(3):278-282
		                        		
		                        			
		                        			Objective:To explore the association of dietary pattern and type 2 diabetes mellitus (T2DM) risk.Methods:In 2013, 3 747 participants from 87 coalmine branches of a large coal mine group in Datong City, Shanxi Province were selected by using a two-stage cluster stratified sampling method. Data on demographic characteristics, smoking, drinking, and family history of diabetes were collected by using a self-made questionnaire, and the International Physical Activity Questionnaire was used to assess the level of physical activity. Physical, glucose and lipid metabolism indicators were measured and subjects were divided into high-risk groups and low-risk groups of T2DM according to the T2DM risk score. Dietary data were collected by using Semi-quantitative Food Frequency Questionnaire, and dietary patterns were derived by using the exploratory factor analysis and cluster analysis. The unconditional logistic regression model was used to assess the association of dietary patterns and T2DM risk.Results:The age of the subjects was(41.48±8.62) years old, and 2 843 of them were males (84.31%). A total of 1 819 subjects were in the high-risk group and 1 553 in the low-risk group. Four dietary patterns, healthy diet, high-salt diet, meats diet, and carbohydrate-rich diet, were identified in this study. The unconditional logistic regression analysis showed that compared with the healthy diet pattern, after the adjustment of demographic characteristics, smoking, and drinking, the OR (95% CI) of T2DM risk in high-salt diet, carbohydrate-rich diet and meats diet patterns was 1.54 (1.26-1.88), 1.80 (1.43-2.28) and 1.20 (0.99-1.46), respectively. Conclusion:High-salt diet and carbohydrate-rich diet were positively associated with T2DM risk, whereas there was no association of meats diet and T2DM risk.
		                        		
		                        		
		                        		
		                        	
7.Association of dietary patterns and diabetes risk level among adult residents in Datong city of Shanxi Province
Qian SUN ; Hui WANG ; Nan QIAO ; Haixia ZHANG ; Yan CUI ; Jianjun HUANG ; Tong WANG
Chinese Journal of Preventive Medicine 2020;54(3):278-282
		                        		
		                        			
		                        			Objective:To explore the association of dietary pattern and type 2 diabetes mellitus (T2DM) risk.Methods:In 2013, 3 747 participants from 87 coalmine branches of a large coal mine group in Datong City, Shanxi Province were selected by using a two-stage cluster stratified sampling method. Data on demographic characteristics, smoking, drinking, and family history of diabetes were collected by using a self-made questionnaire, and the International Physical Activity Questionnaire was used to assess the level of physical activity. Physical, glucose and lipid metabolism indicators were measured and subjects were divided into high-risk groups and low-risk groups of T2DM according to the T2DM risk score. Dietary data were collected by using Semi-quantitative Food Frequency Questionnaire, and dietary patterns were derived by using the exploratory factor analysis and cluster analysis. The unconditional logistic regression model was used to assess the association of dietary patterns and T2DM risk.Results:The age of the subjects was(41.48±8.62) years old, and 2 843 of them were males (84.31%). A total of 1 819 subjects were in the high-risk group and 1 553 in the low-risk group. Four dietary patterns, healthy diet, high-salt diet, meats diet, and carbohydrate-rich diet, were identified in this study. The unconditional logistic regression analysis showed that compared with the healthy diet pattern, after the adjustment of demographic characteristics, smoking, and drinking, the OR (95% CI) of T2DM risk in high-salt diet, carbohydrate-rich diet and meats diet patterns was 1.54 (1.26-1.88), 1.80 (1.43-2.28) and 1.20 (0.99-1.46), respectively. Conclusion:High-salt diet and carbohydrate-rich diet were positively associated with T2DM risk, whereas there was no association of meats diet and T2DM risk.
		                        		
		                        		
		                        		
		                        	
8. Clinical value of suprapubic Trocar puncture lithotripsy in the treatment of benign prostatic hyperplasia and bladder stones
Haixia WANG ; Chaohong CHEN ; Lingling WANG ; Zhao YANG ; Qiao JIN ; Qihao RUI
Chinese Journal of Primary Medicine and Pharmacy 2019;26(11):1347-1350
		                        		
		                        			 Objective:
		                        			To evaluate the clinical value of suprapubic Trocar puncture lithotripsy in the treatment of benign prostatic hyperplasia and bladder stones.
		                        		
		                        			Methods:
		                        			From February 2016 to August 2018, 60 patients with benign prostatic hyperplasia and bladder stones in the Second Hospital of Pujiang County were randomly selected.The patients were divided into transurethral prostatic bipolarplasma electrotomy group(control group, 30 cases) and transurethral prostatic bipolar excision procedure combined with suprapubic Trocar puncture cystinolithotomy group(study group, 30 cases) according to the operation methods.The operation time, stone extraction time, removal of bladder fistula time, catheter extraction time, success of one stone extraction, postoperative complications of the two groups were statistically analyzed.
		                        		
		                        			Results:
		                        			The operation time, stone removal time, bladder fistula removal time and catheter removal time of the study group were significantly shorter than those of the control group(
		                        		
		                        	
9. Heterogeneous phenotypes, genotypes, treatment and prevention of 1 003 patients with methylmalonic acidemia in the mainland of China
Yi LIU ; Yupeng LIU ; Yao ZHANG ; Jinqing SONG ; Hong ZHENG ; Hui DONG ; Yanyan MA ; Tongfei WU ; Qiao WANG ; Xiyuan LI ; Yuan DING ; Dongxiao LI ; Ying JIN ; Mengqiu LI ; Zhaoxia WANG ; Yun YUAN ; Haixia LI ; Jiong QIN ; Yanling YANG
Chinese Journal of Pediatrics 2018;56(6):414-420
		                        		
		                        			 Objective:
		                        			To analyz the current situation of the diagnosis, treatment and prevention of methylmalonic acidemia, the phenotypes, biochemical features and genotypes of the patients in the mainland of China, were investigated.
		                        		
		                        			Methods:
		                        			Tottally 1 003 patients of methylmalonic acidemia from 26 provinces and municipalities of the mainland of China were enrolled. The clinical data, biochemical features and gene mutations were studied. Blood aminoacids and acylcarnitines, urine organic acids, and plasma total homocysteine were determined for the biochemical diagnosis. Gene analyses were performed for the genetic study of 661 patients. The patients were treated with individual intervention and long-term follow up. Prenatal diagnoses were carried out for 165 fetuses of the families.
		                        		
		                        			Results:
		                        			Among 1 003 patients (580 boys and 423 girls), 296 cases (29.5%) had isolated methylmalonic acidemia; 707 cases (70.5%) had combined homocysteinemia; 59 patients (5.9%) were detected by newborn screening; 944 patients (94.1%) had the onset at the ages from several minutes after birth to 25 years and diagnosed at 3 days to 25 years of age. The main clinical presentations were psychomotor retardation and metabolic crisis. Multi-organ damage, including hematological abnormalities, pulmonary hypertension, kidney damage, were found. MMACHC, MUT, MMAA, MMAB, HCFC1, SUCLG1, SUCLA2 mutations were found in 631 patients (96.6%) out of 661 patients who accepted gene analysis. MMACHC mutations were detected in 460 patients (94.7%) out of 486 cases of methylmalonic acidemia combined with homocysteinemia. MUT mutations were found in 158 (90.3%) out of 169 cases of isolated methylmalonic acidemia. The development of 59 patients detected by newborn screening were normal; 918 cases (97.2%) were diagnosed after onset accepted the treatment. Forty-five of them completely recovered with normal development. Twenty-six patients (2.7%) died; 873 (92.5%) patients had mild to severe psychomotor retardation. Methylmalonic acidemia were found in 35 out of 165 fetuses by metabolites assay of amniotic fluid and amniocytes gene analysis.
		                        		
		                        			Conclusion
		                        			Combined methylmalonic acidemia and homocysteinemia is the common type of methylmalonic acidemia in the mainland of China. CblC defect due to MMACHC mutations is the most common type of methylmalonic acidemia combined with homocysteinemia. MUT gene mutations are frequent in the patients with isolated methylmalonic acidemia. Newborn screening is key for the early diagnosis and the better outcome. Combined diagnosis of biochemical assays and gene analysis are reliable for the prenatal diagnosis of methylmalonic acidemia. 
		                        		
		                        		
		                        		
		                        	
10.Effect of transcranial direct current combined with mirror neuronal rehabilitation training
Yabin LI ; Haixia FENG ; Jiao LI ; Hongxia WANG ; Xiaohong QIAO ; Zhongrui MA ; Ning CHEN ; Yanchen WANG ; Aiqiang BAO ; Liyuan HAN ; Dang WEI
Chinese Journal of Postgraduates of Medicine 2018;41(7):589-593
		                        		
		                        			
		                        			Objective To observe the effect of transcranial direct current stimulation (tDCS) with mirror neuronal rehabilitation training system (MNST-V1.0) in post-traumatic unconscious patients after severe craniocerebral injury. Methods A prospective, self controlled and open-label method was used. Thirty-six post-traumatic unconscious patients with severe craniocerebral injury from January 2016 to July 2017 were selected. Four cases of the patients did not complete the treatment and the last 32 cases completed the study. All patients were given routine wake-up therapy, and tDCS combined with MNST-V1.0 (20 min/time, 1 time/d, 6 times/week, a total of 8 weeks) was given at the same time. The Glasgow coma scale (GCS), JFK coma recovery scale and Four coma rating scale before treatment and 2, 4, 8 weeks after treatment were recorded. Results The scores of open reaction, language and motor response score of GCS 2, 4, 8 weeks after treatment were significantly higher than those before treatment:(1.56 ± 0.82), (2.06 ± 1.01) and (3.11 ± 1.45) scores vs. (1.00 ± 0.45) scores, (2.23 ± 1.06), (2.56 ± 1.08) and (3.02 ± 1.04) scores vs. (1.00 ± 0.61) scores, (2.79 ± 1.12), (3.22 ± 1.33) and (4.44 ± 1.07) scores vs. (1.00 ± 0.54) scores, and there were statistical differences (P < 0.01 or <0.05). The scores of hearing, vision, movement, speech response, communication and arousal of JFK coma recovery scale 2, 4, 8 weeks after treatment were significantly higher than those before treatment, and there were statistical differences (P<0.01). The scores of open reaction, sport reaction, brainstem response of Four coma rating scale 2, 4, 8 weeks after treatment were significantly higher than those before treatment, and there were statistical differences (P<0.05); there was no statistical difference in respiratory score of Four coma rating scale before and after treatment (P>0.05). Conclusions The tDCS combined with MNST-V1.0 can improve the consciousness level in post-traumatic unconscious patients with severe craniocerebral injury, and have the effect of promoting awakening.
		                        		
		                        		
		                        		
		                        	
            

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