1.Synthesis and characterization of matrix metalloproteinase-responsive BDNF controlled-release materials
Jun-Ru HEI ; Cui WANG ; Meng-Wen SONG ; Sheng-Qiang XIE ; Bing-Xian WANG ; Xiao-Juan LAN ; Han-Bo ZHANG ; Gang CHENG ; Zhi-Qiang LIU ; Xi-Qin YANG ; Jian-Ning ZHANG
Medical Journal of Chinese People's Liberation Army 2024;49(11):1319-1326
Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.
2. FNDC5 Regulates the Adipogenic Differentiation of C3H10T1/2 Cells by Inhibiting the Phosphorylation of ERK1/2
Wei HEI ; Zhi-Qiang HE ; Yan-Wei ZHANG ; Wan-Feng ZHANG ; Chun-Bo CAI ; Yang YANG ; Peng-Fei GAO ; Xiao-Hong GUO ; Guo-Qing CAO ; Bu-Gao LI
Chinese Journal of Biochemistry and Molecular Biology 2021;37(5):644-652
The aim of this study was to explore the regulatory mechanism of Type Ⅲ domain-containing protein5 (FNDC5) on adipogenic differentiation in C3H10T1/2 cells. qRT-PCR and Western blot were used to detect the expression of FNDC5 during adipogenic differentiation of C3H10T1/2 cells. The lentivirus-coated overexpression and interference vector of FNDC5 were constructed and transfected into C3H10T1/2 cells. qRT-PCR was used to detect the expression of the key genes of adipogenic differentiation. Oil red O staining was used to detect the formation of lipid droplets; Western blot was used to detect the content of ERK1/2 and ERK1/2 phosphorylated protein (P-ERK1/2). After 8 days of adipogenic differentiation of C3H10T1/2 cells, the expression of Fndc5 increased significantly. After overexpression of FNDC5 in C3H10T1/2 cells, the expression of key genes for adipogenic differentiation, including peroxisome proliferator-activated receptor-酌 (PPAR酌), CCAAT enhancer binding protein beta (C/EBP茁), fatty acid binding protein 4 (FABP4) and CCAAT enhancer binding protein alpha (C/EBPα), all decreased significantly. The content of lipid droplets and P-ERK1/2 also decreased significantly. On the contrary, after interference of FNDC5 in C3H10T1/2 cells, the expression of key genes for adipogenic differentiation, including PPARγ, C/EBP茁, FABP4 and C/EBPα were significantly increased. Meanwhile, the content of lipid droplets and P-ERK1/2 also increased significantly. This study found that FNDC5 can inhibit the adipogenic differentiation of C3H10T1/2 cells by inhibiting the phosphorylation level of ERK1/2, which can provide reference data for the mechanism of FNDC5 in regulating fat deposition.
3.Efficacy comparison of hippocampal transection and traditional approaches in treatment of medial temporal lobe epilepsy
Quanjun ZHAO ; Wei WANG ; Jia WANG ; Tao WANG ; Shaojie CUI ; Tiejun SHI ; Peixin WANG ; Lianfeng LI ; Bo HEI
Chinese Journal of Neuromedicine 2018;17(1):62-67
Objective To observe the outcomes of seizure control by three different surgical approaches,hippocampal transection,anterior temporal lobectomy and selective amygdalo-hippocampectomy,for the treatment of intractable medial temporal epilepsy,and explore their influences in the impairments of cognitive and memorial functions.Methods Twenty-nine patients with intractable medial temporal epilepsy,admitted to our hospital from January 2012 to October 2015,were chosen in our study;8 patients accepted hippocampal transection,10 accepted anterior temporal lobectomy and 11 accepted selective amygdalo-hippocampectomy.Seizure controls after treatment with these 3 approaches were compared and results of neuropsychological examinations (verbal intelligence quotient [VIQ],performance intelligence quotient [PIQ],full intelligence quotient [FIQ] and memory quotient [MQ]) were compared before and after operation.Results The effective rates of seizure controls were all higher than 80% and seizure free rate was about 60% in the 3 groups;Engel grading showed no significant differences among the three groups (P>0.05).Results of all the neuropsychological examinations in the hippocampal transection group before and after operation had no significant differences (P>0.05);however,all results in the anterior temporal lobectomy group after operation were significantly declined as compared with those before operation (P<0.05);and PIQ,FIQ and MQ scores in the selective amygdalo-hippocampectomy group after operation were significantly lower as compared with those before operation (P<0.05).Conclusions Hippocampal transection will not cause significant damage in intelligence and memory functions.As compared with both anterior temporal lobectomy and selective amygdalo-hippocampectomy,hippocampal transection can have good seizure control and preserve memory function.
4.Effectiveness of family-integrated-care for preterm infants with moderate to severe bronchopulmonary dysplasia
Bo LYU ; Xirong GAO ; Mingyan HEI ; Lihui ZHU ; Yunqin WU ; Yuee XIONG
Chinese Journal of Neonatology 2017;32(3):189-192
Objective To study the effectiveness of family-integrated-care (FICare) for preterm infants with moderate to severe bronchopuhnonary dysplasia (BPD) in neonatal intensive care unit (NICU).Method Preterm infants with moderate to severe BPD in Hunan Children's Hospital from January 2015 to March 2016 were selected as the objects.These infants were assigned into two groups (FICare group and control group) in the base of whether the parents agreed to implement FICare.If the infant was enrolled into FICare group,the parents need to spend 3 hours in ward every day,and participate in nursing services under the guidance of nurses.The nursing services included bathing,cuddling,skin care,breast-feeding,and so on.If the infant was enrolled into control group,these nursing services were implemented by nurses.Oxygen exposure time,breast-feeding rate,time of begin oral feeding,time of total oral feeding,weight growth rate during hospitalization,weight of discharge,length of stay,readmission rate within 30 days,the rate of parents that mastered basic care knowledge and skills when discharge from hospital,the rate of satisfaction,and the rate of follow-up within 30 days of the two groups were compared.Result There were 106 cases in our study,54 in the FICare group and 52 in the control group.Compare the FICare group and the control group,there were statistical differences between two groups in the follow aspects (all P < 0.05):oxygen exposure time [(57.1 ±20.9) d vs.(71.4 ±32.6) d],breast-feeding rate (77.8% vs.44.2%),time of total oral feeding [(46.1 4 19.6) d vs.(59.4 ± 30.2) d,length of stay [(65.8 ± 18.4) d vs.(84.3 ±35.0) d],the rate of parents that mastered basic care knowledge and skills when discharge from hospital (96.3% vs.82.7%),the rate of satisfaction (94.4% vs.84.6%),the rate of follow-up within 30 days (92.6% vs.73.1%).Conclusion FICare could significantly reduce oxygen exposure time of preterm infants with moderate to severe BPD,could improve the level of parents mastered basic care knowledge and skills of preterm infants,especially in critically ill preterm children,and could shorten length of stay of them.FICare is beneficial to the healthy growth of premature infants with BPD.
5.Advance research of Acetaminophen treatment for symptomatic patent ductus arteriosus in pretermature infant
Bo YANG ; Xiangyu GAO ; Mingyan HEI
Chinese Journal of Applied Clinical Pediatrics 2017;32(2):152-155
Due to the dysontogenesis of the arterial duct wall and the abnormal secretion of prostaglandin,symptomatic patent ductus arteriosus is thus often presented in preterm infants.In the past,Indomethacin or Ibuprofen (cyclooxygenase inhibitor) was always chosen to be the interventional medication.While in recent years,Acetaminophen (prostaglandin synthetase inhibitor) has become another therapeutic option for symptomatic patent ductus arteriosus with similar efficacy but less adverse events.The latest research of the mechanism,the therapeutic strategy of time,mode,dosage and duration,the efficacy and the adverse events of Acetaminophen were reviewed.
6.Changes of three cardiac markers at pre - and post -treatment in preterm infants with patent ductus arteriosus
Bo YANG ; Niannian TONG ; Xiangyu GAO ; Xiuli WANG ; Xiangjun CUI ; Honglin LEI ; Yi REN ; Mingyan HEI
Chinese Journal of Applied Clinical Pediatrics 2016;(3):212-216
Objective To investigate the changes of cardiac function at pre -and post -treatment in preterm infants with patent ductus arteriosus (PDA)in order to guide drug treatment.Methods Totally 84 preterm infants with PDA admitted to Neonatal Intensive Care Unit of Xuzhou Hospital Affiliated to Medical College of Southeast University from July 201 2 to June 201 4 were divided into 4 groups according to treatment drug:Ibuprofen group (27 cases),Indo-methacin group (24 cases),control group (1 1 cases),and Paracetamol group (22 cases).Patients were also divided into symptomatic PDA group (38 cases)and asymptomatic PDA group (46 cases)according to severity;PDA closed group (69 cases)and PDA unclosed group (1 5 cases)according to sequel.The level of plasma brain natriuretic pep-tide (BNP),cardiac troponin I (cTnI),correct QT intervals dispersion (QTcd)were monitored pre -and post -treat-ment.Data were analyzed by using SPSS 1 9.0 software.Results Three cardiac markers at post -treatment were of no significant difference among 4 treatment drugs.The changes of the cTnI and QTcd at pre -and post -treatment were of no significance.The level of BNP in symptomatic PDA group was significantly higher than that in asymptomatic PDA group at pre -treatment [(378 ±94)ng/L vs (1 47 ±75)ng/L,t =2.584,P =0.01 4].In the symptomatic PDA group,the level of BNP at post -treatment [(1 82 ±81 )ng/L]was significantly decreased than that at per -treatment (t =2.741 ,P =0.009).In the asymptomatic PDA group,there was no significant difference between the pre - and post -treatment [(1 21 ±61 )ng/L]in the level of BNP (t =1 .254,P =0.207).There was no significant difference in the level of BNP at per -treatment between PDA closed group and PDA unclosed group [(274 ±91 )ng/L vs (289 ± 87)ng/L,t =-0.874,P =0.391 ].In PDA closed group,the level of BNP at post -treatment [(1 21 ±74)ng/L] was significantly decreased compared with that at per -treatment (t =3.580,P =0.000).In PDA unclosed group, there was no significant difference between the pre - and post -treatment [(245 ±74)ng/L]in the level of BNP (t =0.854,P =0.392).Conclusion Early medication intervention for symptomatic PDA of preterm infants is benefi-cial for the closure of PDA and for attenuating negative effects on cardiac function of PDA.
7.Effect of electroacupuncture at different acupoints on hormones and neurotransmitters of hypotha- lamic-pituitary-adrenal axis in rats under simulated weightlessness.
Hei ZHANG ; Guozhen ZHAO ; Desheng WANG ; Baixiao ZHAO ; Bo JI ; Yan SONG ; Ping ZHANG ; Yali LIU ; Yinghui LI
Chinese Acupuncture & Moxibustion 2015;35(12):1275-1279
OBJECTIVETo explore the change pattern of hypothalamic-pituitary-adrenal (HPA) axis and related neurotransmitters under simulated weightlessness.
METHODSA total of 40 clean-grade male Wistar rats were randomly divided into a normal group, a tail-suspension group, an electroacupuncture (EA) at Neiguan (PC 6) group, an EA at Sanyinjiao (SP 6) group, 10 rats in each group. Rats in the tail-suspension group, EA at "Neiguan" (PC 6) group and EA at "Sanyinjiao" (SP 6) group were treated with tail suspension to simulate weightlessness effect. Rats in the normal group were treated with normal diet. Rats in the tail-suspension group were treated with tail suspension for 28 d. During the time of tail suspension, rats in the EA at "Neiguan" (PC 6) group were treated with EA at "Neiguan" (PC 6), 30 min per treatment, once every two days for 14 treatments, while rats in the EA at "Sanyinjiao" (SP 6) group were treated with EA at "Sanyinjiao" (SP 6), 30 min per treatment, once every two days for 14 treatments. Samples were all collected after 4 weeks. The contents of corticotropin releasing hormone (CRH) , adrenocorticotropic hormone (ACTH), corticosterone (CORT) in as well as 5-hydroxy tryptamine (5-HT), dopamine (DA), norepinephrine (NE) were measured by using radioimmunoassay.
RESULTSCompared with the normal group, in the tail-suspension group the content of ACTH in pituitary was significantly decreased (P< 0.05), and the content of 5-HT in hypothalamus was significantly decreased (P < 0.01); the content of CRH and 5-HT in hypothalamus was significantly decreased (P < 0.01, P < 0.05) in the EA at "Neiguan" (PC 6) group; the content of CRH and 5-HT in hypothalamus was significantly decreased (P < 0.01), and the content of CORT in serum was significantly decreased (P < 0.05) in the EA at "Sanyinjiao" (SP 6) group. Compared with the tail-suspension group, the content of ACTH in hypothalamus was significantly decreased (P< 0.05) in the EA at "Neiguan" (PC 6) group; the content of CRH, ACTH and CORT was significantly decreased (P < 0.01, P < 0.05) in the EA at "Sanyinjiao" (SP 6) group. Compared with the EA at "Neiguan" (PC 6) group, the content of CORT was decreased (P < 0.05) in the EA at "Sanyinjiao" (SP 6) group.
CONCLUSIONEA can regulate the content of 5-HT in hypothalamus in tail-suspension rats, inhibit the hyperactivity of the HPA axis, in which EA at "Sanyinjiao" (SP 6) had more significant effects than "Neiguan" (PC 6), but no obvious effects on NE and DA were observed.
Acupuncture Points ; Adrenocorticotropic Hormone ; metabolism ; Animals ; Corticotropin-Releasing Hormone ; metabolism ; Dopamine ; metabolism ; Electroacupuncture ; Hormones ; metabolism ; Hypothalamus ; metabolism ; Male ; Neurotransmitter Agents ; metabolism ; Norepinephrine ; metabolism ; Pituitary-Adrenal System ; metabolism ; Rats ; Rats, Wistar ; Serotonin ; metabolism ; Weightlessness
8.Application of three kinds of non-invasive positive pressure ventilation as a primary mode of ventilation in premature infants with respiratory distress syndrome: a randomized controlled trial.
Xiangyu GAO ; Bo YANG ; Mingyan HEI ; Xiangjun CUI ; Jing WANG ; Guangling ZHOU ; Shenying QU
Chinese Journal of Pediatrics 2014;52(1):34-40
OBJECTIVENon-invasive positive pressure ventilation has increasingly been chosen as the primary ventilation mode in respiratory distress syndrome (RDS) in preterm infants. In order to further understand the application of various non-invasive positive pressure ventilation modes, we compared the advantages and disadvantages of three modes as a primary mode of ventilation in premature infants with RDS.
METHODFrom December 2011 to March 2013, 107 preterm infants with RDS who received intubation-pulmonary surfactant (PS) -extubation in our NICU were randomly divided (by means of random number table) into three groups based on the primary mode of ventilation: nasal continuous positive airway pressure [NCPAP, n = 39, male/female ratio was 27/12, mean gestational age (GA) was (32.0 ± 2.1)weeks, mean birth weight (BW) was (1752 ± 457)g], bi-level positive airway pressure [BiPAP, n = 35, male/female ratio was 25/10, GA was (31.4 ± 2.0) weeks, BW was (1530 ± 318) g], and synchronized bi-level positive airway pressure [SBiPAP, n = 33, male/female rate was 25/8, GA was (31.5 ± 2.2) weeks, BW was (1622 ± 447) g]. Ventilation settings including FiO(2) were adjusted according to transcutaneous SPO(2) monitoring or blood gas analysis. Various settings and adverse events were recorded as well. The main parameter was the FiO(2) at 24 h post-positive-pressure ventilation. Statistical analyses were performed using χ(2) test, rank sum test, one-way analysis of variance for least-significant difference value, paired-sample t-test, two related sample Wilcoxon signed rank sum test and Logistic regression.
RESULTThe PaCO(2) (mmHg, 1 mmHg = 0.133 kPa), oxygen index (OI) at 12-24 h, and FiO(2) at 24 h post-ventilation in BiPAP and SBiPAP groups were lower than that in NCPAP groups with significant difference (44 ± 9 and 45 ± 9 vs. 50 ± 9, 2.76 ± 0.96 and 2.79 ± 0.60 vs. 3.24 ± 0.72, 0.34 ± 0.10 and 0.35 ± 0.07 vs. 0.39 ± 0.07; F = 4.456, 5.146 and 4.123; P = 0.014, 0.007 and 0.019, respectively). There was no significant difference between BiPAP and SBiPAP groups. There was no significant difference among three groups (all P > 0.05) in the following events: respiratory index (RI) at 12-24 h post-ventilation, abdominal distension, period of non-invasive ventilation, ratio of intubation for invasive ventilation if failed noninvasive ventilation, air-leak syndrome, neonatal necrotizing enterocolitis, periventricular-intraventricular haemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity, mortality rate after 36 h of age or rate of abandon for discharge. The independent risk factors for failure of non-invasive positive pressure ventilation were gender, gestational age, antepartum steroid at 24 h before birth to 7 d, and birth weight, with the OR (95% confidence interval) being 14.120 (1.135, 175.662), 2.862 (1.479, 5.535), 61.084 (3.115, 1 198.031), and 8.306 (1.488, 46.383), respectively.
CONCLUSIONAs the primary mode of ventilation in premature infants with RDS, both BiPAP and SBiPAP are more beneficial than NCPAP in improving oxygenation and reducing CO(2) retention without increasing the incidence of adverse events.
Blood Gas Analysis ; Carbon Dioxide ; blood ; Continuous Positive Airway Pressure ; methods ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Intensive Care Units, Neonatal ; Intubation, Intratracheal ; Male ; Oxygen ; blood ; Pulmonary Surfactants ; therapeutic use ; Respiratory Distress Syndrome, Newborn ; therapy ; Risk Factors ; Treatment Outcome ; Ventilator Weaning
9.Relation of IL-17 polymorphisms and serum levels in patients with chronic HCV infection.
Yue-min NAN ; Yu-guo ZHANG ; Ling-bo KONG ; Huan-wei ZHENG ; Dian-xing SUN ; Chun-mian AN ; You-sheng LI ; Cang-you LI ; Li KONG ; Er-hei DAI ; Li-Xin TONG ; Su-xian ZHAO ; Shan-shan SU
Chinese Journal of Hepatology 2013;21(6):425-428
OBJECTIVETo investigate the association of single nucleotide polymorphisms (SNPs) in the interleukin 17 (IL-17) gene and serum protein levels in patients with chronic hepatitis C virus (HCV) infection.
METHODSA total of 228 patients with chronic HCV infection and 81 healthy controls were enrolled in the study. The frequencies of IL-17 rs8193036 and rs2275913 polymorphisms were detected by the TaqMan SNP genotyping assay. Serum levels of IL-17 protein were detected by ELISA. Pairwise comparisons were made by the Chi-square test, and the significance of between-group differences was assessed by the Student's t-test with P less than 0.05.
RESULTSThe patients with chronic HCV infection and the healthy controls showed similar frequencies of the rs8193036 C/T allele (x2 = 1.428, P = 0.232) and the rs2275913 A/G allele (x2 = 0.106, P = 0.744). In addition, the two groups showed similar distribution of the rs8193036 CC (chronic HCV infection: 46.49% vs. healthy controls: 41.98%), CT (45.61% vs. 44.44%) and TT (7.89% vs. 13.58%) genotypes (x2 = 2.346, P = 0.309), and of the rs2275913 AA (16.23% vs. 13.58%), AG (48.25% vs. 50.62%) and GG (35.53% vs. 35.80%) genotypes (x2 = 0.340, P = 0.844). Subgroup analysis of chronic HCV infection patients stratified according to HCV genotypes 1 and 2 showed no differences in the distribution of rs8193036 and rs2275913 alleles (x2 = 1.127, P = 0.288; x2 = 1.088, P = 0.297) and genotypes (x2 = 2.825, P = 0.246; x2 = 0.970, P = 0.616). However, the chronic HCV infection group did show significantly higher levels of serum IL-17 than the controls (97.67+/-39.68 vs. 71.60+/-19.78 pg/ml, t = 2.414, P = 0.033).
CONCLUSIONChronic HCV infection is associated with increased serum IL-17; however, the IL-17 polymorphisms rs8193036 and rs2275913 were not associated with chronic HCV infection susceptibility in this study's Chinese cohort.
Adolescent ; Adult ; Aged ; Alleles ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Hepacivirus ; Hepatitis C, Chronic ; blood ; genetics ; virology ; Humans ; Interleukin-17 ; blood ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Young Adult
10.Meta-analysis of post-transfusion necrotizing enterocolitis in neonates.
Hui-Kang TAO ; Qin TANG ; Ming-Yan HEI ; Bo YU
Chinese Journal of Pediatrics 2013;51(5):336-339
OBJECTIVETo quantitatively assess the association between transfusions and the risk of necrotizing enterocolitis (NEC) in neonates.
METHODBoth Chinese and English literature published from Jan. 1985 to Nov. 2011 about the case-control study of the association between transfusions and neonatal NEC were retrieved by searching the electronic resource databases. A meta-analysis was then performed on the comparison and synthesis of findings from included studies. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using RevMan 5.0 software. Sensitivity analysis was conducted and possible publication bias was tested as well.
RESULTA total of 7 case-control studies (480 blood transfusion cases, 2845 control cases) were included. The meta-analysis with a random-effects model found a pooled OR of 3.35 (95% CI: 1.54-7.27). Sensitivity analysis showed that OR for post-transfusion NEC within 48 h was 4.21 (95% CI: 2.17-8.16). The OR was 4.29 (95% CI: 1.39-13.24) after factors such as gestational age and birth weight were de-confounded. The fail-safe number was 263.
CONCLUSIONBlood transfusion can increase the risk of NEC in neonates. The clinical application of this conclusion should be cautious due to limited reports. High-quality randomized control trials are still needed for the further proof of the association between blood transfusion and neonatal NEC.
Bias ; Case-Control Studies ; Enterocolitis, Necrotizing ; epidemiology ; etiology ; Female ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; epidemiology ; etiology ; therapy ; Infant, Premature ; Literature Based Discovery ; Male ; Odds Ratio ; Risk Factors ; Transfusion Reaction

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