Objective To study the effects of constant and intermittent high glucose on the apoptosis of cultured bovine retinal capillary pericytes (BRPs), and to investigate the role of mitochondrial apoptotic pathway in the apoptosis of BRPs. Methods After being cultured under glucose with different concentrations tot 6 days, the change of uhrastructure of BRPs was observed under electronmieroscope, the apoptosis of pericytes was detected by TUNEL method, the mitochondrial inner transmembrane potential (△Ψm) was detected by laser scanning confocal microscopy, the change of cytochrome c (cyt-c) was assayed by spectrophotometer and the expression of apoptotic genes was detected by immunohistochemical method and RT-PCR. Results (1) BRPs showed typical changes of apoptosis in constant and intermittent high glucose concentrations. The apoptosis induced by constant high glucose concentration was more obvious than that by intermittent high glucose. (2) Constant and intermittent high glucose concentrations obviously decreased △Ψm compared with control group. The △Ψm of BRPs was correlated negatively with the apoptotie rate of BRPs (r = - 0.89, P < 0.01) ; (3) Constant and intermittent high glucose concentrations increased the release of cyt-c from mitochondria to cytoplasm, and the concentration of cyt-c in the cytoplasm was correlated positively with the apoptotic rate of BRPs (P < 0.01) ; (4) Constant and intermittent high glucose concentrations increased the expression of proapoptotie gene Bax and decreased the expression of prosurvival gene Bcl-2, resulting in increased Bax/Bcl-2 ratio. Bax/Bcl-2 ratio was negative correlatied with the △Ψm of BRPs, and positively eorrclaticd with the concentration of cyt-c in cytoplasm and apoptotic rate (both P < 0.01).Conclusion Constant and intermittent high glucose concentrations could decrease △Ψm, increase the release of cyt-c and induce the apoptosis of BRPs, the effects being stronger with constant high glucose concentration. The mitochondrial apoptotic pathway plays an important role in the apoptosis of BRPs, in which Bax and Bcl-2 are involved.

Objective To study the relationship of Wnt receptor signaling pathway and severe retinopathy of prematurity (ROP).Method From January 2011 to June 2015,preterm infants with severe ROP admitted to the NICU of our hospital were enrolled prospectively.Preterm infants with similar gestational age,gender,and age (in days) admitted to our hospital during the same period were selected as the control group.FZD4,LRP5,and ND gene mutations in Wnt receptor signaling pathway were examined.Result A total of 61 Chinese preterm infants were screened for these three candidate genes of Wnt receptor signaling pathway,32 in ROP group and 29 in control group.ND and FZD4 gene mutations were not found among all cases.Eight types of LRP5 mutations were found in 26 cases of ROP group,including 7 cases of Exon18 missense mutation [c.3989C ＞ T;p.Ala1330Val (rs3736228)],5 cases of Exon8 synonymous mutation (c.1647T ＞ C;p.Phe549Phe),5 cases of Exon6 intronic mutation [c.1412 + 8G ＞ A (rs4988319)],3 cases of Exon2 missense mutation [c.266A ＞ G;p.Gln89Arg (rs41494349)],2 cases of Exon21 intronic mutation [c.4349-17C ＞ T (rs372086596)],2 cases of Exon19 synonymous mutation (c.4089C ＞ T;p.Asp 1363 Asp),one case of Exon9 synonymous mutation (c.1 932G ＞ A;p.Glu644Glu),and one case of Exon16 missense mutation (c.3580C ＞T;p.Arg1194Cys).Three types of LRP5 mutations were found in 6 cases of the control group,including 4 cases of Exon8 synonymous mutation,one case of Exon19 synonymous mutation,and one case of Exon9 synonymous mutation.The positive rates of Exonl8 missense mutation and Exon6 intronic mutation in severe ROP group were significantly higher than the control group (P ＜ 0.05).Conclusion LRP5 gene mutations in Wnt receptor signaling pathway may be associated with the occurrence of severe ROP.

Objective To investigate the effects of early tracheotomy on the prognosis of patients with severe brain lesions .Methods The clinical data of 68 patients with severe brain lesions were retrospectively analyzed . According to the time of tracheotomy ,we assigned 68 patients to receive either early tracheotomy or late tracheotomy . 34 patients who were given tracheotomy within 72 hours in Intensive Care Unit were selected as the early tracheotomy group (ET group).34 patients who were given tracheotomy after 14 days in Intensive Care Unit were selected as the late tracheotomy group(LT group).The time of mechanical ventilation,length of hospital stay,and the incidence of ventilator associated pneumonia ( VAP ) , sedative drug use time , antibiotic use time , in-hospital mortality were compared between the two groups.Results In ET group,the hospitalization time,mechanical ventilation time, incidence of VAP,sedative drug use time,antibiotic use time were (4.2 ±2.4)d,(3.5 ±0.6)d,(14.5 ±3.2)%, (1.5 ±0.5)d,(3.3 ±0.3)d,those in LT group were (12.5 ±4.8)d,(8.5 ±5.6)d,(28.6 ±8.6)%,(6.3 ±1.2)d, (13.2 ±1.1) d respectively,the differences between the two groups were statistically significant ( t =3.14,2.96, 3.28,3.46,2.57,all P<0.05).The hospitalization mortality rates of ET group ,LT group were (23.8 ±4.38)%, (24.5 ±4.16)%,respectively no significant difference between the two groups ( t=1.49,P<0.05).Conclusion The use of early tracheotomy can reduce the hospitalization time ,shorten the time of mechanical ventilation ,reduce the incidence of ventilator associated pneumonia ,and reduce the time of using sedative drugs and antibiotics ,but the mor-tality has no significant effect in the severe craniocerebral injury patients .

Background and purpose: As a member of Catenin family, little is known about expressive signiifcance and mechanism of Delta-catenin in numerous tumors. In present study, we investigated the expression of Delta-catenin in breast cancer tissues and its correlation with the prognosis of patients. Methods:We examined the expression of Delta-catenin and its correlation with clinicopathological factors of patients by immunohistochemistry in 92 cases of breast cancer tissues with tissue micro-array. The mRNA and protein expression of Delta-catenin were also detected in another 32 cases of frozen paired breast cancer tissues and normal breast tissues. Results:Compared with normal breast tissues, the mRNA and protein expression of Delta-catenin were increased in breast cancer tissues, and expression of Delta-catenin was closely associated with histological grade and lymph node metastasis (P=0.016 and 0.022, respectively). Moreover, Kaplan-Meier survival analysis revealed that patients with high Delta-catenin expression had shorter survival than patients with low expression (P=0.015), and multivariate Cox analysis revealed that high Delta-catenin expression was also an independent prognostic factor (P=0.017). Conclusion:Our results suggest that Delta-catenin acts as an oncoprotein when overexpressed in breast cancer, and its expression is associated with poor prognosis of patients.

Objective To evaluate the clinical curative effect of ulinastatin combined with CRRT in the treatment of multiple organ dysfunction syndrome(MODS).Methods Sixty eight patients with MODS who were admitted to ICU from July 2013 to July 2015 were randomly divided into three groups:control group,CRRT group,combined group;Patients' APACHE Ⅱ,SOFA scores level of inflammatory markers were recorded before treatment and after treatment of 72 hours and 7 days.The mortality of the three groups in ICU were compared.Results After 72 hours and a week of treatment,the level of IL-10,IL-6,TNF-α,WBC、PCT、CRP in CRRT group and combined group were significantly better than that of control group(P＜0.05),and combined group were significantly better than that of CRRT group.Compared with the control group,the oxygen index,lactic acid,ALT significantly im proved in CRRT group and combined group were better than control group,after 72 hours and a week of treatment(P＜0.05),and the cornbined group was the most obvious.After a week of treatment,the mortality rate of CRRT group and combined group was significantly better than the control group (P＜0.05),while there was no statistical differences between CRRT group and combined group(P＞0.05).Conclusion Ulinastatin combined with CRRT is an effective method for the treatment of MODS.

Objective To explore the effect of the transcutaneous tracheostomy tube in patients with pneumothorax and its clinical value. Methods A prospective randomized controlled trial was conducted. Thirty-two patients with pneumothorax admitted to Department of Critical Care Medicine of Harrison International Peace Hospital of Hebei Medical University from June 2010 to June 2014 were enrolled. The patients were divided into control group and observation group,with 16 cases in each group. Beside the treatment for primary disease,the patients in control group received thoracic close drainage with traditional silica gel tube as performed by thoracic surgeons,and those in observation group received thoracic close drainage with transcutaneous tracheostomy tube by intensive care doctors. The curative effect and complications of the two groups were observed. Results Compared with control group,the time from diagnosis to operation(minutes:8.00±1.36 vs. 23.06±3.83,t=14.790,P=0.000)and the operation time were significantly shortened(days:5.37±1.02 vs. 7.31±1.70,t=7.286,P=0.000),the frequency of drainage tube replacement(times:0.18±0.40 vs. 3.87±1.14,t=12.128,P=0.000)and the times of repeated chest radiography(times:1.12±0.34 vs. 2.93±0.77,t=8.589,P=0.000)in observation group were significantly reduced,the length of hospital day was significantly shortened(days:8.30±1.37 vs. 24.56±5.62,t=17.289, P=0.000),the rates of dislocation of drainage tube(0 vs. 3 cases),obstruction of the tube(0 vs. 5 cases),and subcutaneous emphysema(3 vs. 16 cases)were reduced obviously,but there was no difference in incidence of incision infection(1 vs. 3 cases)and infection of thoracic cavity(0 vs. 2 cases). Conclusions The usage of transcutaneous tracheostomy tube in patients with pneumothorax is safe and simple. Doctors in ICU can independently do this procedure,and its effect is positive.

Objective:To explore the construction and mechanism of Mindin gene specific macrophage knockout mice in acute lung injury induced by lung ischemia-reperfusion injury(IRI).Methods:Mindin gene knockout mice were constructed by CRE-LOP system, Mice were divided into four groups of C57/B6 wild-type mice sham operation(n=10), C57/B6 mice operation(n=10), Mindin-/-macrophage-specific knockout mice operation(n=10)and C57/B6 mice operation + Mindin recombinant protein intervention(n=10). And lung ischemia-reperfusion injury model was established by clamping pulmonary portal.The effects of Mindin gene knockout and recombinant protein intervention on acute lung injury were observed in vivo and in vitro.t-test and ANOVA test were employed for data processing.Results:Mindin gene macrophage specific knockout mice was successfully constructed.Surgery(Mindin-/-)group significantly reduced pulmonary edema, release of inflammatory factors(IL1β: 2.73±0.19 vs. 5.81±0.61; IL-18: 6.52±0.63 vs. 11.03±0.34; TNF-α 2.18±0.14 vs. 4.76±0.20; HMGB1: 4.57±0.33 vs. 8.76±0.87), expression of NLRP3(2.07±0.27 vs. 4.91±0.22)and secretion of GSDMD(2.78±0.37 vs. 5.78±0.29)as compared with surgery group in vivo.In surgery(WT)+ Mindin group, the expression of lung IRI, inflammatory factors and cell pyroptosis were opposite, And the results were consistent in vitro and in vivo.As compared with surgery group, the above parameters were up-regulated in surgery(WT)+ Mindin protein group.And inter-group differences were statistically significant(all P<0.05). In vitro, the expressions of NLRP3(1.00±0.36, 0.41±0.06, 4.13±0.23), GSDMD(1.00±0.17, 0.34±0.16, 6.32±0.46)and integrin β4(1.00±0.11, 0.28±0.07, 3.53±0.17)were detected in different groups including hypoxia-recovery oxygen(HR), HR+ Mindin siRNA and HR+ Mindin protein groups in macrophage cell line(J774A); As compared with HR group, the above parameters were up-regulated in HR+ Mindin protein group and down-regulated in HR+ Mindin siRNA group.And the differences were statistically significant( P<0.05). The expressions of NLRP3(1.00±0.07, 1.13±0.11, 0.51±0.14)and GSDMD(1.00±0.09, 0.87±0.16, 0.37±0.12)were detected in Mindin, Mindin protein+ vehicle and Mindin protein+ integrin β4 knockout groups.The above parameters were down-regulated in Mindin protein+ integrin β4 knockout group as compared with Mindin protein and Mindin protein + vehicle groups.And the inter-group differences were statistically significant(all P<0.05). Conclusions:During pulmonary IRI, Mindin knockdown can alleviate pulmonary IRI.Mindin gene may promote the expression of inflammatory factors, NLRP3 and GSDMD protein by activating integrin β4 and aggravate cell pyroptosis to promote the development of pulmonary IRI.

Objective:To analyze and screen microRNA (miRNA) related to the prognosis of gastric cancer(GC) by bioinformatics analysis, and to construct and validate a risk score model.Methods:The human genome miRNA sequencing data and corresponding clinicopathological data of the 491 samples (446 GC tissue samples and 45 normal gastric tissue samples) were downloaded from the cancer genome atlas (TCGA) database. The differentially expressed microRNA (DEM) was analyzed with edgeR package of R 4.0.2 software and the obtained DEM’s profile was randomly divided into training set and test set according to the ratio of 1∶1. The miRNA related to prognosis were analyzed and screened with univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis was further performed to analyze the screened prognostic-related miRNA and then the prognostic risk score model was constructed. Kaplan-Meier curve, receiver operating characteristic curve (ROC), and dynamic area under the ROC were drawn to evaluate the predictive power of the model.Results:A total of 175 DEM in GC tissues were screened out based on the cut-off criteria of |log2 Fold Change|>1.5 and P<0.01. Six DEMs related to the overall survival rate of patients with GC were screened out by univariate Cox regression and LASSO regression analysis, and then a five-miRNA risk score model was successfully constructed by multivariate Cox regression. The risk score=0.183×hsa-miRNA-184+ 0.086×hsa-miRNA-675-0.231×hsa-miRNA-2115+ 0.548×hsa-miRNA-3943-1.455×hsa-miRNA-1246. In the training set, test set and overall data set, the cumulative survival rates of the patients with higher risk score were lower than those of the patients with lower risk score, respectively, and the differences were statistically significant ( χ2=18.90, 9.50 and 26.70, all P<0.05). The prediction power of the model was better than that of TNM stage. And the results of stratified analysis showed the predictive ability of the model in patients with early GC. The results of univariate Cox regression and multivariate Cox regression demonstrated that the risk score of the model, gae and M stage were independent risk factors for poor prognosis in patients with GC (hazard ratio(95% confidence interval)1.19(1.07 to 1.32), 1.20(1.06 to 1.40), 1.50(1.01 to 2.23), 1.90(1.28 to 2.90), 1.34(1.15 to 1.57), 2.10(1.05 to 4.40); all P<0.05). Conclusion:The 5-miRNA risk score model based on 5 miRNAs which was an independent prognostic factor had high accuracy in predicting the prognosis of patients with GC.

OBJECTIVE: To evaluate the feasibility of applying intracranial lead reconstruction in deep brain stimulation (DBS) therapy for Parkinsonism. METHODS: We retrospectively collected the clinical data from 27 patients with Parkinson's disease (PD), who received bilateral subthalamic nucleus (STN) DBS therapy between January, 2016 and December, 2017. According to the position of the selected optimal stimulating contact of the implanted leads, the patients were divided into group A with the stimulating contacts of the bilateral leads in the STN, group B with unilateral stimulating contacts in the STN, and group C with bilateral stimulating contacts outside the STN. All the patients were assessed for improvement using Hoehn-Yahr stage, the third part of United Parkinson's Disease Rating Scale (UPDRS Ⅲ), Schwab and England Activities of Daily Living (SE-ADL), and L-dopa equivalent daily dose (LEDD). The consistency between the optimal stimulating contact selected by lead reconstruction and that by standard postoperative programming procedure was also evaluated. RESULTS: The patients in all the 3 groups showed postoperative improvements in Hoehn-Yahr stage, UPDRS Ⅲ score, SE-ADL score, and LEDD in the medication-off state. But at 12 months of the follow-up, such improvements were maintained only in the patients of group A. The optimal stimulating contacts selected by lead reconstruction and standard postoperative programming procedure had a matching rate of up to 77.78% (42/54), and the coordinates of the optimal contacts selected by the two methods showed no significant difference. CONCLUSIONS Intracranial lead reconstruction facilitates the study of the association between the implant site of the leads and the clinical outcome of DBS therapy for PD and allows the precise selection of the optimal contact of the implanted leads in postoperative programming of DBS.
Activities of Daily Living ; Deep Brain Stimulation ; Humans ; Parkinson Disease ; Retrospective Studies ; Treatment Outcome

Objective To investigate the changes of serum cardiac-specific troponin I (cTnI) level in patients after lung transplantation. Methods Clinical data of patients undergoing lung transplantation in our hospital from December 2016 to December 2022 were retrospectively analyzed. The relationship between postoperative serum cTnI level and clinical characteristics were explored. Results Finally 20 patients were collected, including 15 males and 5 females with an average age of (51.65±12.79) years. The serum cTnI level was significantly increased after lung transplantation. The serum cTnI reached the highest level on the first day after transplantation, and significantly decreased from the third day after transplantation. The serum cTnI levels in patients with obstructive pulmonary disease and bilateral lung transplantation were significantly higher than those in patients with restrictive pulmonary disease and unilateral lung transplantation on the day after surgery and on the first day after transplantation. Conclusion Transient myocardial injury can occur after lung transplantation, which is characterized by an abnormal increase in serum cTnI level.