Objective:To explore the influencing factors of recovering to normal atrioventricular nodal conduction (AVNC) in patients with acute myocardial infarction (AMI) complicated III atrioventricular block (AVB) .Meth‐ods:According to III AVB recovered to normal or not ,a total of 82 AMI complicated III AVB patients were divid‐ed into recovery group (n=51) and non- recovery group (n=31 ,including three cases undergoing permanent pace‐maker implantation and 28 dead cases) .The relationship among diabetes mellitus (DM) history ,ischemic precondi‐tioning (IP) ,levels of creatinine (Cr) and hemoglobin (Hb) at hospitalization ,systolic blood pressure (SBP) ,Killip class , cardiogenic shock and recovering to normal AVNC etc .were observed in two groups .Results:There were no significant difference in age ,sex proportion ,smoking history ,hypertension history ,DM history ,IP ,duration from onset to arriving at emergency room ,heart rate and SBP at hospitalization ,Hb level and early reperfusion treatment between two groups , P>0.05 all .Compared with recovery group ,there were significant rise in percentages of Kil‐lip ≥class II (39.2% vs .80.6% ) ,cardiogenic shock (21.6% vs .45.2% ) ,anterior wall infarction (7.8% vs . 32.3% ) ,Cr level [ (107.25 ± 6.69) μmol/L vs .(132.43 ± 11.52) μmol/L] and mortality (0% vs .90.3% ) ,and significant reduction in percentage of inferior wall infarction (92.2% vs .67.7% ) in non - recovery group , P<0.05 or < 0.01. Multifactor Logistic regression analysis indicated that Killip class was the independent predictor (OR=0.190 , P= 0.002 ) influencing recovering to normal AVNC in AMI + III°AVB patients .Conclusion:Killip class is an independent predictor influencing recovering to normal AVNC in AMI +III°AVB patients .

Objective:To define impact of spontaneous TIMI-3 flow before angioplasty on outcomes of percutaneous coronary intervention strategy and the prognosis in patients with acute myocardial infarction (AMI ). Methods: The consecutive 301 patients enrolled in the ongoing register of emergent coronary angioplasty within 12 hours from symptoms who were diagnosed as having ST elevation AMI in our hospital from 2000 to 2006 were analyzed, they were followed up for one year and the clinical characteristics and survival rates were analysed. Results: Among the 301 patients enrolled in the ongoing register of emergent coronary angioplasty, spontaneous reperfusion (TIMI-3 flow) was present in 14.6% at initial angiography. Compared with patients without TIMI-3 flow, those with TIMI-3 flow before coronary intervention were less likely to present in new-onset heart failure(2.3% versus 16%, P=0.016), Patients with initial TIMI-3 flow had significantly lower 30-day mortality (0% versus 9.3%, P=0.035) , and cardiogenic shock (0%versus 8.6%, P=0.044) and had a shorter hospital stay (P=0.008). Cumulative 1-year mortality was 0% in patients with initial TIMI-3 flow, 11.3% with TIMI 0-2 flow (P=0.019). By COX regression analysis, postprocendural TIMI-3 flow was an independent determinant of survival (OR=0.285,P=0.004) , however,TIMI-3 flow before coronary intervention was not found as an independent determinant of survival significantly. The lenitive symptoms and current smoking were the independent determinants of TIMI-3 flow before coronary intervention (P=0.005, P=0.048, respectively).Conclusion: Patients undergoing primary percutaneous transluminal coronary intervention in whom TIMI-3 flow is present before angioplasty may present with greater clinical and angiographic evidence of myocardial salvage, be less likely to develop complications related to left ventricular failure, and improve early and late survival.

Objective:To explore whether BHLHE40 can affect the sensitivity of thyroid cancer (TC) cells to cisplatin by activating oxidative phosphorylation (OXPHOS) pathway by targeting high mobility group A2 (HMGA2) .Methods:The mRNA expression of HMGA2 and its upstream transcription factor BHLHE40 in TC tissues was analyzed by TCGA-THCA and hTFtarget online databases. The si-HMGA2, oe-HMGA2, oe-BHLHE40, negative control si-NC and oe-NC were transfected into TC cells (K1 and SW579) by liposome transfection method. The mRNA expression levels of BHLHE40 and HMGA2 in TC cells (SW579, FTC-133, and K1) and normal thyroid cells (Nthy ori3-1) were detected by real-time quantitative PCR (qRT-PCR). The cell viability was detected by MTT assay, the half inhibitory concentration (IC 50) value of cisplatin was calculated by CCK-8 assay, the apoptosis level was detected by flow cytometry, and the expression of OXPHOS complex was detected by Western blotting. Seahorse XFe 96 was used to analyze the oxygen consumption rate of the TC cells. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay were used to analyze the binding relationship between BHLHE40 and HMGA2. Results:TCGA database results showed that the mRNA expression levels of HMGA2 and BHLHE40 in TC tissues (10.57±2.58, 13.89±1.13) were higher than those in normal thyroid tissues (4.82±1.69, 12.28±1.01), with statistically significant differences ( t=16.69, P<0.001; t=10.43, P<0.001). The results of qRT-PCR showed that the relative mRNA expression levels of HMGA2 in normal thyroid cells (Nthy ori3-1) and TC cells (SW579, FTC-133, and K1) were 1.00±0.13, 2.94±0.23, 4.71±0.41 and 6.29±0.49, while those of BHLHE40 were 1.00±0.12, 2.60±0.23, 3.39±0.35 and 6.18±0.51 respectively, both with statistically significant differences ( F=130.50, P<0.001; F=125.20, P<0.001). Further pairwise comparison showed that mRNA expression levels of HMGA2 and BHLHE40 in TC cells were significantly higher than those in normal thyroid cells (all P<0.001). According to MTT experimental results, si-HMGA2 treatment significantly reduced the cell viability of K1 cells compared to the si-NC group (all P<0.05). In addition, compared to the oe-NC group, oe-HMGA2 treatment significantly increased the cell viability of SW579 cells (all P<0.05). Compared to the oe-NC+DMSO group, the oe-HMGA2+DMSO group showed enhanced cell viability of SW579 cells, while the OXPHOS pathway inhibitor Gboxin was able to reverse the effect of overexpressing HMGA2 on cell viability (all P<0.05). The results of flow cytometry and CCK-8 experiments showed that compared to the si-NC group (apoptosis level: 6.19%±0.28%; cisplatin IC 50 value: 17.47 μmol/L), knocking down HMGA2 could increase the apoptosis level (11.96%±0.32%; t=19.17, P<0.001) and cisplatin sensitivity (IC 50 value: 1.49 μmol/L) of K1 cells. In addition, compared to the oe-NC group (apoptosis level: 9.98%±0.32%; cisplatin IC 50 value: 8.17 μmol/L), overexpressing HMGA2 significantly decreased the apoptosis level (4.32%±0.25%; t=19.65, P<0.001) and cisplatin sensitivity (IC 50 value: 34.95 μmol/L) of SW579 cells. The results of dual-luciferase assay showed that compared with the si-NC group, knocking down the expression of BHLHE40 in human kidney epithelial 293T cells significantly reduced the luciferase activity of wild-type HMGA2 (0.31±0.02 vs. 1.00±0.11; t=10.69, P=0.004). However, there was no significant effect on the luciferase activity of mutant-type HMGA2 (1.06±0.11 vs. 1.00±0.07; t=0.80, P=0.470). ChIP results showed that the mRNA expression level of HMGA2 in K1 cells was significantly increased in the anti-BHLHE40 group (6.57±0.62) compared with the IgG group (1.00±0.10; t=15.36, P<0.001). Compared to the oe-NC+DMSO group, the oe-HMGA2+DMSO group showed decreased apoptosis level ( P<0.05) and cisplatin sensitivity of SW579 cells, with a significant increase in the expression of OXPHOS complexes Ⅰ-Ⅴ and cellular oxygen consumption rates (all P<0.05). The effect of overexpressing HMGA2 was reversed by treatment with oe-HMGA2+Gboxin (all P<0.05). The recovery experiment showed that compared to the oe-NC+si-NC group, overexpression of BHLHE40 in SW579 cells increased cell viability and the expression of OXPHOS complexes Ⅰ-Ⅴ, while decreasing apoptosis levels and increasing cellular oxygen consumption rates and cisplatin IC 50 values (all P<0.05). However, simultaneous knockdown of HMGA2 reversed the effect of overexpressing BHLHE40 (all P<0.05) . Conclusion:BHLHE40 can activate the OXPHOS pathway by targeting and regulating the expression of HMGA2, thereby affecting the sensitivity of TC cells to cisplatin.

Objective To evaluate the clinical value of free glycoprotein non-metastatic melanoma protein B(GPNMB)as a drug resis-tance and prognostic marker for non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)amplifica-tion accompanied by mutations.Methods Fifty-five cases of NSCLC patients with EGFR amplification associated with mutations who received treatment from March 2018 to September 2019 were included as the observation group.All patients received an EGFR-tyrosine kinase inhibitor(EGFR-TKI)as the first-line treatment;67 blood samples from the physical examination center during the same period were randomly included as healthy control.We compared the expression levels of free GPNMB between the two groups,explored the correlation between GPNMB expression and the clinicopathological information in the observation group;and combined the clinical efficacy to evaluate its value as a drug resistance marker.Through follow-up,the progress free survival(PFS)of patients was statistically analyzed,and through multivariate Cox regression analysis,independent risk factors affecting the survival in the observation group were explored.Results Compared with that in the control group,the expression level of free GPNMB in the observation group was signi-ficantly up-regulated.The expression level of free GPNMB in the observation group is significantly related to the clinical efficacy of EGFR-TKI(P = 0.016).Patients with high GPNMB expression have significantly stronger drug resistance,and patients with high GPNMB expression have significantly shorter PFS duration(P = 0.032).A high free GPNMB expression(HR = 4.029,95%CI:1.942-8.358,P＜0.001)is also an independent risk factor affecting patient survival.Conclusion The expression level of free GPNMB in patients with EGFR amplification accompanied by mutant NSCLC is significantly up-regulated,and its high expression is significantly related to the enhancement of the patient's drug resistance.High GPNMB expression is significantly related to the poor prognosis of patients and is an independent risk factor affecting patient survival.

As an essential component of intracranial venous circulation,cortical veins are prone to be injured or compressed,and cortical venous thrombosis was formed after traumatic brain injury (TBI) because of their special anatomical position,which could result in intracranial venous retum disorders,intracranial hypertension,and brain parenchymal damage in drainage areas.The cortical venous related circulation disorders after TBI are summed up in this review.

Objective To investigate the risk factors,mechanism and treatment strategies of expanding regional brain injury (traumatic intracerebral contusion or hematoma) in patients with acute traumatic epidural hematoma (ATEDH) after surgical evacuation.Methods Fifty-nine patients with ATEDH,admired to and accepted surgical evacuation in our hospital from February 2013 to September 2018,were chosen in this study;their clinical data and CT imaging data were retrospectively analyzed.The volume ofintracranial hematoma was measured by 3D Slicer software.According to the progress of local brain injury revealed by first CT examination after surgical evacuation,patients with ATEDH were divided into progressive group and non-progressive group.Risk factors of patients with expanding regional brain injury after surgery were analyzed by univariate and multivariate Logistic regression analyses.Results After surgery,22 showed expanding regional brain injury,accounting for 37.29％:9 occurred expanding intracerebral hematoma,and 2 of them died after conservative treatment;two had both expanding intracerebral contusion and hematoma;11 expanding intracerebral contusion patients developed into hematoma,and three of them occurred delayed intracerebral hematoma adjacent to the area of ATEDH,and two underwent secondary craniotomy with good recovery.As compared with patients from the non-progressive group,progressive group had significantly higher percentages of patients with preoperative hyperglycemia (＞9.1 mmol/L),patients with preoperative abnormal coagulation and patients accepted decompressive craniectomy (P＜0.05).Multivariate Logistic regression analysis revealed that preoperative abnormal coagulation was an independent risk factor for expanding intracerebral contusion or hematoma after surgery (OR=6.498,95％CI:1.076-39.253,P=0.041).Conclusion Expanding regional brain injury has high morbidity in patients with ATEDH after surgery evacuation;preoperative abnormal coagulation is an independent risk factor for its occurrence.

Objective To investigate the effect of resveratrol (Res) on temozolomide (TEM) against gliomas in vivo.Methods Human glioma cell line T98G was transplanted into BALB/C-nu female nude mice to establish orthotopic human glioma cell transplanted models.Five d after modeling,the 48 successfully modeled nude mice were randomly divided into solvent control group,Res group,TEM group,combination drug group,Wnt signaling pathway agonist group,and Wnt signaling pathway inhibitor group(n=8);and dimethyl sulfoxide (10 mg/kg),Res (10 mg/kg),TEM (25 mg/kg),Res (10mg/kg+TEM (25 mg/kg),Res (10 mg/kg)+TEM (25 mg/kg)+lithium chloride (2 mg/kg),and Res (10mg/kg)+TEM (25 mg/kg)+IWR-1 (5 mg/kg) were given,respectively,once/d for 30 d.During the administration,the survival status of nude mice in each group was continuously observed,tumor volume was measured by MR imaging every 5 d.Thirty d after administration,TUNEL was used to detect the apoptosis of tumor cells,and immunofluorescence was used to detect the immunofluorescent intensity of O6-methylguanine-DNA methyltransferase (MGMT) and β-catenin in the tumor tissues.Western blotting was used to detect the protein expression levels of Wnt signaling pathway-related proteins (Wnt2,and β-catenin),MGMT,and glycogen synthase kinase 3β (GSK3β).Results As compared with the TEM group,the combination drug group and Wnt signaling pathway inhibitor group had significantly decreased tumor volumes 20,25,30,and 35 d after modeling (/P＜0.05);as compared with the combination drug group,the Wnt signaling pathway inhibitor group had significantly decreased tumor volumes while Wnt signaling pathway agonist group had significantly increased tumor volumes 20,25,30,and 35 d after modeling (P＜0.05).TUNEL showed that the apoptosis rate of tumor cells in the combination drug group and Wnt signaling pathway inhibitor group was significantly increased as compared with that in the temozolomide group (P＜0.05);as compared with that in the TEM group,the apoptosis rate of tumor cells in the Wnt signaling pathway inhibitor group was significantly increased while that in the Wnt signaling pathway agonist group was statistically decreased (P＜0.05).Western blotting results showed that as compared with those in the combination drug group,the protein expression levels ofWnt2,β-catenin,and MGMT in the Wnt signaling pathway inhibitor group were significantly reduced,and GSK-3β protein expression level was significantly increased;while the protein expression levels of Wnt2,[β-catenin,and MGMT in the Wnt signaling pathway agonist group were significantly increased,and GSK-3β protein expression level was significantly decreased (P＜0.05).Conclusion Res inhibits Wnt signaling pathway by reducing expressions of Wnt2 and β-catenin,leading to decrease in MGMT expression,thereby enhancing the anti-glioma effect of TEM.

Objective To explore the risk factors,mechanism and treatment strategies of secondary brain injury (cerebral hemorrhage or cerebral infarction/encephaledema) adjacent to acute epidural hematoma after surgical evacuation.Methods Forty-four patients with acute epidural hematoma underwent craniotomy in our hospital from March 2013 to December 2018 were chosen in this study.According to postoperative CT or MR imaging examination results,patients were divided into group of secondary brain injury (n=11) and group of non-secondary brain injury (n=33).The clinical data of the two groups were compared,and the significance of epidural hematoma thickness in assessing secondary brain injury was analyzed by receiver operating characteristic (ROC) curve.Binary Logistic regression analysis was used to analyze the independent risk factors affecting secondary brain injury.Results After surgery,11 showed secondary brain injury:3 occurred cerebral hemorrhage,one of whom was diagnosed as having cerebral venous hemorrhage in the cortical vein drainage area caused by traumatic cerebral venous circulation disorder;6 had cerebral infarction/encephaledema,and 2 occurred hemorrhagic cerebral infarction/encephaledema;two underwent secondary craniotomy and both achieved satisfactory effect.As compared with patients from the non-secondary brain injury group,patients fromsecondary brain injury group had significantly higher percentage of patients with epidural hematoma thickness ≥ 33.5 mm (P＜0.05).ROC curve analysis showed that the thickness of epidural hematoma had predictive value in secondary brain injury after surgery (P＜0.05),and area under the curve was 0.722 and diagnostic threshold was 33.5 mm.Binary Logistic regression analysis revealed that epidural hematoma thickness ≥33.5 mm was an independent risk factor for secondary brain injury adjacent to epidural hematoma after surgery (odds ratio=7.367,P=0.024,95％CI=1.298-41.797).Conclusions Acuteepidural hematoma thickness ≥33.5 mm is a high-risk factor associated with secondary brain injury adjacent to epidural hematoma after surgery.Intracranial venous circulatory disorders have non-negligible effect on occurrence of secondary brain injury.