Objective To investigate the effects of GABAergic inhibition medicated by the intemeurons on the induction of long-term potentiation (LPT), and determine the concentration of bicuculline required to block GABAA receptor-mediated inhibition and affect LIT induction at CA1 hippocampal synapse. Methods Using whole-cell recording technique, the mini-inhibitory postsynaptic current (mIPSC) and evoked fcedforward inhibitory post synaptic current (IPSC) were measured from the CA1 neurons in the hippocampal slices. Extracellular recording of field excitatory postsynaptic potential (fEPSP) by Schaffer collateral stimulation was used to study the synaptic plasticity in adult mice hippocampal slices, and the effects of bicuculline at different concentrations on mlPSC, IPSC, fEPSP and LTP induction were evaluated. Results Bicuuclline at 10 and 20 μmol/L abolished mIPSC and IPSC currents. The action of 20 μmol/L bicuuclline were more obviously. The slope of fEPSPs were significantly enhanced by application of bicuculline at 20 μmol/L, but not at 5 or 10 μmol/L. In the presence of 5, 10, 20 and 50 μmol/L bicuculline, LTP of the fEPSP slope following 100 Hz tetanization was enhanced, but the increment was significant only for 10 and 20 μmol/L bicuculline (P<0.05). Conclusion Bicuculline can abolish GABAA receptor-mediated inlaibition and affect the excitatory postsynaptic potential in a dose-dependent manner, and at a critical level, bicuculline induces GABAergic disinhibition to result in enhanced LTP in hippocampal slices.

This study was aimed to investigate the correlation of thrombosis with increased platelet turnover in essential thrombocythemia. According to presence or absence of thrombosis, 26 patients with ET were divided into two groups. Reticulated platelets (RP) were measured by flow cytometry and 26 healthy volunteers were selected as healthy controls. The ET patients with thrombosis were treated with hydroxyurea and interferon-alpha. The results demonstrated that the ET patients with thrombotic events had a significantly higher RP percentage (14.8% +/- 7.2%) than that in both asymptomatic ET patients (4.5% +/- 2.3%) and normal control (3.3% +/- 1.5%), (P < 0.05); the RP percentage in asymptomatic ET patients did not differ significantly from controls. ET patients with thrombosis also had a significantly higher absolute RP (ARP) count than those in ET patients without thrombosis [(176 +/- 37) x 10(9)/L vs (46 +/- 12) x 10(9)/L]. The ET patients with thrombosis were successfully treated with hydroxyurea plus INF-alpha, the RP percentage and ARP counts obviously reduced. In conclusion, when the ET patients had thrombotic events, those patients had a significantly higher RP percentage and ARP compared with patients without thrombosis and healthy controls. The ET patients with thrombosis were successfully treated with hydroxyurea plus INF-alpha.
Adult ; Aged ; Aged, 80 and over ; Blood Platelets ; cytology ; physiology ; Female ; Humans ; Male ; Middle Aged ; Platelet Count ; Thrombocythemia, Essential ; blood ; complications ; Thrombosis ; blood ; complications

OBJECTIVETo investigate the effect of neurogulin-1 (NRG1) on the transmission and plasticity of CA1 synapses in mouse hippocampal slices at different temperatures.

METHODSUnder room temperature (26-/+1 degrees C) or physiological temperature (32-/+1 degrees C), field excitatory postsynaptic potential (fEPSP) evoked by extracellular microelectrode recording technique was recorded in the CA1 region in adult mouse hippocampal slices, and the long-term potentiation (LTP) was induced by high frequency stimulation (HFS). The effects of NRG1 on the baseline fEPSP and induction of LTP in CA1 region were observed.

RESULTSNo significant variation in the slope of fEPSP relative to the baseline fEPSP was observed after perfusion with NRG1 at room temperature or physiological temperature (P > 0.05). After HFS at the room temperature, the mean slope of fEPSP in the slices perfused with NRG1 was similar to that of the control group (P > 0.05), but HFS at the physiological temperature resulted in significant reduction in the mean slope of fEPSP in the slices perfused with NRG1 (P < 0.01).

CONCLUSIONNRG1 may temperature-dependently inhibit the induction of LTP in the CA1 region in mouse hippocampal slices.

Animals ; Hippocampus ; physiology ; Long-Term Potentiation ; physiology ; Male ; Mice ; Mice, Inbred C57BL ; Neuregulin-1 ; physiology ; Neuronal Plasticity ; physiology ; Synaptic Transmission ; physiology ; Temperature

Objective To study the changes in Bcl-2/adenovirus EIB 19kD-interacting protein 3(BNIP3)expression in the hippocampus of rats following transient forebmin ischemia. Methods Ten adult male Wistar rats were randomized into sham operation group(n=5)andischemia-rcperfosion group(n=5),and the rats in the latter group were subjectedto global ischemia for 15 min followed by repeffusion for 72 h.Nissl's staining was used to examine the neuronal death in the hippocampus induced by global brain isehemia.Another 14 adult male Wistar rats Were randomly divided into 3 groups,namely group 1 with sham operation(n=4),group 2 with global cerebral isehemia followed by reperfusion for 1 h(n=5),and group 3 with global isebemia and reperfusion for 6 h(n=5).All the rats were sacrificed to examine BNIP3 expression in the hippocampus using Western blotting. Results Compared with the sham operation group,the ischemia-reperfusion(72 h)group showed obvious neuronal death in the hippoeampal Cal region,where the neurons presented with irregular shape,cell shrinkage and nuclear fragmentation. BNIP3 monomer expression significantly increased in the hippocampus after isehemia-reperfusion in comparison with that in the sham operation group(P<0.05),but the length of reperfusion time(1 and 6 h)did not significantly affected BNIP3 monomer expression (2.543±0.473vs3 2.942±0.777,P>0.05).No significant difference was found in the expression level of BNIP3 dimers between the sham operation, ischemia-reperfusion 1 h and 6 h groups(P>0.05).Conclusion The expression of BNIP3 is up-regulated in the hippocampus of rats with transient forebrain ischemia.

OBJECTIVETo explore the diagnostic value of whole-organ magnetic resonance imaging score (WORMS) in knee osteoarthritis (KOA).

METHODSFrom November 2009 to January 2011,70 patients with KOA combined with knee effusion among outpatient and inpatient were analyzed retrospectively. Among the patients, 12 patients were male, 58 patients were female,ranging in age from 46 to 75 years,with a mean age of (59.66 +/- 9.93) years. The clinical symptoms were evaluated by WOMAC, the imaging of KOA was assessed by K-L score and WORMS, and COMP and CTX- II were measured respectively by ELISA. The correlation analyses and multiple linear regression analysis were studied to determine associations among biomarkers, clinical variables and radiographic findings of knee joints.

RESULTSThe average scores of WOMAC and WORMS were (57.50 +/- 8.20) and (64.54 +/- 16.45) respectively. The median of CTX- II nd COMP were 2.42 ng/ml and 4.56 ng/ml respectively. Grouped by less than the lowest quartile and more than the highest quartile of WORMS, COMP was significantly different (Z=2.04, P=0.039), but there was no significant difference in CTX-II (Z=0.79, P=0.427). WORMS were positively correlated with WOMAC and K-L score (r=0.777, P<0.01; r=0.716, P<0.01; respectively); WOMAC was also positively correlated with K-L score (r=0.692, P<0.01). WORMS's cartilage, osteophytes and synovitis were positively correlated with WOMAC, K-L score and COMP respectively (r=0.771, P<0.01; r=0.509, P<0.01; r=0.917, P<0.01). It was determined by stepwise regression that the KOA was mainly affected by WORMS, K-L score (P=0.015, P=0.025 respectively) when WOMAC as a dependent variable, age, gender, K-L score, WORMS, COMP and CTX- II as independent variables (F=20.327, P<0.01).

CONCLUSIONWORMS has a better reference value for diagnosis of KOA. The expression of COMP is high in the synovial fluid when WORMS at the high point. The clinical symptoms of knee osteoarthritis are mainly affected by WORMS and K-L score.

Aged ; Cartilage Oligomeric Matrix Protein ; Collagen Type I ; analysis ; Extracellular Matrix Proteins ; analysis ; Female ; Glycoproteins ; analysis ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Matrilin Proteins ; Middle Aged ; Osteoarthritis, Knee ; diagnosis ; metabolism ; physiopathology ; Peptides ; analysis

BACKGROUNDIt remains a challenge to inhibit the local recurrence or distant metastasis of localized or locally advanced renal cell carcinoma (RCC) after surgical resection. We investigated the feasibility, safety and efficacy of immunotherapy using autologous tumor lysate (TL)-pulsed dendritic cells (DCs) and cytokine-induced killer (CIK) cells in patients with localized or locally advanced RCC.

METHODSFrom January 2001 to July 2009, we collected 137 patients that met the selection criteria and randomly divided them into three groups. After surgery, immunotherapy with TL-pulsed DCs-CIK cells (DC-CIK group) and interferon (IFN)-α (IFN-α group) was performed in 46 patients, respectively. The other 45 patients received no postoperative adjuvant therapy (the control group). The changes in the numbers of T lymphocyte subsets, including CD4(+)CD25(high) regulatory T cells (Treg), were determined before the operation and after immunotherapy. The overall survival was compared among the three groups.

RESULTSAn increase of the CD4(+)/CD8(+) ratio and a decrease of CD4(+)CD25(high) cells were observed after TL-pulsed DC-CIK cells or IFN-a immunotherapy. All patients tolerated the TL-pulsed DC-CIK cells immunotherapy very well, and side effects in the DC-CIK group were less than in the IFN-α group. The metastasis and recurrence rates were significantly decreased after TL-pulsed DC-CIK cells or IFN-α immunotherapy compared with the control group (P < 0.01). The Log-rank test showed that the overall survival rates were significantly higher in the DC-CIK group and IFN-α group than that in the control group (P < 0.01), but there was no difference between the DC-CIK group and IFN-α group (P > 0.05).

CONCLUSIONPostoperative immunotherapy with TL-pulsed DC-CIK cells may prevent recurrence/metastasis and increase the overall survival rate after surgery in localized or locally advanced RCC.

Adult ; Aged ; Carcinoma, Renal Cell ; immunology ; mortality ; therapy ; Cytokine-Induced Killer Cells ; immunology ; Dendritic Cells ; immunology ; Female ; Humans ; Immunotherapy ; Kidney Neoplasms ; immunology ; mortality ; therapy ; Male ; Middle Aged ; T-Lymphocyte Subsets ; immunology

Effective biomarkers for clinical usage of osteoarthritis are still limited. It was confirmed that C-terminal crosslinking telopeptide of type I collagen (CTX- II) was a specific marker reflecting degradation of articular cartilage. Detection of CTX- II could promptly reflect level of cartilage injury and degradation ,diagnose OA,predict its progress,monitor effects of drug treatment, thus, reflect the condition of osteoarthritis patient indirectly. Application of CTX- II focused mainly on in the early stage of OA and need together to detect with other biomarkers,in order to more accurately reflection of the pathological changes of OA,but the specific clinical significance of CTX- II results still need to improve further.
Biomarkers ; analysis ; Cartilage, Articular ; pathology ; Collagen Type II ; analysis ; Early Diagnosis ; Humans ; Osteoarthritis ; diagnosis ; Peptide Fragments ; analysis

Objectives:To describe the early and long-term survival of off-pump coronary artery bypass grafting(OPCAB)and to analyze the impact and risk factors of peri-operative events on mortality and long-term survival in OPCAB patients aged over 75 years old. Methods:From January 2001 to December 2012,233 patients aged over 75 underwent OPCAB in our hospital, 173 cases (74.25%) were male,the average age was (77.1±2.3) years.The perioperative data was retrospectively collected.Binary Logistic regression was used to define the risk factors related to the perioperative events and mortality.Follow-up was performed regularly post-surgery. Univariate analysis and Cox regression model were used to find out factors affecting the long-term outcomes. Results:Fifteen out of 233 patients died during the perioperative period. Binary Logistic regression showed that preoperative arrhythmia (OR=6.767, P=0.002),IABP ( intraoperative, post-operative) (OR=4.292, P=0.040;OR=19.455, P＜0.001), ICU stay time (OR=1.500, P=0.001), mechanical ventilation time (OR=1.004, P=0.002), reintubation or tracheotomy (OR=30.000, P＜0.001), re-thoracotomy (OR=26.750, P＜0.001), postoperative cerebral infarction (OR=5.889, P=0.041) were risk factors of perioperative mortality. The remaining 218 patients were followed up for a mean of (92.84±45.52) months, 121 patients died during follow-up. The survival rate at l, 3, 5, 8 and 10 years was 90.99%, 87.55%, 85.31%, 68.93% and 56.70%, respectively. Univariate analysis showed that sex(male), hypertension, preoperative arrhythmia, reintubation or tracheotomy were risk factors of the long-term mortality (P＜0.05). Cox regression analysis showed that reintubation or tracheotomy (HR 4.387, 95%CI=1.876-10.259,P＜0.010) was the independent risk factor affecting the long-term survival. Conclusions:Preoperative arrhythmia, IABP (intraoperative, postoperative), ICU stay time, mechanical ventilation time, reintubation and tracheotomy, re-thoracotomy, postoperative cerebral infarction are risk factors of perioperative mortality. Reintubation or tracheotomy is the independent risk factor affecting the long-term survival.Taken together, OPCAB in patients aged over 75 is associated with favorable perioperative and long-term outcome,and it serves a safe and effective operative strategy for coronary artery revascularization in patients aged over 75.

Objective To compare the efficacy, safety, and survivability of TCbHP versus AC-THP in the neoadjuvant therapy of HER2-positive breast cancer in real-world. Methods Clinical data of patients with HER2 positive breast cancer, who have received TCbHP or AC-THP as neoadjuvant therapy and completed surgery in 11 third-class hospitals in various cities of Hebei Province, were retrospectively collected.The total pathological complete remission (tpCR) rate, the incidence of grade 3 or higher adverse reactions and the completion rate of the given approaches were compared. Results A total of 110 cases were collected, including 78 cases in the TCbHP group and 32 cases in the AC-THP group.The tpCR rate of the TCbHP group was higher than that of the AC-THP group, but the difference was not statistically significant (64.10% vs. 56.25%, P=0.441).No significant difference was found in the breast pathologic complete response (bpCR) and axillary pathologic complete response (apCR) rates between the TCbHP group and the AC-THP group (70.51% vs. 56.25%, P=0.150;78.21% vs. 84.38%, P=0.462).Exploratory analysis revealed that the tpCR rate of the TCbHP group was significantly higher than that of the AC-THP group in patients with HR-positive breast cancer (51.11% vs. 22.22%, P=0.036).As for the patients with HR-negative breast cancer, the tpCR rate of the AC-THP group tended to be higher than that of the TCbHP group (100% vs. 81.82%, P=0.088).The incidence of grade 3 or higher adverse reactions in the TCbHP group was slightly higher than that in the AC-THP group (12.82% vs. 9.38%, P=0.753).No deaths occurred in the whole group.Moreover, no significant difference was observed in the completion rate of the given approaches between the TCbHP group and the AC-THP group (92.31% vs. 90.63%, P=0.718). Conclusion In real-world clinical practice, the neoadjuvant therapy of TCbHP and AC-THP are effective, safe, and well tolerated among patients with HER2-positive breast cancer.The tpCR rate between the two approaches was not significantly different.The AC-THP regimen could also be considered as one of the optimal regimens for HER2-positive breast cancer in neoadjuvant therapy.

Objective To explore the influencing factors of mild cognitive impairment(MCI)in patients with atrial fibrillation and diabetes mellitus,and to establish the prediction model,so as to provide guidance for the treatment of MCI in patients with atrial fibrillation and diabetes mellitus.Methods 199 patients with atrial fibrillation and diabetes diagnosed in the second ward of Cardiovascular Department of the Fifth Affiliated Hospital of Zhengzhou University from January 2023 to January 2024 were analyzed.The related factors of MCI in patients with atrial fibrillation and diabetes mellitus were analyzed by univariate analysis and multivariate logistic regres-sion.According to the results of multivariate logistic regression analysis,the prediction model of MCI in patients with atrial fibrillation and diabetes mellitus was established.Results Univariate analysis showed that age(P=0.002 3),homocysteine(P＜0.000 1),fasting blood glucose(P=0.022 5),glycated hemoglobin(P=0.006 6),and blood uric acid(P=0.032 2)were the influencing factors of MCI.Multivariate logistic regression analysis:age(OR=1.08,P=0.000 4),homocysteine(OR=1.37,P＜0.000 1),fasting blood glucose(OR=1.22,P=0.023 5),glycated hemoglobin(OR=1.61,P=0.004 2),and blood uric acid(OR=1.29,P=0.009 1)were the independent influencing factors of MCI.The optimal threshold is when the Youden index(YI=sensitivity+speci-ficity)is maximum.At the optimal threshold,the sensitivity was 0.74,the specificity was 0.80,and the area under the curve(AUC)was 0.809,indicating that the model can effectively predict the occurrence of MCI.Conclusion Age,fasting blood glucose,blood homocysteine,blood uric acid and glycosylated hemoglobin are independent risk factors for MCI in patients with atrial fibrillation and diabetes.The clinical prediction model based on multivariate logistic regression has a certain predictive value for the occurrence of MCI in patients with atrial fibrillation and diabetes mellitus.