Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective To expand the application of EOS in orthopedic diagnosis and treatment by comparing EOS and CT in the measurement of tibial tubercle-trochlear groove(TT-TG)distance of patellar dislocation.Methods The clinical and complete imaging data(EOS and CT)of 35 cases of patellar dislocation(dislocation group)and 35 cases of non-patellar dislocation(non-dislocation group)were analyzed retrospectively.Results The age difference between the dislocation group and the non-dislocation group was statistically significant(P＜0.05).The TT-TG distance was measured by EOS in the dislocation group(20.19±1.05)mm and the non-dislocation group(13.33±1.17)mm,and the difference between the two groups was statistically significant(P＜0.05).The TT-TG distance was measured by CT in the dislocation group(21.51±1.11)mm and the non-dislocation group(14.21±1.11)mm,and the difference between the two groups was statistically significant(P＜0.05).Bland-Altman plot showed that only three cases were outside the 95％confidence interval.Conclusion Accurate TT-TG distance can be obtained by using EOS system in imaging evaluation of patients with patellar dislocation,which provides a new measurement method for diagnosis and treatment evaluation of patellar dislocation.

Objective:To explore therapeutic effects of sodium nitroprusside (SNP) combined verapamil on no-reflow during percutaneous coronary intervention (PCI).Methods: A total of 106 patients, who suffered from no-reflow during PCI in our department from Jan 2011 to Dec 2013, were selected.According to random number table method, patients were divided into SNP group (n=55, received SNP based on routine treatment) and combined treatment group (n=51, received verapamil based on SNP group).Cardiac troponin I (cTnI) level before and 16h~18h after PCI, cardiac function indexes after 12-month follow-up, incidence of major adverse cardiovascular events (MACE) were measured and compared between two groups.Results: Compared with before PCI, there were significant rise in cTnI level in both groups on 16~18h after PCI, P=0.001 both;compared with SNP group, there were significant reductions in cTnI level [(1.31±0.44)μg/L vs.(0.11±0.02)μg/L] and percentage of cTnI>0.10μg/L (94.5% vs.54.9%) in combined treatment group, P=0.001 both.Compared with SNP group after 12 months, there was significant rise in left ventricular ejection fraction [(62.29±3.06)% vs.(65.65±3.94)%], and significant reductions in left ventricular end-diastolic dimension[(50.24±3.73)mm vs.(47.60±4.72)mm] and left ventricular end-systolic dimension [(33.29±2.11)mm vs.(31.00±4.33)mm] in combined treatment group, P<0.05 all.There were no significant adverse reactions during hospitalization and follow-up in both groups.Conclusion: When no-reflow occurs during PCI, intracoronary injection of SNP combined verapamil can improve cardiac function, and its safety is good, which is worth extending.

Objective: To evaluate the predictive value of cardiac magnetic resonance (CMR)-derived parameters on the improvement of left ventricular function in patients with acute viral myocarditis. Methods: Forty patients, who referred for acute viral myocarditis in our hospital from September 2011 to September 2015, were prospectively enrolled in this study.All patients were examined by CMR during hospitalization for acute viral myocarditis (baseline) and after 12 months.The CMR sequences include: two dimension steady state free precession, 2D SSFP; triple inversion recovery, triple IR; early gadolinium enhancement; phase sensitive inversion recovery turbo field echo, PSIR TFE. Results: Thirty out of 40 patients with susceptive acute viral myocarditis met the CMR criteria of acute viral myocarditis (Lake Louise Criteria) (LL+ ) and the other 10 patients did not meet the diagnostic criteria (LL-). Left ventricular ejection fraction (LVEF) values were significantly lower in LL+ group than in LL- group at baseline and at 12 months after discharge (P<0.01 or 0.05, respectively). The baseline left ventricular end-systolic volume index (LVESVI) was significantly higher in LL+ group than in LL- group (P<0.05) and was similar between the groups at 12 months follow up.Left ventricular end-diastolic volume index (LVEDVI )was similar between the two groups at baseline and at 12 months follow up.LVEF was significantly higher during 12 months follow up compared to baseline in LL+ group and remained unchanged in LL- group during the two time points.LVESVI and LVEDVI remained unchanged at baseline and during 12 months follow up both in LL+ and LL- groups (P>0.05). Results showed that LL+ , edema ratio (ER) positive and global relative enhancement (gRE) positive were associated with significant increase of LVEF at 12 months follow up.However, LL-, ER negative, gRE negative, late gadolinium enhancement(LGE) negative and LGE positive linked with unchanged LVEF at 12 months follow up (P>0.05). Patients were further divided into LVEF increase (ΔLVEF≥5%) group and non LVEF increase group (ΔLVEF<5%), the results of Chi-square test showed that LL+ and ER positive were related to the improvement of LVEF (P<0.05), while gRE and LGE were not associated with improvement of cardiac function (P>0.05). Multiple linear regression analysis, using ER, gRE and LGE as independent variables and LVEF as dependent variables, showed that the presence of myocardial edema was the strongest independent predictor of an increase in LVEF at follow up (full model: non-standardized coefficient 0.445, P=0.043; reduced model: non-standardized coefficient 0.442, P=0.12). Conclusion Cardiac magnetic resonance imaging monitoring is valuable to observe the cardiac function and morphology changes in patients with acute viral myocarditis, and myocardial edema imaging is the most powerful parameter to predict the improvement of LVEF in this patient cohort.

Objective To compare the efficacy and safety of singular double antithrombotie therapy (DT) using warfarin plus clopidogrel and the combined antithrombotie therapy of 3-month triple antithrombotie therapy (TT) using warfarin, aspirinand clopidogrel and 9-month double antithrombotie therapy (DT) for the patients with atrial fibrillation undergoing PCI. Methods Ninety patients with atrial fibrillation undergoing PCI were randomly divided into two groups evenly: one group was treated with dual antithrombotic therapy group (DT) and the other group with the combined therapy, e. g. 3-month triple antithrombotie therapy (TT) and 9-month double antithrombotie therapy (DT + TT for short). All patients were followed-up by 12 months. The two groups were compared in terms of incidences of death , myocardial infarction , stroke , target-vessel revascularisation , stent thrombosis and bleeding adverse events. Results The incidences of myocardial infarction, stroke, target-vessel revascularisation , stent thrombosis and bleeding adverse events in the TT + DT group were all significantly lower than the DT group (P < 0.05). The follow-up on the safety indicated that the rate of bleeding in the TT +DT group was insignificantly higher than the DT group (P > 0.05). Conclusion There is no significant difference in safety between the two groups. However, the therapy of TT + DT is more effective.

Objective To assess the diagnostic value of cardiac magnetic resonance (CMR) in patients with acute viral myocarditis.Methods Thirty patients with suspected acute viral myocarditis admitted in first people's hospital of Shunde from June 2011 to June 2013 were included in this prospective study.The diagnostic sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV) and accuracy of acute viral myocarditis were evaluated by clinical diagnosis.Diagnostic value among different scan methods and Lake Louise criteria were compared.Results Acute viral myocarditis was diagnosed in 63.33％ (19/30) patients.Values for sensitivity,specificity,PPV,NPV,and diagnostic accuracy within the overall cohort were 57.89％,72.73％,78.57％,50.00％,63.33％,respectively by edema imaging(ER).Values for sensitivity,specificity,PPV,NPV,and diagnostic accuracy within the overall cohort were 78.95％,63.64％,78.95％,63.64％,73.33％,respectively using global relative enhancement (gRE).Values for sensitivity,specificity,PPV,NPV,and diagnostic accuracy within the overall cohort were 78.95％,54.55％,75.00％,60.00％,70.00％,respectively using late gadolinium enhancement (LGE) criteria.Values for sensitivity,specificity,PPV,NPV,and diagnostic accuracy within the overall cohort were 84.21％,81.82％,88.89％,75.00％,83.33％ using Lake Louise criteria.The sensitivity,specificity,PPV,NPV,and diagnostic accuracy using Lake Louise criteria were significantly higher than using ER,gRE,LGE alone (all P ＜ 0.05).Specificity was higher using ER than using gRE and LGE(both P ＜ 0.05).The sensitivity,NPV,and diagnostic accuracy were significantly higher using gRE than using ER (all P ＜ 0.05) and was similar as using LGE (all P ＞ 0.05).Conclusion Cardiac magnetic resonance is an excellent imaging modality for the diagnosis of acute viral myocarditis.

OBJECTIVETo characterize unknown glycometabolic state in patients with essential hypertension (EHT) and normotensive patients and determine which EHT patients are candidates for oral glucose tolerance tests (OGTTs).

METHODSThis cross-sectional study consecutively recruited 895 EHT patients and 486 normotensive patients. The data including blood glucose, blood pressure, blood lipids, angiography profiles, and left ventricular parameters were collected.

RESULTSOGTTs performed in all patients revealed that the prevalence of abnormal glucose metabolism (AGM) was significantly higher in EHT patients than in normotensive patients at both baseline (P<0.001) and post-OGTT analysis (P<0.001). In total, 76.4% of the individuals with impaired glucose tolerance and 78.2% of individuals with newly diagnosed diabetes would have remained undetected if OGTTs had not been performed. Newly diagnosed AGM was significantly correlated with the presence and severity of coronary stenosis and left ventricular structure abnormalities and dysfunction. EHT patients with fasting glucose ≥5.6 mmol/L, hypertension duration exceeding 10 years, coronary artery disease, high-sensitivity C-reactive protein >3 mg/L, or high levels of apoB/apoA-1 ratio were at high risk of AGM.

CONCLUSIONSAGM is more common in patients with EHT than in normotensive patients, and OGTTs is a cost-effective strategy to detect AGM in EHT patients.

Aged ; Blood Glucose ; metabolism ; Blood Pressure ; Cross-Sectional Studies ; Female ; Glucose Metabolism Disorders ; metabolism ; physiopathology ; Glucose Tolerance Test ; Humans ; Hypertension ; metabolism ; physiopathology ; Male ; Middle Aged

A sort of absorbable Bondi of dura, whose main body is glue capsule, to compensate the deficiency of previous craniotomy, which easily causes delayed epidural hematoma. This device will help conglutinate dura to skull plate tightly, to stop bleeding and other purposes.
Absorbable Implants ; Adhesives ; Craniotomy ; Dura Mater ; Hemorrhage ; prevention & control ; Prosthesis Design

Objective To observe the clinical effect and safety of platdet GP Ⅱb/Ⅲa receptor antagonist firofiban on acute coronary syndrome(ACS)patients with nO reflow after intevention procedure.Methods 48 ACS patients with no reflow were randomly divided into tirofiban group(n=26)and control group(n=22),the tirofiban group received intravenous tirofiban for 48-36homs,control group received nitroglycerin and urokinase.The rate of the TIMI grade offorward flow and the primary end pints(death,persistent myocardial isehemic and new onset myocardial infarction)and adverse reactions of drags were observed Resalts Tirofiban improved target vessel TIMI flow significantly than control groug(73.8%vs 18.2%,P＜0.01),the rate of the main end point events significantly decreased(15.4%vs 63.6%,P＜0.05),the bleeding complications was similar between two groups,no severe bleeding events occurred.Condusion Tirofiban is effecfive and safe in treating ACS patients with no reflow.

Objective To analyze the immediate and following up result of 122 patients with acute myocardlal infarction(AMI)which underwent emergency percutaneous coronary interventlon(PCI).Methods 122 cases of AMI patients underwent the emergency PCI by transfemoral artery approach during June 1998 to December 2005.119 casea performed primary PCI,3 performed rescue PCI.Results The successful rate of vessel visualization and operation were 95.1%.93.4%.respectively.5 eases were with the help of intra-aortic balloon pumping.Subacute instent thrombosis occurred in 2 patients.In-hopital mortality was 4.1% (5/122).The left ventricular ejection fraction in echocardiography one after week was(0.55±0.16).Average hospital day is(9.5±5.8)(1～36).6-month mortality was 5.7%(7/122).Conclusion Primary PCI expanded the indication for the treatment of STEMI patients wlth establishment of patent infarct related artery and normal blood flow,increased tlle survival of high-risk patients,and shortened the hospitalization.Rescue PCI was an effective measure for the patients failing to intravenous thrombolysis.