Objective To evaluate the correlation between RPA or the polymorphism of CYP 2C19 and the incidence of ischemic events and the influence on the clinical prognosis .Methods A case-control study was used.A total of 202 patients [male 66%,(63 ±11) years] with ACS on aspirin and clopidogrel treatment were recruited , whose RPA were measured by whole blood aggregometry ( WBA ) , and their CYP2C19 polymorphism were also tested .Their clinical ischemic events were recorded in the mean follow-up period of 16 months.The RPA cut-off values for antiplatelet low-responsiveness were defined by the receiver operator characteristic curve ( ROC); the relationships of clinical outcomes with RPA and CYP 2C19 were assessed by the Kaplan-Meier survival analysis.Results CYP2C19*2 (681G>A) present in 52.5% of recruited patients and*3 (636G>A) present in12.9%.RPA induced by adenosine diphosphate ( ADP) showed significant difference among CYP 2C19*2 or *3 heterozygotes, CYP2C19*2 or *3 homozygotes and noncarriers (χ2 =9.318, P=0.009);whereas, RPA induced by arachidonic acid (AA) (χ2 =2.441, P=0.295) and the incidence of ischemic events (χ2 =0.513, P=0.774) were not.During follow-up, 18 (9%) patients experienced clinical ischemic episodes , and their RPA were higher than patients without ischemic episodes [(8.6 ±4.8) Ωvs (5.2 ±3.7) Ω, P =0.013; (8.6 ±6.8) Ωvs (1.6 ±3.7) Ω, P <0.001].Moreover, employing 6.5 Ω(induced by ADP) and 2.5 Ω(induced by AA) as cutoff values,RPA showed optimal negative predictive values (97%, 96%) and poor positive predictive values (16%,29%).Survival analysis showed, statistically, patients with clopidogrel low-responsiveness had higher riskof ischemic episodes than patients with clopidogrel responsiveness (HR =2.86, χ2 =11.27,P =0.0008);however, patients with aspirin low responsiveness (HR =1.77, χ2 =1.74, P =0.19) or patients withCYP2C19*2 or *3 (HR =0.89, χ2 =0.12, P =0.73) did not.Conclusion Clopidogrel lowresponsiveness is associated with the occurrence of clinical ischemic events ; however, patients withCYP2C19 function reduced genetypes do not show higher risk of ischemic episodes though it presented slighlyhigher RPA.

Objective To investigate on the gender and age distribution characteristics of serum lipid levels among apparently healthy adult population in Beijing and analyse its related risk factors .Methods This is a prospective study.1 712 healthy individuals between 18 and 79 years old were recruited from medical examination center of Peking University Third Hospital .By strict exclusion criteria , 951 healthy individuals (429 males and 522 females) were included in our study.A calibrated automatic biochemical analyzer was used to measure TC, TG, HDL-C, LDL-C, ApoA1, ApoB concentrations in serum.Test results were stratified by gender , age, related risk factors, and statistically analysed.Two groups of normally disthibuted data were compared using t test;multiple groups of data were compared using variance analysis . Results Results for TC (t=4.013, P<0.050), HDL-C(t=9.162, P<0.05) and ApoA1( t=8.225, P<0.05) appear generally higher in women than in men .On the contrary, males had greater levels of TG (Z=3.119, P<0.05) compared to females.There was an obvious increasing trend in TC ( F=47.984, P<0.05), TG(Chi square =146.616, P<0.05), LDL-C(F=46.024, P <0.05), non-HDL-C(F =45.027, P<0.05) and ApoB levels(F=52.020, P<0.05), as well as peaked in the 60-69 age group, decreased in 70-70 years old.The population of beneath the bachelor-degree had greater levels of ApoB ( t=5.989, P<0.05), LDL-C(t=4.445, P<0.05), TC(t=2.885, P<0.05), non-HDL-C(t=4.332, P<0.05) and TG(Z=3.346, P<0.05) compared to the group of bachelor degree or above .Meanwhile, The levels of TC(t=8.273, P<0.05), HDL-C(t=3.346, P<0.05), LDL-C(t=5.768, P<0.05), non-HDL-C(t=7.213, P<0.05), ApoA1(t=3.683, P<0.05), ApoB(t=6.267, P<0.05), TG(Z=5.626, P<0.05) of the population lived in urban area were higher than rural areas .Interestingly, the concentration of ApoA1(t=3.238, P<0.05), HDL-C( t=6.011, P<0.05) and TC(t=2.712, P<0.05) were much higher in the population of mental worker than the manual worker .BMI and waistline positively correlated with serum TG(rs=0.379, 0.443, P<0.01), TC(rs =0.160, 0.176, P<0.01), LDL-C(rs =0.238, 0.263, P <0.01), ApoB (rs =0.326, 0.371, P <0.01) and non-HDL-C(rs =0.304, 0.336, P<0.01) respectively, but negatively correlated with HDL-C(rs =-0.358, -0.386, P<0.01) and ApoA1 ( rs =-0.203, -0.209, P <0.01 ) .Conclusions The study obtained the distribution of lipid levels among apparently healthy a dult population in Beijing .It may offer objective basis for clinical risk assessment of ASCVD , and guid the clinician to choose the optimal individualized treatment .

BACKGROUND:Previous studies have suggested that the risks for coronary atherosclerotic plaque progression and in-stent restenosis are increased in patients with coronary heart disease combined with type 2 diabetes. OBJECTIVE:To explore the predictive factors for in-stent late loss and non-culprit coronary lesion progression in patients with type 2 diabetes mel itus. METHODS:A total of 399 stenting patients were enrol ed, including 179 diabetic patients and 220 non-diabetic patients. The clinical materials, angiography parameters and biochemical markers were col ected. The difference between the two groups was compared, and also we conducted subgroup analysis in the diabetic patients. Low-density lipoprotein cholesterol, hemoglobin A1c, fibrinogen and high-sensitivity C-reactive protein were detected at days 3, 120, 210 and 360 after stenting. RESULTS AND CONCLUSION:Compared with non-diabetic patients, the stent length (P=0.18) was longer and the stent diameter (P=0.002) was smal er in the diabetic patients. The minimal lumen diameters of post-procedure and fol ow-up angiography in the diabetic group were significantly decreased (P=0.001, P=0), and the diabetic patients also showed severe coronary artery stenosis instantly and within the fol ow-up after stenting (P=0.038, P=0.004). The fol ow-up angiography showed that the diabetic patients had more late loss and restenosis (P=0, P=0.097). Furthermore, in the subgroup analysis of diabetic patients, the levels of hemoglobin A1c, fibrinogen and high-sensitivity C-reactive protein were significantly increased in the patients with restenosis and non-culprit lesion progression. These findings indicate that diabetic patients appear to have the higher incidence of restenosis and non-culprit lesion progression. Moreover, hemoglobin A1c, fibrinogen and high-sensitivity C-reactive protein are effective predictors for in-stent late loss and non-culprit coronary lesion progression.

Background and purpose:In recent years, the studies indicated that postoperatively induced myeloid-derived suppressor cells (MDSCs) were qualified with potent proangiogenic and tumor-promotive ability. Bone marrow mesenchymal stem cells (BMSCs) significantly inhibited the induction and proliferation of MDSCs. However, the relationship of MDSCs and tumor metastasis during perioperative period, and whether BMSCs could prevent tumor metastasis through inhibiting MDSCs are not clariifed. This study aimed to investigate the change of MDSCs during perioperative period and its correlation with tumor metastasis after surgery, and the inlfuence of BMSCs on the induction of MDSCs and the development of postoperative tumor metastasis.Methods:LLC cells were injected intravenously into C57BL/6 mice. Two hours later, these mice were divided into 4 groups: controls (C group); mice given anesthesia (A group); mice given anesthesia and laparotomy (AL group) and mice given anesthesia, laparotomy, and hepatic lobectomy (ALH group). The AL mice were divided into 2 groups after surgical operation: the AL mice without treatment (ALL group) and the AL mice treated with syngeneic BMSCs (ALB group). The percentage of Gr-1+CD11b+ cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. The numbers of metastases on the lung surface were counted on the 14th day after LLC infusion. BMSCs were also co-culturedin vitro with myeloid cells in order to illustrate the effects of BMSCs on the generation of MDSCs.Results:The numbers of lung metastases in AL and ALH group signiifcantly increased as compared with C and A group (P<0.01). The number of lung metastases in ALH group signiifcantly increased as compared with AL group (P<0.05). The percentage of Gr-1+CD11b+ cells in PBMCs during postoperative period signiifcantly increased in AL and ALH group as compared with C and A group, and the percentage of Gr-1+CD11b+ cells in ALH group also signiifcantly increased as compared with AL group. The numbers of lung metastases in AL and ALB group were (38.00±9.57) and (6.54±1.49), the difference was statistically signiifcant (P<0.01) on day 14 after LLC infusion. Meanwhile, the percentage of Gr-1+CD11b+ cells in ALB group signiifcantly decreased as compared with AL1 group. This study also demonstrated that BMSCs inhibited the induction and proliferation of MDSCs from myeloid cells in vitro.Conclusion:Surgery stress induces MDSCs and promotes tumor metastasis. Syngeneic BMSCs could inhibit the generation of MDSCs and further suppress tumor metastasis after surgery.

Objective To investigate the mechanism of recurrent laryngeal nerve injury during total thyroidectomy.Methods The clinical data of 36 patients suffering from recurrent laryngeal nerve injury in total thyroidectomy from 2003 to 2014 was analyzed retrospectively.Results 21 cases had temporary recurrent laryngeal nerve injury while 16 cases had permanent injury.The cases of injury included giant thyroid goitre,with variation of recurrent laryngeal nerve,undergoing secondary surgery,with tumor invasion and complicating thyroiditis.During the first surgery,the incidence of temporary recurrent laryngeal nerve injury was 0.43％,and the incidence of permanent damage was 0.27％.The temporary and permanent injury incidence of secondary surgery after initial subtotal thyroidectomy was 4.59％ and 4.59％,respectively.For patients with grade 3 thyroid gland,that was 1.81％ and 0.30％,respectively and 0.51％,0.72％ respectively in malignant cases.In cases complicating thyroiditis temporary recurrent laryngeal nerve injury occurred in 1.01％.Conclusions There is increased risk of recurrent laryngeal nerve injury in giant goiter cases undergoing secondary operations.Hence it is suggested that initial surgical procedure be hemithyroidectomy or total thyroidectomy

Adrenal Hyperplasia, Congenital ; metabolism ; pathology ; Female ; Humans ; Menstrual Cycle ; physiology ; Ovarian Hyperstimulation Syndrome ; enzymology ; pathology

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

The quality markers (Q-markers) of traditional Chinese medicine (TCM) have become a topic of interest in TCM research in recent years. Nonetheless, there is still no consensus on how to scientifically characterize TCM Q-markers. Our study establishes an identification method for TCM Q-markers based on the analytical hierarchy process (AHP) and the entropy weight comprehensive method. By constructing an evaluation system encompassing the target layer, the factor layer and the control layer, AHP can be used to analyze the weight of three core TCM quality attributes, including effectiveness, testability and specificity. Following that, the entropy weight method is employed to analyze the specific indicators for each attribute based on the literature and experimental data. Finally, the comprehensive weight of each index is obtained by combining the two weights, and the comprehensive weight and the specific value of each component is multiplied and summed to obtain the integrated score ranking, and thereby identify the TCM Q-markers. Taking Shaoyao Gancao decoction as an example, the analysis revealed that the top 8 components are as follows: paeoniflorin > quercetin > albiflorin > glycyrrhizic acid > naringenin > liquiritin > oxypaeoniflorin > benzoylpaeoniflorin, and can be identified as Q-markers of Shaoyao Gancao decoction. This study not only provides support for the establishment of quality standards and process quality control of TCM formulae, but also provides innovative ideas and methods for quantitative evaluation and accurate identification of TCM Q-markers.

Objective To observe the correlation between conventional coagulation tests and Dabigatran concentration in order to find proper test method to predict the bleeding risk of patients receiving Dabigatran.Methods The clinical data of forty-nine non-valvular atrial fibrillation (NVAF) patients who took Dabigatran in Peking University Third Hospital from 2015 to 2017 were analyzed and the bleeding rates were calculated.The plasma samples from twenty healthy volunteers were collected and mixed up into normal pooled plasma (NPP).Different doses of active Dabigatran were mixed with NPP,making Dabigatran concentrations from 0 to 1 000 ng/mL.Prothrombin time (PT),activated partial thromboplastin time (APTT),thrombin time (TT),fibrinogen (Fib) and diluted Russell viper venom time (dRVVT) were determined.Fresh whole blood samples from three normal volunteers were collected and mixed with Dabigatran in the same way to perform thromboelastogram (TEG).Results The total bleeding rate of NVAF patients receiving Dabigatran was 28.6％,among which gastrointestinal bleeding accounts for the most.APTT,dRVVT,R time (R) and clot index (CI) showed a good linear correlation with Dabigatran concentration.The sensitivity of dRVVT was the best,followed by APTT.R and CI showed low sensitivity compared with APTT and dRVVT.Conclusion APTT and dRVVT should be good parameters for monitoring the bleeding risk of Dabigatran and helpful for physicians to choose proper point-in-time for withdrawal of Dabigatran and reduce bleeding events.

Objective:To investigate the risk factors of deep venous thrombosis in patients before hip arthroplasty, and to explore the possible causes of postoperative thrombosis.Methods:The clinical data of 361 patients with hip arthroplasty treated in the Department of Orthopaedic Trauma of Xi′an Honghui Hospital from September 2015 to December 2019 were studied retrospectively, including 102 males and 259 females, aged 65 to 94 years, and the average age was 72.25 years old. All fracture patients were given subcutaneous injection of low molecular weight heparin calcium to prevent lower extremity thrombosis. The deep veins of both lower extremities were examined before and after operation. The general data of the two groups of patients were collected and recorded, including age, sex, whether complicated with medical diseases (essential hypertension, type 2 diabetes, coronary heart disease), serological indexes, time from injury to admission, and time from admission to operation. The software of SPSS 19.0 was used for statistical analysis.Results:The incidence of lower limb DVT, before operation was 29.92%, including 26 males (24.07%) and 82 females (75.93%). The results of multivariate logistic regression analysis showed that diabetes mellitus ( OR=2.127, 95% CI: 1.134-3.989, P=0.019), coronary heart disease ( OR=1.692, 95% CI: 1.056-2.713, P=0.029) and the time from injury to admission ( OR=1.677, 95% CI: 1.037-2.712, P=0.035) were independent risk factors for DVT in elderly patients undergoing hip arthroplasty. The incidence of lower limb DVT, after operation was 46.54%. After operation, proximal thrombus were occurred in 2 cases (1.19%), distal thrombus in 143 cases (85.12%), and mixed thrombus in 23 cases (13.69%). Postoperative thrombus was ipsilateral to the fracture limb in 84 cases (50.00%), thrombus was located in the healthy side of the fracture in 19 cases (11.31%), and DVT occurred in 65 cases (38.69%) in both lower limbs. Conclusions:Delayed admission longed than 48 hours, coronary heart disease and diabetes mellitus are the risk factors for the formation of DVT. The thrombus that existed before operation and did not disappear after operation accounted for 48.81% of the total incidence of postoperative thrombosis, and the new thrombus accounted for 51.19% of the total incidence of postoperative thrombosis. For the elderly patients with femoral neck fracture undergoing hip arthroplasty, ultrasonic examination of both lower limbs should be performed before and after operation to find the changes of thrombus in time and do a good job of prevention and treatment.