Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in lipid reg-ulation through interaction with low-density lipoprotein cholesterol receptors , and several types of PCSK 9 inhibi-tors are gradually becoming research hotspots due to their lipid lowering effect .Among them PCSK9 monoclonal antibodies are the closest to clinical application , and a number of phase Ⅲclinical trials in PCSK9 monoclonal antibodies have been completed in recent years .We systemically reviewed the current clinical research on PC-SK9 monoclonal antibodies in this paper , in order to understand their efficacy and long-term safety in reducing the risk of cardiovascular diseases .

Objective To study the early clinical outcome of patients undergone minimally invasive direct coronary bypass(MIDCAB) surgery,and the mid-term patency of left internal mammary artery(LIMA)-left anterior descending(LAD) anastomosis.Methods From Jannuary 2007 to May 2014,47 cases underwent MIDCAB surgery in our department,with 35 males and 12 females,aged 48-76 years,with the average of (62.9 ± 8.1) years old.Types of LAD lesions were as followed:1 case was ostial total obstruction,28 severe stenosis at proximal segment,10 long and severe stenosis,3 calcified lesion with severe stenosis,5 myocardial bridge.All patients had symptomatic angina,typical myocardial ischemia could be detected by electrocardiogram for all patients with myocardial bridge.Comorbidities included:hypertension 38 cases,27 diabetes mellitus,3 COPD and 3 chronic kidney disease.Results All surgery went well without transfer to mid-sternotomy.LIMA harvest time was 38-53 minutes,mean LIMA flow rate was(22 ± 6) ml/min after anastomosis.Surgery duration was 117-143 minutes,blood loss was less than 100 ml for each operation.No blood transfusion was required.Tracheal intubation time was 4-16 hours,ICU stay time was 22-45 hours,hospital stay time was 6-10 days.There was no peri-operative death,either no myocardial infarction or cerebral vessel accident.During follow-up,all LIMA-LAD appeared to be patent by coronary CT angiography.Conclusion High patency rate of LIMA-LAD anastomosis could also be obtained during MIDCAB surgery.It was reserved as a safe and effective surgery for well-selected patients.

Objective To evaluate the values of continuous subcutaneous insulin/rapid insulin analoguc infusion in desensitization for allergy to recombinant human insulin. Methods Two patients allergic to recombinant human insulin received desensitization therapy by continuous subcutaneous insulin lispro infusion. The diluted insulin lispro solution was pumped with initial basal rate of O. O1 U/h, and the basal rate and insulin lispro concentration increased gradually until the insulin dosage for clinical treatment was reached. After that, continuous subcutaneous insulin lispro infusion was replaced by regimen of insulin lispro subcutaneous injection plus oral hypoglycemic agents. Results Local wheals were not observed in both two patients during continuous subcutaneous insulin lispro infusion or during bolus subcutaneous injection of insulin lispro after desensitization. Conclusion The desensitization therapy by continuous subcutaneous insulin/rapid insulin analogue infusion can be applied for allergy to recombinant human insulin.

Objective To investigate clinical and pathological characteristics of insulin-induced localized lipoatrophy and treatment.Methods We retrospectively analyzed clinical manifestation, skin biopsy pathology, treatment regimen and follow-up of 6 diabetic patients with insulin-induced localized lipoatrophy in Peking Union Medical College Hospital from January, 2010 to March, 2016, with systemic review of related literatures.Results Among 6 cases with insulin-induced localized lipoatrophy, 5 patients were with insulin allergy.5 patients were with positive insulin-autoimmune antibody, which was similar to the ratio reported in the systematic review (18 out of 19).Insulin-induced lipoatrophy could be caused by various types of preparations of insulin and insulin analogs.Subcutaneous biopsy, performed on the atrophied area, revealed the decrease of the number and volume of adipocytes and tissue fibrosis, probably accompanied with lymphocytes, eosinophils or mast cells infiltration.Lipoatrophy could sometimes be relieved by changing injection sites, types of insulin preparations or drug-delivery way, sometimes by application of systemic/local glucocorticoid or local cromolyn sodium.Conclusions Insulin-induced localized lipoatrophy is a rare adverse reaction of insulin preparations.It might be related to immune response of local tissue and heterogeneous pathological manifestations.The lipoatrophy might be improved by changing injection sites, changing the type of insulin preparations or drug-delivery way, and with possibility to carry out targeted immunosuppressive therapy according to the biopsy pathology in the future.

Objective: To determine whether microtubule-associated protein 2 (MAP2) and microtubule-associated protein 1B (MAP1B) could be prognostic biomarkers for patients with pancreatic neuroendocrine tumors (PNETs). Methods:With immunohisto-chemical staining, the expressions of MAP2 and MAP1B were examined in 193 and 120 primary tumors and peritumoral tissues, re-spectively. Then, the relationship between the expression of each protein and clinicopathological characteristics, including prognosis was analyzed. Results:MAP2 and MAP1B were expressed in 88 of 193 (45.6%) and 77 of 120 (64.2%) tumors, respectively. The expres-sion of MAP2 was significantly associated with the favorable overall survival of patients with PNETs (P=0.012). Moreover, MAP2 expres-sion was associated with the improved overall survival in a subset of patients with stageⅡand stageⅢtumors (P=0.017). The MAP1B expression did not correlate with other clinicopathological features and prognosis. Conclusion:MAP2 could be a novel, independent prognostcbiomarker for PNETs.

Autoantibodies are related to occurrence of some types of severe hypertriglyceridemia. Resear-ches showed that autoantibodies of lipoprotein lipase, glycosylphosphatidylinositol-anchored high-density lipo-protein binding protein 1 and apolipoprotein C-Ⅱcould induce hypertriglyceridemia. This review focused on hy-pertriglyceridemia induced by autoantibodies and its treatment.

Objective To explore the difference of gut microbiota between type 2 diabetes mellitus (T2DM) and non-diabetic population in Beijing. Methods 83 T2DM patients were selected as T2DM group and 64 non-diabetic subjects were selected as control group. Fecal samples were collected from all the subjects. The intestinal flora was detected by metagenome sequencing technology. Results 11 bacterialphyla were detec-ted in the two groups, there were significant differences in species diversity of Actinobacteria (P=0. 013), Firmicutes (P=0. 005), Fusobacteria (P=0. 001), Proteobacteria (P<0. 001) between the two groups. Actinobacteria, Fusobacteria and Proteobacteria were all enriched in the T2DM group, Firmicutes were enriched in the control group. 152 bacterial genera were detected in the two groups with 31 bacterial genera ofsignificant differences. In T2DM group, the levels of Roseburia, Eubacterium and Faecalibacterium decreased, while the levels of Bifidobacterium, Lactobacillus and Escherichia increased. Conclusion There are significant differ-ences in the composition of gut microbiota between T2DM patients and non-diabetic population. Regulation of gut microbiota in T2DM patients may be helpful to improve the condition of T2DM.

Glucocorticoids are widely used in clinical practice,and abnormal glucose metabolism due to the use of glucocorticoids is prevalent.There has been progress in studies evaluating post-glucocorticoid changes in blood glucose levels using continuous glucose monitoring.This paper reviews glycemic patterns and protocols for insulin treatment of abnormal glucose metabolism following the use of glucocorticoids as shown by continuous glucose monitoring.

Objective    To evaluate the feasibility and safety of modified Yacoub technique with aortic annuloplasty in the patients with aortic root aneurysm and dilatation of aortic annular base. Methods    We performed a retrospective review of 6 patients with aortic root aneurysm undergoing modified Yacoub technique with aortic annuloplasty from November 2017 to January 2019. There were 5 males and 1 female, with a mean age of 54.1±12.3 years. The preoperative cardiac function of 3 patients was in New York Heart Association (NYHA) classⅡand the other 3 patients were in class Ⅲ. There were two patients with bicuspid aortic valve, and no Marfan syndrome. There was aortic regurgitation in the patients measured by the echocardiogram, 1 in mild aortic regurgitation, 1 in moderate aortic regurgitation, and 4 in severe aortic regurgitation. The diameter of aortic annular base was 27.8±1.9 mm, and the largest diameter of aortic root was 49.8±3.7 mm. Six patients underwent modified Yacoub technique with aortic annuloplasty, including 5 patients who underwent aortic cusp repair at the same time. Results    All 6 identified patients survived. There was no severe complication (bleeding, stroke, or acute renal failure). The cardiopulmonary bypass time was 204.6±13.5 min, aortic cross-clamping time 168.0±17.1 min, mechanical ventilation time 21.3±19.5 h, ICU stay time 67.8±62.2 h. The follow-up time ranged from 4 to 18 months with an average time of 12.8±4.7 months. Patients' cardiac function improved postoperatively with four patients in NYHA classⅠand two patients with classⅡ. Two patients had no aortic valve regurgitation, four patients had mild regurgitation. Left ventricular end diastolic volume decreased significantly (118.6±20.4 mL vs. 169.1±58.4 mL, P<0.05). Conclusion    The modified Yacoub technique with aortic annuloplasty is effective and safe for the patients with aortic root aneurysm and dilatation of aortic annular base, and the early- and mid-term outcomes are satisfactory.

Objective    To evaluate the data of preoperative aortic root CT angiography (CTA), compare it with two-dimensional transthoracic echocardiography and investigate the correlation of the two measurements with the actual intraoperative measurement data. Methods    Clinical data of 53 patients with aortic valve diseases who underwent aortic valve repair in our hospital from January 2018 to August 2020 were retrospectively analyzed, including 38 males and 15 females with an average age of 42.9±18.3 years ranging from 10 to 77 years. Preoperative two-dimensional transthoracic echocardiography (TTE) and aortic root CTA measurements were collected, including aortic valve annulus (AVA), aortic sinus (Sinus) and sino-tubular junction (STJ). In comparison with the intraoperative measurements during the aortic valve repair surgery, the consistency analysis was performed. Results    Both the preoperative echocardiography AVA measurements and the CT AVA measurements were positively correlated with the intraoperative AVA measurements (P<0.001). Compared with the echocardiography AVA data [correlation coefficient (ρ)=0.74, mean squared error (MSE)=12.78], the CT AVA data were more accurate and consistent with the intraoperative AVA measurements (ρ=0.95, MSE=2.72). CT AVA data had a higher correlation coefficient with the intraoperative measurements, compared to that of  the echocardiography AVA data (P<0.001). Conclusion    In comparison with two-dimensional transthoracic echocardiography, preoperative morphological evaluation of aortic root CTA is more consistent with the actual intraoperative measurements during aortic valve repair surgery.