Objective To analyze the global research status,hotspots,and frontiers of proprotein convertase subtilisin/Kexin type 9(PCSK9)monoclonal antibodies,and to provide a reference for related scientific research and the rational drug use in clinical practice in China.Methods The research literature related to PCSK9 monoclonal antibody included in the Web of Science database was searched for the period from January 2011 to February 2022,and the literature included in the study was visually analyzed by the CiteSpace software.Results A total of 723 articles were included,and the annual number of publica-tions showed an overall upward trend.The top three countries were the United States,France,and the United Kingdom.Sanofi was the organization with the largest number of articles,and the organization with the highest citation of articles was Brigham and Women's Hospital.The hotspots of research mainly included the use of PCSK9 monoclonal antibody in the treatment of patients with hypercholesterolemia,patients who do not tolerate statins,patients with high cardiovascular risk,and the efficacy and safety of PCSK9 monoclonal antibody in lipid-lowering therapy combined statins;The frontiers of research in recent two years is the appli-cation of PCSK9 monoclonal antibodies in patients with acute coronary syndrome and the clinical benefits after reducing the level of lipoprotein(a).Conclusion A large number of studies have confirmed the efficacy and safety of PCSK9 monoclonal anti-bodies in reducing blood lipids,but there is still a lack of research on its economics and application in special populations,which should be the focus of future research.

Objective To explore the effect of galangin(Gal)on inflammation in hepatitis B rats.Methods The rats were randomly divided into control group,hepatitis B group,Gal-L and Gal-H groups,positive drug lamivudine group and Gal-H+AMPK inhibitor(compound C)group with 12 in each.After modeling,medication treatment was performed once a day for 8 weeks.The level of alanine aminotransferase(ALT),total bilirubin(TBIL)and aspartate aminotransferase(AST)in the serum of rats were detected.HE staining microscopy was ap-plied to detect pathological changes in liver tissue.TUNEL staining microscopy was applied to detect cell apoptosis in liver tissue.Chromatin immuno-precipitation was applied to detect HBV viral load in liver tissue.ELISA was ap-plied to detect the levels of monocyte chemotactic protein-1(MCP-1),interleukin-12(IL-12),and tumor necrosis factor-α(TNF-α)in liver tissue.Western blot was applied to detect the expression of caspase-3,Bcl-2 associated X protein(Bax),p-AMPK and SIRT1 proteins in liver tissue.Results Compared with hepatitis B group,the liver damage of rats in the Gal-L group,Gal-H group and lamivudine group was alleviated;The level of serum AST,TBIL,and ALT,apoptosis rate,HBV viral load and the level of MCP-1,IL-12,TNF-α as well as the expression of caspase-3 and Bax proteins in liver tissue were all reduced.The expression of p-AMPK and SIRT1 proteins in liv-er tissue increased(P＜0.05).Compound C baffled inhibitory effects of high-dose Gal on inflammation,cell apopto-sis,and HBV viral load in liver tissue of hepatitis B rats.Conclusions The mechanism of Gal in inhibiting inflam-mation,cell apoptosis and HBV virus replication in hepatitis B rats is potentially attributed to up-regulation of the AMPK/SIRT1 pathway.

Objective:To explore the correlation between hip muscle factors measured with CT imaging and recovery of independent mobility within 1 year after surgery in elderly patients with hip fractures.Methods:A prospective cohort study was conducted on the clinical data of 680 elderly patients with hip fractures admitted to Beijing Jishuitan Hospital of Capital Medical University from November 2018 to December 2019. The patients were assigned to dependent group and assistant group according to whether they regained pre-injury independent mobility within 1 year after surgery. Gender, age, body mass index, personal history, living habits, past diseases, Charlson comorbidity index, laboratory test indicators, fracture types, anesthesia types, surgical methods, rehabilitation training, time from injury to surgery, and hip muscle parameters in both groups were recorded. OsiriX software was employed in the measurement of the hip muscles to measure the muscle area and density of the gluteus maximus and gluteus medius/minimus on CT images, and the average values were calculated as hip muscle area and density. Then the variables of hip muscle area and density were converted seperately to gender-normalized Z-scores, and were divided into high-area group ( Z≥0) and low-area group ( Z<0), and high-density group ( Z≥0) and low-density group ( Z<0) respectively. Observable variables were primarily analyzed using univariate analysis between the independent group and assistant group. Those variables with statistically significant differences in the univariate analysis or would potentially affect mobility recovery according to previous researches although there were no statistical significance were included in a multivariate Logistic regression analysis. Three Logistic regression models were designed (Model 1 uncorrected, Model 2 corrected for gender, age and body mass index, Model 3 corrected for variables in Model 2 and other variables included after above-mentioned analysis) to analyze whether muscle parameters were risk factors for recovery of independent mobility. Additionally, generalized estimating equations were used for repeated measurement to analyze the correlation between hip muscle area and recovery of independent mobility after surgery. Results:Compared to the assistant group, the independent group were younger in age, with lower rate of living alone, being housebound, cognitive impairment, and Charlson comorbidity index, lower level of hemoglobin and albumin, higher rate of femoral neck fractures, lower rate of internal fixation, shorter time from injury to surgery, larger hip muscle area, and higher hip muscle density ( P<0.05 or 0.01). Multivariate Logistic regression analysis showed that, in the fully corrected Model 3, only hip muscle area remained significantly correlated with recovery of independent mobility ( P<0.05), while no significant difference was found between the high-density group and low-density group ( P>0.05). In the repeated measurement, patients in the high-area group were 1.84 times more likely to restore independent mobility than those in the low-area group ( OR=1.84, 95% CI 1.33, 2.53, P<0.01). Conclusions:Hip muscle area measured with CT imaging is closely correlated to the recovery of independent mobility within 1 year after surgery in elderly patients with hip fractures. Moreover, larger hip muscle area indicates a larger likelihood of recovery of independent mobility.

Objective:To analyze the patterns of antibacterial agents in Chinese children surveyed by the China multi-center monitoring network for the application of antibacterial agents in children and neonates in 2019 by using World Health Organization (WHO) Access, Watch, Reserve and Not-recommended (AWaRe) and typical anatomical/therapeutic/chemical (ATC) in this study.Methods:The cross-sectional method was adopted.A multi-center cross-sectional survey was conducted on one day from September to December 2019.The information of all inpatients taking antibiotics was uploaded to the network-based data collection system (https: //garpec-31.mobilemd.cn/login.aspx? relogin=true). This study covered 13 hospitals from 10 provinces and cities in China.All hospitalized children in the Respiratory Department, Infectious Disease Department, General Surgery Department, Pediatric Intensive Care Units, Neonatal Intensive Care Units and Neonatology joined in this survey.The clinically used antibacterial agents were classified by AWaRe and ATC, and the AWaRe and ATC distributions of antibacterial agents prescribed for Chinese children and neonates were described.Results:Of the 2 644 antibiotic prescriptions included from 13 hospitals, 2 134 (80.71%) were for children and 510 (19.29%) were for neonates.Of all antibiotic prescriptions, there were 368 (13.92%) Access antibiotics prescriptions, 1 973 (74.62%) Watch prescriptions, 60 (2.27%) Reserve prescriptions and 243 (9.19%) Not-recommended prescriptions.The top-five antibiotics prescribed for children and neonates were third-generation cephalosporins (1 056, 39.94%), macrolides (492, 18.61%), carbapenems (275, 10.40%), beta lactam-beta lactamase inhibitors (246, 9.30%), and second-generation cephalosporins (136, 5.14%). The use ratios of Access, Watch, Reserve and Not-recommended antibiotics in each center ranged from 0 to 30.00%, 36.67% to 97.20%, 0 to 17.02% and 0 to 33.33%, respectively.In 1 360 antibiotic prescriptions for children and neonates with pneumonia, there were 152 (11.18%) Access antibiotics, 1 051 (77.28%) Watch antibiotics, 37 (2.72%) Reserve antibiotics, and 120 (8.82%) Not-recommended antibiotics.The top-five antibiotics prescribed for children with pneumonia were third-generation cephalosporins (522, 38.38%), macrolides (388, 28.53%), beta lactam-beta lactamase inhibitors (141, 10.37%), carbapenems (117, 8.6%) and penicillins (49, 3.60%).Conclusions:Watch antibiotics and broad spectrum antibiotics such as third-generation cephalosporins and macrolides prone to induce resistance are the main antibacterial agents used in Chinese children and neonates with pneumonia.Broad-spectrum antibiotics may be overused in Chinese children and neonates.

Cardiovascular diseases is a kind of circulatory system disease,circulatory system mainly includes the heart and blood vessels,the common disease including myocardial ischemia,cardiomyopathy,heart failure,arrhythmia and sudden cardiac death.With the change of human living environment and habits, cardiovascular diseases has become the leading cause of human death[1].Autophagy is an important regulation method for the steady state of eukaryotic cells,which has been proved to be closely related to various diseases and is a hotspot in the research of human diseases in recent years.Autophagy is closely related to the occurrence of cardiovascular diseases,and plays an important role in the prevention and control of cardiovascular diseases, but the specific mechanism still needs to be further studied.This paper introduces the concept and mechanism of autophagy,and summarizes the mechanism of autophagy in cardiovascular disease.

Aim To investigate the skeletal effects of ginseng flower bud(GF)on osteopenia induced by D-galactose using histomorphometry and biomechanical properties.Methods Fifty three-month-old male Sprague-Dawley rats were randomly divided into five groups.Rats in NS group(NS)were treated with NS(5 mL·kg-1·d-1)by subcutaneous injection and daily oral gavage with vehicle as control.Rats in the other four groups were given D-galactose at the dose of 100 mg·kg-1·d-1 by subcutaneous injection.Solvent control was performed between NS and DG: gastric irrigation with distilled water of 10 mL·kg-1·d-1.Other groups were: CP was gastric irrigated with integrated medicine(stanozolol 0.54 mg·kg-1·d-1+piracetam 432 mg·kg-1·d-1),GF(L)with ginseng flower bud of 0.486 g·kg-1·d-1 and GF(H)with ginseng flower bud of 2.43 g·kg-1·d-1 for 14 weeks.The longitudinal proximal tibial metaphyseal(PTM),the fifth lumbar vertebral body(LVB)and tibial shaft(Tx)sections were performed undecalcifiedly and used for bone histomorphometric analysis.858 Mini Bionix materials testing system was used to analyze the biomechanic properties of right femur via three-point bending test.The left femur was dried and assimilated,whose bone calcium(Ca),phosphate(P)content and bone hydroxyproline content were tested.Results Compared with D-glagatose group,in PTM of D-galactose treated rats,the％Tb.Ar was increased both in GF(L)and GF(H)treated groups.While the Tb.Sp was decreased.％Oc.S.Pm and Oc.N/mm decreased in GF(L),and those in GF(H)were decreased as well.In Tx,％Ct.Ar was raised,while％Ma.Ar was decreased in GF(L)and GF(H).The elastic load of femur was increased.Conclusions Compared with DG group,there are significant differences in bone histomorphometry of Tx and PTM in all doses of GF,but no significant changes are detected in hydroxyproline,Ca,and P content of femur.

Objective The aim of this study is to analyze the association between IgM anti-mitochon-drial antibody subtypeⅡ(AMA-M2-IgM) and the anti-centromere antibody IgG (ACA-IgG) in primary biliary cirrhosis (PBC) patients, and to investigate the clinical significance of M2-IgM and ACA-IgG in the diagnosis of PBC. Methods We selected 36 cases of PBC patients as research subjects whose AMA-IgG and AMA-M2-IgG were both negative. The M2-IgM positive rate in the ACA-IgG positive group and negative group was compared. We also analyzed the course of disease, pathological changes and the positive conversion rate of M2-IgG between the M2-IgM positive group and negative group. Results There were 9 cases of M2-IgM positive patients (64%) and 5 cases of M2-IgM negative patients (36%) in the ACA-IgG positive group. In the ACA-IgG negative group we found 3 cases of M2-IgM positive patients (14%) and 19 cases of M2-IgM negative patients (86%). So the M2-IgM positive rate in the ACA-IgG positive group was significantly higher than that of the ACA-IgG negative group (P=0.003). According to the tracking detection results, the M2-IgG positive conversion rate in the M2-IgM positive group was 67% (8 patients), which was significantly higher than the M2-IgM negative group 8%, (2 patients) (P=0.001). Conclusion M2-IgM is a specific antibody for PBC in the early stage, which presents earlier than M2-IgG. In the PBC patients whose AMA-IgG and AMA-M2-IgG antibodies are both negative, the M2-IgM positive rate is closely related to the ACA-IgG, so the ACA-IgG detection is very important in the early diagnosis of PBC. Therefore, we speculated that patients with ACA-IgG antibody are more susceptible to PBC.

Objective To report the clinical,myopathological and genetic features of a patient with distal myopathy caused by caveolin-3 (CAV3) deficiency.Methods The patient was a 27-year-old female.She had an onset symptom of asymmetric lower extremities weakness.The proximal limb-girdle muscles were involved subsequently.Clinical data of this patient were collected.The leg muscle magnetic resonance imaging (MRI) and an open biopsy of left tibialis anterior muscle were performed.In addition to histological,enzyme histochemical staining and ultrastructural examination,immunohistochemical staining with antibody against CAV3 was done.CAV3 gene was analyzed in the patient and her parents.Results Tl-weighted enhanced skeletal muscle MRI of the lower limbs showed the abnormal signal in distal and proximal muscles.Muscle biopsy showed moderate dystrophic changes and immunostaining for CAV3 showed reduced plasmalemma in the muscle fibers.Gene analysis disclosed a heterozygous c.136G ＞ A (p.Ala46Thr)mutation in the CAV3 gene,and the patient's parents did not have this mutation.Conclusions We report a distal myopathy case caused by c.136G ＞ A (p.Ala46Thr) mutation in the CAV3 gene,who had an onset symptom of asymmetric lower extremities weakness.The proximal limb-girdal muscles were also involved.This would help clinical doctors to know more about this rare myopathy.

Aim To investigate the effects of predni-sone on trabecular microstructure and biomechanical properties of femur in a rat model of type II collagen-induced arthritis (CIA ) using micro-CT and biome-chanics.Methods Forty 8-week-old male Lewis rats were randomly divided into 2 groups:control (CON ) group with 6 rats,and the remaining 34 rats were used to establish the CIA model.3 weeks after immunization screening CIA rats were randomly divided into CIA group,CIA plus prednisone 4.5 mg · kg-1 · d -1 group and CIA plus prednisone 9 mg · kg-1 · d -1 group.Rats in CON group were given vehicle as well as in CIA group.Rats in the other two groups were treated with prednisone at 4.5 mg·kg-1 ·d -1 or 9 mg ·kg-1 · d -1 .After 90 days treatment,all rats were euthanized,and the left femur was collected for biome-chanics,micro-CT scanning and three-dimensional re-construction.Results Micro-CT data showed that tra-becular thickness,trabecular number,bone volume/total volume,bone mineral density in CIA group were significantly lower than those in CON group.While tra-becular separation,structure model index were signifi-cantly higher than those in CON group.Compared with CON group,biomechanical properties (elastic load, maximum load,break load and stiffness)were signifi-cantly decreased in CIA group.Compared with CIA group,bone volume/total volume and trabecular num-ber were increased,while trabecular separation was significantly decreased in two prednisone groups.Com-pared with CIA group,there was no significant change in biomechanical properties in two prednisone groups. Conclusions Treatment with prednisone for 3 months can ameliorate the damage of trabecular microstructure of the femur in CIA rats,but it has no effect on biome-chanical properties and bone mineral density.