Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Abstract Social network of adolescents is one of the important factors affecting the initiation and development of their unhealthy eating behaviors, and different types of social networks shows varied influences on adolescents eating behaviors through divergent mechanisms. In the context of the new media era, social networks of adolescents establish via social media appear more complex and extensive. Based on relevant previous literature, the paper explores the impact and possible mechanisms of social network on eating behavior of adolescents, as well as its development and application in the new media era to provide references for better intervention strategies and healthier eating behaviors among adolescents from the perspective of social network.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Under the background of efficiency medical reform, the authors introduced the nursing efficiency management system of a large public hospital, which was divided into two dimensions: nursing resource allocation efficiency and nursing service efficiency. The specific four measures included the establishment of multi-campus unified management organization structure based on nursing management committee, nursing performance reform based on structured big data information platform, the construction of nurse-led patient whole process management model and the accelerated rehabilitation nursing practice from surgery to the whole hospital, so as to provide reference for the nursing efficiency management of large general public hospitals under the medical reform.

Objective : To learn the characteristics of second-line drug resistance and related gene mutations of multidrug-resistant Mycobacterium tuberculosis ( MDR-TB ) Beijing genotype strains. Methods: The MDR-TB isolates in Hwa Mei Hospital from 2017 to 2019 were enrolled and detected using RD105 deletion-targeted multiplex polymerase chain reaction (PCR). The proportion method for drug susceptibility test was used to detect the drug-resistant profiles against kanamycin, amikacin, capreomycin, ofloxacin and levofloxacin. The gene sequencing of rrs, tlyA, eis, gidB, gyrA and gyrB was conducted by PCR compared with H37RV strain. The differences in the rates of drug resistance and mutation between Beijing and non-Beijing genotype strains were examined to understand the characteristics of Beijing genotype strains. Results: There were 106 Beijing genotype and 27 non-Beijing genotype strains in 133 MDR-TB isolates. The drug resistance rates of kanamycin, amikacin, capreomycin, ofloxacin and levofloxacin in Beijing genotype strains were 9.43%, 7.55%, 3.77%, 32.08% and 32.08%, respectively. The rates of quasi-extensive and extensive drug resistance in Beijing genotype strains were 30.19% and 7.55%. The gene mutation rates of rrs, tlyA, eis, gidB, gyrA and gyrB in Beijing genotype strains were 7.55%, 7.55%, 1.89%, 2.83%, 36.79% and 2.83%, respectively. There were no significantly differences between Beijing and Non-Beijing genotype strains in the factors above ( P>0.05 ). The gene rrs, tlyA, eis, gidB, gyrA and gyrB had 2, 1, 2, 2, 5 and 3 mutation types, respectively, with single base substitution as the main type. Conclusion Beijing genotype strains are dominant in MDR-TB, with high resistance to fluoroquinolones and mainly gyrA gene mutation.

Objective:To observe the effect of evidence-based early activity training on postoperative delirium in patients with brain tumor resection.Methods:This study used non-contemporary comparison method, a total of 238 patients admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine in 2019, were included. 121 patients who met the inclusion criteria and signed informed consent after craniotomy during January 1st,2019 to June 31th,2019 were included in the control group, and 117 patients who met the criteria and obtained informed consent after craniotomy during July 1 to December 31,2019, were included in the experimental group. Neurosurgical postoperative routine nursing care were given to the control group. The experimental group received evidence-based early activity training. The incidence of delirium, duration of delirium, Barthel Index (BI), delirium-related adverse events and other indicators of postoperative hospitalization were compared between two groups.Results:The incidence of delirium, duration of delirium and postoperative hospital stay in the experimental group were 9.5%, 2.0 (1,3) days and 7 (5,10) days, lower than 23.3%, 3.0 (1,5) days and 8 (6,11) days in control group, and the differences were statistically significant ( χ2 value was 8.17, Z value were 2.96 and -2.01, P<0.05). BI index 1 week and 1 month after discharge in the experimental group was 90 (85, 90), 100 (100, 100), higher than the control group of 90 (86, 90) and 100 (100,100), with statistically significant difference ( Z values were -2.41 and -2.46, P<0.05), the comparison of adverse events, 0 case in experimental group, 1 case in control group, there was no statistically significant difference ( χ2 value was 0.97, P>0.05). Conclusions:Early evidence-based activities in patients with brain tumor resection can reduce the incidence of postoperative delirium, shorten the duration of postoperative delirium and postoperative hospital stay, and improve the ability of patients to take care of themselves after surgery, which is safe and effective.

Objective:To investigate the serum level of low density lipoprotein cholesterol (sdLDL-C) in elderly patients (age≥65 years) with type 2 diabetes mellitus (T2DM) and the its predictive value in evaluatingthe risk of cardiovascular and cerebrovascularevents in elderly patients with T2DM.Methods:In this retrospective study,386 elderly patients with T2DM were collected from December 2014 to December 2016, the averageage was (72.7±5.4) years old, including 269 males and 117 females; 92 of whom had cardiovascular events during follow-up, the averageage was (72.9 ± 5.2) years old, including 65 males and 27 females, and serum sdLDL-C level was detected. Meanwhile, biomarkers such as lipoprotein (a), apolipoprotein B, apolipoprotein AI and hypersensitive c-reactive protein were analyzedin all the patients.Univariate and multivariate factors were used to analyze the relationship between each variable and the occurrence of cardiovascular and cerebrovascular events. The correlation between LDL-C, sdLDL-C of all subjects with age and other lipid indexes were analyzed. ROC curve was used to determine the predictive value of sdLDL-C elevation for cardiovascular and cerebrovascular events in elderly patients with T2DM.Results:The levels of LDL-c, sdLDL-C, non-HDL-C, GLU, HbA1c and ApoB were significantly higher in theCardio-cerebral vascular event group ( t=3.26, 3.46, 2.91, 2.47, 4.03, 3.00, P<0.05). While the levels of apolipoprotein AI was significantly lower than those in theNon-cardio-cerebral vascular event group ( t=-2.39, P<0.05). Cox regression analysis showed that sdLDL-C per 10 mg/dl was independently correlated with the risk of cardiovascular and cerebrovascular events( HR 1.281, 95 %CI 1.225-16.032, P<0.01)after adjusted for age. SdLDL-C was positively correlated with TG, non-HDL-C and ApoB ( r=0.323, 0.588, 0.623, P<0.01) and was negativelycorrelated correlation with age, HDL-C and apolipoprotein AI ( r=-0.363, -0.301, P<0.01), ROC curve analysis showed that sdLDL-C had a strong ability to predict the occurrence of cardiovascular and cerebrovascular events (AUC=0.736, 95 %CI 0.554 9-0.918 2, P=0.003), while HbA1c also had a strong ability to predict the occurrence of cardiovascular and cerebrovascular events(AUC=0.725, 95 %CI 0.524 3-0.927 3, P=0.006). Combined sdLDL-C with HbA1had the strong ability to predict the occurrence of cardiovascular and cerebrovascular events (AUC=0.837, 95 %CI 0.711 4-0.973 5, P=0.001). Conclusions:The elevation of serum sdLDL-C in elderly patients with T2DM wasa significantly independentrisk factorof cardiovascular and cerebrovascular events. Serum sdLDL-C had a higher clinical value than LDL-C, which was expected to be the most effective predictor of lipid profile in riak assessment of cardiovascular and cerebrovascular events in elderly patients with T2DM.

Objective:To investigate the levels and the clinical signficance of matrix metalloproteinase 3 (MMP-3) in different activities of rheumatoid arthritis (RA).Methods:Case-control study. A total of 130 patients [24 cases of male, 106 cases of female, age (52.98±13.24)years, the median age was 51 years] with RA diagnosed in the Department of Rheumatology from the Second Affiliated Hospital of Soochow University, Suzhou Hospital of Traditional Chinese Medicine and Suzhou Ninth People′s Hospital from 2017 to 2018, and 100 healthy controls [28 cases of male, 72 cases of female, age (45.04±11.55) years, the median age was 44 years] from the physical examination center of the Suzhou Ninth People′s Hospital. The basic clinical data was used to determine the MMP-3 on groups of RA patients and healthy controls by immunoturbidimetry. The discriminating validity of MMP-3 in disease was evaluated using receiver operating characteristic (ROC) curve analysis.Results:Compared with that in healthy controls[28.0 (21.7-36.1)ng/mL], the MMP-3 in the low groups [51.8(41.8-73.1)ng/mL] increased dramatically ( Z=2.942, P<0.01). However, there was no significant difference between the MMP-3 in remission patients [28.8 (21.9-38.7)ng/mL] compared with the healthy controls ( Z=1.09, P>0.05). The area under the curve (AUC) of MMP-3 for diagnosis of RA was 0.877. the sensitivity was 73.1%, and the specificity was 93%.The AUC of MMP-3 diagnosis of low groups was 0.906, the sensitivity was 77.8%, and the specificity was 88%. In addition, the MMP-3 level was correlated with CRP and ESR ( r=0.242, r=0.243), and it was significantly correlated with DAS 28 ( r=0.361). Conclusions:It was indicated that the level of MMP-3 increased with the severity of rheumatoid arthritis. And the clinically low level of MMP-3 in RA patients could be used to indicate the remission condition. Meanwhile, the serum MMP-3 was closely related to DAS28.

Objective: This study conducted a tobacco control intervention practice on vocational school students based on social cognitive theory, for exploring the practical and feasible tobacco control strategies among students, so as to reduce adolescents’ smoking behaviors. Methods: Cluster random sampling method was used to select students in four vocational schools in Shanghai, which were randomly divided into the intervention group (2 schools 1 003 students) and the control group (2 schools 1 096 students). The intervention was conducted on the intervention group based on the social cognitive theory and lasted for 6 months. The control group was blank. Descriptive and analytical statistical methods were used to evaluate the effect of intervention. Results: After the intervention, in the intervention group, the current smoking rate (2.77%) and the smoking intention in the next 1 year (8.50%) both decreased, the scores of the cognition of the harm of smoking as well as second hand smoking and the attitudes towards tobacco all increased(39.04%, 32.93%), the self-efficacy of refusing smoking increased (88.93%), the social pressure decreased(12.40%), the exposure rate of secondhand smoke in family decreased(35.45%), and the exposure to tobacco control message on media increased (36.68%). The difference was statistical significant compared to the control group (χ2=8.67，19.32，17.87，8.32，13.51，14.71，17.36，20.09，P<0.01). Conclusion The tobacco control model based on social cognitive theory could effectively improve adolescents’ self-efficacy, increase their tobacco-related knowledge, and significantly reduce their future smoking intention and behavior.

Objective: To understand current situation of the awareness of tobacco hazards among middle school personnel in Shanghai and to explore its influencing factors,and to provide reference for making targeted measures to control tobacco hazards in schools. Methods: A total of 30 middle schools in Shanghai were selected by stratified cluster sampling method. The questionnaires were used to investigate the smoking prevalence and tobacco hazard awareness of 3 007 faculty members. Results: The total smoking rate of school personnel in Shanghai was 8.25%; the complete correct rate on the harm of smoking and second-hand smoke was only 19.72% and 23.74%, respectively. The correct awareness rate of harm caused by tobacco, such as stroke, osteoporosis and heart disease, was less than 50%. Gender, education level, smoking behavior and tobacco control training were related with tobacco hazards perception level. Conclusion The smoking rate among middle school personnel in Shanghai has been generally improved, but the faculty and staff have an unbalanced understanding of tobacco hazards. The school's tobacco control education should be targeted. Smoking, men and personnel with relatively low education levels are the key groups in school tobacco control education.