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.

Objective This study aims to develop and validate a dynamic web-based nomogram for predicting kinetophobia in patients following percutaneous coronary intervention(PCI).Methods A prospective design was employed to selectively enroll 330 PCI patients admitted to a hospital in Hangzhou from December 2022 to July 2023.Single-factor analysis and Lasso regression were utilized to identify independent risk factors for kinesophobia post-PCI.Logistic regression was performed using R software,and a nomogram was constructed.The model was assessed through the area under the receiver operating characteristic curve(AUC)and Hosmer-Lemeshow tests.Results There were 206 cases of kinesiophobia in 330 patients after PCI,and the incidence was 62.4％.Logistic regression analysis identified combined heart failure,emergency surgery,NYHA cardiac function grade,ADL level,sedentary behavior,Chinese version of PROMIS Physical Function Summary Table score,and Chinese version of Perceptive Social Support Scale score as independent influencing factors for kinesophobia after PCI(P＜0.05).The AUC value of the model was 0.821,with a sensitivity of 70.4％and specificity of 82.0％.The Hosmer-Lemeshow fit test yielded a non-significant result(x2=9.350,P=0.314).Calibration and decision curves demonstrated the model's favorable calibration and clinical practicability.The C-index of the nomogram prediction model was 0.778,0.774,and 0.800,respectively,by 5-fold cross-validation,10-fold cross-validation,and the Bootstrap method.Conclusion The dynamic nomogram model developed in this study effectively predicts kinesophobia in patients after PCI.It provides valuable references and support for clinical staff in early identification of high-risk patients,enabling the formulation of individualized health education strategies and exercise rehabilitation plans.

ObjectiveTo explore the association between social support， parent-child relationships， and depression， anxiety， and loneliness among adolescents， in order to provide a reference for improving mental health in youth. MethodsA total of 11，596 middle school students from two districts of Shanghai were investigated with the stratified random cluster sampling method. The Chinese version of Patient Health Questionnaire （PHQ-2-C）， Generalized Anxiety Disorder （GAD-7）， UCLA Loneliness Scale （ULS-6）， Perceived Social Support Scale and Parent-child Cohesion Questionnaire were used in the survey. Statistical inferences were made using t-test， ANOVA， and logistic regression analysis. ResultsGirls， non-graduates， students ranking in the top 25%， adolescents living with parents and with higher socioeconomic status had higher scores of social support and parent-child cohesion than boys， graduates， students ranking in the middle or in the bottom 25%， adolescents not living with parents and with lower socioeconomic status （P<0.05）. Adolescents' parent-child cohesion and social support were negatively correlated with all kinds of emotions. Parent-child cohesion was an associated factor of depression （OR=0.93， 95%CI：0.91‒0.94）， loneliness （OR=0.94， 95%CI：0.94‒0.95） and anxiety （OR_mild=0.98， 95%CI： 0.98‒0.99； OR_{moderate or severe}=0.96， 95%CI： 0.95‒0.98）， but there were differences in the correlation between emotions and social support in different dimensions. ConclusionSocial support and parent-child relationship are significantly associated with depression， anxiety and loneliness in adolescent students. Paying more attention to youth with different characteristics， taking targeted measures to improve the level of social support and establishing a good family relationship are conducive to promoting the mental health of adolescents.

Objective:To investigate the correlation between serum 25-hydroxyvitamin D (serum 25(OH)D) and Meige syndrome.Methods:A retrospective analysis was performed on 47 patients with Meige syndrome (Meige syndrome group) treated in Yuquan Hospital of Tsinghua University admitted from August 2012 to July 2018 in our hospital.In the same period, 69 healthy people of the same age group were selected as the healthy control group.The difference of serum 25(OH)D concentration among different subtypes of Meige syndrome (type I, II, III) was compared.Logistic regression analysis was used to analyze the correlation between serum 25(OH)D level and Meige syndrome.Results:The serum 25(OH)D concentration in patients with Meige syndrome was (12.68±6.77) μg/L, which was significantly lower than that in the healthy control group ((17.93±6.93) μg/L). The difference was statistically significant ( t=4.044, P<0.001). The serum 25(OH)D concentrations of subtypes I, II and III in patients with Meige syndrome were (14.7±8.14), (11.4±5.02), (8.38±4.99) μg/L, respectively. There was no significant difference among the three types ( F=1.892, P=0.231). Logistic regression results showed that serum 25(OH)D levels were correlated with Meige syndrome ( OR=0.938, 95% CI: 0.885-0.995, P=0.034). Conclusion:The serum 25(OH)D expression level in patients with Meige syndrome is low, suggesting that vitamin D deficiency may be involved in the pathogenesis of Meige syndrome.

Objective:To investigate the correlation between activities of daily living and hemoglobin level in patients with acute ischemic stroke (AIS).Methods:A retrospective analysis was performed in 190 patients with acute ischemic stroke from August 2015 to April 2017. The hemoglobin (Hb) levels at admission were analyzed . According to the Barthel index (BI) score, the patients were divided into good improvement group ( n=119) and poor improvement group ( n=71). Spearman correlation analysis was used to study the relationship between hemoglobin level and short-term activities of daily living in patients with acute ischemic stroke. Results:(1)The short-term activities of daily living was improved in 119 patients. Among them, 62 (52.1%) were under 65 years old and 57 (47.9%) were over 65 years old, 9 (7.56%) male patients with hemoglobin <120 g/L and 39 (32.77%) male patients with hemoglobin > 150 g/L. There were 71 patients with poor short-term activities of daily living. Among them, 23(32.39%)were under 65 years old and 48(67.61%)were over 65 years old, 1(1.41%)male patients with hemoglobin <120 g/L and 12(16.9%) male patients with hemoglobin > 150 g/L. There were significant differences in age (χ 2= 6.985, P=0.008) and male hemoglobin level (χ 2= 8.069, P=0.005) between patients with good activities of daily living and patients with poor activities of daily living.(2)Regression analysis showed that age > 65 years ( β =1.386, OR=4.000, 95% CI=1.189-3.461, P=0.025) and abnormal hemoglobin levels in men (Hb<120 g/L or > 150 g/L) ( β =1.089, OR=2.972, 95% CI=1.383-6.388, P=0.005) were the influencing factors of poor short-term quality of life in patients with acute ischemic stroke.(3)Spearman correlation analysis showed that abnormal hemoglobin levels in men (Hb<120 g/L or>150 g/L) were positively correlated with poor short-term activities of daily living in patients with acute ischemic stroke( r=0.244, P=0.004). Conclusion:Abnormal hemoglobin level is associated with poor short-term activities of daily living improvement in patients with acute ischemic stroke.

Objective To prospectively survey the well-known experts of critical care and endocrine secretion to summarize their experience in treating diabetes mellitus complicated by sepsis for the purpose of providing guidance of theory and practice in making treatment schemes of traditional Chinese medicine for such disease.Methods The questionnaires were designed and submitted to the experts.The statistic analysis was undertook to investigate the rules.Results A total of 30 questionnaires were released and 28 were retrieved.The experts generally believed that eight-principle syndrome differentiation was the most useful method in the syndrome differentiation and treatment of this disease.The heat,stasis and toxin were usually acted as the main pathogenic factors while damp and phlegm commonly act as secondary pathogenic factors.They thought that weak body resistance under the invading of evil was the key mechanisms in the deterioration of the disease and they chose clearing heat,activating blood and detoxication as 3 core treatment principles.Conclusions The summarized opinions from the experts should be act as important reference in treating this disease,but its effectiveness and possibility for further generalization need to be validated in the clinical practice.

Objective To systematically evaluate the optimal dose of early enteral nutrition support in critically ill patients.Methods Systematic search database including PubMed,Web of science,Scopus,CINAHL,CBM,CNKI.RCTs about early enteral nutrition dose selections in critically ill patients were chosen according to include and exclude criteria by two researchers independently.Cochrane system evaluation manual bias risk assessment was used to evaluate quality of literature.RevMan5.3 Meta analysis software was used to analyze the data.Results A total of 1 571 literatures were retrieved and 8 RCT studies were included,2 713 subjects in total.Meta analysis results showed that there were statistically significant differences in mechanical ventilation time,incidence of diarrhea,and utilization rate of gastro dynamic drugs between trophic feeding and full feeding (P＜0.05).There were no statistically significant differences in mortality,length of stay,incidence of nosocomial infections,reflux,vomiting,constipation,etc.(P＞0.05).Conclusions Trophic feeding has familiar effects on mortality,length of hospital stay compared to full feeding,but it can help to shorten ICU mechanical ventilation time,improve the gastrointestinal tolerability.

Objective Invasive candidiasis is associated with a significant mortality clinically.The purpose of this study was to observe the T cells immune response to fructose bisphosphate aldolase (Fba), an immunodominant antigen of Candida albicans, and determine whether the antigen has the possibility of priming cellular immune protection in invasive candiasis.Methods Using ELISPOT assay, we determined the frequencies of positive spot-forming cells (SFCs) of Fba antigen-specific T cells secreting IFN-γ, IL-4 and IL-17A in the peripheral blood mononuclear cells (PBMCs) of 26 healthy individuals.Results After Fba stimulation, the frequencies of positive SFCs of IFN-γ, IL-4 and IL-17A in the 26 healthy subjects were 23 (9.75, 42.50), 0 (0, 0.25) and 1.5 (0.75, 8.25), respectively, with statistically significant differences among the three (P<0.01).The response rates of IFN-γ (100% [26/26]) and IL-17A (76.92% [20/26]) were significantly higher than that of IL-4 (15.38% [4/26]) (P<0.01).Fba-induced strong response (SCFs ≥20) for IFN-γ was observed in 57.69% (15/26) of the healthy individuals, that for IL-17A in only 1, while that for IL-4 in none.Responses of both Th1 and Th17 cells to Fba were found in 65.38% (17/26) of the subjects, that of Th1 cells in 19.23% (5/26), but that of Th2 cells in none.Conclusion Fba of Candida albicans can induce immunodominant responses of Th1 and Th17 cells and is a potential vaccine against invasive candiasis.

Objective To discuss on nursing of patients multiple- patient burn- blast combined injury, the cooperation of processes and quality control. Methods For 35 cases of burn- blast combined injury, emergency plan was initiated immediately, including staffing allocation, supplies allocation, nursing quality control and monitoring the inpatient areas, etc. Results 35 cases of burn- blast combined injury acquired immediate treatment of burn shock and nursing. Rescue rate of multiple- patient burn blast arrived 77.14%(27/35), with no case of nursing complication. Conclusions Timely allocation of nursing staff, rational quantity and structure, forceful organization and coordination, complete and timely supplies, correct quality control of emergence nursing and beneficial solutions are keys to ensure successive nursing of intensive patients of burn-blast combined injury, and also reflection of nursing quality guarantee.

Objective To study the influence of the early ambulation on postoperative patients' comfort and complications with the femoral artery puncture interventional therapy.Methods After searching for related literatures with computer,we evaluated the quality of the literatures and screened them.12 random controlled trials met the inclusion criterion.Using RevMan 5.1.2 software,we respectively made Meta analysis for patients with sense of comfort and complications after operations.Results Compared with the control groups,the experimental groups were better in back pain,abdominal pain,limb numbness and acid bilges,sleep disorder,dysuria and urinary retention than those of the control groups.And the difference in the site of puncture bleeding and hematoma had no statistical significance between the two groups.Conclusions It can improve comfort for patients without increasing incidence rate of complications by lying in bed and rest for 12 hours after interventional therapy.It reflects the patient-centered nurs-ing service concept and can improve the patients' quality of life.