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:To explore the impact of transcatheter edge-to-edge repair (TEER) devices on mitral valve regurgitant flow convergence post-procedure using computational fluid dynamics(CFD), and to seek solutions for accurately measuring effective regurgitant orifice area(EROA) after TEER.Methods:Multimodal fusion was conducted based on preoperative cardiac CT images and intraoperative three-dimensional transesophageal echocardiography(3DTEE) of 33 patients with mitral valve regurgitation undergoing TEER at Renmin Hospital of Wuhan University from January 2020 to August 2023. Using this data, CFD models of mitral valve regurgitation post-TEER, including with and without the TEER device, were constructed. The distance (D) from the midpoint of the mitral regurgitation orifice to the TEER device was measured. The proximal isovelocity surfice area(PISA) radius with and without the TEER device was measured, and the corresponding EROA1 and EROA2 based on this was calculated. The EROA correction factor CC=EROA2/EROA1 was calculated.Results:A total of 42 sets of CFD models with mild or greater residual mitral regurgitation, both with and without the TEER device, and 50 sets of PISA were obtained. Based on the relative position of PISA to the TEER device, four types of PISA were observed: Type 1: PISA away from the TEER device (D>R, 14 cases), with a CC of 0.93±0.07; Type 2: PISA adjacent to the TEER device (D

Self-efficacy can affect the confidence of adolescent patients with chronic diseases in coping with disease and management, and then affect their disease management and health behavior. This paper introduced the concept of self-efficacy of adolescent patients with chronic diseases, and summarized self-efficacy scale for adolescent patients with chronic diseases from aspects of development, application scope and the reliability and validity, to provide reference for clinical evaluation of self-efficacy level of adolescent patients with chronic diseases during treatment and formulation of targeted intervention plan.

Objective:To summarize the best evidence for the prevention of medical device related pressure injuries in patients in ICU, and to provide a basis for clinical nursing practice.Methods:Using evidence-based method and computer 6S evidence model, the relevant literature was retrieved. The resource types included clinical guidelines, evidence summaries, systematic reviews and expert consensus. The retrieval time was from the establishment of the databases to January 2021. Three researchers who received evidence based nursing training independently evaluated various types of literature, and extracted evidence from literature that met inclusion criteria.Results:A total of 11 articles were included with 8 guidelines, 1 systematic review, 1 evidence summary, and 1 expert consensus. The 24 best evidences related to risk assessment, skin assessment and cleaning, selection and wearing of medical devices, preventive use of dressings, and education and training were summarized.Conclusions:This study summarized the clinical practice basis for the prevention of medical device related pressure injuries in patients in ICU, which can provide scientific and effective theoretical guidance for clinical nursing staff to implement changes in practice. And it is recommended that the evidence should be combined with the clinical reality when using evidence. Analyze the facilitating factors and obstacles in the process of using evidence and formulate reform strategies suitable for clinical transformation, and then apply them to daily clinical work to improve the quality of nursing work.

Objective:To establish the acute symptomatic osteoporotic thoracolumbar fracture (ASOTLF) classification system, and to examine the reliability and evaluate the effect of clinical application.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 293 patients with osteoporotic thoracolumbar fracture(OTLF) admitted to Honghui Hospital from January 2016 to December 2018. There were 514 males and 779 females, aged 57-90 years [(71.4±6.3)years]. The T value of bone mass density was -5.0--2.5 SD [(-3.1±-0.4)SD]. According to the clinical symptoms a and fracture morphology, OTLF was divided into 4 types, namely type I(I occult fracture), type II(compressed fracture), type III (burst fracture) and type IV(unstable fracture). The type II was subdivided into three subtypes (type IIA, IIB, IIC), and the Type III into two subtypes (type IIIA, IIIB). of all patients, 75 patients (5.8%) were with type I, 500 (38.7%) with type II A, 134 (10.4%) with type IIB, 97 (7.5%) with type IIC, 442 (34.2%) with type IIIA, 27(2.1%) with type IIIB and 18 (1.4%) with type IV. After testing the validity of the classification, different treatment methods were utilized according to the classification, including percutaneous vertebroplasty (PVP) for Type I, PVP after postural reduction for Type II, percutaneous kyphoplasty (PKP) for Type IIIA, posterior reduction and decompression, bone graft fusion and bone cement-augmented screw fixation for Type IIIB, and posterior reduction, bone graft fusion and bone cement-augmented screw fixation for Type IV. The visual analog score (VAS), Oswestry disability index (ODI), Frankel grade of spinal cord injury, local Cobb Angle, and vertebral body angle (vertebral body angle) were recorded in all patients and in each type of patients before surgery, at 1 month after surgery and at the last follow-up. The neurological function recovery and complications were also recorded.Results:The patients were followed up for 24-43 months [(29.9±5.1)months]. A total of 3 000 assessments in two rounds were conducted by three observers. The overall κ value of inter-observer credibility was 0.83, and the overall κ value of intra-observer credibility was 0.88. The VAS and ODI of all patients were (5.8±0.7)points and 72.5±6.6 before surgery, (1.8±0.6)points and 25.0±6.3 at 1 month after surgery, and (1.5±0.6)points and 19.5±6.2 at the last follow-up, respectively (all P<0.05). The Cobb angle and vertebral body angle of all patients were (13.0±9.1)° and (8.0±4.6)° before surgery, (7.9±5.2)° and (4.6±2.9)° at 1 month after surgery, and (9.1±6.0)° and (5.8±3.0)° at the last follow-up, respectively (all P<0.05). At the last follow-up, VAS, ODI, Cobb Angle and VBA of each type of patients were significantly improved compared with those before surgery (all P<0.05). The spinal cord compression symptoms were found 1 patient with type IV and 5 patients with type IIIB preoperatively. At the last follow-up, neurological function improved from grade C to grade E in 1 patient and from grade D to grade E in 5 patients ( P<0.05). The lower limb radiation pain or numbness in 3 patients with type IV and 22 patients with type III preoperatively were fully recovered after surgical treatment at the last follow-up except for three patients. Conclusions:The ASOTLF classification is established and has high consistency and reliability. The classification-oriented treatment strategy has achieved a relatively satisfactory effect, indicating that the classification has a certain guiding significance for treatment of OTLF.

Objective:To explore the risk factors of residual back pain (RBP) in patients undergone PVP within 1 month and further analyze the correlation.Methods:Between March 2013 and January 2015, 1 316 patients with OVCF were treated by PVP. RBP after PVP was defined as a visual analogue scale (VAS) score of > 4 both 1 week and 1 month post-operatively. According to the pain relief, the patients were divided into two groups, the satisfied group and the unsatisfied group. All patients were scheduled for follow-up at1 week, 1 month, 3 months, and 1 year post-operatively, during which radiography and magnetic resonance imaging (T1-weighted, T2-weighted, and short time inversion recovery (STIR) sequences) were recommended to detect the existence of secondary OVCF. VAS scores and Oswestry disability index (ODI) were recorded. Demographic data, surgical information, anesthesia method, number of OVCF, injection amount of cement of single vertebral bone, imaging data and other comorbidity informations of patients in the two groups were analyzed by Logistic regression for the factors related to RBP after PVP.Results:Among 1 316 patients, 60 cases complained RBP, and the prevalence was 4.6%. VAS score and ODI of the two groups were significantly different at 1 week, 1 month and 3 months after surgery, suggesting there was a certain degree of residual pain in the lower back of patients in the unsatisfied group, which was more severe than that in the satisfied group. However, the above differences disappeared in the follow-up of 12 months after surgery.Univariate analysesshowed that preoperative bone mineral density (BMD), number of fracture, cement distribution and volume injected per level and lumbodorsal fascia contusion were associated with RBP after PVP ( P< 0.01, retrospectively). Multivariate analysis revealed that the absolute value of pre-operative BMD(odds ratio ( OR)=3.577, P=0.029), combined withlumbodorsal fascia contusion ( OR=3.805, P=0.002), number of fracture ( OR=3.440, P<0.001), satisfactory cement distribution ( OR=3.009, P=0.013) and combined with depression ( OR=3.426, P=0.028) were positively correlated with RBP after PVP, and these were risk factors. The injection amount of cement of single vertebral bone ( OR=0.079, P<0.001) was negatively correlated with RBP after PVP, which was a protective factor. Conclusion:Pre-operative low BMD, lumbodorsal fascial injury, multiple segment OVCF, insufficient cement injected volume, unsatisfactory cement distribution and depression were risk factors associated with RBP after PVP in patients with OVCF.

Objective:To explore the feasibility of three-dimensional(3D) printing combined with mock circulatory system of flexible mitral valve model for hemodynamic testing in vitro based on ultrasound image data, making the transformation of 3D printing valve model from static to dynamic and from anatomical to functional, as well as assisting surgical plan for mitral valve diseases. Methods:A total of 10 subjects underwent three-dimensional transesophageal echocardiography (3D-TEE) and proved to be without mitral diseases were collected as mitral normal group from February 2017 to December 2018 in Renmin Hospital of Wuhan University, 10 mitral stenosis patients were collected as mitral stenosis group, and 10 mitral regurgitation patients were collected as mitral regurgitation group. Hemodynamic parameters of velocity (peak E), pressure gradient were obtained by two-dimensional transthoracic echocardiography in three groups, and the degree of mitral valve stenosis and regurgitation were also evaluated. Then 3D-TEE was performed to obtain the 3D volume image of mitral valve. After image post-processing and 3D modeling, the valve mold was printed with soluble material polyvinyl alcohol (PVA). The mixture of human skin silicone, silicone oil, starch and curing agent were poured into the mitral valve mold in a certain proportion to make flexible silicone mitral valve model. Then, the compliant valve model was placed in mock circulatory system (MCS), regularly opening and closing as it in vivo in the heart cycle. The hemodynamic parameters of mitral valve were measured again in vitro and the degree of stenosis and regurgitation was also evaluated respectively. Paired t test was used for statistical analysis of in vivo and in vitro measurements in two groups, and the consistency test was performed. Results:The mitral valve 3D-TEE images of all patients were successfully post-processed, mitral valve molds were printed and flexible models were made. In vitro hemodynamic tests were all completed. The opening and closing state of the valve model in vitro was similar to that in vivo. Mitral valve regurgitation was detected in mitral regurgitation group in vitro, with degree to that in vivo. There were no statistically significant differences in hemodynamic parameters measured in vivo and in vitro models (all P>0.05), with a high consistency ( r=0.76). Among the 10 patients with mitral stenosis and 10 patients with mitral regurgitation, 18 patients were evaluated as same degree as in vivo. Conclusions:3D printing of compliant mitral valve model based on ultrasound image is feasible, which reproduced hemodynamic features of mitral valve in vitro, setting foundation for further surgery simulation and clinical decision-making.

Objective To analyze the secular trends and geographic disparities of all-cause mortality among Chinese adolescents aged 10-24 years over the period of 1953-2010.Methods Data were extracted from the Chinese National Census in 1953-2010.We calculated the all-cause mortality and annualized rates of the changes.Using the provincial gross domestic product (GDP) per capita as an indicator of regional socio-economic development level,we calculated the Wagstaff normal concentration indices for adolescent mortality.Results Over the period of 1953-2010,the general patterns of Chinese adolescent mortality appeared higher in males than those in females,higher in the 20-24-year-old than those in the 15-19 year-old and in the 10-14 year-old groups,higher in adolescents from the western than those in the eastern regions.The mortality of adolescents decreased from 554.6/100 000 in 1953-1964 to 55.7/100 000 in 2010 in males and decreased from 488.4/100 000 to 26.7/100 000 in females,respectively.The percentage of decrease for females (94.5％) was higher than that for males (90.0％).In 1981-2010,the highest annualized rate of decline for males was seen in Beijing (4.4％),with the lowest seen in Qinghai (0.1％).For girls,Hubei showed the highest annualized rate of decline (6.4％) while Qinghai the lowest (0.8％).Provinces that with higher mortality tended to have lower annualized rate of decline.The concentration indices for boys were-0.07 (95％ CI:-0.11--0.03),-0.13 (95 ％ CI:-0.18--0.08),and-0.16 (95 ％ CI:-0.22--0.10) in 1990,2000,and 2010,respectively,and were-0.07 (95％CI:-0.13--0.02),-0.18 (95％CI:-0.24--0.12),and-0.18 (95％CI:-0.26--0.09) respectively in girls.The indices among 1990,2000,and 2010 did not show statistically significantly differences,both for boys and girls (P＞0.05).Conclusions Over the half century,the mortality of Chinese adolescents showed dramatic decreasing trend.However,in terms of death rates,gender and geographic disparities were consistently seen in the adolescents.

Objective:To compare the probability of physical activity (PA) time ≥1 hour at school and influencing factors in students in China between 2010 and 2014.Methods:We used the data of 2010 and 2014 Chinese National Survey on Students’ Constitution and Health (CNSSCH). The surveys covered the Han students aged 9-22 years and Tibetan students aged 9-18 years (Tibet). The participants were primary school students (9-12 years old), junior high school students (13-15 years old), senior high school students (16-18 years old) and college students (19-22 years old). The probability of PA time ≥1 hour at school was compared using χ2 tests between 2010 and 2014 survey years. Log-binomial Regression was used to estimate the relative risk ( RR) for the probability of PA time ≥1 hour at school in different age groups. Results:The overall probability of PA time ≥1 hour at school in students aged 9-22 years was 20.5 % in 2010, and 23.8 % in 2014. The difference between 2010 and 2014 was significant ( P<0.001). On the whole, the probability of PA time ≥1 hour at school increased in the eastern, central and western areas in 2014 compared with 2010 ( P<0.05), and the increase range was highest in eastern area, followed by western area and central area ( P<0.05). The probability of PA time of 1 hour at school in all age groups increased in 2014 compared with 2010 ( P<0.05). The increase in the probability of PA time ≥1 hour at school was larger in primary school students than that in high school students and college students ( P<0.05). The probability of PA time ≥1 hour at school increased in all age groups in three areas, except in junior and senior high school students in the central area where the probability of PA time ≥1 hour at school decreased. The probability of PA time ≥1 hour at school in primary and junior/senior high school students in the eastern area had the greatest increase, but in college students it had the smallest increase in the three areas. From 2010 to 2014, the changes in the probability of PA time ≥1 hour at school in students in different provinces were quite different, especially in primary school students. The probability of PA time ≥1 hour at school in four age groups increased in only three provinces. With the probability of PA time ≥1 hour at school in primary school students as the reference, the RR in junior high students had no significant change between 2010 and 2014. The RR in senior high school increased from 0.34 (0.33-0.35) in 2010 to 0.36 (0.36-0.37) in 2014, and the RR in college students increased from 0.33 (0.32-0.34) in 2010 to 0.43 (0.42-0.44) in 2014. Conclusions:The probability of PA time ≥1 hour at school in all age groups increased in 2014 compared with 2010, but there were great differences among provinces. The findings of our study suggests that although the national policy played a certain role, the provinces should take specific measures to improve the probability of PA time ≥1 hour at school in students according to their own conditions. In addition, more attention should be paid to PA of older students.

Objective: To examine the relation between physical fitness and frequency of having breakfast among Chinese Han college students so as to provide proper intervention and theoretical basis for improving college students’ physical fitness. Methods: The data from 2014 Chinese National Survey on Students’ Constitution and Health (CNSSCH) was used. The data of 47 172 Han students were calculated, the chi-square test wasused to compare the differences of the physical fitness passing rate in different subgroups of college students. The Log-binomial model was established to assess the relation between physical fitness and breakfast consumption. Results: The unqualified rate of physical fitness was 22.8%. Boys(24.7%), urban students (25.7%), and those who exercised less than one hour per day (23.3%) had lower physical fitness passing rates than girls(20.9%), rural students (19.9%) and those who exercised more than one hour per day (20.3%)respectively(χ2=101.38, 223.33, 32.20,P<0.01). The unqualified rate of physical fitness increased by age. The unqualified rate of physical fitness in eastern, central and western regions was 21.2%, 21.7% and 25.1% respectively. The unqualified rate of physical fitness for those with normal nutritional status (18.2%) was significantly lower than those who were underweight (26.0%) or overweight/obese(42.6%)(χ2=1 660.50, P<0.01). In this study, 53.2% of college students had breakfast every day,unqualified rate of physical fitness was higher among students with less regular consumption of breakfast(χ2=393.50, P<0.01). The Log-binomial model showed that the college students who had 3-5 breakfasts(PR=1.16, 95%CI=1.11-1.20), 1-2 breakfasts(PR=1.34, 95%CI=1.28-1.40), never had breakfast (PR=1.43, 95%CI=1.32-1.53) per week had higher physical fitness failure rates than those who had breakfast every day. Conclusion There is a significant association between physical fitness and breakfast consumption among college students. Developing the good habit of having breakfast is not only the component of healthy lifestyle but also an indispensable part to the improvement of college students’ physical fitness.