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 clinical and electrophysiological characteristics of peripheral neuropathy in prediabetic patients.Methods:Subjects aged 20-65 years with high-risk factors of impaired glycemia enrolled in Beijing Tiantan Hospital, Capital Medical University from 2019 to 2022 were recruited to conduct oral glucose tolerance test, after excluding other causes of neuropathy or radiculopathy. Patients with impaired fasting glucose or impaired glucose tolerance were defined by American Diabetes Association criteria. These patients were divided into clinical polyneuropathy (PN) and clinical non-PN groups, according to the 2010 Toronto consensus criteria and the presence of PN symptoms and signs or not. Nerve conduction studies (NCS), F wave, sympathetic skin response (SSR), R-R interval variation (RRIV) and current perception thresholds (CPT) were performed and the abnormal rate was compared between different electrodiagnostic methods and between clinical subgroups.Results:Among the 73 prediabetic patients ultimately enrolled, only 20 (27.4%) can be diagnosed as clinical PN according to the Toronto consensus criteria. The abnormal rate of CPT (68.5%, 50/73) was significantly higher than those of F wave (2.7%, 2/73), lower limb NCS (0, 0/73), upper limb NCS changes of carpal tunnel syndrome (26.0%, 19/73), SSR (6.8%, 5/73) and RRIV (5.5%, 4/73; McNemar test, all P<0.001). With sinusoid-waveform current stimuli at frequencies of 2 000 Hz, 250 Hz and 5 Hz, the CPT device was used to measure cutaneous sensory thresholds of large myelinated, small myelinated and small unmyelinated sensory fibers respectively. CPT revealed a 21.9% (16/73) abnormal rate of unmyelinated C fiber in the hands of prediabetic patients, significantly higher than that of large myelinated Aβ fibers [8.2% (6/73), χ2=5.352, P=0.021]. Both abnormal rates of small myelinated Aδ [42.5% (31/73)] and unmyelinated C fibers [39.7% (29/73)] in the feet of prediabetic patients were significantly higher than that of large myelinated Aβ fibers [11.0% (8/73), χ2=18.508, 15.965, both P<0.001]. Compared with the clinical non-PN group, the abnormal rates of CPT [90.0% (18/20) vs 60.4% (32/53), χ2=5.904, P=0.015] and SSR [20.0% (4/20) vs 1.9% (1/53), P=0.016) were significantly higher in the clinical PN group. Conclusions:Peripheral neuropathies in prediabetic patients are usually asymptomatic or subclinical, and predispose to affect unmyelinated and small myelinated sensory fibers. Selective electrodiagnostic measurements of small fibers help to detect prediabetic neuropathies in the earliest stages of the disease.

Objective To investigate the role of delta/notch-like epidermal growth factor-related receptor(DNER)in gastric cancer and its regulatory mechanism.Methods The mRNA and protein levels of DNER in gastric cancer tissues and cells were detected with quantitative real time polymerase chain reaction(qRT-PCR)and Western blot.Gastric cancer cell line SGC7901 with silenced DNER expression was constructed,and cells were treated with mitochondrial dynamin-related protein 1(DRP1)inhibitor Mdivi-1.CCK-8 assay,Transwell assay,and flow cytometry were used to detect cell viability,invasion ability and apoptosis,respectively.Western blot was used to detect DNER protein levels,apoptosis-associated proteins[Cysteinyl aspartate-specific proteinase-3(Caspase-3),Bcl-2 Associated X(Bax)],autophagy associated proteins[microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ,LC3 Ⅱ/Ⅰ),p62,PTEN induced putative kinase 1(PINK1)and Parkin],and mitochondrial fission and fusion protein[DRP1,mitochondrial fission factor(MFF),mitochondrial fission protein 1(FIS1),Optic Atrophy 1(OPA1),mitofusin 1(MFN1)and MFN2]levels.Results The expression levels of DNER mRNA and protein in gastric cancer tissues were higher than those in adjacent normal tissues(t=-52.485,-46.955),while expression levels of DNER mRNA and protein in gastric cancer cells were higher than those in normal gastric epithelial cells(F=60.551,60.652),and the differences were significant(P＜0.001).Silencing DNER inhibited the proliferation and invasion of SGC7901 cells,induced apoptosis,and increased the expression of apoptosis-related proteins,with significant differences(t=8.026～25.903,all P＜0.05).Silenced DNER increased LC3 Ⅱ/Ⅰ ratio(t=18.086),decreased p62 protein level(t=6.747),promoted the aggregation of PINK1 and Parkin proteins in mitochondria(t=15.630,18.171),inhibited the expression of mitochondrial fusion proteins OPA1,MFN1 and MFN2(t=12.835,8.963,9.732),and promoted the expression of mitochondrial fission proteins DRP1,MFF and FIS1(t=16.034,16.939,15.971),with significant differences(all P＜0.05).Mdivi-1 treatment could counteract the effects of silencing DNER on mitochondrial autophagy,proliferation,invasion and apoptosis of gastric cancer cells.Conclusion DNER can reduce mitochondrial autophagy by inhibiting mitochondrial dynamic imbalance,promote cell proliferation and invasion,and inhibit cell apoptosis,thus promoting the progression of gastric cancer.

Cardiovascular disease risk communication is an important tool to help risk individuals understand risk information and guide them to improve their health behaviors.Effective cardiovascular disease risk communication by nurses,who are the subjects of risk communication,is essential to reduce the growing burden of cardiovascular disease and the prevalence of cardiovascular disease.This article provides a 3-aspect overview of the concept and development of health risk communication,factors influencing cardiovascular disease risk communication,and recommendations for its development.It is suggested that when nursing staff carry out CVD risk communication,they should fully consider the actual situation and preference of the communication target and design a personalized risk communication program,to provide references for clinical nursing practice.

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 investigate the cognition of e-cigarette compositions and hazards and its influencing factors among secondary school personnel （junior， senior and vocational high school） in Shanghai， so as to provide ideas for improving the cognition level of e-cigarettes among the school personnel and tobacco control efforts on campus in the future. MethodsA multi-stage stratified cluster random sampling method was used to conduct an anonymous online questionnaire survey among 1 767 secondary school personnel in Shanghai. ResultsThe proportion of school staff who had used e-cigarettes was 3.79%. The participants who were not sure whether the e-cigarette smoke was “mainly water vapor （incorrect）” and whether the e-cigarette smoke “contained nicotine （correct）” and “contained formaldehyde （correct）” accounted for 62.71%， 54.44% and 61.91%， respectively. Among them， 68.48%， 55.46% and 50.37%， respectively， agreed that e-cigarettes would be “addictive”， “harmful” and “that second-hand smoke was harmful”. Binary logistic regression analysis showed the following risk factors for the low level of school personnel’s awareness of e-cigarette compositions： age ≥40 years （OR=1.65， 95%CI： 1.32‒2.06）， working in junior high school （OR=1.37， 95%CI： 1.09‒1.73）， educational attainment level as junior college or below （OR=1.67， 95%CI： 1.02‒2.74）， and not having participated in tobacco control education activities （OR=1.37， 95%CI： 1.08‒1.73）. Meanwhile， working in junior （OR=1.43， 95%CI： 1.12‒1.83） or senior （OR=1.44， 95%CI： 1.08‒1.92） high school， educational attainment level as junior college or below（OR=2.10， 95%CI： 1.24‒3.56）， having used e-cigarettes （OR=2.98， 95%CI： 1.63‒5.42）， not having participated in tobacco control education activities （OR=1.49， 95%CI： 1.16‒1.92） and low level of awareness of e-cigarette compositions （OR=4.24， 95%CI： 3.44‒5.23） were risk factors for the low level of school personnel’s awareness of e-cigarette hazards. ConclusionsThe level of e-cigarette awareness among school personnel in Shanghai is low， especially those who are older， had low educational attainment level and had used e-cigarettes. In the future， tobacco control education for school personnel should be strengthened to improve their cognition and ability of tobacco control on campus.

Objective:To analyze the effect of intestinal fluid reinfusion after anterior resection of rectum and preventive ileostomy in patients with low rectal cancer.Methods:A prospective research method was used, and 60 patients with low rectal cancer in Zhejiang Jinhua Guangfu Tumor Hospital from January 2021 to June 2022 were enrolled. The patients were divided into control group (treated with anterior resection of rectum and preventive ileostomy) and observation group (treated with anterior resection of rectum and preventive ileostomy combined with intestinal fluid infusion) by random number table method with 30 cases each. On the next day and 3 months after surgery, the low anterior resection syndrome (LARS) scale was used to evaluate anal function, the patient-generated subjective global assessment (PG-SGA) method was used to evaluate nutritional status, the stoma-quality of life (stoma-QOL) was used to evaluate the quality of life. The complications were recorded.Results:Both groups of patients were successfully completed the scheduled surgery. There were no statistical differences in LARS score and incidence of LARS on the next day after surgery between the two groups ( P>0.05); the LARS score and incidence of LARS 3 months after surgery in observation group were significantly lower than those in control group: (18.63 ± 3.15) scores vs. (24.90 ± 6.11) scores and 23.33% (7/30) vs. 46.67% (14/30), and there were statistical differences ( P<0.01 or <0.05). There were no statistical differences in PG-SGA score and incidence of malnutrition on the next day after surgery between the two groups ( P>0.05); the PG-SGA score and incidence of malnutrition 3 months after surgery in observation group were significantly lower than those in control group: (3.07 ± 0.82) scores vs. (5.13 ± 1.01) scores and 26.67% (8/30) vs. 46.67% (14/30), and there were statistical differences ( P<0.01 or <0.05). There were no statistical differences in the scores of psychological burden, social interaction, stoma management and daily living of stoma-QOL on the next day after surgery between the two groups ( P>0.05); the scores 3 months after surgery in observation group were significantly higher than those in control group: (27.70 ± 4.28) scores vs. (21.47 ± 5.16) scores, (14.33 ± 2.03) scores vs. (11.90 ± 1.64) scores, (14.87 ± 1.92) scores vs. (11.57 ± 2.38) scores and (15.30 ± 1.03) scores vs. (12.37 ± 2.11) scores, and there were statistical differences ( P<0.01). The incidence of complications in observation group was significantly lower than that in control group: 30.00% (9/30) vs. 60.00% (18/30), and there was statistical difference ( χ2 = 5.45, P<0.05). Conclusions:For the patients with low rectal cancer, the anterior resection of rectum and preventive ileostomy combined with intestinal fluid reinfusion can reduce LARS, improve nutritional status, improve quality of life, and also reduce complications.

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).

Objective: To assess the status of current e cigarette perception and its influencing factors among adolescents in Shanghai, so as to provide reference for the refinement of the prevention and control measures of teenagers e cigarette use. Methods: From May to June 2021, a stratified random cluster sampling was used to investigate 7 456 junior high and high school students in Shanghai. Harm and benefit perception of e cigarette as well as its social environment benefits were collected. Results: The rate of adolescents ever and current e cigarette use was 3.19% and 1.09%, respectively. The top four risk factors for low harm perception of e cigarette were adolescent e cigarette use( OR=2.74, 95%CI =2.10-3.59), high school students ( OR=1.47, 95%CI = 1.32 - 1.64 ), family members ( OR=1.45, 95%CI =1.24-1.70) and friends ( OR=1.36, 95%CI =1.20-1.54) using e cigarette. Adolescent ecigarette use ( OR=2.77, 95%CI =1.97-3.89), high school students( OR=2.11, 95%CI =1.89-2.36), friends ( OR= 1.63, 95%CI =1.42-1.87) and family members using e cigarette( OR=1.39, 95%CI =1.18-1.65) were the top four associated factors for high benefit perception of e cigarette. And, adolescent e cigarette use ( OR=1.95, 95%CI =1.47-2.59), high school students ( OR= 1.73, 95%CI =1.55-1.93), friends ( OR=1.60, 95%CI =1.40-1.82) and pocket money≥200 yuan using e cigarette( OR= 1.29 , 95%CI =1.17-1.43) were the top four risk factors for high social environmental benefit perception of e cigarette. Moreover, perception of e cigarette harm, benefit and social environmental benefit were associated with the risk of future use of e cigarette( OR = 0.78,1.44,1.21, P <0.01). Conclusion Being high school students and using e cigarette by oneself, friends, and family members are the important influencing factors for adolescents e cigarette perception. Both low harm and high benefit perception of e cigarette elevate the risk of future e cigarette use among adolescents, so effective measures should be taken to promote control education about e cigarette and smoke free environment construction.

Objective:To explore the effect of transitional care led by special disease nurses in patients with venous thromboembolism (VTE) after intervention.Methods:From February 2020 to April 2021, 124 patients undergoing VTE intervention in Vascular Surgery of Xinxiang Central Hospital were selected by convenient sampling. According to the propensity matching score of 1∶1, the patients were divided into the control group and the observation group, with 62 cases each. The control group was given routine nursing, and the observation group received transitional care led by special disease nurses on the basis of the control group. The follow-up lasted for 12 months. The severity of post-venous thrombosis syndrome (Villalta Scale score), medication compliance, follow-up compliance and quality of life score were compared between the two groups.Results:The completion rates of follow-up at the end of 3, 6 and 12 months in the control group were 95.16% (59/62), 82.26% (51/62) and 70.97% (44/62), respectively. The completion rates of follow-up at the end of 3, 6 and 12 months in the observation group were 100.00% (62/62), 96.77% (60/62) and 91.94% (57/62), respectively. The completion rate of follow-up at each time point in the observation group was higher than that in the control group, and the differences were statistically significant at the end of 6 and 12 months ( P<0.05). The Villalta score of the control group and the observation group increased gradually. The Villalta scores of the observation group at the end of 3, 6 and 12 months were lower than that of the control group, with statistically significant differences ( P<0.05). The score of medication compliance in the control group decreased gradually, while the score of medication compliance in the observation group increased gradually. The scores of medication compliance in the observation group at the end of 3, 6 and 12 months were higher than that in the control group, with statistically significant differences ( P<0.05). The quality of life score of the observation group gradually increased, and the quality of life scores of the observation group at the end of 6 and 12 months were higher than those of the control group, the differences were statistically significant ( P<0.05) . Conclusions:The transitional care led by special disease nurses can effectively increase the postoperative follow-up and medication compliance of VTE patients, reduce the severity of post-venous thrombosis syndrome and improve the quality of life.