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 describe the characteristics and change trends of incidence, mortality and disease burden of acute myocardial infarction (AMI) in Qingdao from 2014 to 2020.Methods:We analyzed the incidence data of AMI retrieved from Qingdao Chronic Diseases Surveillance System. The average annual percent change (AAPC) of morbidity and mortality of AMI were evaluated by using Joinpoint log-linear regression model. Disability adjusted life year (DALY) was used to estimate disease burden of AMI in Qingdao.Results:A total of 70 491 AMI cases and 50 832 deaths of AMI occurred in Qingdao from 2014 to 2020. The age-standardized morbidity and mortality were 54.71/100 000 and 36.55/100 000, respectively. During 2014-2020, the AAPC of age-standardized morbidity was 2.86% (95% CI: 0.42%-5.35%), and 4.30% (95% CI: 1.24%-7.45%) in men and 0.78% (95% CI: -0.89%-2.47%) in women, respectively. The log-linear regression model showed that age-standardized morbidity in age groups 30-39, 40-49 years increased rapidly, with the AAPCs of 8.92% (95% CI: 2.23%-16.06%) and 6.32% (95% CI: 3.30%-9.44%), respectively. The trend was also observed in age groups 30-39, 40-49 and 50-59 years in men, with the AAPCs of 11.25% (95% CI: 3.54%-19.54%), 6.73% (95% CI: 2.63%-10.99%) and 6.72% (95% CI: 2.98%-10.60%), respectively. There was no significant change in age-standardized mortality. The DALY rate increased from 7.49/1 000 in 2014 to 8.61/1 000 in 2020, with the AAPC of 1.97% (95% CI: 0.36%-3.60%). Conclusions:The age-standardized morbidity of AMI in men increased in Qingdao, especially in those aged 30-49 years, while age-standardized mortality rate of AMI was relatively stable from 2014 to 2020. The burden of disease of AMI increased in both men and women.

Objective:To evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for early colorectal cancer and its precancerous lesions by using novel lifting clip-assisted traction.Methods:From March to July 2021, 42 patients with colorectal lesions who received ESD at the Digestive Endoscopy Center of Shanghai Tenth People's Hospital were included in the retrospective study. Nineteen patients were enrolled as the observation group using the novel lifting clip, and 23 others in the control group without the help of an auxiliary method. The operation time, the hospital stay, hospital expenses and the incidence of complications of the two groups were compared.Results:All 42 patients successfully received ESD. The operation time of the observation group was significantly shorter than that of the control group [31.00 (21.00, 58.00) min VS 60.00 (30.00, 75.00) min, Z=-2.04, P=0.04]. The postoperative hospital stay of the observation group was significantly shorter than that of the control group [2.00 (1.00, 2.00) d VS 2.00 (2.00, 3.00) d, Z=-1.99, P=0.04]. The hospital cost was lower than that of the control group, but the difference was not statistically significant (19 331.42 ± 3 481.20 yuan VS 19 802.40 ± 2 548.50 yuan, t=-0.49, P=0.63). No intraoperative perforation occurred in either group. There was no significant difference in intraoperative blood loss between the observation group and the control group [0.00 (0.00, 5.00) mL VS 3.00 (0.00, 7.00) mL, Z=-1.42, P=0.16]. There was 1 case of postoperative abdominal pain in the observation group, 2 cases of postoperative abdominal pain and 1 case of fever in the control group. There was no significant difference in the overall incidence of postoperative complications between the observation group and the control group [5.3% (1/19) VS 13.0% (3/23), χ2=0.73, P=0.39]. Conclusion:The novel lifting clip-assisted colorectal ESD is safe and effective, which can significantly shorten the ESD operation time and postoperative hospital stay without increasing the economic burden of patients.

Objective:To investigate the level of self-compassion among residents and related influencing factors, and to help them improve self-compassion ability, achieve learning goals, and increase the degree of satisfaction with learning.Methods:In July 2022, the random sampling method was used to select 330 residents (postgraduate students majoring in clinical medicine after national unified recruitment) from two grade A tertiary hospitals in Shenyang of Liaoning province in China, and Self-Compassion Scale was used for investigation. SPSS software was used to analyze the degree of satisfaction with industry, learning pressure, the balance between learning and life, and occupational burnout among residents and their association with the level of self-compassion through the chi-square test, the one-way analysis of variance, and the multilevel regression analysis.Results:The residents had a mean self-compassion score of (40.90±6.81), and the residents of the second grade had a lower level of self-compassion than those of the other grades. Major satisfaction and balance between learning and life were positively correlated with self-compassion, and occupational burnout was negatively correlated with self-compassion.Conclusion:There is a relatively insufficient level of self-compassion among residents, and improving self-compassion level may effectively regulate occupational burnout, professional satisfaction, and the balance between learning and life, thereby helping to improve learning and mental health.

Objective:The study aims to gain information on medical research status and cooperative needs of medical universities/colleges from China and Association of Southeast Asian Nations (ASEAN) and provide evidence to guide the regional cooperation and development in medical reserach.Methods:A self-constructed questionnaire survey was adopted to collect information on the cooperative intentions, expertise and challenges of the 43 member institutions of China-ASEAN University Consortium on Medicine and Health in medical research.Results:In total, 20 Chinese members and 10 ASEAN members completed the survey. The study found that both Chinese and ASEAN medical universities/colleges were particularly interested in cooperation in academic conferences, multi-center clinical trials and joint research projects /flagship projects, followed by large cohort studies and medical journal/publication. In terms of research priority, both Chinese and ASEAN institutions were very interested in big data, followed by cancer precision medicine; while ASEAN members were more interested in natural drugs and dengue than Chinese ones.Conclusions:Both Chinese and ASEAN medical universities/colleges had strong interest in international cooperation in medical research. They should further explore the advantages and characteristics of both sides in medical research based on the interests of two sides, adopt appropriate scientific research cooperation methods, and establish sound scientific research cooperation mechanism so as to deepen cooperation in medical research, promote the development and improve the outcome of regional medical research, and facilitate the building of a community of common health for mankind.

Objective:To evaluate the relationship between the application of statins and the risk of hepatocellular carcinoma in patients with chronic liver disease.Methods:PubMed, the Cochrane Library, EMBASE, Web of science, WeiPu, Wanfang Med online, and China National Knowledge Infrastructure database were searched. The literatures about statins and the risk of hepatocellular carcinoma in patients with chronic liver disease were collected, with a search deadline of February 2020. Two researchers independently conducted literature screening, data extraction, quality evaluation and proofreading. RevMan5.3 software was used for data analysis. The I2 combined with χ2 test was used to evaluate the heterogeneity. Funnel plots were used to evaluate the publication bias of the included literature. Results:A total of 12 articles were included. Statins application had significantly reduced the risk of hepatocellular carcinoma in patients with chronic liver disease ( OR = 0.50, 95% CI: 0.43~0.58, P < 0.01). Subgroup analysis showed that statins had reduced the incidence rate of hepatocellular carcinoma in patients with chronic hepatitis B ( OR = 0.56, 95% CI: 0.47~0.66, P < 0.01) and chronic hepatitis C ( OR = 0.56, 95% CI: 0.45~0.71, P < 0.01). Lipophilic statins had significantly reduced the risk of chronic liver disease development to hepatocellular carcinoma ( OR = 0.48, 95% CI: 0.39~0.59, P < 0.01), but hydrophilic statins did not reduce the incidence rate of chronic liver disease development to hepatocellular carcinoma, and the difference was not statistically significant ( OR = 0.64, 95% CI: 0.36~1.14, P = 0.13). Conclusion:Statins can effectively reduce the risk of hepatocellular carcinoma development in patients with chronic liver disease, including chronic hepatitis B and C. Among them, the lipophilic statins have a significant preventive effect on the development of chronic liver disease to hepatocellular carcinoma, but hydrophilic statins have no obvious effect.

Objective: To revised the Taiwan version successful aging inventory (SAI), and verify its reliability and validity in urban elderly in mainland China. Methods: SAI was adjusted by culture and revised by pre-test to form a formal questionnaire. A sample of 600 elderly people in Guangzhou was chosen for a face-to-face questionnaire survey through convenient sampling. Half of the sample (n=300) was randomly selected for exploratory factor analysis, and the other was used to confirm the structural validity of SAI. Results: Exploratory factor analysis extracted six common factors, including health autonomy, economic security, life adaptation, society and relative relationship, study and family. The cumulative contribution rate of six common factors was 65.366%. The fitting indexes of confirmatory factor analysis were χ²/df=1.861, CFI=0.930, IFI=0.930, TLI=0.923, GFI=0.823, RMSEA=0.054, RMR=0.073. There were significant ceiling effects in the four dimensions of health autonomy, economic security, life adaptation, and family. The internal consistency coefficient (Cronbach's α) of SAI was 0.930, and the test-retest reliability was 0.943. An average score of SAI ≥ 3.95 points was considered successful aging. Conclusion Reliability and validity of SAI are good, which can be used to measure the successful aging status of Chinese elders and track the effectiveness of health promotion measures.

OBJECTIVE To explore the possible role and mechanism of vitamin D on the pathogenesis of allergic rhinitis by adjuvant therapy with vitamin D3. METHODS A total of 60 allergic rhinitis patients and 30 healthy subjects were selected as the combination therapy group, standard treatment group and control group. Vitamin D3 nasal drops to nasal cavity and oral Desloratadine Citrate Disodium at the same time 8.8 mg once a day were given in combined treatment group patients. Standard treatment group patients received oral Desloratadine Citrate Disodium 8.8 mg once a day. The total course of treatment was 4 weeks and then to assess the changes of serum 25(OH)D concentration, eosinophils, IL-4 levels and the therapeutic effect before and after treatment. RESULTS The serum 25(OH)D levels before and after treatment in combination therapy group were(23.67±4.47)ng/ml and (47.57±2.83)ng/ml, the IL-4 levels were (14.576 ± 4.472)pg/ml and (10.381 ± 3.41l)pg/ml, and the eosinophils of peripheral blood counts were (0.71±0.14)× 109/L and (0.34 ± 0.09)×109/L. The total effective rate was 97％. The serum 25(OH)D levels before and after treatment in standard treatment group were (23.42±3.83)ng/ml and(31.51 ±2.95)ng/ml, the IL-4 levels were (15.187±5.144)pg/ml and (12.794 ±5.396)pg/ml, and the eosinophils of peripheral blood counts were (0.67±0.12)×109/L and (0.41 ±0.10)×109/L. The total effective rate was 84％. CONCLUSION Nasal vitamin D3 drops combined with antihistamines for allergic rhinitis can effectively improve the clinical symptoms and reduce the related inflammatory markers.

Objective To investigate the correlation of suicidal ideation with social support and quality of life among only-child loss people.Methods Totally 320 only-child loss people were collected by using stratified cluster random sampling method.Social support rating scale(SSRS) and general quality of life inventory(GQOLI) were used to investigate the suicidal ideation status.The association of suicidal ideation with social support and quality of life was analyzed by Pearson correlation analysis.Results The suicidal risk rate of only-child loss people was 45.0％.Compared with control group((4.87±2.32),(35.50±9.33),(139.46±37.80)),only-child loss group had lower scores in suicidal ideation,SSRS,GQOLI ((8.94±3.99),(29.97±9.15),(29.97±9.15) respectively,t=1.997-15.009,P＜0.05 or P＜0.01).The suicidal ideation total score was negatively correlated with scores of SSRS and all its 4 items,GQOLI,physical function,psychological function(r=-0.121--0.270,P＜0.05 or P＜0.01).The score of suicidal ideation in the past year was positively correlated with scores of material function (r=0.135,P＜ 0.05).Regression analysis showed that age,marriage,objective support,subjective support and GQOLI were the influencing factors(t=-3.251-3.160,P＜ 0.01 or P＜0.05).Conclusion Only-child loss people have higher suicidal risks,which is negatively correlated with lower social support and quality of life,and influenced by age,marriage,SSRS and GQOLI factors.

Objective:To research the anti-dysmenorrhea effect of different extracts of Rupixiao granules. Methods:The anti-dys-menorrhea effect of different extracts of Rupixiao granules was studied by writhing test induced by oxytocin in mice. Results:Compared with the model group, the extracts of Rupixiao granules could reduce the writhing times induced by oxytocin significantly (P<0. 05,P<0. 01 or P<0. 001), and the water-soluble extract showed the best effect (P<0. 001) without significant difference when compared with the positive control group(P>0. 05). Conclusion:The water-soluble parts of Rupixiao granules have significant anti-dysmenor-rhea effect.