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 investigate symptoms of anxiety and depression among primary and middle school students quarantined in hotels during the COVID-19 epidemic.Methods:Anxiety and depression symptoms among 726 primary and middle school students quarantined in hotels were investigated with The Screen for Child Anxiety Related Emotional Disorders(SCARED)and Depression Self-rating Scale for Children(DSRSC)from September to October 2022 in Chifeng City,Inner Mongolia Autonomous Region.There were 624 students completed investi-gation with response rate of 86％.The positive score of SCARED was ≥23 and DSRSC was ≥ 15.Results:The detection rates of anxiety and depression were 17.9％and 15.4％respectively.The detection rates of anxiety and depression were higherin middle school students than inprimary school students(Ps＜0.05).The scores of general-ized anxiety and social phobia factors were higher in female students than in male students(Ps＜0.05).The scores of dissociative anxiety factor and depression were higher in middle school students than in primary school students(Ps＜0.05).Conclusion:During the COVID-19 epidemic,middle school students quarantined in hotels are more likely to have anxiety and depression symptoms than primary school students,and female students are more likely to have anxiety symptoms than male students.

Objective:To compare the application effect among Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scale, Medical Outcomes Study 36-item Short Form (SF-36) scale and "Assessment for Therapeutic Efficacy on Kashin-Beck Disease" (WS/T 79-2011) standard in the evaluation of therapeutic effect of patients with Kashin-Beck disease, which could provide basis for the treatment evaluation of patients with Kashin-Beck disease.Methods:A total of 213 patients with Kashin-Beck disease in Gansu Province were investigated. WOMAC scale, SF-36 scale and standard of WS/T 79-2011 were used to analyze the quality of life of patients before and after treatment. The reliability, construct validity, content validity, discriminant validity of WOMAC and SF-36 scales were compared. Correlation between WOMAC, SF-36 scales and standard of WS/T 79-2011 were evaluated.Results:Both WOMAC and SF-36 scales had good construct validity and content validity (construct validity showed WOMAC and SF-36 scales contained 1 and 2 common factors, respectively; content validity showed WOMAC and SF-36 scales contained 3 and 8 common factors, respectively). The reliability and discriminant validity of WOMAC scale were better than those of SF-36 seale (reliability showed WOMAC reliability coefficient ≥0.934, the reliability coefficient of SF-36 scale was ranged from 0.386 to 0.999. Discriminant validity showed there were differences in 3 dimensions of the WOMAC scale before and after treatment, while there were differences in 6 out of 8 dimensions of the SF-36 scale). The correlation coefficients between WOMAC scale and standard of WS/T 79-2011 ranged from 0.175 to 0.437, the correlation coefficients between SF-36 scale and standard of WS/T 79-2011 ranged from - 0.434 to - 0.099 ( P < 0.05). Conclusion:The reliability, discriminant validity and correlation with the standard of WS/T 79-2011 of WOMAC scale are better than those of SF-36 scale in efficacy evaluation of patients with Kashin-Beck disease.

Objective:To master the epidemic trend of Kashin-Beck disease (KBD) in Gansu Province and provide a scientific basis for prevention and treatment of KBD.Methods:All children aged 7 - 12 or 16 years old were selected as the survey subjects in 37 KBD districts and counties in Gansu Province, clinical and X-ray monitoring results of KBD in children from 2004 to 2018 were collected to analyze the epidemic trend of the disease.Results:From 2004 to 2018, a total of 97 190 children were examined clinically and 94 180 X-ray films were taken in Gansu Province. Four hundred and twenty-eight clinical positive cases were detected, with a detection rate of 0.44%. There were 649 X-ray positive cases, and the detection rate was 0.69%. There were 435 metaphyseal positive cases, the detection rate was 0.46%. There were 214 positive cases of bone end, and the detection rate was 0.23%. The clinical positive rate was the highest (7.17%, 58/809) in 2004, followed by 2007 (4.60%, 51/1 109) and 2005 (4.48%, 187/4 173), and the positive rate in other years was less than 3%. The positive rate of X-ray was the highest (9.59%, 58/605) in 2004, followed by 2005 (5.10%, 213/4 173), 2008 (3.66%, 45/1 228) and 2006 (3.04%, 125/4 107), the positive rate of other years was less than 3%.Conclusions:The clinical positive rate and X-ray positive rate of KBD in children in Gansu Province are decreased rapidly and then maintain a low fluctuation. The effect of comprehensive prevention and control measures is remarkable.

Objective:To analyze the epidemic range of tea-drinking-borne endemic fluorosis in Gansu Province and accurately grasp the information of tea-drinking-borne endemic fluorosis patients, so as to provide basis for popularizing low fluorine brick tea and carrying out patient rescue and treatment.Methods:From 2019 to 2020, 12 counties (cities) in Gansu Province with a history of drinking brick tea were selected as the survey points according to the "Investigation Plan of Endemic Fluorosis of Tea Drinking Type in China in 2019" and the relevant information in Gansu Province. A cross-sectional survey was conducted in all villages with the habit of drinking brick tea (including the investigation of the fluoride content in drinking water, tea, the fluoride intake of the population, the dental fluorosis and urinary fluoride content of children aged 8 to 12, and the skeletal fluorosis and urinary fluoride content of adults), and the survey results were analyzed.Results:The survey covered 125 townships in 12 counties (cities), with 8 625 households in 860 villages. One thousand six hundred and seventy-two drinking water samples were collected, and the fluoride content in water ranged from 0.01 to 1.81 mg/L. Six villages with fluoride content > 1.0 mg/L were screened. A total of 3 664 tea samples were collected, the average fluorine content of brick tea was 481.33 mg/kg, and the fluorine content ranged from 31.88 to 1 643.40 mg/kg. There were 1 076 tea samples with fluorine content less than 300 mg/kg, and the qualified rate of fluorine content in brick tea was 29.37% (1 076/3 664). Among the 12 counties (cities), 92 townships and 496 villages were still drinking brick tea. The drinking rate of brick tea in villages was 57.67% (496/860), and the annual per capita consumption of brick tea was 1.21 kg. The average daily intake of tea fluoride in adults was 1.57 mg/d. In Maqu County, Aksai County, Tianzhu County and Sunan County, the daily intake of tea fluoride of adults in 31 villages of 13 townships was more than 3.5 mg, involving 5 272 households and 15 272 people. Sixty-five patients with dental fluorosis were found in the above 31 villages. The detection rate of dental fluorosis was 3.50% (65/1 856), mainly in very mild and mild cases. Urine samples were collected from 326 children. The median of urinary fluoride was 1.44 mg/L. The clinical investigation of skeletal fluorosis was carried out in 2 189 adults. X-ray examination of bones and joints was performed in 123 patients with definite clinical symptoms and/or signs of skeletal fluorosis. Seven cases of skeletal fluorosis were positive, the detection rate was 0.32% (7/2 189). Urine samples were collected from 83 adults. The median of urinary fluoride was 1.83 mg/L. Two villages with moderate disease were identified as Yehuwan Village in Anyuan Town of Tianzhu County and Nannigou Village in Zhuaxixiulong Town. Four villages in the mild diseased areas were identified as Daiqian Village in Zhuaxixiulong Town, Xiding Village in Dahonggou Town, Tuta Village in Danma Township of Tianzhu County and Annanba Village in Akeqi Township of Akesai County.Conclusion:Most of the endemic areas of tea-drinking-borne endemic fluorosis in Gansu Province have been under control, but the risk of tea fluoride exposure still exists in some areas, so it is urgent to take targeted prevention and control measures.

Objective:To comprehensively investigate the epidemic scope, geographic features and threatened population of tea drinking type endemic fluorosis in Gansu Province.Methods:From June 2019 to December 2020, according to the "2019 Investigation Plan on the Epidemic Situation of Tea Drinking Type Endemic Fluorosis" and the relevant information about the living habits of residents in cities (prefectures) in Gansu Province, 12 counties (cities) in 4 cities (prefectures) of Gannan, Wuwei, Jiuquan and Zhangye, which had the habit of drinking border-sale tea, were selected as the survey sites. The survey contents included temperature, altitude, the number of townships (towns), the number of administrative villages (residents' committees, referred to as villages), the total population under its jurisdiction, ethnic composition, production methods, drinking condition of border-sale tea, fluoride content of tea, etc. The fluoride content of tea was tested according to "The Fluoride Content of Brick Tea" (GB 19965-2005), and the evaluation of whether the fluoride content exceeded the standard (> 300 mg/kg) was carried out.Results:The annual average temperature of the survey sites ranged from 0.2 to 12.7 ℃, except for Zhouqu County, the annual average temperature of the other 11 counties (cities) was < 10 °C; the average altitude ranged from 1 200 to 4 874 m, and there were 6 counties (Maqu, Tianzhu, Subei, Sunan, Aksay and Luqu) with an altitude > 3 000 m. The total population of the 12 counties (cities) was 1 051 843, of which 492 597 (46.83%) were ethnic minorities who had the habit of drinking border-sale tea; among them, there were 474 620 Tibetans, 10 152 Yugurs, 4 660 Mongolians and 3 165 Kazaks. In 860 villages of 125 townships (towns), a survey was conducted on drinking condition of border-sale tea, and the survey rate was 79.48% (860/1 082); the drinking border-sale tea rates of villages and families were 57.67% (496/860) and 42.41% (3 658/8 625), respectively. From the perspective of production methods, the drinking border-sale tea rates of villages and families in the pastoral counties such as Aksay, Subei, Maqu, Luqu and Sunan, as well as in the semi-agricultural and semi-pastoral county of Tianzhu, were all > 95%. A total of 3 664 tea samples were tested, with an average fluoride content of 481.33 mg/kg. There were 2 588 tea samples with a fluoride content > 300 mg/kg, accounting for 70.63% (2 588/3 664).Conclusions:There are still a large number of populations who drink border-sale tea in Gansu Province, mainly distributes in the low-temperature and high-altitude pastoral counties such as Aksay, Subei, Maqu, Luqu and Sunan. The ethnic group most threatened by tea drinking type endemic fluorosis is Tibetans.

Objective:To investigate the lung protective effect of driving pressure-guided lung protective ventilation strategy (LPVS) combined with pressure-controlled ventilation (PCV) in elderly patients undergoing thoracoscopic radical resection of lung cancer.Methods:One hundred elderly patients scheduled for thoracoscopic radical resection of lung cancer from April 2021 to April 2022 in the Second Hospital of Shanxi Medical University were selected. Patients were aged 60-80 years old and American Society of Anesthesiologists (ASA) classification Ⅰ-Ⅱ. All patients were divided into 4 groups by using the random number table method, with 25 cases in each group. Group A received volume-controlled ventilation (VCV) + 5 cm H 2O (1 cm H 2O = 0.098 kPa) PEEP, group B received PCV+5 cm H 2O PEEP, group C received VCV+driving pressure-guided individualized PEEP, and group D received PCV+driving pressure-guided individualized PEEP. The arterial oxygen partial pressure (PaO 2) was recorded before one-lung ventilation (OLV) (T 0), 30 min after OLV (T 1) and 60 min after OLV (T 2). The serum concentrations of neutrophil elastase (NE) in radial artery blood samples of patients were measured at T 0 and 10 min after the end of OLV (T 3). The occurrence of postoperative pulmonary complications (PPC) within 5 d after surgery was recorded. Results:The PaO 2 of group A and B at T 1 [(135±50), (146±51) mmHg (1 mmHg = 0.133 kPa)] and T 2 [(137±46), (143±47) mmHg] were lower than those of group C and group D at T 1 [(168±27), (190±30) mmHg] and T 2 [(180±30), (183±24) mmHg] (all P < 0.05). The incidence of PPC within 5 d after surgery in group A was higher than that in group D [36% (9/25) vs. 4% (1/25)] ( P = 0.005). The concentration of NE at T 3 in group A [(202.8±9.7) ng/ml] was lower than that in group B, C and D [(182.5±12.0), (180.0±10.3), (160.6±13.0) ng/ml] ( P < 0.05). Conclusions:During OLV, driving pressure-guided LPVS combined with PCV can not only improve oxygenation, but also show obvious advantages in reducing inflammatory response. It is a safe and effective intraoperative ventilation strategy for elderly patients undergoing thoracoscopic radical resection of lung cancer.

Objective:To investigate the application and problems existing in the implementation of the standard of "Assessment for Therapeutic Efficacy of Kashin-Beck Disease" (WS/T 79-2011, referred to as new standard), and to provide technical basis and suggestions for further improving the standard.Methods:In 2019, a questionnaire survey was conducted and analyzed in Sichuan, Shaanxi, Qinghai and Gansu provinces and Tibet Autonomous Region on basic information, standard implementation, publicity, training and application of scoring method of joint dysfunction index of Kashin-Beck disease prevention and control technicians.Results:One hundred and thirty-four questionnaires were distributed in this survey and 132 valid questionnaires were recovered, of which 88.64% (117/132) of Kashin-Beck disease prevention and control technicians received training in the new standard and 89.39% (118/132) used the new standard; 78.03% (103/132) thought that the standard terms were clear and easy to master; 71.97% (95/132) thought it was simple, convenient and easy to operate; 49.24% (65/132) thought that the standard evaluation results were consistent with the actual improvement of patients, and 50.75% (67/132) thought that it was generally consistent; 72.73% (96/132) thought that the design was scientific, reasonable and feasible. When using the scoring method of joint dysfunction index, more than 90% of the technicians thought that the five index terms of "joint rest pain", "joint movement pain", "morning stiffness", "maximum walking distance" and "limb activity ability" were easy to understand and ask questions. When patients with Kashin-Beck disease were investigated, the constituent ratios of easy to understand the five index terms were 96.21% (127/132), 83.33% (110/132), 90.15% (119/132), 78.79%(104/132), 90.15%(119/132) and the constituent ratios of easy to answer were 95.45% (126/132), 83.33% (110/132), 89.39% (118/132), 75.00% (99/132) and 89.39% (118/132), respectively.Conclusions:The new standard terms are clear, the design is scientific and reasonable, the operation is convenient and the feasibility is strong. The evaluation results are basically consistent with the actual improvement of patients. It is suggested to add objective evaluation indexes to the scoring method of joint dysfunction index.

Objective:To explore the effect of health education on drinking-water-borne endemic fluorosis in Gansu Province, and provide evidence for further development of health education measures.Methods:In 2011-2013, 2016 and 2017, using prospective method, 16-19 drinking-water-borne endemic fluorosis counties (cities, districts) were selected as project counties in Gansu Province each year, and 3 townships (towns) were selected in each project county. To carry out public health education activities on prevention and treatment of drinking-water-borne endemic fluorosis, school health education activities were carried out in the classes of grade 4-6 in the central primary school; 3 administrative villages were selected in each township (town) to carry out community health education activities. Before and after the health education activities, questionnaire surveys on health education of drinking-water-borne endemic fluorosis prevention knowledge were conducted among 30-50 students of grade 5 in the central primary school and 15-30 housewives lived near the schools in each township (town). Comparative analysis of the effects of health education activities was carried out.Results:The total awareness rates of prevention and treatment of drinking-water-borne endemic fluorosis in students of grade 5 and housewives were 89.55% (28 164/31 452) and 86.61% (14 976/17 292) after the intervention, respectively, which were significantly higher than those before the intervention [53.40% (16 518/30 933) and 51.88% (8 925/17 202)], and the differences were statistically significant (χ 2=1 586.16, 4 886.16, P < 0.05). Among the primary school students and housewives, the knowledge awareness rates of prevention and treatment of drinking-water-borne endemic fluorosis were increased by 36.15% and 34.73%, respectively. Conclusions:After implementation of drinking-water-borne endemic fluorosis health education intervention, the awareness rates of prevention and treatment knowledge in primary school students and housewives in Gansu Province are significantly increased. However, there are still weakness such as shortage of primary health education staff and insufficient investment in work funds, which means we can further expand the scope of health education.

Objective:To spread the knowledge of Keshan disease prevention and control, enhance the awareness of disease prevention among the population in the diseased areas, and provide the basis for formulating scientific intervention strategies for health education of Keshan disease.Methods:From October 2017 to April 2018, 10 counties (districts) with Keshan disease were selected as project counties(districts) in Gansu Province, and 3 towns were selected in each project county (district). To carry out Keshan disease health education activities in grade 4 - 6 of each township (town) central primary school, 3 villages were selected in each township to carry out community health education activities. We carried out 6-month propaganda on knowledge of Keshan disease prevention and control among pupils and residents, distributed health education materials and held lectures. Before and after the intervention, we conducted a questionnaire survey on health education among the target population (residents under 50 and primary school students in Grade 5), evaluated the improvement level of knowledge about keshan disease, and made statistical analysis.Results:Four hundred and fifty residents were investigated pre intervention and 451 residents post intervention, the awareness rate of Keshan disease prevention and control knowledge among residents in the diseased areas increased from 45.4% (2 041/4 500) before intervention to 79.5% (3 584/4 510) after intervention (χ 2 = 1 115.9, P < 0.05). Nine hundred and forty-eight pupils were investigated before intervention and 906 pupils (primary school students in Grade 5) after intervention, the awareness rate of Keshan disease prevention and control knowledge among pupils increased from 50.8% (4 818/9 480) before intervention to 84.2% (7 631/9 060) after intervention (χ 2 = 2 343.3, P < 0.05). Conclusion:The comprehensive intervention mainly based on health education can significantly improve the awareness rate of prevention and treatment knowledge of Keshan disease among primary school students and residents, and improve their bad life style, which is of great significance to the prevention and treatment of Keshan disease.