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 the effects of dapagliflozin on inflammatory cytokines, blood glucose control and cardiac function in elderly with preserved ejection fraction heart failure (HFpEF) combined with type 2 diabetes. Methods A total of 80 elderly HFpEF patients with type 2 diabetes mellitus were randomly divided into control group (40 cases) and study group (40 cases). The control group received hypoglycemic and anti-heart failure standard therapy, and the study group received hypoglycemic and anti-heart failure standard therapy and dapagliflozin therapy. Both groups were treated for 6 months. The levels of inflammatory factors, blood glucose control, myocardial markers, exercise endurance [6 min walking distance (6MWD)], cardiac ultrasound related indexes and adverse drug reactions were compared between the two groups. Results After 6 months of treatment, serum interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP) and tumor necrosis factor (TNF)-α in the study group were significantly lower than those in the control group (P<0.05); the glycated hemoglobin (HbA1c), fasting blood glucose (FPG), amino terminal B-type brain natriuretic peptide precursor (NT-proBNP) and hypersensitive troponin (hs-TNT) of the study group were significantly lower than those of the control group (P<0.05); the 6MWD and left ventricular ejection fraction (LVEF) of the study group were higher than those of the control group, and the left ventricular end-diastolic diameter (LVEDD), right atrial and right ventricular diameter, left atrial and left ventricular diameter, right ventricular wall thickness and pulmonary artery pressure of the study group were significantly lower than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion The use of dapagliflozin in the treatment of elderly HFpE patients complicated with type 2diabetes can effectively control their blood sugar level, reduce inflammation, improve exercise endurance, and improve patients' heart function without increasing adverse drug reactions.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Objective:To explore the molecules mechanism of Pin1 in severe heat stroke induced acute lung injury by observing Pin1 regulate oxidative stress and apoptosis formation in pulmonary microvascular endothelial cells (PMVECs) and lung tissue in heat stressed mice.Methods:In vitro, a PMVECs heat stress (HS) model was established. In the control group, PMVECs were placed in a standard 37 °C, 5% CO 2 cell incubator; in the HS group, PMVECs were placed in a 43 °C cell incubator for 2 h, then the cells were further incubated at 37 °C for 1, 3, 6 or 12 h. PMVECs were pretreated with Pin1 inhibitor Juglone (1 μmol/L) 1 h before 43 °C of HS. In vivo, a severe heat stroke mouse model was established. In the HS group, the mice were kept at the simulation of climate chamber with temperature (35.5±0.5) °C, humidity (60±5)%, the rectum temperature in mice was measured by the anal rectal temperature table, when the temperature reached 42 °C, the heat exposure was stopped, and the mice were sacrificed at 1, 3, 6 or 12 h after HS. In the control group, the mice were kept at room temperature (25±0.5) °C. Mice received daily intraperitoneal administration of Pin1 inhibitor Juglone (1 mg/kg) for 3 d before HS. The protein level of Pin1, cleaved caspase-9 and cleaved caspase-3 were analyzed by Western blot, the level of O 2-˙ in cells was observed by DHE staining and fluorescence microscopy, the levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in lung tissue were measured by ELISA, the pathological changes of mice in different group were detected by HE staining, and the expression of Pin1 in the lung tissue of different groups was detected by immunohistochemical staining, the apoptosis rate of the lung tissue in different groups was tested by TUNEL staining. Results:At 1 h after HS, the protein expression of Pin1 in PMVECs and lung tissue began to increase in a rewarming time-dependent manner ( F=771.6, P<0.05; F=1 035, P<0.05). Cleaved caspase-9 protein in PMVECs and lung tissue started to increase at 3 h post-HS, then increased with a rewarming time-dependent manner ( F=729.8, P<0.05; F=1 773, P<0.05). The protein expression of cleaved caspase-3 in PMVECs and lung tissue also started to increase at 3 h after HS and the expression continued to be increased with prolonged rewarming time, and the trend was consistent with cleaved caspase-9 ( F=1 084, P<0.05; F=1 252, P<0.05). In addition, HS induced the increased release of O 2-˙ from PMVECs, HS induced the imbalance of oxidation-antioxidant system in lung tissue of mice after HS which verified by the continuous release of MDA ( F=114.2, P<0.05) and the continuous inhibition of SOD activity ( F=99.15, P<0.05). Compared with the HS group, pretreatment with Pin1 inhibitor Juglone in PMVECs and mice before HS significantly inhibited the protein expression of Pin1, cleaved caspase-9 and cleaved caspase-3 (all P<0.05), pretreatment with Pin1 inhibitor greatly reduced the release of O 2-˙ in PMVECs after HS, and promoted the restore of the oxidation-antioxidant system balance of lung tissue in mice with severe heat stroke. In addition, compared with the HS group, inhibiting the expression of Pin1 significantly decreased HS induced MDA release [(11.53±0.84) nmol/mL vs (9.65±0.69) nmol/mL, t=12.52, P<0.05], promoted the restore of SOD activity [(41.18±3.45) U/mL vs (57.52±4.83) U/mL, t=5.57, P<0.05] and improved the pathological damage of lung tissue as well as decreased the occurrence of apoptosis in post-HS mice. Conclusion:It was confirmed that Pin1 is involved in heat stress induced acute lung injury mainly through mediating oxidative stress response and apoptosis.

OBJECTIVE：To optimize the primary processing technology of Gentiana rigesce ns. METHODS ：HPLC method was adopted for content determination of loganic acid ，swertiamarin and gentiopicroside in G. rigescens ，and overall desirability value （OD value ） of the contents of above 3 components was taken as index to carry out single factor test on blanching temperature，blanching time and drying temperature. Based on that ，Box-Behnken design-response surface methodology was used to optimize primary processing technology of G. rigescens . Validation test was also performed. The samples prepared by optimized technology were compared with those dried in the shade. RESULTS ：The optimal primary processing technology of G. rigescens included blanching time of 5 min，blanching temperature of 40 ℃ and drying temperature of 60 ℃. Validation test showed that the average OD value of the 3 components was 0.565 2，with a deviation of 0.94％ from the predicted value （0.570 6）. Compared with samples dried in the shade ，OD value of 3 components in samples prepared by optimized technology were increased significantly ， indicating the quality of the samples prepared by the optimized technology was better. CONCLUSIONS ：The optimal technology is stable and feasible ，and can be used for the primary processing of G. rigescens .

The pneumonia caused by the novel coronavirus (2019-nCoV), which began in December 2019, has become the most serious public health problem, threatening people's health and life. This threat is posing a severe challenge on the diagnosis and treatment of 2019-nCoV infection, the prevention and control of hospital cross infection of medical staff. It is suggested that in addition to strengthening the organization and leadership of the abovementioned work, establishing and improving the prevention and control mechanism deserve greater attention. Furthermore, special attention should be given to the safety of the medical staff, strengthening their infection monitoring and outbreak management. Medical staff in different work areas and positions should be placed under careful protection, cleaning and disinfection measures. The protection during specimen collection, transportation and medical waste management should also be prioritized. This paper also put forward management suggestions for the outpatient department, isolation ward and other key departments. These measures are proposed to provide a guidance for the prevention and control of 2019-nCoV nosocomial infection in the pediatric outpatient and ward.

Objective:APOBEC3B (A3B) is an important member of the apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) family. The study aims to investigate the relationship between A3B expression and prognosis as well as resistance to cisplatin in non-small cell lung cancer (NSCLC).Methods:Real-time quantitative polymerase chain reaction (qRT-PCR) was used to analysis the A3B mRNA expression in 40 NSCLC tissues; Kaplan Meier plotter was used to analyse the correlation between A3B expression and clinical prognosis; in addition, the knock-down A3B expression cell line in human lung adenocarcinoma cell A549 was constructed; MTS and plate cloning experiment were performed to observe the changes in cell cisplatin sensitivity, and γ-H2AX immunofluorescence was used to quantitate the DNA damage.Results:Compared with adjacent tissues, A3B was highly expressed in NSCLC tissues (27/40). Kaplan Meier plotter analysis showed that A3B expression was positively correlated with NSCLC overall survival (OS) [adenocarcinoma: HR=0.64(0.47-0.86), P=0.002 6; squamous cell carcinoma: HR=0.77(0.59-1.01), P=0.006]. Cell-based studies showed that the knock-down A3B expression contributed to sensitivity to cisplatin in A549 cells. Conclusions:A3B mediates the sensitivity of lung cancer to cisplatin. This effect may partly explain why NSCLC patients with high A3B expression have a better prognosis.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

The epidemic of COVID-19 has become the topmost public health threat worldwide. The authors suggested that in addition to strengthening the organization and leadership of the abovementioned work, greater attention be paid to establishing and improving the prevention and control mechanism.Furthermore, special efforts should be given to the safety of the medical workers, by strengthening their infection monitoring and outbreak management. Medical workers in different work areas and positions should be placed under careful protection with due cleaning and disinfection measures. The protection during specimen collection, transportation and medical waste management should also be prioritized. Such special issues in the management of pediatric patients, as allocation of nurses, the screening and management of caregivers, the problem of breastfeeding, and the disinfection of children′s toys and diapers were discussed. This paper also put forward management suggestions for the outpatient department, isolation ward and other key departments, which aim to guide the prevention and control of COVID-19 nosocomial infection in the pediatric outpatient and ward.

AIMS: This study focused on the newest evidence of the relationship between forest environmental exposure and human health and assessed the health efficacy of forest bathing on the human body as well as the methodological quality of a single study, aiming to provide scientific guidance for interdisciplinary integration of forestry and medicine. METHOD: Through PubMed, Embase, and Cochrane Library, 210 papers from January 1, 2015, to April 1, 2019, were retrieved, and the final 28 papers meeting the inclusion criteria were included in the study. RESULT: The methodological quality of papers included in the study was assessed quantitatively with the Downs and Black checklist. The methodological quality of papers using randomized controlled trials is significantly higher than that of papers using non-randomized controlled trials (p < 0.05). Papers included in the study were analyzed qualitatively. The results demonstrated that forest bathing activities might have the following merits: remarkably improving cardiovascular function, hemodynamic indexes, neuroendocrine indexes, metabolic indexes, immunity and inflammatory indexes, antioxidant indexes, and electrophysiological indexes; significantly enhancing people's emotional state, attitude, and feelings towards things, physical and psychological recovery, and adaptive behaviors; and obvious alleviation of anxiety and depression. CONCLUSION Forest bathing activities may significantly improve people's physical and psychological health. In the future, medical empirical studies of forest bathing should reinforce basic studies and interdisciplinary exchange to enhance the methodological quality of papers while decreasing the risk of bias, thereby raising the grade of paper evidence.