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 distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

Objective:To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

Objective:To explore the effect of discharge preparation service based on timing theory on the care readiness and benefit finding of caregivers for elderly dementia patients.Methods:From January 2021 to December 2022, 100 caregivers of elderly dementia patients from the Neurology Department and Rehabilitation Department of Jingjiang People's Hospital were selected as the subject by convenient sampling. Caregivers were divided into a control group and a study group based on their enrollment time, with 50 cases in each group. The control group received routine nursing, while the study group was treated with discharge preparation services based on timing theory. The effect was evaluated using the Caregiver Preparedness Scale (CPS) and Caregiver Benefit Finding Questionnaire.Results:After intervention, the CPS score of the study group was (22.80±2.83), which was higher than the control group's (17.92±2.60), and the difference was statistically significant ( P<0.05). After three months of discharge, the score of the Caregiver Benefit Finding Questionnaire in the study group was (117.50±6.25), which was higher than the control group's (109.98±9.89), and the difference was also statistically significant ( P<0.05) . Conclusions:The discharge preparation service based on timing it right can improve the care readiness and benefit finding of caregivers for elderly dementia patients.

Objective:To investigate the effect of adenovirus-mediated short hairpin RNA (shRNA) downregulating SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) on the apoptosis of human hepatic stellate cells LX-2 cultured in vitro.Methods:The recombinant adenovirus Ad-shRNA/SHP2 carrying shRNA targeted SHP2 and expressing green fluorescent protein (GFP), and the empty control virus Ad-GFP expressing GFP were transfected into LX-2 cells cultured in vitro. Real-time fluorescence quantitative PCR was used to detect SHP2 mRNA expression in LX-2 cells. Western blot was used to detect the protein expressions of SHP2, Bax, and Bcl-2 in LX-2 cells. TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry were used to detect apoptosis in LX-2 cells. Experimental group: (1) Control group: LX-2 cells were transfected with DMEM instead of adenovirus; (2) Ad-GFP group: transfected with empty virus Ad-GFP; (3) Ad-shRNA/SHP2 group: transfected with recombinant adenovirus Ad-shRNA/SHP2. The means between multiple groups were compared using a one-way ANOVA and the LSD test was used for inter group comparisons.Results:shRNA-targeted SHP2 significantly down-regulated the expression of SHP2 protein and mRNA in LX-2 cells ( P < 0.05). The TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry results showed that the apoptosis rate of LX-2 cells in the Ad-shRNA/SHP2 group (12.755%±1.606%, 19.340%±2.505%) ( P < 0.05) was significantly higher compared to the control group (3.077%±0.731%, 9.438%±0.804%) and the Ad-GFP group (3.250%±0.851%, 8.893%±1.982%), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Western blot analysis of Bax and Bcl-2 protein expression in LX-2 cells of each group revealed that the Bax protein expression was significantly higher in the Ad shRNA/SHP2 group (2.493 ± 0.203) ( P < 0.05) compared to the control group and Ad-GFP group (1.989 ± 0.147, 1.999 ± 0.162), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05), while the Bcl-2 protein was significantly decreased in the Ad-shRNA/SHP2 group (1.042±0.148) compared with the control group and the Ad-GFP group (1.707±0.146, 1.521±0.142), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Conclusions:SHP2 expression down-regulation induces apoptosis of human hepatic stellate cells LX-2 in vitro by reducing Bcl-2/Bax.

Objective: To improve the N biomarker in the amyloid/taueurodegeneration system by radiomics and study its value for predicting cognitive progression in individuals with mild cognitive impairment (MCI). Materials and Methods: A group of 147 healthy controls (HCs) (72 male; mean age ± standard deviation, 73.7 ± 6.3 years), 197 patients with MCI (114 male; 72.2 ± 7.1 years), and 128 patients with Alzheimer’s disease (AD) (74 male; 73.7 ± 8.4 years) were included. Optimal A, T, and N biomarkers for discriminating HC and AD were selected using receiver operating characteristic (ROC) curve analysis. A radiomics model containing comprehensive information of the whole cerebral cortex and deep nuclei was established to create a new N biomarker. Cerebrospinal fluid (CSF) biomarkers were evaluated to determine the optimal A or T biomarkers. All MCI patients were followed up until AD conversion or for at least 60 months. The predictive value of A, T, and the radiomics-based N biomarker for cognitive progression of MCI to AD were analyzed using Kaplan-Meier estimates and the log-rank test. Results: The radiomics-based N biomarker showed an ROC curve area of 0.998 for discriminating between AD and HC. CSF Aβ42 and p-tau proteins were identified as the optimal A and T biomarkers, respectively. For MCI patients on the Alzheimer’s continuum, isolated A+ was an indicator of cognitive stability, while abnormalities of T and N, separately or simultaneously, indicated a high risk of progression. For MCI patients with suspected non-Alzheimer’s disease pathophysiology, isolated T+ indicated cognitive stability, while the appearance of the radiomics-based N+ indicated a high risk of progression to AD. Conclusion We proposed a new radiomics-based improved N biomarker that could help identify patients with MCI who are at a higher risk for cognitive progression. In addition, we clarified the value of a single A/T/N biomarker for predicting the cognitive progression of MCI.

Objective To explore the formulation and adjustment of nutritional therapy by nutrition support pharmacists in patient with acute prerenal failure complicated with urinary tract infection, and to provide a reference for nutritional therapy in such patient. Methods With nutrition support pharmacists participated in nutrition treatment management and case analysis of a patient with acute prerenal failure complicated with urinary tract infection, we explored the nutritional support treatment plan for this type of patient. Results Nutrition support pharmacists provided pharmaceutical care throughout the course for patient with acute prerenal failure and designed an individualized low-calorie and high-protein nutritional support treatment according to the change of patient's condition, to increase the patient's serum albumin level and maintain at 35 g/L, at the same time the infection was effectively controlled and the creatinine value decreased to normal. Conclusion Small-volume, low-calorie, high-protein nutritional support solution ≤1 000 ml, calorie intake is about 1, 000 kcal, and protein is maintained at 1.2 g/(kg·d) throughout the course of acute prerenal renal failure with urinary tract infected patients can obtain better clinical outcomes and prognosis, and can better maintain clinical operability, and fully improve the safety, effectiveness and economics of nutritional support treatment.

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.

Objective:To explore the application and effect of detailed nursing in atelectasis children undergoing bronchoscopy.Methods:From January to December 2017, we selected 100 atelectasis children with bronchoscopy in Respiratory Department of Tangshan Maternity and Child Health Care Hospital. All patients were divided into control group and observation group with the method of random number table, 50 cases in each group. Control group carried out the routine nursing, while observation group received the detailed nursing. We compared the success rates of bronchoscope, compliances of children, incidence of complications, operation time of bronchoscopy and satisfaction of family members on nursing between two groups.Results:The success rate of bronchoscope, compliance of children, satisfaction and treatment comfort in observation group were higher than those in control group; the incidence of complications and operation time of bronchoscopy in observation group were lower than those in control group; the differences were all statistically significant ( P<0.05) . Conclusions:Application of detailed nursing in atelectasis children undergoing bronchoscopy can effectively improve the compliance of children, reduce the incidence of postoperative complications and increase the satisfaction of family members of children which is conducive to successful implementation of bronchoscopy.

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.