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.

This study was performed to explore the effects of berberine(BBR)and berbamine(BA)on the apoptosis and activity of eosinophils,and to provide new ideas for the treatment of eosinophil-related diseases.Anticoagulated whole blood was taken from hospitalized patients,and eosinophils were purified by magnetic bead sorting technology,and the cell purification rate was compared by using flow cytometry.The purified eosinophils were cultured and stimulated with different concentrations of BBR and BA,and the apoptosis of eosinophils was observed using immunofluorescence microscopy.Flow cytometry was used to detect the apoptosis rate,reactive oxygen species(ROS)release,mitochondrial membrane potential,and CD11b,CD62L and CD63 molecular expression of eosinophils.Data showed that 10 μmol/L BBR displayed significant anti-apoptosis effect on eosinophils at 18 h,24 h,48 h,however,100 μmol/L and 150 μmol/L BBR displayed significant apoptosis-promoting effects on eosinophils at 24 h,48 h,especially in the early stage.BA at 5 μmol/L,15 μmol/L and 25 μmol/L showed significant apoptosis-promoting effects on eosinophils at 24 h,48 h,especially in the late stage.In eosinophils,BA stimulated the production of ROS and the decrease of mitochondrial membrane potential in a concentration-dependent manner,reaching the maximum effect at 25 μmol/L,while BBR stimulation did not change mitochondria and ROS.Pretreatment with 25 μmol/L BA significantly inhibited the increase of CD11b expression and the decrease of CD62L expression in eosinophils after eotaxin-2 stimulation.In conclusion,berberine has a bidirectional regulatory effect on the quantity of eosinophils,while berbamine promotes eosinophil apoptosis and inhibits eosinophil activation.Both compounds hold significant potential for regulating the progression of eosinophil-associated diseases,and their regulatory mechanisms need further investigation.

Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB). Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115 patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,GeneXpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS). Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%. Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

The wide use of crystalline silicon solar cells in the field of new energy is an important boost for China to achieve the environmental protection goal as soon as possible. However, the production and manufacturing processes of these cells give rise to various occupational hazards at workplace, thus posing health risks to workers. This review provided an overview of production processes of crystalline silicon solar cells, the characteristics of occupational health hazards (productive dust; physical factors, productive toxicant) and proposed occupational protection suggestions.

The wide use of crystalline silicon solar cells in the field of new energy is an important boost for China to achieve the environmental protection goal as soon as possible. However, the production and manufacturing processes of these cells give rise to various occupational hazards at workplace, thus posing health risks to workers. This review provided an overview of production processes of crystalline silicon solar cells, the characteristics of occupational health hazards (productive dust; physical factors, productive toxicant) and proposed occupational protection suggestions.

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.

Objective:To investigate the efficacy and safety of AcoStream peripheral thrombus aspiration system combined with catheter-directed thrombolysis in the treatment of lower extremity deep vein thrombosis.Methods:The clinical data of 16 lower extremity deep vein thrombosis cases treated with AcoStream peripheral thrombus aspiration system combined with catheter-directed thrombolysis, admitted to the authors′ hospital from May 2022 to November 2022, were retrospectively analyzed. The differences in circumferential diameter between the affected limb and the healthy side, venous patency score, thrombus clearance grade and intraoperative blood loss were observed and compared. The Villalta score was used during the follow up. Paired sample t-test and Wilcoxon rank sum test were used to compare the changes in the observed indicators before and after treatment to evaluate the efficacy. Results:Treatment were successfully performed in all patients. Before treatment, the circumference differences between the affected and unaffected thighs and calves were (3.69±0.97) and (3.34±0.75)cm, respectively, the venous patency score of the affected side was 8(7.25,9) points. After treatment, the circumference differences between the affected and unaffected thighs and calves were (0.81±0.68) and (0.84±0.70)cm, respectively. The venous patency score of the affected side was 1(0,1)points, with statistically significant differences ( P<0.001). Grade Ⅲ thrombus clearance was achieved in 7 patients, grade Ⅱ thrombus clearance was achieved in 9 patients. The average blood loss during thrombus aspiration was (133.1±12.0) ml. Following up for 6 months, the Villalta score was 0(0,1.75) points. Conclusion:Acostream peripheral thrombus aspiration system combined with catheter-directed thrombolysis is safe and effective for the treatment of lower extremity deep venous thrombosis, with satisfactory short-term efficacy and high clinical application value.

Objective:To design a new jaw-lifting auxiliary tool and explore its effect in painless bronchoscopy.Methods:From January to December 2023, convenience sampling was used to select 160 patients who underwent painless bronchoscopy at the Endoscopy Center of the First Hospital of Jiaxing as subjects. The subjects were divided into an experimental group ( n=80) and a control group ( n=80) using a random number table method. During painless bronchoscopy, the experimental group used a new jaw-lifting auxiliary tool to open the airway, while the control group used traditional manual methods to open the airway. Two groups were compared patient oxygen saturation at different time points, and bronchoscopy passage time through the glottis. Results:The number of cases in which blood oxygen saturation <95% occurred at different time points in the experimental group was lower than that in the control group (all P<0.05). The time for bronchoscopy to pass through the glottis in the experimental group was shorter than that in the control group, and the difference was statistically significant [ (2.86±0.69) s vs. (3.20±0.96) s, P<0.05] . Conclusions:Using a new jaw-lifting auxiliary tool during painless bronchoscopy can reduce the decreased oxygen saturation in patients and shorten the time for bronchoscopy to pass through the glottis. It can be further promoted and applied in clinical practice.

Purpose/Significance To investigate and analyze the current status and influencing factors of digital health literacy(DHL)of the elderly,and to provide references for relevant departments.Method/Process The eHEALS scale is used to investigate the DHL status of 419 elderly people aged 60 and above in Shanghai through convenience sampling,and the influencing factors are explored through binary logistic regression analysis.Result/Conclusion Low education,smoking,and health anxiety are risk factors,while regular physical exami-nation is protective factor.Relevant departments should focus on the elderly people with lower education,and strengthen research and edu-cation on health examinations,smoking hazards,and the alleviation of anxiety.