To provide theoretical and practical basis for the successful formulation design of physically-mixed inhalation dry powder of proteins and peptides, related references were collected, analyzed and summarized. In this review drug micronization technology and commonly used carriers for inhalation dry powder preparation were introduced. For proteins and peptides, supercritical fluid technology and spray-drying are more suitable because of their capabilities of keeping drug activity. Being approved by U. S. Food and Drug Administration, lactose has been extensively used as carriers in many inhalation products. Formulation and process factors influencing drug deposition in the lung, including carrier properties, drug-carrier ratio, blending order, mixing methods, mixing time and the interaction between drug and carrier, were elucidated. The size, shape and surface properties of carries all influence the interaction between drug and carrier. Besides, influence of micromeritic properties of the dry powder, such as particle size, shape, density, flowability, charge, dispersibility and hygroscopicity, on drug deposition in the lung was elaborated. Among these particle size plays the most crucial role in particle deposition in the lung. Moreover, based on the mechanisms of powder dispersity, some strategies to improve drug lung deposition were put forward, such as adding carrier fines, adding adhesive-controlling materials and reprocessing micronized drug. In order to design physically-mixed inhalation dry powder for proteins and peptides with high lung deposition, it is essential to study drug-carriers interactions systematically and illustrate the potential influence of formulation, process parameters and micromeritic properties of the powder.

Using high pressure homogenization method combined with spray-drying, budesonide-loaded chitosan microparticles were prepared and the in vitro release profile was investigated. The microparticles were then blended with lactose using a vortex mixer, influence of mixing speed, mixing time on drug recovery rate and content homogeneity were investigated. Meanwhile, influence of lactose content on drug recovery rate, content homogeneity, powder flowability and in vitro deposition were studied. It turned out that budesonide was released from the microparicles in a sustained manner, with fine particle fraction as high as 46.0%, but the powder flowability was poor. After blending with 10 times of lactose, the drug recovery rate was 96.5%, with relative standard deviation of drug content 2.5%, and fine particle fraction of the formulation increased to 59.6% with good flowability. It's demonstrated that using a vortex mixer, budesonide sustained-release dry powder for inhalation with good recovery and content homogeneity could be prepared, the formulation had good flowability and was suitable for pulmonary inhaling.

Objective:To evaluate the application of visual feedback coaching method, which is embedded in an optical surface monitoring system, in deep inspiration breath holding during the radiotherapy in left breast cancer patients after breast-conserving surgery.Methods:Thirty patients with left breast cancer, who were scheduled to receive the whole breast radiotherapy after breast-conserving surgery, met the requirements of deep inspiration breath holding after respiratory coaching with the visual feedback coaching module in the optical surface monitoring system. Active breathing control equipment was used to control breath-holding state and CT simulation was performed. During treatment, optical surface monitoring system was used to guide radiotherapy. All patients were randomly divided into two groups. In group A ( n=15), visual feedback respiratory training method was utilized and not employed in group B ( n=15). In group A, the visual feedback coaching bar of the optical surface monitoring system was implemented, while audio interactive method was employed to guide patients to hold their breath. Real-time data of optical body surface monitoring were used to compare the interfraction reproducibility and intrafraction stability of breath holding fraction between two groups. Besides, the number of breath holding and treatment time per fraction were also compared. GraphPad prism 6.0 software was used for data processing and mapping, and SPSS 21.0 software was used for analyzing mean value and normality testing. Results:Compared with the control group, the reproducibility in the experiment group was reduced from 1.5 mm to 0.7 mm, the stability was reduced from 1.1 mm to 0.8 mm, the mean number of breath holding required per fraction was decreased from 4.6 to 2.4, the mean beam-on time per fraction from 336 s to 235 s, and the treatment time per fraction was shortened from 847 s to 602 s (all P<0.05), respectively. Conclusions:The application of visual feedback coaching method can improve the reproducibility and stability of breath holding during radiotherapy for left breast cancer, and it can also effectively reduce the number of breath holding and shorten the treatment time per fraction.

Objective To analyze the changes of serum markers of liver function and liver fibrosis in patients with fatty liver,and to explore the relationship between them,so as to provide scientific basis for the prevention and treatment of fatty liver into hepatic fibrosis. Methods From January 1st,2015 to December 31st, 2015,one thousand three hundred and forty-six healthy cases were selected,and 361 cases of fatty liver were diagnosed by ultrasound. Liver function index of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected by automatic biochemical analyzer. Hyaluronic acid (HA),laminin (LN),serum type Ⅲprocollagen peptide ( PC Ⅲ) and type Ⅳ collagen ( C-Ⅳ) were detected by enzyme-linked immunosorbent assay. The correlation between liver function and serum liver fibrosis indexes was analyzed by Pearson parameter analysis. Results The liver function index ALT,AST((69. 04±18. 72) U/L,(59. 78±15. 65)U/L) in fatty liver group were higher than those in the non-fatty liver group((25. 71±10. 25) U/L,(23. 68±8. 23) U/L),the differences were statistically significant ( t＝279. 283,388. 461,P＜0. 05) . Four serum fibrosis index HA,LN, PCⅢ,C-Ⅳ in the fatty liver group were (112. 64±21. 63) μg/L,(125. 85±27. 52) μg/L,(127. 28±29. 37) μg/L,(79. 38±18. 52) μg/L,respectively,which were higher than those in the non-fatty liver group ( (53. 98 ±16. 84) μg/L,(86. 31±20. 46) μg/L,(53. 31±18. 23) μg/L,(57. 26±15. 86 ) μg/L),the differences were statistically significant ( t＝727. 724,170. 432,941. 357,71. 169,P＜0. 001) . The correlation analysis of liver function and serum liver fibrosis indexes showed that ALT and AST were positively correlated with the fibrosis indexes HA,LN,PCⅢ( correlation coefficient r＝0. 230,0. 119,0. 370;0. 363,0. 361,0. 509,P＜0. 001),and which had no significant correlation with C-Ⅳ(P＞0. 05). Conclusion Liver function and serum liver fibrosis index can be used as the important basis for monitoring and diagnosis on the progression of fatty liver disease.

Objective:To explore the influencing factors of the long-term quality of life(QOL).Methods:According to the standard of diagnosis of primary lung cancer, a total of 74 patients with primary lung cancer were included in the study, who were first diagnosed by pathology and /or cytology and /or clinic from 1 January 2010 to 30 June 2016 in Tangshan Third Hospital, Heibei Province, and whose data were analyzed retrospectively.The Chinese version of FACT-L (4.0) QOL questionnaire was used to evaluate the QOL in 74 patients with primary lung cancer who survived more than three years.Multivariate regression statistical method was used to analyze the main influencing factors.Results:All patients with long-term survival lung cancer were treated by operation, their average QOL score was ( 126.62±13.29). Age, type of medical insurance and clinical stage had significant influence on QOL ( P<0.05). There was no significant difference in the total QOL scores between<50-year-old group(138.18±13.92) and ≥50-<60-year-old group(138.18±13.92, 137.04±12.82)(all P>0.05), but they were higher than that in ≥60-year-old group (115.28 ±13.11) (all P<0.05). The QOL of residents′ medical insurance patients (117.92 ±13.13) was lower than that of employees′ medical insurance patients (142.69±13.07) ( t=10.849, P=0.002). The QOL scores of stage Ⅰ and Ⅱ (140.34 ±12.88, 133.31±12.07) had no significant difference, but which were higher than that of stage III (96.84 ±13.46) ( P<0.05). Conclusion:Patients with long-term survival lung cancer after surgery could maintain a better QOL by early detection, timely surgery and constantly improving the medical security system to reduce the financial burden of patients.

Vascular cognitive impairment(VCI)includes a range of illnesses from mild cognitive impairment to dementia,attributable to cerebrovascular factors.Although appropriate animal models are needed to allow clinicopathological research and drug development,there are currently no animal models that can perfectly simulate the pathogenesis of VCI.At present,carotid artery and vertebral artery stenosis or occlusion are the main method for VCI modeling;however,increasing numbers of non-surgical method have recently emerged,providing new ideas and prospects for the study of this disease.In this paper,we consider the construction method,model mechanisms,and model characteristics of non-surgical animal models of VCI,to provide a reference to help researchers choose the most suitable animal model.

Objective To explore the categories of dyadic mental health literacy among stroke patients and their caregivers,and to analyze the differences in the characteristics of different classes of stroke patients and their caregivers.Methods A convenient sampling method was used to select 287 dyads of stroke patients and their caregivers who were treated at a tertiary general hospital in Henan province from July to October 2020.The general information questionnaire,Multicomponent Mental Health Literacy and Social Support Rating Scale were used for investigation.Latent profile analysis was adopted to explore the categories of dyadic mental health literacy,and multiple logistic regression was used to analyze the influencing factors of each category.Results Stroke patients and their caregivers were divided into 4 categories based on scores of mental health literacy:dyadic low resource group(19.86％),dyadic low literacy group(54.36％),dyadic low belief group(11.15％),dyadic high literacy group(14.63％).The patient's age,average monthly household income,the caregiver's age,the caregiver's Social Support Rating Scale score,the caregiver's educational level,daily care time and total time length of care were the factors influencing the categories of dyadic mental health literacy among stroke patients and their caregivers(P＜0.05).Conclusion Stroke patients and their caregivers were divided into 4 categories based on scores of mental health literacy.Medical staff should carry out comprehensive psychological interventions for stroke patients and their caregivers with different dyadic mental health literacy characteristics,so as to improve dyadic mental health literacy.

Objective To test the immune therapeutic effects of PICKCa adjuvant rabies vaccine for the post-exposure mice and beagle dogs and immune memory effect for human.Methods For the mice and beagle dogs first to infect with rabies wild virus and then immunize with PICKCa rabies vaccine.For volunteers, first to immunize with PICKCa rabies vaccine after 2.5 years to take peripheral blood mononuclear cell and then to check cells secreted interferon-gwith flow cytometry. Results In 3 independent assays of post-explosure immunization of mice and beagle dogs PICKCa rabies vaccine were much better then commercial adjuvant-free rabies vaccines, the protective rate from 20%-30%to 70%-100%Also, in the assay of cells secreted IFN-γby peripheral blood mononuclear cells from volunteers immunized by PICKCa rabies vaccine the IFN-γcell levels were much higher than control.Conclusions Compared with commercial adjuvant-free rabies vaccines the PICKCa rabies vaccine had significant immune therapeutic effects in the mice and dogs.Also PICKCa rabies vaccine had good immune memory effect in human.

Objective:To observe the short-and mid-term efficacy of left subclavian artery(LSA) laser in situ fenestration combined with arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection aged 60 years and above. Methods:This is a retrospective cohort study. A total of 41 Stanford type A aortic dissection patients aged 60 years and above who received combined surgery in Department of Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed. There were 25 males and 16 females, aged (67.3±5.9)years(range: 60 to 75 years). Among them, 19 patients underwent LSA laser in situ fenestration combined with arch debranching surgery(combined surgery group) and 22 patients underwent hybrid aortic arch debranching surgery(non-combined surgery group). Independent sample t test, χ2 test and Fisher exact probability method were used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used for survival analysis, and the 5-year survival rate of the two groups was compared by Log-rank test. Results:Body mass index in the combined operation group was significantly higher than that in the non-combined operation group ((27.1±1.6)kg/m 2vs.(26.9±1.9)kg/m 2; t=2.766, P=0.006), and the difference was statistically significant. There was no statistical significance in the comparison of other general data (all P>0.05). The operation time ((321.3±11.4) minutes vs. (329.6±7.3)minutes; t=-2.733, P=0.010) and LSA reconstruction time ((32.4±3.0)minutes vs. (42.4±6.0)minutes; t=-6.842, P<0.01) in the combined operation group were significantly shortened, and the difference was statistically significant. The rate of LSA reconstruction in the combined operation group (100% vs. 72.7%; P=0.023) was significantly higher than that in the non-combined operation group, and the difference was statistically significant. There were no significant differences in the incidence of pulmonary infection, unplanned second operation, continuous renal replacement therapy, neurological complications and the in-hospital mortality between the two groups. Compared with the non-combined surgery group, the total complication rate related to LSA reconstruction was significantly lower in the combined surgery group (0 vs. 27.3%; P=0.023). Kaplan-Meier survival analysis showed that there was no difference in 5-year survival rate between the combined operation group and the non-combined operation group (84.2% vs. 77.3%; χ2=0.310, P=0.578). Conclusion:Laser in situ fenestration of the LSA combined with arch debranching surgery to reconstruct the aortic arch can significantly shorten the operation and LSA reconstruction time in patients aged 60 years and above with Stanford type A aortic dissection, improve the success rate of LSA reconstruction, and reduce the occurrence rate of LSA reconstruction complications.

Objective:To observe the short-and mid-term efficacy of left subclavian artery(LSA) laser in situ fenestration combined with arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection aged 60 years and above. Methods:This is a retrospective cohort study. A total of 41 Stanford type A aortic dissection patients aged 60 years and above who received combined surgery in Department of Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed. There were 25 males and 16 females, aged (67.3±5.9)years(range: 60 to 75 years). Among them, 19 patients underwent LSA laser in situ fenestration combined with arch debranching surgery(combined surgery group) and 22 patients underwent hybrid aortic arch debranching surgery(non-combined surgery group). Independent sample t test, χ2 test and Fisher exact probability method were used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used for survival analysis, and the 5-year survival rate of the two groups was compared by Log-rank test. Results:Body mass index in the combined operation group was significantly higher than that in the non-combined operation group ((27.1±1.6)kg/m 2vs.(26.9±1.9)kg/m 2; t=2.766, P=0.006), and the difference was statistically significant. There was no statistical significance in the comparison of other general data (all P>0.05). The operation time ((321.3±11.4) minutes vs. (329.6±7.3)minutes; t=-2.733, P=0.010) and LSA reconstruction time ((32.4±3.0)minutes vs. (42.4±6.0)minutes; t=-6.842, P<0.01) in the combined operation group were significantly shortened, and the difference was statistically significant. The rate of LSA reconstruction in the combined operation group (100% vs. 72.7%; P=0.023) was significantly higher than that in the non-combined operation group, and the difference was statistically significant. There were no significant differences in the incidence of pulmonary infection, unplanned second operation, continuous renal replacement therapy, neurological complications and the in-hospital mortality between the two groups. Compared with the non-combined surgery group, the total complication rate related to LSA reconstruction was significantly lower in the combined surgery group (0 vs. 27.3%; P=0.023). Kaplan-Meier survival analysis showed that there was no difference in 5-year survival rate between the combined operation group and the non-combined operation group (84.2% vs. 77.3%; χ2=0.310, P=0.578). Conclusion:Laser in situ fenestration of the LSA combined with arch debranching surgery to reconstruct the aortic arch can significantly shorten the operation and LSA reconstruction time in patients aged 60 years and above with Stanford type A aortic dissection, improve the success rate of LSA reconstruction, and reduce the occurrence rate of LSA reconstruction complications.