Background Silicosis, an occupational lung disease induced by chronic silica (SiO₂) exposure, is pathologically defined by progressive pulmonary fibrosis, and its associated molecular mechanisms are not yet fully elucidated. Objective To understand the critical role of macrophage-derived vesicles in silicotic pulmonary fibrosis via their carried complement component 1r (C1R). Methods Through integrated analysis of human plasma vesicle proteomics and spatial transcriptomics in silicosis mouse models, the key molecular C1R was identified in silicotic fibrosis. Spatial transcriptomic data were further employed to analyze the expression distribution of C1R in lung tissues. In animal experiments, a mouse silicosis model was established via tracheal instillation of silica dust, followed by pulmonary fibrosis assessed by Sirius Red staining, and C1R expression levels in plasma and lung tissue vesicles examined by Western blot. In cellular experiments, an in vitro model was constructed by stimulating macrophages with silica. Extracellular vesicles isolated from this system were then co-cultured with mouse lung fibroblasts (MLG),followed by intervention with a C1R-neutralizing antibody. Results The proteomic analysis of human plasma vesicles revealed a significant upregulation of C1R in silicosis patients, confirmed by Western blot. The spatial transcriptomics in silicotic mice indicated elevated C1R expression in lung tissues after 56 d of SiO₂ exposure, colocalizing with fibrotic lesions. The results of Western blot further demonstrated increased C1R levels in both lung tissue-derived and peripheral blood-derived vesicles during silicosis progression, consistent with the findings in an ex vivo macrophage model. The results of functional assays demonstrated that macrophage-derived vesicles significantly increased the expression of fibrosis markers, including fibronectin 1 (FN1), collagen type I alpha 1 (COL1A1), and alpha-smooth muscle actin (α-SMA), as well as the migratory capacity of lung fibroblasts; these effects were blocked by the C1R-neutralizing antibody. Conclusion Macrophage vesicles drive fibroblast activation and migration through C1R. Since a C1R-neutralizing antibody blocks this pro-fibrotic effect, C1R represents a key mediator in silicosis and thus is considered a new potential therapeutic target.

Inflammatory bowel disease(IBD)is an immune-mediated inflammatory disorder with high heterogeneity.The safety of its treatment,particularly adverse reactions,is a crucial area that physicians need to focus on.Currently,the biologic agents and small molecule drugs for treating IBD,such as anti-tumor necrosis factor-α agents,anti-integrin agents,interleukin(IL)-12/IL-23-targeting biologic agents,Janus kinase(JAK)inhibitors,and sphingosine-1-phosphate(S1P)receptor modulators,can induce both acute and chronic adverse reactions.Chronic adverse reactions mainly manifest as opportunistic infections,malignancies in different organs,especially lymphomas,as well as adverse reactions in the cardiovascular and nervous systems.The adverse reactions caused by the above-mentioned drugs exhibit both homogeneity and heterogeneity.Employing artificial intelligence(AI)techniques to summarize the patterns of biologic agents and small molecule drugs in the treatment of IBD and constructing models to predict the adverse reactions in heterogeneous individuals might be an important technological approach to enhance the safety of biologic treatments for IBD.This article reviews the research progress on the adverse reactions of biologic agents and small molecule drugs in the treatment of IBD.

Inflammatory bowel disease(IBD)is an immune-mediated inflammatory disorder with high heterogeneity.The safety of its treatment,particularly adverse reactions,is a crucial area that physicians need to focus on.Currently,the biologic agents and small molecule drugs for treating IBD,such as anti-tumor necrosis factor-α agents,anti-integrin agents,interleukin(IL)-12/IL-23-targeting biologic agents,Janus kinase(JAK)inhibitors,and sphingosine-1-phosphate(S1P)receptor modulators,can induce both acute and chronic adverse reactions.Chronic adverse reactions mainly manifest as opportunistic infections,malignancies in different organs,especially lymphomas,as well as adverse reactions in the cardiovascular and nervous systems.The adverse reactions caused by the above-mentioned drugs exhibit both homogeneity and heterogeneity.Employing artificial intelligence(AI)techniques to summarize the patterns of biologic agents and small molecule drugs in the treatment of IBD and constructing models to predict the adverse reactions in heterogeneous individuals might be an important technological approach to enhance the safety of biologic treatments for IBD.This article reviews the research progress on the adverse reactions of biologic agents and small molecule drugs in the treatment of IBD.

【Objective】 To investigate the compatibility of human albumin and its internal packaging materials of Sinopharm Lanzhou Biopharmaceutical Co., Ltd. 【Methods】 One batch of inner packaging materials (medium borosilicate glass-molded injection bottle and halogenated butyl rubber plug for injection) was extracted with 4 extraction solvents to conduct the toxicological evaluation of potential inner packaging extracts. Through the simulated acceleration test, the trend analysis of the elements in the sample and the inner surface of the glass bottle were observed, and the routine drug inspection items during the long-term stability test process were determined. 【Results】 The detection results of the leaching elements of the internal packaging materials did not exceed the limit of 50%, and the organic matter safety threshold (margin of safety, MOS) was greater than 1.0, indicating that both the leaching elements and the organic matter had no safety risk to the user under the current exposure. The results of the simulated acceleration test show that the drug will not have the risk of peeling tablets after the long-term stability condition was placed for a period of time, and the routine inspection items of the long-term stability test drugs all meet the requirements of the pharmacopoeia. 【Conclusion】 The inner packaging material has no significant impact on the quality of drugs and has good overall compatibility, making it suitable for packaging human albumin.

Objective:To describe the current status of registration and design characteristics of clinical trials of new drugs for curing hepatitis B through domestic and foreign websites, so as to provide references for the follow-up clinical trials of new hepatitis B drugs.Methods:A search was conducted on the US Clinical Trials Database and the Chinese Clinical Trial Registry Center. The search date was from the establishment of the database to May 26, 2020, and the registration trials of new drugs for curing hepatitis B at home and abroad were included. Two researchers independently searched and screened the literature and extracted the data.Results:A total of 106 registered clinical trials of new drugs for curing hepatitis B were included (94 English registration websites and 12 Chinese registration websites), and the number of registrations had increased year by year. Among them, the proportion of therapeutic vaccines and core protein inhibitors were the highest, accounting for 27.4% ( n = 29) and 22.6% ( n = 24), respectively. The vast majority of clinical trials ( n = 96, 90.6%) were in the early stages (Phase I and II). The subjects in phase I clinical trial were mainly healthy people and treated CHB patients, while the subjects in phase II clinical trial were mainly CHB patients who had achieved viral suppression after initial or post-treatment. The main evaluation indicators of Phase I clinical trials were the safety and tolerability of new drugs. The main evaluation indicators in about half of Phase II clinical trials were HBsAg negative conversion/quantitative decline. Overall, the number of clinical trials with the new design was small, accounting for 3.8% (4 / 106). There were relatively few trials of new drugs for curing hepatitis B on domestic registration websites, and the information provided was incomplete. Conclusion:The number of clinical trials of new hepatitis B drugs at home and abroad is increasing year by year, but most of them are in phase I and II, with few adopting new designs. In addition, the information integrity of the domestic website registration center needs to be improved.

Objective: To investigate the effects of family-integrated care (FIC) on postoperative outcomes in children with enterostomy and their caregivers. Methods: From August 2017 to August 2018, 50 children with enterostomy and 50 family members of the Children′s Hospital of Hunan Province were selected as subjects. According to the random number table, the children and their families were divided into control group and the observation group, each group was 25 cases. The control group was given a routine nursing mode to intervene, and the observation group was given an FIC mode for intervention. Postoperative outcomes were evaluated using the incidence of ostomy complications and readmission rates. The pre-intervention and outpatient follow-up were used to assess the psychological status of the family members using the Self-rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS), and to assess the postoperative care of the family's intestines using the postoperative evaluation of the postoperative intestines. The level of knowledge mastery. The self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were used to assess the psychological state of the family members, and the postoperative care knowledge evaluation form for the postpartum was used to evaluate the postoperative care of the family. Results: The incidence of ostomy complications in the observation group was 8.70% (2/23), which was lower than that in the control group (34.78% (8/23) (P<0.05). The readmission rate of the observation group was 0(0/23), which was lower than the control group 17.39% (4/23) (P<0.05). After intervention, the SAS scores and SDS scores of the families of the two groups were lower than those before the intervention, and the SAS scores and SDS scores of the observation group were lower than the control group(P<0.05). Before discharge and 3months of follow-up, the scores of postoperative care knowledge evaluation scores of the observation group were higher than those of the control group(P<0.05). Conclusions FIC mode can effectively reduce the incidence of complications and readmission rate in children with enterostomy. It has positive significance for improving the negative emotions of children′s family members and improving the mastery of postoperative care.

OBJECTIVE:To explore basic technology for synthesis of active ingredients of Ophiocordyceps xuefengensis,and provide necessary technical support for comprehensive development of O. xuefengensis sourse. METHODS:Submerged fermenta-tion method was used to cultivate the mycelium,achieving efficient synthesis of active ingredients by controlling medium composi-tion and cultivation conditions. Using the bacteria as starting strain,the effects of different carbon sources (sucrose,glucose and soluble starch),different nitrogen sources (peptone,yeast extract powder,yeast extract,sodium nitrate,potassium nitrate and urea),different vitamin B(vitamin B1 and vitamin B complex)and different initial pH(pH was set at 4,5,6,7,8 and 9,re-spectively)on mycelial growth,extracellular and intracellular polysaccharide synthesis,cordycepin synthesis and intracellular triter-penoid synthesis were investigated to screen the optimal medium composition. RESULTS:The optimal carbon source,nitrogen source,vitamin B and initial pH were sucrose,yeast extract powder,vitamin B1 and 8,respectively. High biomass and metabolite accumulation levels can be obtained when carbon source was sucrose,nitrogen source was yeast extract powder,adding 0.1 g/L vi-tamin B1 with initial pH of 8. CONCLUSIONS:O. xuefengensis can efficiently accumulate metabolites,and achieve the optimiza-tion of strain cell growth and synthesis of active metabolite by optimizing and controlling the fermentation process.

Objective To understand the distribution and change in drug resistance of common pathogens before and after the implementation of special rectification activity on antimicrobial use in 2011-2015,and provide guidance for clinical application of antimicrobial agents.Methods Antimicrobial use in hospitalized patients and pathogens isolated from patients in a hospital from 2011 to 2015 were collected,changing trend of resistance rates of major pathogens to commonly used antimicrobial agents was analyzed.Results From 2011 to 2015,antimicrobial utilization rate in hospitalized patients dropped from 75.84%to 37.35%,antimicrobial use density decreased from 59.53 per 100 patient days to 33.63 per 100 patient days,both showed a downward trend(both P<0.05).A total of 10 091 strains of pathogens were isolated,2 338(23.17%)of which were gram-positive bacteria,7 110(70.46%)were gram-negative bacteria,and 643(6.37%)were fungi.The top five pathogens were Escherichia coli(20.85%),Klebsiella pneumoniae(15.90%),Pseudomonas aeruginosa(11.70%),Staphylococcus aureus(7.35%),and Acinetobacter baumannii(6.82%).Resistance rates of major pathogens to commonly used antimicrobial agents decreased year by year(P<0.05),resistance rates of Escherichia coli and Klebsiella pneumoniae to piperacillin/tazobactam,cefoxitin,and amikacin declined most obviously(all<4%in 2015);compared with Acinetobacter baumannii,Pseudomonas aeruginosa had higher sensitivity to commonly used antimicrobial agents,resistance rates to piperacillin/tazobactam,cefoperazone/sulbactam,ceftazidime,cefepime,amikacin,and ciprofloxacin decreased obviously,resistance rate to above antimicrobial agents was <20%,to carbapenems was higher than other commonly used antimicrobial agents.Resistance rates of Acinetobacter baumannii to amikacin,levofloxacin decreased most obviously,to meropenem and imipenem increased obviously,in 2015 were both above 50%.Resistance rate of Staphylococcus aureus to fluoroquinolones declined most obviously(<2%),vancomycin-resistant strains were not found.Conclusion After the implementation of special rectification activity,resistance rates of common pathogens decreased with the decline of antimicrobial use,rational use of antimicrobial agents may be related to delaying bacterial resistance.

BACKGROUND:The cultivation of mammary gland stem cel s is of great significance for the development of mammary gland and breast cancer.
OBJECTIVE:To seek an easy method to isolate and culture mammary gland stem cel in vitro, and verify the safety of cel s.
METHODS:Mammary epithelial cel s were isolated from normal tissues surrounding breast cancer, and CD49f-and EPCAM-positive cel s were sorted using flow cytometry fol owed by surface marker analysis and cel colony formation ability analysis. Afterwards, real-time fluorescent quantitative PCR was used to detect C-erbB-2 and Maspin mRNA expression in mammary gland stem cel s, breast cancer tissues and normal tissues surrounding breast cancer.
RESULTS AND CONCLUSION:Human mammary gland stem cel s were successful y cultured and highly expressed CD49f and EPCAM, with the presence of mixed colony, pleural epithelial cel colony, and myoepithelial cel colony. c-erbB-2 was lowly expressed while Maspin highly expressed in mammary gland stem cel s. Our experimental findings indicate that the mammary gland stem cel s derived from normal tissue surrounding breast cancer have biological safety.