In the era of precision medicine,integrating radionuclide-based molecular imaging with targeted internal radiotherapy,integrated theranostics of nuclear medicine emerged as a promising and rapidly advancing field to achieve both visualization and precise treatment of tumors.The advances of commonly used and emerging radiotheranostic agents in oncology were systematically reviewed in this article.

Allergen specific immunotherapy（AIT）, as an effective treatment for allergic rhinitis, asthma, and other allergic diseases, has received widespread attention in the field of health economic evaluation in recent years. This article reviews the current status and progress of economic research on AIT, mainly discussing the socioeconomic burden of allergic rhinitis, the results of health economic studies from different countries, and the primary methods used in health economic research on allergic rhinitis. Existing studies indicate that, although AIT involves high initial costs, it offers significant long-term economic benefits by reducing healthcare resource utilization, improving patient quality of life, and decreasing medication dependence. Moreover, reducing initial costs, applying standardized assessment tools, and conducting cross-national comparative analyses have become key directions for future research. Overall, AIT demonstrates strong potential in terms of long-term health benefits and cost savings, providing solid economic evidence for the management of allergic diseases.
Humans ; Desensitization, Immunologic/economics* ; Cost-Benefit Analysis ; Rhinitis, Allergic/economics* ; Economics, Medical

Objective:To explore the molecular mechanism of miR-4508 regulating the inflammatory response of human bronchial epithelial cells induced by representative chrysotile asbestos.Methods:The chrysotile asbestos was ground into ultrafine dust using a horizontal planetary instrument, and human bronchial epithelium (16HBE) cells were taken as the object of infection. Cell survival rate was detected by cell counting kit-8 method, cytotoxicity was detected by lactate dehydrogenase (LDH) kit. The released of inflammatory factor IL-6 was detected by electrochemical luminescence. The released inflammatory factor IL-8 was detected by enzyme-linked immunosorbent assay. The expression level of miR-4508 was screened and verified by reverse transcription-quantitative real-time polymerase chain reaction. After 16HBE cells were treated with AKT inhibitor MK2206, the phosphorylation levels of AKT and PTEN were detected by western blot. The expression levels of AKT and PTEN and the contents of IL-6 and IL-8 were detected in miR-4508 overexpression and interference experiments.Results:With the increase of chrysotile asbestos exposure concentration, the cell survival rate decreased in a concentration-dependent manner, and the LDH content gradually increased. The secretion of IL-6 and IL-8 in chrysotile 25, 50 and 75 μg/ml groups were (325.92±8.61) pg/ml, (331.51±4.96) pg/ml, (378.74±13.77) pg/ml, and (94.95±3.11) pg/ml, (357.60±1.80) pg/ml, (537.19±3.11) pg/ml, respectively, while the group with 0 μg/ml chrysotile was (95.85±1.20) pg/ml and (7.81±0.00) pg/ml ( P＜0.05). In addition, chrysotile asbestos exposure to 16HBE could induce the high expression of miR-4508 . After pretreatment with MK2206, the phosphorylation levels of AKT and PTEN were decreased, the contents of IL-6 and IL-8 were significantly decreased, and the expression level of miR-4508 was significantly reduced. Overexpression of miR-4508 significantly increased the expressions of AKT and PTEN, and the contents of IL-6 and IL-8 ( P＜0.01). After interfering with miR-4508, the expressions of AKT and PTEN were significantly decreased, and the contents of IL-6 and IL-8 were significantly decreased ( P＜0.01). Conclusions:Chrysotile asbestos can induce the inflammatory response of 16HBE cells and up-regulate the expression level of miR-4508. The up-regulation of miR-4508 promotes the 16HBE inflammatory response induced by chrysotile asbestos through the PI3K/AKT pathway.

In the era of precision medicine,integrating radionuclide-based molecular imaging with targeted internal radiotherapy,integrated theranostics of nuclear medicine emerged as a promising and rapidly advancing field to achieve both visualization and precise treatment of tumors.The advances of commonly used and emerging radiotheranostic agents in oncology were systematically reviewed in this article.

Objective:To explore the molecular mechanism of miR-4508 regulating the inflammatory response of human bronchial epithelial cells induced by representative chrysotile asbestos.Methods:The chrysotile asbestos was ground into ultrafine dust using a horizontal planetary instrument, and human bronchial epithelium (16HBE) cells were taken as the object of infection. Cell survival rate was detected by cell counting kit-8 method, cytotoxicity was detected by lactate dehydrogenase (LDH) kit. The released of inflammatory factor IL-6 was detected by electrochemical luminescence. The released inflammatory factor IL-8 was detected by enzyme-linked immunosorbent assay. The expression level of miR-4508 was screened and verified by reverse transcription-quantitative real-time polymerase chain reaction. After 16HBE cells were treated with AKT inhibitor MK2206, the phosphorylation levels of AKT and PTEN were detected by western blot. The expression levels of AKT and PTEN and the contents of IL-6 and IL-8 were detected in miR-4508 overexpression and interference experiments.Results:With the increase of chrysotile asbestos exposure concentration, the cell survival rate decreased in a concentration-dependent manner, and the LDH content gradually increased. The secretion of IL-6 and IL-8 in chrysotile 25, 50 and 75 μg/ml groups were (325.92±8.61) pg/ml, (331.51±4.96) pg/ml, (378.74±13.77) pg/ml, and (94.95±3.11) pg/ml, (357.60±1.80) pg/ml, (537.19±3.11) pg/ml, respectively, while the group with 0 μg/ml chrysotile was (95.85±1.20) pg/ml and (7.81±0.00) pg/ml ( P＜0.05). In addition, chrysotile asbestos exposure to 16HBE could induce the high expression of miR-4508 . After pretreatment with MK2206, the phosphorylation levels of AKT and PTEN were decreased, the contents of IL-6 and IL-8 were significantly decreased, and the expression level of miR-4508 was significantly reduced. Overexpression of miR-4508 significantly increased the expressions of AKT and PTEN, and the contents of IL-6 and IL-8 ( P＜0.01). After interfering with miR-4508, the expressions of AKT and PTEN were significantly decreased, and the contents of IL-6 and IL-8 were significantly decreased ( P＜0.01). Conclusions:Chrysotile asbestos can induce the inflammatory response of 16HBE cells and up-regulate the expression level of miR-4508. The up-regulation of miR-4508 promotes the 16HBE inflammatory response induced by chrysotile asbestos through the PI3K/AKT pathway.

Background Chrysotile is widely used in construction and industry. Research has shown that it is associated with lung fibrosis in occupational groups, but the involvement of microRNAs (miRNAs) in chrysotile-induced lung fibrosis has been less well studied, and the specific mechanism is still unclear. Objective Using next-generation sequencing technology to analyze the effects of chrysotile exposure on the miRNAs expression profiles of human lung epithelial cells (BEAS-2B cells), to explore the variations of differentially expressed miRNAs and related signaling pathways, and to identify potential targets and molecular mechanisms of chrysotile-induced lung fibrosis. Methods Chrysotile was analyzed with a laser particle size analyzer and an X-ray diffractometer for particle size and physical phase. BEAS-2B cells were exposed to chrysotile for designed time sessions (12, 24, and 48 h) and doses (0, 50, 100, and 200 μg·mL⁻¹). Cell viability was detected with a cell viability assay kit (CCK8); expression levels of Fibronectin, Collagen-Ⅰ, and α-smooth muscle actin (α-SMA) were detected by Western blot after exposure to 200 μg·mL⁻¹ chrysotile for 24 h. Sample correlation and changes in miRNAs expression profiles between the chrysotile-exposed and the control groups were analyzed by next-generation sequencing technology. The target genes of differentially expressed miRNAs were predicted and subjected to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results The average particle size of the chrysotile dust sample used in this study was 3.58 μm, and the results of X-ray diffraction analysis confirmed the characteristic peaks of chrysotile. Compared with the control group, the chrysotile gradually inhibited the survival rate of BEAS-2B cells with increasing concentration and exposure time (P<0.01). The survival rates of the 50, 100, and 200 μg·mL⁻¹ chrysotile-exposed cells after 12 h exposure were 83.88%±1.86%, 78.07%±3.97%, and 71.95%±2.99%, respectively; the survival rates after 24 h exposure were 77.41%±1.58%, 69.57%±2.23%, and 62.79%±3.65%, respectively; the survival rates after 48 h exposure were 74.31%±4.93%, 65.84%±2.71%, and 52.74%±6.31%, respectively. The Fibronectin, Collagen-Ⅰ, and α-SMA protein expression levels were elevated in the 200 μg·mL⁻¹ chrysotile-exposed BEAS-2B cells (P <0.05). The results of principal component analysis showed that there were differences in the composition of the samples between the chrysotile exposure group and the control group, and a total of 163 differential miRNAs were screened, of which 79 were up-regulated and 84 were down-regulated. The results of GO analysis showed that the differential miRNAs were mainly associated with biological processes such as regulation of transcription by RNA polymerase II, regulation of DNA templated transcription, cellular differentiation, protein phosphorylation, lipid metabolism, and cell cycle, cellular components such as nucleus, cytomembrane, cytoskeleton, mitochondria, and endoplasmic reticulum, as well as molecular functions such as protein binding, metal ion binding, transferase activity, and DNA binding. The results of KEGG analysis revealed that the differential miRNAs were mainly enriched in cancer pathway, phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) pathway, Ras-associated protein 1 (Rap1) pathway, calcium pathway, cyclic guanosine monophosphate/ protein kinase G (cGMP-PKG) pathway, Hippo pathway, cyclic adenosine monophosphate (cAMP) pathway, and Ras pathway. Conclusion Chrysotile exposure could significantly inhibit BEAS-2B cell survival, elevate the expression of lung fibrosis-associated proteins, and induce differential miRNAs expression, affecting biological processes (such as lipid metabolism, protein phosphorylation, and cell cycle) and cell components (such as mitochondria and endoplasmic reticulum), and interfering with PI3K/AKT pathway, Hippo pathway, cAMP pathway, Rap1 pathway, and Ras pathway.

Objective:To investigate the kinetic metrics of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 in pancreatic cancers and normal organs by using total-body PET dynamic imaging. Methods:From December 2020 to December 2021, 68Ga-FAPI-04 total-body PET/CT dynamic imaging were performed on 6 pancreatic cancer patients (3 males, 3 females, median age 55.5 years) in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Images were respectively analyzed. Manual delineations of volume of interests (VOIs) on multiple normal organs and pathological lesions were performed and time-to-activity curves (TACs) were generated. A reversible two-tissue compartment model (2TCM) was fitted for each tissue TAC. Rate constants including K1, k2, k3 and k4, and the total volume of distribution ( Vt) were obtained and compared by tissue types. Wilcoxon rank sum test and Spearman correlation analysis were used for data analysis. Results:Kinetic metrics varied significantly among normal organs and pancreatic cancer lesions ( z values: 2.00-1 240.00, all P<0.05). The highest K1 among lesions was observed in primary tumor (0.30 min -1), which was observed in the spleen (1.42 min -1) among normal organs. The highest k2 among lesions was observed in peritoneal metastases (0.24 min -1), which was observed in the spleen (2.59 min -1) among normal organs. Primary tumor showed the highest k3 of 0.17 min -1 among lesions, and the pancreas had the highest k3 of 0.16 min -1 among normal organs. Primary tumor had the highest k4 of 0.03 min -1 among lesions, and the heart, lungs, parotid glands had high k4(0.06 min -1) among normal organs. Vt were higher in pathological lesions compared to normal organs, with the highest in primary tumor (13.78 ml/cm 3). There were correlations between Vt in lesions and SUV mean( rs=0.86, P<0.001) or SUV max ( rs=0.77, P<0.001). Conclusion:The rate constants including K1, k2, k3 and k4, and Vt of 68Ga-FAPI-04 vary among normal organs and lesions.

Toxicological pathology is a morphological elucidatet ion of tissue damage caused by drug toxicity,including damage type,location,severity grade and prognosis.It provides objective and accurate data to support preclinical drug safety evaluation.Therefore,toxicological pathology plays an important role in drug safety evaluation,and the pathologic data or conclusion often determines the termination or continuation in many drug development projects.In this paper,the characteristic of toxicological pathology,standardized management,the development of new techniques including in situ hybridization,laser scanning cytometry and laser capture microdissection,and related problems in pathology are discussed briefly.

The immune system is a complex system involving multiple organs,and it is vulnerable to age,gender,environment and other factors.For a variation normal physiological range,it is a great challenge to evaluate drug-induced immunotoxicity in preclinical safety study.Histomorphologic assessment of the immune system is a recognized cornerstone in the identification of immunotoxicity at present.In this paper,the principles of pathological evaluation for immune system,and pathological evaluation for important immune organs including thymus,spleen,lymph nodes are discussed briefly,so that it is intended to assist toxicity pathologists in the accurate and consistent characterization of intended and unintended drug-induced alterations of the immune system.

OBJECTIVE:To provide reference for rational use of antibiotics in the clinic of our hospital. METHODS:Drug re-sistance of Gram-negative bacillus in the inpatients of our hospital were analyzed retrospectively during May 2013-Dec. 2015 as well as the situation of producing metallo-β-lactamase(MBLs). RESTUTS:A total of 2089 strains of Gram-negative bacillus were detected in our hospital during 2013-2015,among which there were 1456 strains of enterobacteria (69.70%) and 633 strains of non-fermentative bacteria,mainly involving Escherichia coli,Pseudomonas aeruginosa,Klebsiella pneumoniae,Acinetobacter bau-mannii and Enterobacter cloacae. A total of 406 strains of carbapenems-resistant bacteria were detected (19.44%),including 367 strains of non-fermentative bacteria and 39 strains of enterobacteria. The resistant rates of carbapenems-resistant strains to 16 antibi-otics were all higher than 50%,but those of non-carbapenems-resistant strains were in relative low level. Except for aztreonam,re-sistant rates of carbapenems-resistant strains to other 15 antbiotics were all higher than those of non-carbapenems-resistant strains, with statistical significance(P<0.05). A total of 36 strains of producing MBLs were detected(8.87%),including 13 strains of pro-ducing MBLs drug-resistant P. aeruginosa and 23 strains of producing MBLs drug-resistant A. baumannii;producing MBLs drug re-sistant enterobacteria had not been found. CONCLUSIONS:Gram-negative bacillus are mainly enterobacteria in our hospital;car-bapenems-resistant strains are mainly non-fermentative bacteria,resistant rate of them are commonly higher than that of non-drug-re-sistant strain. The situation of producing MBLs is serious,and enzyme producing strains are mainly non-fermentative bacteria. It is necessary to strengthen drug resistance of pathogen and enzyme producing strain monitoring,avoid the generation and spreading of drug-resistant strains due to irrational use of antibiotics.