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.

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.

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.

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.

Objective To evaluate the effect of extensive resection and immediate reconstruction based on classification of abdominal wall defects for patients with abdominal wall neoplasms.Methods From Jan 1999 to May 2016,112 patients with abdominal wall neoplasms were treated with extensive resection,including Type Ⅰ (n =20),Type Ⅱ (n =45) and Type Ⅲ (n =47).Immediate abdominal wall reconstruction comprised primary sutures or free skin graft for Type I defects,component separation (CST) with or without a prosthetic or biological mesh reinforcement for Type Ⅱ defects and pedicled or vascularized myocutaneous flap with or without a prosthetic or biological mesh or prosthetic + biological mesh with or without CST for Type Ⅲ defects.Results The average follow up was 76.86 ± 21.22 months,3 patients developed flap necrosis,9 patients suffered from wound infection.Local recurrence was observed in 20 patients,35 patients developed distant metastasis.Conclusions The optimal strategy based on the abdominal wall defect classification for immediate reconstruction of huge abdominal wall defects is safe and effective after resection of abdominal wall neoplasms.

Objective To apply DNA barcoding technology for exploring its taxonomic status and differences in the molecular biology of Cricetulus barabensis in Shaanxi Province.Methods Sixty-five samples of Cricetulus barabensis were collected from Dingbian,Jingbian Counties in northern of Shaanxi and Dali County in Guanzhong plain (Dingbian 58 samples,Jingbian 2 samples,and Dali 5 samples).According to the mitochondrial cytochrome C oxidase subunit I gene (CO I) sequence,the genetic distance was calculated and Neighbor-Joining tree was constructed.Results The genetic distance between two samples (13.16,13.21) and other 56 samples of Dingbian was 9.2％-10.0％.The genetic distance between the 56 samples of Dingbian and Jingbian was less than 1％ and Dali was 7.2％-8.3％;the average intraspecific genetic distance of Jingbian and Dali was less than 1％.The Neighbor-Joining tree showed that all the Cricetulus barabensis samples from the three counties were separated into two large branches.The samples of 13.16,13.21 from Dingbian together were classified into a class and the rest of the samples into another separate branch.At the same time,other samples from Dingbian except 13.16,13.21 and Jingbian were distributed in a small branch,and Dali samples were occupied another small branch.Conclusion Using the DNA barcoding technology,we have determined three subspecies of Cricetulus barabensis in Shaanxi Province,Dingbian has two kinds and Dali has a different subspecies.

OBJECTIVE:To observe clinical efficacy and safety of Ebastine tablet combined with Chushi zhiyang ointment in the treatment of hand keratinizing chapped eczema. METHODS:135 cases of hand keratinizing chapped eczema were divided into control group A(45 cases),control group B(43 cases)and treatment group(47 cases)according to treatment regimen. Control group A was orally given Ebastine tablet,10 mg each time,qd;control group B was given Chushi zhiyang ointment alone,twice a day,morning and evening,applying thin layer of ointment on the affected area;treatment group was given same dose of Ebastine tablet orally and applied Chushi zhiyang ointment on the affected area. 3 groups received treatment for consecutive 4 weeks. Clinical efficacies of 3 groups were observed as well as the scores of pruritus,skin lesion area,keratinization,rhagades and VAS before and after treatment. The occurrence of ADR was compared among 3 groups. RESULTS:The total effective rate of treatment group was 68.09%,which was significantly higher than that of group A(42.22%)and control group B(16.28%),with statistical significance(P<0.05). There was no statistical significance in the scores of pruritus,skin lesion area,keratinization,rhagades and VAS among 3 groups before treatment(P>0.05). After treatment,above scores of 3 groups decreased significantly,and those of treatment group were significant-ly lower than those of control group A and B,with statistical significance(P<0.05). There was no statistical significance in the inci-dence of ADR among 3 groups(P>0.05). CONCLUSIONS:Ebastine tablet combined with Chushi zhiyang ointment is effective for hand keratinizing chapped eczema,and can significantly improve the skin of patients with good safety.

Hospital-acquired conditions (HACs)are key to patient safety.This paper introduced a new classification system of HACs,the CHADx model,and described the principle and method of establishing the model as well as the problems found during its use.The model can provide a basis for studying the problem of incidence,causes and influence factors of hospital acquired conditions,so as to help medical institutions to explore the causes of HACs and to ensure patient safety and improve the quality of health care.

Objective To respectively investigate the impact of perioperative use of antibiotics on incision healing of simple upper limb closed fracture.Methods The study enrolled 124 patients with simple upper limb closed fracture treated from October 2012 to June 2013,including fracture of humerus (surgical neck,shaft,and supracondyla),fracture of forearm (ulna,olecranon,and radius)and fracture of metacarpus.The patients were allocated to non-antibiotic group (n =73) and antibiotictreated group (n =51) according to the random number table.Between-group analysis was made on body temperature,peripheral white blood cell count,C-reactive protein level,drainage fluid culture and incision healing.Results Sex,age,disease entity and operation time were similar between the two groups (P ＞ 0.05).Non-antibiotic and antibiotic-treated groups showed no significant differences in body temperature [preoperation:(36.50 ± 0.27) ℃ vs (36.70 ± 0.39) ℃ ; postoperation:(37.64 ± 0.37) ℃vs (37.41 ±0.41)℃],peripheral white blood cell count [preoperation:(6.1 ±1.0) × 109 mol/L vs (6.5 ±0.8) × 109 mol/L; postoperation:(12.1 ±0.7) × 109 mol/L vs (11.3 ±0.6) × 109mol/L] and C-reactive protein level [preoperation:(7.2 ±0.9)mg/L vs (6.7 ±0.7)mg/L; postoperation:(12.0 ± 1.3) mg/L vs (13.4 ±0.9)mg/L] (P ＞0.05).Incisional infection occurred in 1 case (1％) in non-antibiotic group,but none in antibiotic-treated group (P ＞ 0.05).Conclusions For simple upper limb closed fracture,perioperative use of antibiotic has advantages of slight trauma,short operation time and few bleeding.Likewise,satisfactory bone healing is achieved in the absence of antibiotics during perioperative period.