Objective:To investigate the effects of influenza A virus(IAV)on macrophages based on expression of cytokines mediated by Janus kinase/signal transducer and activator of transcription(JAK/STAT)pathway,and to further explore the intervention effects of Ma Xing Shigan decoction drug containing serum.Methods:RAW264.7 was divided into control group,JAK/STAT signal pathway activator group,inhibitor group,model group,oseltamivir group,antiviral granule group and Ma Xing Shigan decoction group.Cell samples were collected after the intervention of IAV and subsequent treating of drug-containing serum for 24 and 48 hours.Secretion levels of IL-1β and CXCL2 in supernatant were detected by ELISA.mRNA expression levels of influenza virus Nuclear Pro-tein(NP),JAK1/2 and STAT1 of cells were detected by RT-qPCR.Protein expression levels of JAK1/2 and STAT1 were detected by Western blot,and protein expression levels of p-STAT1 was detected by immunofluorescence.Correlation between protein expression levels of p-STAT1 and secretion of IL-1β and CXCL2 were evaluated by Pearson correlation analysis.Results:Secretion levels of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2,STAT1,protein levels of JAK1/2,STAT1 and p-STAT1 were increased,and protein levels of p-STAT1 was positively correlated with the secretion of IL-1β and CXCL2.Ma Xing Shigan decoction could down-regulate secretions of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2 and STAT1,protein expression levels of JAK1,JAK2,STAT1 and p-STAT1.Conclusion:Activation of JAK1/2-STAT1 signal pathway and imbalance of inflammatory factors may be one of the molecular mechanisms of immunopathological damage of macrophages induced by IAV.Ma Xing Shigan decoction may alle-viate pathogenic effects of IAV by regulating this signal pathway.

Objective:To investigate the effects of influenza A virus(IAV)on macrophages based on expression of cytokines mediated by Janus kinase/signal transducer and activator of transcription(JAK/STAT)pathway,and to further explore the intervention effects of Ma Xing Shigan decoction drug containing serum.Methods:RAW264.7 was divided into control group,JAK/STAT signal pathway activator group,inhibitor group,model group,oseltamivir group,antiviral granule group and Ma Xing Shigan decoction group.Cell samples were collected after the intervention of IAV and subsequent treating of drug-containing serum for 24 and 48 hours.Secretion levels of IL-1β and CXCL2 in supernatant were detected by ELISA.mRNA expression levels of influenza virus Nuclear Pro-tein(NP),JAK1/2 and STAT1 of cells were detected by RT-qPCR.Protein expression levels of JAK1/2 and STAT1 were detected by Western blot,and protein expression levels of p-STAT1 was detected by immunofluorescence.Correlation between protein expression levels of p-STAT1 and secretion of IL-1β and CXCL2 were evaluated by Pearson correlation analysis.Results:Secretion levels of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2,STAT1,protein levels of JAK1/2,STAT1 and p-STAT1 were increased,and protein levels of p-STAT1 was positively correlated with the secretion of IL-1β and CXCL2.Ma Xing Shigan decoction could down-regulate secretions of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2 and STAT1,protein expression levels of JAK1,JAK2,STAT1 and p-STAT1.Conclusion:Activation of JAK1/2-STAT1 signal pathway and imbalance of inflammatory factors may be one of the molecular mechanisms of immunopathological damage of macrophages induced by IAV.Ma Xing Shigan decoction may alle-viate pathogenic effects of IAV by regulating this signal pathway.

Objective To analyze the development trajectory and predictors of endocrine therapy associated arthralgia in breast cancer patients.Methods From January 2022 to July 2022,breast cancer patients in the breast medicine department or outpatients of a tertiary cancer hospital in Hunan Province were selected as respondents using a convenience sampling method.A baseline survey was conducted using the General Information Questionnaire,the Symptom Assessment Scale for Patients Treated with Endocrine Therapy for Breast Cancer,and the Self-Rating Anxiety Scale within 1 week prior to patient treatment.The Symptom Assessment Scale for Patients Treated with Endocrine Therapy for Breast Cancer was used to assess patients'arthralgia levels at 3,6,and 9 months after treatment,and data were analyzed using growth mixed model,univariate analysis of variance,and multiple logistic regression.Results A total of 418 breast cancer patients completed the follow-up,with 235 cases(56.22%)developing arthralgia.3 potential categories of arthralgia develop-ment trajectories were identified:high level-slowly increasing group(11.48%),low level-slowly increasing group(44.74%),and asymptomatic group(43.78%).The results of multifactorial analysis showed that anxiety,history of bone and joint disease,sleep duration,place of residence,monthly household income,and frequency of exercise were predictors of potential categories for the development of trajectory of arthralgia levels associated with endocrine therapy in breast cancer patients(P<0.05).Conclusion Arthralgia levels associated with endocrine therapy in breast cancer patients exhibit different trajec-tories,and clinical staff should emphasize the assessment and intervention of pain levels in patients with the anxiety,a history of bone and joint disease,poor sleep,poor finances,living in urban areas,and low frequency of exercise.

ObjectiveTo study the characteristics of animal models of acute lung injury caused by non-physical factors， so as to provide a reference for the standardization of the preparation of such animal models and lay a foundation for the research on the pathogenesis and the diagnosis and treatment of acute lung injury. MethodThe articles about the animal experiments of acute lung injury published in the last decade were retrieved from China National Knowledge Infrastructure （CNKI）， Wanfang， SinoMed， VIP， and PubMed with the theme terms of "acute lung injury" and "animal model". The animal species， drugs used in modeling， modeling period， methods used in molding， model standards， and model evaluation indicators were summarized， and Excel was used for the frequency analysis. ResultA total of 338 articles were included in this study. The results of the frequency analysis showed that SD rats/C57BL/6 mice were mainly used to establish the animal models of acute lung injury. Male mice were mostly used for modeling， and the commonly used modeling agent was lipopolysaccharides （LPS）. In most cases， the modeling lasted for 6 h after drug administration. Hematoxylin-eosin staining was mainly used for the observation of histological changes in the lungs， which were taken as the criteria for modeling. The established models were mainly evaluated based on lung dry/wet weight ratio， lung index， morphological changes in the lung tissue， myeloperoxidase （MPO）， superoxide dismutase （SOD）， and levels of inflammatory cytokines in the serum and bronchoalveolar lavage fluid （BALF）. ConclusionThe models of acute lung injury were mostly prepared by intraperitoneal injection of LPS （5 mg·kg^-1） in SD rats and tracheal instillation of LPS （5 mg·kg^-1） in C57BL/6 mice， which were praised for the simple operation， high success rate， and consistent with the pathogenesis of acute lung injury. This study provides a reference for the basic research on acute lung injury by animal experiments.

Objective To investigate the risk factors for non-curative resection after endoscopic submucosal dissection ( ESD ) for early esophageal cancer and high-grade intraepithelial neoplasia .Methods The clinicopathological data of 427 cases of early esophageal cancer and high-grade intraepithelial neoplasia who underwent ESD was performed from January 2013 to December 2016 in the Department of Gastroenterology , First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed .According to the results of postoperative pathology and immunohistochemistry ,339 patients were defined as curative resection group and 88 patients were defined as non-curative resection group .Chi-square test , univariate analysis and multivariate logistic regression analysis were used for statistical analysis .Results A total of 427 patients were enrolled in this study, with an average age of (63.2 ±7.7) years, including 96 cases of early esophageal cancer and 331 cases of high-grade intraepithelial neoplasia .The enbloc resection rate of ESD was 94.8％(405/427), 88 of them were non-curative resected, and the non-curative resection rate was 20.6％.Univariate analysis showed that early esophageal cancer (odds ratio (OR)=3.682, 95％confidence interval (CI) 2.216 to 6.118, P<0.01), submucosal infiltration (OR=10.220, 95％CI 4.861 to 21.481, P<0.01), ESD indications (OR=6.005, 95％CI 3.545 to 10.172, P<0.01) and lifting sign after injecting at the base of lesions (OR=2.508, 95％CI 1.005 to 6.255, P=0.042) were statistically significant between non-curative resection group and curative resection group . Multivariate unconditional logistic regression analysis revealed that submucosal infiltration (OR =4.329, 95％CI 1.758 to 10.661,P =0.001), not absolute indications of ESD (OR =6.484, 95％CI 2.205 to 19.068, P=0.001) and negative lifting sign (OR=3.182, 95％CI 1.171 to 8.651, P=0.023) were independent risk factors for non-curative resection.Conclusions Patients with early esophageal cancer , submucosal infiltration , not absolute indications for ESD and negative lifting signs are prone to non-curative resection .Moreover , submucosal infiltration , not absolute indications for ESD , and negative lifting signs are the independent risk factors for non-curative resection .

Objective: To explore the relationship between genotype and phenotype of ABCB11 deficiency. Methods: Clinical data of two siblings with ABCB11 deficiency were retrospectively analyzed. Related literature from PubMed, CNKI and Wangfang databases was reviewed to date (up to August 2017) with 'ABCB11 gene’ or 'bile salt export pump’, 'cholestasis’ and 'child’ as key words. Results: The patients were siblings. Both of them presented as jaundice, pruritus and hepatosplenomegaly since 3 days after birth. Significant laboratory findings on admission of the older sister included high total bilirubin, 170 µmol/L;conjugated bilirubin, 115.8 µmol/L;alanine aminotransferase, 168 U/L;total bile acid 186.3 µmol/L and normal gamma-glutamyl transpeptidase. While routine laboratory data of the younger brother were as follows: total bilirubin, 148.8 µmol/L;conjugated bilirubin, 96.3 µmol/L;alanine aminotransferase, 232.8 U/L;total bile acid 226 µmol/L, and normal gamma-glutamyl transpeptidase.Both received ursodeoxycholic acid and fat-soluble vitamins. Liver pathology of the younger brother showed giant hepatocytes with ballooning degeneration, focal necrosis and intrahepatic cholestasis. Both the patients harbor the same compound heterozygous mutations in ABCB11 gene, c.145C>T (p.Q49X) and c.1510G>A (p.E504K). The sister is 9 years old now, with normal liver function. Jaundice faded around 3 months after birth, pruritus relieved at age 5, and medications was stopped since then. The brother progressed to liver failure after an operation on perianal abscess when he was 8-month-old, and received living-related liver transplantation when he was 9 month and 20 days old (from his mother). Now he is 1 year and 5 months old, with normal liver function. Both are under our follow-up. Literature review revealed 18 ABCB11 deficiency patients from 7 families who had apparent different prognoses, within each family the siblings had the same ABCB11 gene mutation. Seven cases relieved after ursodeoxycholic acid therapy and/or partial external biliary diversion, 5 received orthotopic liver transplantation, 2 developed hepatocellular carcinoma and 4 cases died in childhood. Conclusions The clinical manifestations of ABCB11 deficiency may vary greatly in patients carrying the same genotype, even in siblings. Patients should be managed in individualized maner.

Objective: To investigate the effect of local autologous dermal fibroblasts transplantation on hypertrophic scar formation and wound healing quality in early scar formation. To explore the feasibility of fibroblasts for prevention and treatment of hypertrophic scar. Methods: Dermal fibroblasts were isolated from the dorsal skin tissue of New Zealand white rabbits by mechanical method combined with enzyme digestion. Passage 3 cells were induced to differentiate into osteoblasts and adipocytes. The complete epithelialization time and hypertrophic scar formation after full-thickness skin defect were confirmed by pre-experiment study. In the experiment, 6 rabbits were used, left ear as experimental group and right ear as control group. In the experimental group, the passage 4 dermal fibroblasts labeled with 5-bromodeoxyuridine (5-BrdU) were injected subcutaneously around the wound and hypertrophic scar on 20 d (day 2 after epithelialization) and 30 d (most obvious scar hyperplasia) after surgery. As a control group, physiological saline was injected following the same protocol. On 37 days after surgery, the hypertrophic scar tissue were harvested and assessed by gross view and histological examination. The transplanted cells were detected by immunofluorescence staining, transforming growth factor beta 1 (TGF-β1) and decorin(DCN) mRNA expression were assayed by real-time fluorescence polymerase chain reaction (RT-PCR), and the protein expression of TGF-β1、DCN、Collagen type Ⅰ and type Ⅲ were tested by enzyme linked immunosorbent assay(ELISA). Results: Compared with the control group, the scar in the experimental group was flatter and softer, the color was slightly lighter, and the volume was reduced. The histological results showed that compared with the control group, the number of fibroblasts and inflammatory cells in the superficial dermis was reduced, the proliferation of connective tissue and collagen deposition were reduced, and the basal cells and collagen fibers were arranged in order in the experimental group. The results of RT-PCR showed that TGF-β1 mRNA expression level in the hypertrophic scar tissue reduced significantly and DCN increased significantly in the experimental group, compared with the control group (P<0.01). ELISA results showed that TGF-β1, type Ⅰ and Ⅲ collagen contents in hypertrophic scar tissue were significantly lower than that in the control group, while the DCN expression was significantly increased (P<0.01). Conclusions The rabbit dorsal dermal fibroblasts significantly inhibited the hypertrophic scar in rabbit ears. The mechanism may be related to the up-regulation of DCN expression and down-regulation of TGF-β1 expression, reduction of type Ⅰ and Ⅲ collagen synthesis and extracellular matrix deposition, in the hypertrophic scar tissue.

Objective To study the clinical efficacy of Bushen Huoxue Tongluo Recipe in the treatment of type 2 diabetes with hypertension, to provide more basis for clinical treatment.Methods64 patients with type 2 diabetes mellitus complicated with hypertension were selected in our hospital from July 2014 to November 2015.They were divided into two groups, each group was 32.The control group was treated with western medicine, the observation group was treated with Bushen Huoxue Tongluo recipe, and the therapeutic effects of the two groups were observed and compared.ResultsThe total effective rate of the two groups has significantly difference, and the incidence of complications of the two groups also has statistical difference (P<0.05).ConclusionThe treatment of Bushen Huoxue Tongluo recipein in type 2 diabetes with hypertension, has good effect, was very useful to change symptoms of patients, improve the clinical treatment effect of patients.It is conducive to the recovery of patient.

Objective To explore the effect of meropenem on the treatment of children with severe infection and the effect on the level of PCT.MethodsThe clinical data of patients with infectious diseases treated in our hospital from December 2013 to February 2016 were retrospectively analyzed.According to the anti infective drugs were divided into control group and observation group, the control group was given routine antibiotic treatment, the observation group was given meropenem treatment.The treatment effect of the two groups were observed, the difference of serum PCT, cytokine level and blood gas indexes before and after treatment in the two groups were compared, correlation analysis with PCT level and serum levels of inflammatory cytokines and blood indexes of severe infection.ResultsIn the control group, 50 cases were successful, the observation group was successful in the treatment of the patients, there were no significant differences in the success rate between the two groups.Two groups of patients before treatment PCT and inflammatory cytokines level no difference, after treatment, the observation group PCT, IL-18, IL-6 and hs-CRP levels were lower than the control group;Two groups of children before treatment blood gas index no difference, after treatment, the observation group SpO2 level higher than the control group, P ETCO2 level was lower than the control group.PCT levels in children with severe infection were positively correlated with IL-18, IL-6, hs-CRP and P ETCO2 levels and negatively correlated with SpO2 levels.ConclusionMeropenem has better therapeutic effect in the treatment of children with severe infection, can significantly reduce the serum PCT level, has the value of clinical application.

Objective To investigate the effect of apatinib on the proliferation,apoptosis and migration of pancreatic cancer cell line AsPC-1 in vitro.Methods Pancreatic cancer AsPC-1 cells were treated by apatinib in different concentrations.Cell proliferation and apoptosis were measured by CCK-8 and flow cytometry,and the effect of apatinib on cell migration ability was observed by wound healing assay.Results In control and 10,20,30,40 and 50umol/L apatinib treatment group,the inhibitory rates of AsPC-1 cells were 0,(1.45 ±0.68)％,(16.92±0.70)％,(23.84±0.84)％,(34.35±1.55)％ and (37.33± 0.81) ％,respectively.Cell proliferation was obviously inhibited by apatinib as the concentration increased,and the differences were statistically significant (P ＜ 0.05).In control and 20,40 umol/L apatinib treatment group,the apoptotic rates were (9.44 ± 0.18) ％,(16.62 ± 0.19) ％ and (25.42 ± 0.41) ％,respectively.Number of apoptotic cells was obviously increased by apatinib as the concentration increased,and the differences were statistically significant (P ＜ 0.05).In control and 20,40 umol/L apatinib treatment group,the migration ability was (29.5 ± 0.7) ％,(17.4 ± 0.9) ％ and (6.6 ± 0.5) ％,which was greatly decreased as the concentration increased,and the differences were statistically significant (P ＜ 0.05).Conclusions Apatinib can effectively inhibit the proliferation and migration of pancreatic cancer AsPC-1 cells and induce apoptosis.