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Objective To analyze the prognostic factors in the patients with HER2-positive breast cancer adjuvant treated with trastuzumab. Methods We conducted a retrospective analysis of clinical data of 1 246 patients diagnosed with HER2-positive breast cancer between January 2009 and December 2019 who received treatment with trastuzumab. We investigated the factors impacting their prognosis by the Log-rank test univariate analysis and multivariate COX regression analysis. Results HER2-positive patients treated with trastuzumab had a poor prognosis in pT2-3(HR=2.10, P=0.003), pN2-3(HR=2.81, P

Objective To evaluate the safety of immediate breast reconstruction using deep inferior epigastric perforator (DIEP) flaps in the patients after neoadjuvant treatment. Methods From January 2019 to February 2021, the data of patients with breast cancer undergoing total mastectomy and immediate breast reconstruction using DIEP flap in Comprehensive Breast Health Center, Department of General Surgery, Ruijin Hospital were collected. Comparison of clinicopathological features was done between neoadjuvant treatment group and control group. Univariate analysis was used to compare the rate of surgical complications between two groups. Results A total of 110 patients were enrolled with 23 cases (20.9%) in neoadjuvant treatment group and 87 cases (79.1%) in control group. None of carcinoma in situ (0 vs. 19.5%, P=0.003) and higher pTNM stage (P

A history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle-treated controls. In separate studies, endothelial (EC)-specific WWOX knockout (KO) versus WWOX flox control mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31+ CD45-cells. These were grown in culture, confirmed to be WWOX deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing as well as an FITC dextran transwell assay for their barrier properties during methicillin-resistant Staphylococcus aureus or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to cells from WWOX flox controls during either methicillin-resistant S. aureus or LPS treatment as measured by both electric cell impedance sensing and the transwell assay. The increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.

Objective: To analyze the diagnosis, treatment and prognosis of breast cancer patients in Ruijin Hospital for further clinical management and study. Methods Non-metastatic breast cancer patients with surgical treatment in our hospital were included from January 2009 to December 2018. Clinicopathological features of enrolled patients and chan-ging trend of different surgery including breast conserving surgery and sentinel lymph node biopsy (SLNB) in the period of this study were analyzed. Kaplan-Meier curve analysis was used to compare 5-year and 10-year disease free survival (DFS) and overall survival(OS) of patients with different treatments. Results This study had 8 210 patients. There were 959 (11.7%) patients with in situ disease and 5 379(71.3%) patients with negative lymph node in 7 549 patients without neoadjuvant therapy. There were 949(12.6%) cases and 2964 (39.3%) cases with breast cancer at stage 0 and stage I, respectively. A total of 2377(29.0%) patients underwent breast conserving surgery with increase from 16.5% in 2009 to 34.8% in 2013. The patients with SLNB were 4149 cases (52.5%) from 0.6% in 2009 to 69.3% in 2018. All patients from 2009 to 2018 achieved complete follow-up with a median follow-up of 46 months: 5-year and 10-year DFS were 87.6% and 80.5%; 5-year and 10-year OS were 94.2% and 90.7%, respectively. There were 3800 patients with surgery followed from year 2009 to 2014 with a median-follow-up of 79 months: 5-year DFS rate and OS rate were 86.9% and 93.1%; 10-year DFS rate and OS rate were 79.1% and 88.4%, respectively. Conclusions Both rates of breast conserving surgery and SLNB in Ruijin Hospital increased in last 10 years. Patients had more than 93% of 5-year OS with modern treatment modality of breast cancer, which could indicate clinical management and research in future.

Subgroup J avian leukemia virus (ALV-J) and chicken infectious anemia virus (CIAV) are widely acknowledged as significant immunosuppressive pathogens that commonly co-infect chickens, causing substantial economic losses in the poultry industry. However, whether co-infection of ALV-J and CIAV have synergistic pathogenicity remains uncertain. To explore their synergistic pathogenesis, we established a co-infection model of ALV-J and CIAV in HD11 cells and specific-pathogen-free (SPF) chickens. We discovered that ALV-J and CIAV can synergistically promote the secretion of IL-6, IL-10, IFN-α, and IFN-γ and apoptosis in HD11 cells. In vivo, compared to the ALV-J and CIAV mono-infected group, the mortality increased significantly by 27% (20 to 47%) and 14% (33 to 47%) in the co-infected group, respectively. We also discovered that ALV-J and CIAV synergistically inhibited weight gain and exhibited more severe organ damage in co-infected chickens. Furthermore, we found that CIAV can promote the replication of ALV-J in HD11 cells and significantly enhance ALV-J viral load in blood and tissues of co-infected chickens, but ALV-J cannot promote the replication of CIAV. Moreover, by measuring the immune organ indexes and proportions of blood CD3+CD4+ and CD3+CD8+ lymphocytes, more serious instances of immunosuppression were observed in ALV-J and CIAV co-infected chickens than in mono-infected chickens. Taken together, our findings demonstrate that ALV-J and CIAV synergistically enhance pathogenicity and immunosuppression. [ABSTRACT FROM AUTHOR]

BackgroundAsthma is a chronic inflammatory disease with a strong genetic predisposition. A major challenge for candidate gene association studies in asthma is the selection of biologically relevant genes.Methodology/principal findingsUsing epithelial RNA expression arrays, HapMap allele frequency variation, and the literature, we identified six possible candidate susceptibility genes for childhood asthma including ADCY2, DNAH5, KIF3A, PDE4B, PLAU, SPRR2B. To evaluate these genes, we compared the genotypes of 194 predominantly tagging SNPs in 790 asthmatic, allergic and non-allergic children. We found that SNPs in all six genes were nominally associated with asthma (p

Seed aging is a common physiological phenomenon during storage which has a great impact on seed quality. An in-depth analysis of the physiological and molecular mechanisms of wheat seed aging is of great significance for cultivating high-vigor wheat varieties. This study reveals the physiological mechanisms of wheat seed aging in two cultivars differing in seed vigor, combining metabolome and transcriptome analyses. Differences between cultivars were examined based on metabolomic differential analysis. Artificial aging had a significant impact on the metabolism of wheat seeds. A total of 7470 (3641 upregulated and 3829 downregulated) DEGs were detected between non-aging HT and LT seeds; however, 10,648 (4506 up and 6142 down) were detected between the two cultivars after aging treatment. Eleven, eight, and four key metabolic-related gene families were identified in the glycolysis/gluconeogenesis and TCA cycle pathways, starch and sucrose metabolism pathways, and galactose metabolism pathways, respectively. In addition, 111 up-regulated transcription factor genes and 85 down-regulated transcription factor genes were identified in the LT 48h group. A total of 548 metabolites were detected across all samples. Cultivar comparisons between the non-aged groups and aged groups revealed 46 (30 upregulated and 16 downregulated) and 62 (38 upregulated and 24 downregulated) DIMs, respectively. Network analysis of the metabolites indicated that glucarate O-phosphoric acid, L-methionine sulfoxide, isocitric acid, and Gln-Gly might be the most crucial DIMs between HT and LT. The main related metabolites were enriched in pathways such as glyoxylate and dicarboxylate metabolism, biosynthesis of secondary metabolites, fatty acid degradation, etc. However, metabolites that exhibited differences between cultivars were mainly enriched in carbon metabolism, the TCA cycle, etc. Through combined metabolome and transcriptome analyses, it was found that artificial aging significantly affected glycolysis/gluconeogenesis, pyruvate metabolism, and glyoxylate and dicarboxylate metabolism, which involved key genes such as ACS, F16P2, and PPDK1. We thus speculate that these genes may be crucial in regulating physiological changes in seeds during artificial aging. In addition, an analysis of cultivar differences identified pathways related to amino acid and polypeptide metabolism, such as cysteine and methionine metabolism, glutathione metabolism, and amino sugar and nucleotide sugar metabolism, involving key genes such as BCAT3, CHI1, GAUT1, and GAUT4, which may play pivotal roles in vigor differences between cultivars. [ABSTRACT FROM AUTHOR]