Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.

Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER
Biomarkers, Tumor/genetics* ; Breast Neoplasms/pathology* ; Female ; Humans ; Neoplasm Recurrence, Local/pathology* ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics* ; Receptors, Estrogen

Purpose: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC). Materials and Methods: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926). Conclusion RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

Objective:To construct transitional care evaluation system for lung cancer patients with chemotherapy based on Omaha systemtheory.Methods:Based on literature research, the first draft of transitional care evaluation system for lung cancer patients with chemotherapy was preliminarily formulated by combining Omaha system, content analysis, cross-mapping method and expert group meeting. By using Delphi expert consultation method, 15 experts from the field of oncology medicine and oncology nursing were conducted two rounds of expert consultation from January 2019 to March 2019. Finally, the transitional care evaluation system for lung cancer patients with chemotherapy was formed. From April 2019 to May 2019, 30 lung cancer patients with chemotherapy in a cancer specialist hospital were selected to evaluate the importance of the contents of the transitional care nursing evaluation system. The enthusiasm of experts was expressed by the effective recovery rate of the questionnaire, the authority of experts was expressed by the expert authority coefficient ( Cr) , the coordination degree of expert opinions was expressed by the coefficient of variation and Kendall coordination coefficient, and the concentration degree of opinions was expressed by the value of importance. Results:The recovery rates of the two rounds of expert consultation questionnaires were 100%. The expert authority coefficient of the second round of expert consultation was 0.80. Kendall's coordination coefficients of the first-levelindicators and second indicators were 0.300 and 0.160 respectively ( P<0.001) . The evaluation opinions of experts and patients tended to be consistent. The transitional care evaluation system for lung cancer patients with chemotherapy was finally constructed, including 8 first-level indicators and 62 second-level indicators. Conclusions:In this study, contents of transitional care evaluation system for lung cancer patients with chemotherapy are scientific and reasonable, which can provide a reference for the effective implementation of transitional care for lung cancer patients with chemotherapy.

Objective To investigate the risk factors for postoperative prolonged mechanical ventilation in neonates and young infants with complicated congenital heart disease. Methods A retrospective analysis of 150 children (80 males and 70 females, aged ≤ 6 months, RACHS-1 grade ≥ 3) with complex congenital heart disease who were admitted to Children's Heart Surgery Department of Anzhen Hospital from January 2016 to December 2017 was conducted. These data were collected: the demographic data, history of cardicvascular-related diseases, type of surgery, preoperative complications, CPB, CPB time, deep hypothermia, blood gas index, delayed chest closure (DCC), pacemaker; minimum oxygenation index in the first 24 h after operation, maximum vasoactive-inotropic score (VIS), failed extubation and postoperative complications. Logistic regression model was used to analyze the risk factors of prolonged mechanical ventilation within neonates and young infants after complicated congenital heart surgery. Results Forty-two patients (28％) required PMV with mechanical ventilation ≥ 72 h. Univariate analysis showed age, weight, RACHS-1 grade, previous history of cyanosis, history of pneumonia, emergency surgery, preoperative mechanical ventilation, preoperative EF, deep hypothermia, CPB time＞ 132 min, intraoperative minmum pH value, intraoperative maximum blood glucose and lactic acid concentrations, DCC, application of pacemakers, maximum VIS within 24 h after surgery, minimal OI and postoperative complications may be the risk factors of prolonged postoperative mechanical ventilation in neonates and young infants with complicated congenital heart disease (P ＜ 0.05). Multivariate Logistic regression analysis showed that the CPB time＞132 min (OR = 11.04, 95％ CI 2.07-58.96, P = 0.005), intraoperative maximum lactate (OR = 1.53, 95％ CI 1.07-2.20, P = 0.021) and failed extubation (OR = 17.28, 95％ CI 2.46-121.20, P = 0.004) were independent risk factors for prolonged postoperative mechanical ventilation in neonates and young infauts with complicated congenital heart disease. Conclusion CPB time＞132 min, intraoperative maximum lactic acid concentration and failure of extubation can be used as predictors of prolonged postoperative mechanical ventilation in neonates and young infants with complicated congenital heart disease.

[Abstract] Objective：To investigate whether the proliferation and cytotoxicity of NK-92MI cells can be improved by IL-7 and IL-21 genes modification, and determine the effects of this genetically modified NK-92MI cells on T cells from normal human peripheral blood. Methods：IL-7 and IL-21 gene fragments were constructed into electroporation vector by genetic engineering method, and NK92MI/IL-21 and NK-92MI/IL-7&21 cells were constructed by electroporation transfection. The in vitro proliferation and cytotoxicity of NK-92MI, NK-92MI/IL-21 and NK-92MI/IL-7&21 cells were measured by cell count and flow cytometry assays. Then, normal human PBMCs were co-cultured with NK-92MI, NK-92MI/IL-21 and NK-92MI/IL-7&21 cells in vitro respectively, and the phenotype change of T cells was measured by flow cytometry. In addition, the cytotoxicity between the activated T cells and three NK-92MI cell lines (NK-92MI, NK-92MI/IL-21 and NK-92MI/IL-7&21 cells) as well as the cytotoxicity of the three NK-92MI cells on tumor cells after co-incubation with activated T cells were detected. Results: NK-92MI/IL-21 cell line (highly expressing IL-21) and NK-92MI/IL-7&21 cell line (highly expressing both IL-7 and IL-21) were successfully constructed. The toxicity of NK-92MI, NK-92MI/IL-21 and NK92MI/IL-7&21 cells on Jurkat and K562 cells showed no difference, while the proliferation of NK-92MI/IL-21 and NK-92MI/IL-7&21 cells was increased compared with NK-92MI cells. Furthermore, NK-92MI/IL-21 and NK-92MI/IL-7&21 cells promoted the activation of T cells to a certain degree, and the activated T cells showed merely no cytotoxicity on NK-92MI, NK-92MI/IL-21 and NK-92MI/IL7&21 cells; Meanwhile, the activated T cells did not affect the cytotoxicity of the three NK cells (NK-92MI, NK-92MI/IL-21, and NK92MI/IL-7&21 cells) on K562 cells under their co-existence. Conclusion: The in vitro proliferation of NK-92MI/IL-21 and NK-92MI/ IL-7&21 cells were enhanced after gene modification, which could also stimulate and promote the activation of T cells from peripheral blood. The cytotoxicity assay showed that the activated T cells had no cytotoxicity on NK-92MI, NK-92MI/IL-21, and NK-92MI/IL-7& 21 cells. Meanwhile, the presence of the activated T cells did not affect the cytotoxicity of NK-92MI cells.

Objective: To investigate the effect of 21-gene recurrence score on adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive, epidermal growth factor receptor 2 (HER-2)-negative and lymph node (LN)-negative early stage-breast cancer. Methods: One hundred and forty-eight patients with ER+ , HER-2- and LN- early stage breast cancer were recruited in the Ruijin hospital, Shanghai Jiao Tong University School of Medicine. The 21-gene recurrence score (RS)assay was performed and systemic therapeutic decisions were made before and after knowing the RS results under multidisciplinary discussion. The effects of RS assay and the other influential factors on adjuvant chemotherapy decision were further analyzed. Results: After knowing the RS results, treatment decisions were changed in 26 out of 148 patients(17.6%). Among them, 9 out of 26 patients were not recommended for chemotherapy; 16 of 26 had treatment recommendation changed to chemotherapy, and chemotherapy regimen was changed in the last one patient. Multivariate analysis showed that RS, age and histological grade were independent factors of decision-making for adjuvant chemotherapy. Conclusion Our results suggest that 21-gene recurrence score significantly influences decision making for adjuvant chemotherapy in patients with ER+ , HER-2- and LN- early stage breast cancer.

Objective: To investigate the distribution patterns of 21-gene assay and its influencing factors in Chinese patients with early breast cancer. Methods: Nine hundred and twenty-seven early breast cancer patients were retrospectively recruited from January 2009 to December 2015 at Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The 21-gene reverse transcriptase-polymerase chain reaction(RT-PCR) assay were conducted in paraffin-embedded tumor tissues to calculate the Recurrence Score(RS). Immunohistochemistry(IHC) assay was used to measure the expression levels of estrogen receptor(ER), progesterone receptor(PR) and Ki-67. Concordances of RT-PCR and IHC results were assessed. Correlations of RS and classical clinicopathological factors were evaluated, and logistic regression were applied to determine independent predictive factors for RS. Results: The median RS of 927 patients was 23(range: 0~90), and the proportions of patients categorized as having a low, intermediate, or high risk were 26.5%, 47.7% and 25.8%, respectively. The distribution of RS varied significantly according to different tumor grade, T stage, PR status, Ki-67 index and molecular subtypes(P<0.05 for all). Grade, PR status and Ki-67 index were independent predictive factors for RS. ER, PR status and Ki-67 index showed significantly correlation between RT-PCR and IHC assays, and the concordance rates for ER and PR status were 98.7% and 87.8%, respectively. Conclusions RS significantly correlated with tumor grade, T stage, PR status, Ki-67 index and subtypes. Grade, PR status and Ki-67 index can independently predict RS. Remarkable concordances of ER, PR status and Ki-67 index are found between RT-PCR and IHC assays.

Objective To investigate the effects of Dihuang Yinzi (DY) on the receptor for advanced glycation end-products(RAGE)/reactive oxygen species(ROS)/apoptosis pathway in SH-SY5Y cells induced by amyloid-beta1-42 (Aβ1-42) oligomer. Methods Firstly, we adopted methyl thiazolyl tetrazolium(MTT) method to detect the cell vitality in fetal bovine serum (FBS) group, blank serum group, and low-, middle- and high- dose DY-containing serum groups, so as to confirm the optimal concentration and treatment time of DY-containing serum. Secondly, we applied MTT method to detect cell vitality and applied Annexin V/propidium iodide (PI) staining method to observe the apoptosis of SH-SY5Y cells treated with 0~20 μmol/L Aβ1-42 for 24 and 48 h, so as toconfirm the optimal concentration and treatment time of Aβ1-42 for establishing Alzheimer's disease (AD) model in vitro. Thirdly, MTT method was used for the detection of cell vitality, and Annexin V/PI staining method was used for detection of the apoptosis of SH-SY5Y cells in blank serum group, model group, western medicine control group and low-, middle-and high-dose DY-containing serum groups, and Dihydroethidium (DHE) method was used for the assay of ROS contents, so as to observe the effect of DY on the recovery of injured SH-SY5Y cells induced by Aβ1-42. Finally, we applied Western blot method to detect the expression level of RAGE in SH-SY5Y cells of blank group, model group and DY-containing serum group; after Aβ1-42-induced SH-SY5Y cells were transfected with RAGE gene, we adopted DHE staining method and Annexin V/PI staining method to detect ROS content and cell apoptotic rate in all of the above groups, so as to observe the effect of DY on SH-SY5Y cell apoptosis and RAGE expression. Results The cell vitalities were increased in low- and middle-dose DY-containing serum groups at 24 h (P < 0.05 or P < 0.01 compared with that in the blank serum group). The conditions for the establishment of AD model in vitro were as follows: the optimal concentration of Aβ1-42 was 5μmol/L, and the treatment time was 24 h. The cell vitalities were significantly enhanced, the cell apoptotic rate and ROS content were significantly lowered in Aβ1-42-induced SH-SY5Y cells of the medication groups(P <0.05 or P < 0.01 compared with those in the model group) , and the cell vitality was the highest and the cell apoptotic rate was the lowest in the middle-dose DY-containing serum group. The RAGE expression level was decreased in Aβ1-42-induced SH-SY5Y cells of the middle-dose DY-containing serum group(P < 0.05 compared with that in the model group) . ROS content and cell apoptotic rate were decreased in Aβ1-42-induced SH-SY5Y cells transfected with RAGE gene in the middle-dose DY-containing serum group (P<0.01). Conclusion DY may play an anti-oxidative role through inhibiting the production of ROS and cell apoptosis, thus to suppress RAGE protein and to achieve the preventive and therapeutic effect for AD.