Objective:To investigate the survival outcomes and prognostic factors of patients with double primary breast cancer (BC) and endometrial cancer (EC).Methods:A retrospective cohort study was conducted using data for the period 1992-2018 from the Surveillance, Epidemiology, and End Results (SEER) database. There were 3 465 patients with BC as the first primary cancer (BC-EC group) and 2 804 patients with EC as the first primary cancer (EC-BC group). Kaplan-Meier analysis and cumulative incidence function were used to estimate overall mortality, breast cancer-specific mortality, and endometrial cancer-specific mortality, respectively. Cox regression and Fine-Gray regression were used to analyze the prognostic factors of overall mortality, breast cancer-specific mortality, and endometrial cancer-specific mortality, respectively.Results:During a median follow-up of 160 months, 1 616 deaths occurred in the BC-EC group, with EC being the leading cause of death (37.69%); 994 deaths occurred in the EC-BC group, with BC being the leading cause of death (28.77%). Cox regression identified patients with older ages at first primary cancer diagnosis (54-61 years: HR=1.46, 95% CI: 1.26-1.69; 62-68 years: HR=2.64, 95% CI: 2.29-3.03; ≥69 years: HR=4.89, 95% CI: 4.27-5.60), shorter time interval between the diagnoses (0-5 months: HR=6.13, 95% CI: 5.21-7.21; 6-23 months: HR=5.69, 95% CI: 4.95-6.55; 24-59 months: HR=3.44, 95% CI: 3.04-3.89; 60-119 months: HR=2.32, 95% CI: 2.07-2.59), mixed ductal-lobular BC ( HR=1.29, 95% CI: 1.11-1.48), endometrial mixed cell adenocarcinoma ( HR=1.23, 95% CI: 1.01-1.50), advanced tumor grade (grade Ⅱ BC: HR=1.13, 95% CI: 1.01-1.27; grade Ⅲ BC: HR=1.24, 95% CI: 1.10-1.41; grade Ⅱ EC: HR=1.19, 95% CI: 1.06-1.33; grade Ⅲ EC: HR=1.68, 95% CI: 1.48-1.90), advanced tumor stage of the two cancers (distant BC: HR=3.14, 95% CI: 2.50-3.94; regional EC: HR=1.53, 95% CI: 1.36-1.71; distant EC: HR=3.00, 95% CI: 2.59-3.47) had increased risk of overall mortality. Fine-Gray regression showed that compared with BC-EC patients, EC-BC patients had a higher risk of breast cancer-specific mortality [sub-distribution hazard ratio (s HR=1.24, 95% CI: 1.04-1.47], but a lower risk of endometrial cancer-specific mortality (s HR=0.37, 95% CI: 0.30-0.46). Older ages at first cancer diagnosis, shorter intervals between the diagnoses, negative ER and PR status, and advanced BC grades/stages were associated with increased breast cancer-specific mortality ( P＜0.05). Similarly, older ages, shorter intervals, endometrial serous carcinoma/mixed cell adenocarcinoma, and advanced EC grades/stages correlated with elevated endometrial cancer-specific mortality ( P＜0.05). Conclusion:The management of double primary BC and EC patients requires multidisciplinary strategies, with particular attention to patients presenting older ages at first cancer diagnosis, shorter intervals between the diagnoses, and unfavorable tumor characteristics.

ObjectiveTo explore the mechanism of the immunotoxicity induced by dictamnine （DIC） in rats and the recovery effect after drug withdrawal by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry， thereby providing a theoretical basis for elucidating the toxic mechanism of DIC. MethodsSD rats were randomized into blank （normal saline）， DIC （10 mg·kg^-1）， and DIC withdrawal （recovery period） groups （n=8）. The rats were continuously treated for 7 days， once a day， and the body weight and organ weight were recorded. The levels of interleukin-1 （IL-1）， IL-6， and tumor necrosis factor-α （TNF-α） in the serum and immunoglobulin A （IgA）， immunoglobulin G （IgG）， and immunoglobulin M （IgM） in the spleen were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the pathological changes in the spleen. ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was employed to screen the potential biomarkers of immune inflammation caused by DIC， and pathway enrichment analysis and correlation analysis were performed. The mRNA levels of IL-1β， TNF-α， lysophosphatidylcholine acyltransferase 2 （LPCAT2）， and farnesoid X receptor （FXR） in the serum were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the DIC group showed elevated levels of IL-1β， IL-6， and TNF-α in the serum （P<0.01）， and the DIC withdrawal group showcased lowered levels of IL-1β， IL-6， and TNF-α in the serum （P<0.01）. The levels of IgA， IgG， and IgM in the spleen of rats in the DIC group were decreased （P<0.01）， while those in the DIC withdrawal group were recovered （P<0.05， P<0.01）. Untargeted metabolomics of the serum and spleen screened out 14 common differential metabolites and 14 common metabolic pathways. The Spearman correlation analysis between differential metabolites and inflammatory factors identified PC （32∶0）， LysoPC （20∶4/0∶0）， LysoPC （P-18∶0/0∶0）， taurochenodeoxycholic acid， taurocholic acid， LysoPC ［20∶5（5Z，8Z，11Z，14Z，17Z）/0∶0］， chenodeoxycholic acid， arachidonic acid， LysoPC （18∶0/0∶0）， LysoPC （15∶0/0∶0）， LysoPC （16∶0/0∶0）， and LysoPC （17∶0/0∶0） as the biomarkers of immunotoxicity induced by DIC in SD rats. In the process of immunotoxicity caused by DIC， lipid metabolism disorders such as glycerophospholipid metabolism， primary bile acid metabolism， and arachidonic acid metabolism were enriched， which was consistent with the DIC-induced inflammatory factors and pathological characteristics of the spleen. Compared with the blank group， the DIC group exhibited up-regulated mRNA levels of IL-1β， TNF-α， LPCAT2， and FXR （P<0.01）， and the up-regulation was decreased in the withdrawal group （P<0.01）. ConclusionDIC can lead to immune and inflammatory disorders. DIC withdrawal can regulate the expression of biomarkers related to serum and spleen metabolites， regulate the inflammatory metabolic pathway， reduce the inflammation level， and alleviate the metabolic disorders， thus attenuating the potential toxicity induced by DIC.

Objective:To investigate the survival outcomes and prognostic factors of patients with double primary breast cancer (BC) and endometrial cancer (EC).Methods:A retrospective cohort study was conducted using data for the period 1992-2018 from the Surveillance, Epidemiology, and End Results (SEER) database. There were 3 465 patients with BC as the first primary cancer (BC-EC group) and 2 804 patients with EC as the first primary cancer (EC-BC group). Kaplan-Meier analysis and cumulative incidence function were used to estimate overall mortality, breast cancer-specific mortality, and endometrial cancer-specific mortality, respectively. Cox regression and Fine-Gray regression were used to analyze the prognostic factors of overall mortality, breast cancer-specific mortality, and endometrial cancer-specific mortality, respectively.Results:During a median follow-up of 160 months, 1 616 deaths occurred in the BC-EC group, with EC being the leading cause of death (37.69%); 994 deaths occurred in the EC-BC group, with BC being the leading cause of death (28.77%). Cox regression identified patients with older ages at first primary cancer diagnosis (54-61 years: HR=1.46, 95% CI: 1.26-1.69; 62-68 years: HR=2.64, 95% CI: 2.29-3.03; ≥69 years: HR=4.89, 95% CI: 4.27-5.60), shorter time interval between the diagnoses (0-5 months: HR=6.13, 95% CI: 5.21-7.21; 6-23 months: HR=5.69, 95% CI: 4.95-6.55; 24-59 months: HR=3.44, 95% CI: 3.04-3.89; 60-119 months: HR=2.32, 95% CI: 2.07-2.59), mixed ductal-lobular BC ( HR=1.29, 95% CI: 1.11-1.48), endometrial mixed cell adenocarcinoma ( HR=1.23, 95% CI: 1.01-1.50), advanced tumor grade (grade Ⅱ BC: HR=1.13, 95% CI: 1.01-1.27; grade Ⅲ BC: HR=1.24, 95% CI: 1.10-1.41; grade Ⅱ EC: HR=1.19, 95% CI: 1.06-1.33; grade Ⅲ EC: HR=1.68, 95% CI: 1.48-1.90), advanced tumor stage of the two cancers (distant BC: HR=3.14, 95% CI: 2.50-3.94; regional EC: HR=1.53, 95% CI: 1.36-1.71; distant EC: HR=3.00, 95% CI: 2.59-3.47) had increased risk of overall mortality. Fine-Gray regression showed that compared with BC-EC patients, EC-BC patients had a higher risk of breast cancer-specific mortality [sub-distribution hazard ratio (s HR=1.24, 95% CI: 1.04-1.47], but a lower risk of endometrial cancer-specific mortality (s HR=0.37, 95% CI: 0.30-0.46). Older ages at first cancer diagnosis, shorter intervals between the diagnoses, negative ER and PR status, and advanced BC grades/stages were associated with increased breast cancer-specific mortality ( P＜0.05). Similarly, older ages, shorter intervals, endometrial serous carcinoma/mixed cell adenocarcinoma, and advanced EC grades/stages correlated with elevated endometrial cancer-specific mortality ( P＜0.05). Conclusion:The management of double primary BC and EC patients requires multidisciplinary strategies, with particular attention to patients presenting older ages at first cancer diagnosis, shorter intervals between the diagnoses, and unfavorable tumor characteristics.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

Objective:To establish a standardized training assessment index system for newly recruited nurses in the Hematology Department, so as to provide reference for the quality evaluation of standardized training for newly recruited nurses in the Hematology Department.Methods:Taking the Kirkpatrick four-level model as the theoretical framework, combined with literature review, group discussion, and Delphi expert consultation, indicators were screened and weights were determined to ultimately determine the index system.Results:Around two rounds of consultation, the positivity coefficients of experts were 100% (15/15), and the authoritative coefficients of experts were 0.850 and 0.875, respectively. The Kendall's coordination coefficients of indicators at all levels for two rounds of consultation were 0.379 to 0.685 and 0.235 to 0.307, respectively. The final standardized training assessment index system for newly recruited nurses in the Hematology Department included four first-level indicators, 15 second-level indicators, and 57 third-level indicators.Conclusions:The standardized training assessment index system is scientific and standardized, with relatively reasonable content settings, which can provide reference for the standardized training assessment of newly recruited nurses in the Hematology Department.

Objective: To evaluate the efficacy and safety of purified CD34⁺ stem cell boost in the treatment of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (HSCT) . Methods: 12 patients with poor graft function, reported in our hospital during January 2014 to March 2018, were retrospectively analyzed; The donors of 12 patients were HLA mismatched family members, and all treated with donor purified CD34⁺ stem cell after G-CSF mobilization, calculating and statistical analyzing the purity of separation and the recovery rate of CD34⁺ stem cells. The related complications and the recovery of blood cells after infusion were observed. Results: The purity of CD34⁺ cells in the separation products was 92.0% (44.0%-97.0%) , and the recovery rate was 55.0% (45.0%-96.7%) . The median number of CD34⁺ cells was 1.9 (0.9-4.4) ×10⁶/kg with CD3⁺ cells as 0.6 (0.3-2.0) ×10⁴/kg. The median durations of white blood cells, platelet and red blood cells recoveries were 18 (14-39) , 29 (16-153) and 60 (9-124) days, respectively. All 12 patients didn’t experience serious adverse reactions in the process of infusion, 10 patients achieved hematopoietic recovery, 1 case partial remission, 1 case no recovery, without occurrence of aggravated infection, graft versus host disease and other complications. Conclusion The infusion of donor purified CD34⁺ stem cell was a safe and effective method for PGF after allogeneic HSCT.

Objective To evaluate the feasibility of low tube voltage (80 kV)with low concentration contrast medium iodixanol (270 mg I/mL)in cerebral perfusion using 640-slice volume CT.Methods Patients who underwent CT cerebral perfusion were randomly divided into two groups.Group A:100 kV,320 mg I/mL contrast medium;group B:80 kV,270 mg I/mL contrast medium.The effective dose(ED)was record,the frontal cortex,temporal cortex and occipital cortex were selected as regions of interest(ROI),and the cerebral perfusion parameters (rCBV,rCBF,MTT,TTP)were measured separately.The CT value of the M1 segment of cerebral middle artery, the C7 segment of internal carotid artery,the basilar artery and the surrounding brain tissue were measured.The signal-to-noise radio (SNR)and the contrast-to-noise ratio(CNR)of two groups were compared and analyzed.All data will be statistically analyzed,and the consistency of two physicians for image quality evaluation was analyzed by Kappa analysis.Results The ED of group B was 4.56 mSv, which was reduced by 35.2% compared to group A(7.04 mSv).The perfusion parameters,the CT value of ROI and the SNR,CNR for two groups were of no statistical difference(P>0.05).Conclusion The feasibility of low tube voltage combined with low concentration contrast media is better,which not only meets the requirements of clinical diagnosis,but also reduces the radiation dose and the probability of contrast induced nephropathy.

Objective To explore the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in refractory or relapsed leukemia patients undergoing total body irradiation and FLAG regimen consisting of fludarabine,cytarabine,granulocyte colony stimulating factor (TBI/FLAG).Methods Forty-seven cases of refractory or relapsed leukemia treated in our hospital between May 2012 and December 2015 were analyzed retrospectively,including 14 cases of acute lymphoblastic leukemia,31 cases of acute myeloid leukemia,2 cases of acute transformation of chronic myelocytic leukemia.All patients did not achieve remission before bone marrow transplantation.The proportion of blast cells was 10％-98％.The TBI/FLAG was the main conditioning regimen.Kaplan-meier curve was used to analyze the cumulative incidence of GVHD,cumulative recurrence rate,overall survival rate (OS) and disease-free survival rate (DFS).Results Of 47 cases,there was only one patient with infection during the preconditioning and the cell engraftment was not successful,and the rest 46 patients were successfully engrafted.The median time of leukocyte engraftment was 17 (11-25) days,and the median time of platelet engraftment was 21 (11-70) days.The cumulative incidence of acute GVHD was (62.3 ± 7.3)％,including 51.1％ and 28.4％ in Ⅱ and Ⅲ-Ⅳ grade respectively.Twenty-four patients suffered chronic GVHD in 44 assessable patients,and the cumulative incidence was (77.1 ± 11.2)％.The bone marrow was assessed 28 days after transplantation,and the results showed that 46 patients achieved complete remission,and DNA test confirmed complete donor chimerism.The median follow-up time was 12 (1-44) months,25 patients survived (53.19％,25/47),and 13 relapsed (27.65％,13/47).The 1-yearOS and DFS was 47.9％ and 45.5％ after transplantation.Conclusion TBI/FLAG-based regimen is safe and effective for refractory or relapsed leukemia,and the major risk still is relapse for refractory or relapsed leukemia patients after transplantation.The method of preventing recurrence needs to be further explored.

Objective To evaluate the safety and efficacy of haploidentical hematopoietic stem cell transplan-tation(haplo-HSCT)treatment in children with hematological diseases.Methods Fifty-nine cases of less than 14 years old children with hematonosis were analyzed retrospectively,who were enrolled in the Aerospace Central Hospital from July 2012 to June 2016.And the evaluation was carried out by analyzing the success rate of implantation,occu-rrence rate of graft versus host disease(GVHD),infection rate and transplant related mortality(TRM),cumulative re-currence rate,overall survival rate(OS)and disease-free survival rate(DFS).Results In total of 59 cases,the 59 engraftments were successfully transplanted,the median time of leukocyte engraftment was 18(8-23)days,the median time of platelet engraftment was 21(11-68)days,the bone marrow was assessed 28 days after transplanta-tion,which showed that 59 patients achieved complete remission(CR)and DNA test confirmed complete donor chime-rism.With a median of follow-up time of 19(5-56)months,the cumulative recurrence rates ofⅠ,Ⅱgrade andⅢ,Ⅳ grade acute GVHD were(38.3 ± 6.3)%(23 cases)and(16.7 ± 4.8)%(10 cases),respectively,the chronic GVHD cumulative recurrence rate was(65.6 ± 7.5)%(30 cases),the cytomegalovirus(CMV)viremia cumulative recurrence rate was(45.1 ± 6.5)%(27 cases),the Epstein-Barr virus(EBV)viremia cumulative recurrence rate was(10.0 ± 3.9)%(6 cases),the viral cystitis cumulative recurrence rate was(20.0 ± 5.5)%(12 cases),the transplant related mortality was(12.8 ± 6.0)%,the 2-year cumulative recurrence rate of CR group was(8.0 ± 5.4)%,and that of non-remission(NR)group was(64.1 ± 11.9)%.The 2-year OS of CR group was(78.9 ± 7.5)%,the 2-year OS of NR group was(32.5 ± 12.9)%,the 2-year DFS of CR group was(79.5 ± 9.8)%,the 2 years DFS of NR group was(27.4 ± 7.9)%.Conclusions Haplo-HSCT is safe and effective in treating children with hematonosis,and haplo-HSCT has high survival rate and low recurrent,especially when transplantation is per-formed in the remission stage.But the prognosis of haplo-HSCT is poor in the refractory and relapsed patients,and to explore the preventing recurrence measures are very urgent.

BACKGROUND:There is no clear understanding about the effect of let-7f and interleukin-6 (IL-6) on the proliferation of bone marrow mesenchymal stem cels and their relationship.
OBJECTIVE: To explore the effects of expression levels of let-7f and IL-6 on the proliferation of bone marrow mesenchymal stem cels and their relationship.
METHODS:(1) LV-rno-let-7f-up and LV-rno-let-7f-down were constructed and transfected into bone marrow mesenchymal stem cels of Sprague-Dawley rats, respectively. Then, there were four groups in the study: transfection upregulation group transfected with LV-rno-let-7f-up), transfection inhibition group (transfected with LV-rno-let-7f-down), negative control group (transfected with FU-RNAi-NC-LV), and untransfected group. The expression level of let-7f in each group was detected by qRT-PCR. The proliferation ability of cels and expression levels of IL-6 when let-7f expression was at different levels were detected by MTT, flow cytometry and ELISA. The expression of Cyclin D1 at mRNA and protein levels was detected by qRT-PCR and western blot, respectively. (2) To predict the potential target gene of let-7f, the wild-type/mutant IL-6 3’UTR reporter gene vectors were constructed, and cotransfected with let-7f/let-7f inhibitor respectively into the 293T cels to measure the luciferase.
RESULTS AND CONCLUSION: Compared with the negative control group, the proliferative and cloning capacities of cels in the transfection upregulation group were higher; the number of cels was significantly decreased at G1 stage and increased at S stage, and the apoptotic cels were reduced in number (P < 0.05). However, the transfection inhibition group had opposite results. The expression level of IL-6 in the transfection upregulation group was lower than that in the untransfected group and negative control group (P < 0.05); while in the transfection inhibition group, the expression level of IL-6 was significantly increased (P < 0.05). The expression of Cyclin D1 at mRNA and protein levels was up-regulated in transfection upregulation group (P < 0.05) and down-regulated in the transfection inhibition group (P < 0.05), but there was no significant difference between the negative control group and untransfected group (P > 0.05). Luciferase activity of cels transfected with wide-type IL-6 3’UTR and let-7f was significantly reduced (P < 0.05). These findings indicate that up-regulation of let-7f can promote the proliferative and cloning capacities of bone marrow mesenchymal stem cels and reduce cel apoptosis, but downrelation of let-7f exhibits an inhibitory effect. Overexpression of IL-6 can suppress the proliferation of bone marrow mesenchymal stem cels, which is considered to be a target gene of let-7f, and let-7f may suppress the expression of IL-6 to promote the cel proliferation.