Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Ischemia-reperfusion injury after lung transplantation is the main cause of primary graft dysfunction, which will subsequently reduce the function of lung allograft and lower the overall survival rate of lung transplant recipients. As a physiological regulatory molecule, hydrogen molecule has the functions of anti-inflammation, easing oxidative stress, alleviating direct cell injury and mitigating epithelial edema. Recent studies have demonstrated that hydrogen molecule and its products (hydrogen and hydrogen-rich solution) could significantly mitigate ischemia-reperfusion injury and postoperative complications after lung transplantation. In this article, the protective effect and exact mechanism of hydrogen molecule and its products in lung transplantation were reviewed, aiming to provide theoretical basis for the application of hydrogen molecule and its products as a novel treatment for lung transplantation-related complications, enhance the overall prognosis and improve the quality of life of lung transplant recipients

Objective To modify the mouse model of orthotopic left lung transplantation from different perspectives, aiming to establish a simpler, faster and stabler mouse model of lung transplantation. Methods Based on preliminary modified rat model of orthotopic left lung transplantation established by our team, varying extent of modifications were made regarding the tracheal intubation, cannula preparation and anastomosis procedures of orthotopic left lung transplantation in the recipient mice. Orthotopic left lung transplantation in 40 mice were performed by an operator with microsurgical experience. The dissection of the recipient's hilar structure was carried out at the plane of the hilar clamp model within the reverse-view, and the three branches (left main bronchus, pulmonary artery and pulmonary vein) of the pulmonary hilum were anastomosed in turn by the "pendulum" anastomosis method. The operation time of each procedure was recorded. The recipient mice were sacrificed at postoperative 2 weeks, and the incidence of postoperative complications was recorded. Results Lung transplantation was successfully completed in 40 mice, with no bronchial and vascular tearing or twisting, and no bleeding at the anastomosis site. The overall cardiopulmonary procurement time was (10.7±1.5) min, cannula preparation time was (16.2±1.5) min, cold ischemia time was (25.1±2.4) min, warm ischemia time was (19.4±1.6) min, and the total operation time was (57.2±2.9) min, respectively. During the follow-up from 6 to 14 days after surgery, one recipient mouse died of pleural effusion, probably caused by infection. No pneumothorax, thrombosis or atelectasis was found in the remaining recipient mice during postoperative follow-up. Conclusions The modified mouse model of orthotopic left lung transplantation based on "pendulum" anastomosis of the reverse-view plane possesses multiple advantages of short operation time, high success rate and few complications, which is expected to become an alternative model of studying pathological changes after lung transplantation and worthy of further application.

Objective To investigate and clarify the effect of Stat5a on proliferation of human breast cancer cells (MCF‐7) and to detect the changes of epigenetic signature on the promoter region of p53 gene .Methods Stat5a was over expressed in human breast cancer cells (MCF‐7) by using adenovirus mediated gene transfer technology .The cell proliferation was examined by MTS assay .ChIP assay was used to check the trimethylation of lysine 27 on histone 3 (H3K27Me3) of p53 gene promoter region .Fur‐thermore ,qRT‐PCR and western blot were also applied to confirm the expression of p53 gene .Results The number of MCF 7 in‐creased in a dose dependent manner .Compared with that of control group ,the cell density of MCF‐7 increased 7 .603 1% , 18 .123 7% and 24 .898 7% when the MOI were 10 ,20 and 30 .Chromatin Immunoprecipitation showed that Stat5a significantly in‐creased H3K27Me3 and down regulated the expression level of p53 gene .Conclusion Stat5a promotes proliferation of breast cancer cells through trimethylation of H3K27 and inhibition of p53 gene expression .

BACKGROUNDProlactin (PRL) is a pituitary polypeptide hormone characterized by multiple biological actions including stimulation of growth in the prostate and formation of secretory alveoli and stimulation of milk protein gene expression in the mammary gland. PRL exerts its effect by dimerizing its receptor (PRLR) on the plasma membrane and regulating gene expression through the JAK-Stat signal pathway. We have previously described a natural variant of the PRLR in which the S2 subdomain of the extracellular domain is missing (Delta S2). Delta S2 PRLRs are dimerized in the absence of PRL and have constitutive activity in the promotion of breast cancer cell growth. Enhancer of zeste homolog 2 (EZH2), as one of the histone-modifying enzymes, is a key factor regulating gene expression by epigenetic modification. We hypothesized that these constitutive activated Delta S2 PRLRs played a pathogenic role in breast cancer in part through alterations in the expression of EZH2 and the trimethylation of histone 3 on lysine 27 (H3K27Me3).

METHODSIn order to verify the clinical significance and to establish the link between Delta S2 PRLR expression and epigenetic change, EZH2, H3K27Me3, and Delta S2 PRLR were detected in both normal and cancerous human breast tissues. Also, overexpression of Delta S2 PRLR in breast epithelial cells was achieved by infection with adenovirus carrying the cDNA. Western blotting and chromatin immunoprecipitation (ChIP assay) and acid histone extraction were applied to detect the expression of EZH2 and the trimethylation of histone 3, respectively.

RESULTSIn breast tissue, higher EZH2 expression and higher H3K27Me3 were found associated with higher Delta S2 expression in breast cancer samples. In breast epithelial cells, overexpression of Delta S2 PRLR increased EZH2 methyltransferase mRNA and protein, induced EZH2 methyltransferase recruitment to chromatin, increased the trimethylation of H3K27Me3, and decreased the expression of p53 gene.

CONCLUSIONSDelta S2 PRLR plays an important pathogenic role in breast cancer through epigenetic modification. Elevated expression of Delta S2 PRLR, achieved by alternate splicing of the pre-mRNA of the full-length form, is a new mechanism contributing to human breast cancer.

Breast Neoplasms ; metabolism ; Enhancer of Zeste Homolog 2 Protein ; Female ; Gene Expression Regulation, Neoplastic ; Histones ; metabolism ; Humans ; MCF-7 Cells ; Polycomb Repressive Complex 2 ; metabolism ; Receptors, Prolactin ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Objective To investigate the application effect of Problem based learning (PBL) combined with role play teaching method in the training of emergency internal medicine.Methods Totally 60 medical students were randomly divided into two groups.The students in the observation groop were trained with PBL teaching method while those in control group were trained with traditional teaching method.The practical performances of the students in both groups were evaluated by virtual experience of dealing with patients in the emergency department through the role play teaching method.The grasp of basic knowledge was assessed by writing tests.Finally all the students in the observation group answered a survey about the teaching methods.Results There was uo difference in the scores of the basic knowledge test between the two groups ( P ＞ 0.05 ).The practical ability of the observation group was much better than that of the control group in the role play practice ( P ＜ 0.05 ).Almost all the students in the observation group accept the PBL teaching method.Conelusion PBL combined with role play teaching method is effective based on the characteristics of emergency medicine.

Objective To investigate the possible association of IRAK4 polymorphisms with susceptibility to and prognosis of severe sepsis.Methods A total of 192 patients hospitalized in emergency department of Zhongshan Hospital from February 2006 to December 2009,and another 192 healthy volunteers were enrolled in this case-control study.Patients were excluded if they had metastatic tumors,autoimmune diseases,AIDS or received immunosuppressive drugs.This study was approved by the ethical committee of Zhongshan Hospital,Fudan University.Sepsis patients were divided into survival group(n =124)and non-survival group(n =68)according to the 30-day mortality.Primer 3 software was used to design the PCR and sequencing primers.Genomic DNA was extracted from peripheral blood mononuclear cells.Seven tagSNPs were selected based on the data of Chinese Han in Beijing from the Hapmap projectand genotyped by direct sequencing.We used x2 analysis to evaluate the significance of differences in genotype and allele frequencies between different groups.Results The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium.The allele and genotype frequencies of rs4251545(G/A)were significantly different between severe sepsis and healthy control groups(P =0.015,P =0.035,respectively).Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G(OR =1.69,95％ CI:1.10-2.58).The allele and genotype frequencies of all SNPs were not significantly different between survivor group and non-survivor group.Conclusions These findings indicated that the variants in IRAK4 are significantly associated with severe sepsis susceptibility in the Chinese Han population.

Objective To investigate the myocardial injury in the early stage of acute dichlorvos poisoning in rats. Method A total of 24 Sprague Dawley rats were randomly (random number) divided into control group(n = 12) and poisoning group(n = 12). Hemodynamic variables were monitored by using an arterial cannula inserted into right arteria carotis communis. Serum levels of cardiac troponin T(CTnT) and brain natriuretic peptide (BNP) were measured. Myocardial tissue was observed with HE stain under microscope. Results The rats of poisoning group showed that the heart rate (HR) and maximum ascending rates of left ventricular pressure(+ dp/dtmax)were significant decreased in an hour after poisoning (P ＜0.01). The maximum descending rates of left ventricular pressure(-dp/dtmax)and left ventricular end diastolic pressure (LVEDP)were markedly increased (P＜0. 01) and reached peak in 7 minutes in the poisoning group. Compared with the control group, cardiac troponin T obviously changed in rats poisoned with dichlorvos in the first hour. BNP was not affected after poisoning(P ＞ 0. 05). Myocardial damage was found in the poisoning rats.Conclusions Myocardial injury and heart failure occurred in the early stage of acute organophosphorus pesticides poisoning(AOPP) in rats. CTnT could play a major role in AOPP while BNP might not be involved in.

Objective To investigate the early diagnostic value of plasma D-dimer level in acute aortic dissection (AAD) . Method A total of 80 patients with chest pain were enrolled from January 2006 to March 2009, and 40 patients of them were confirmed to be AAD with computerized tomographic angiography (CTA), and these patients were matched with 40 controls presenting suspected dissection, which were ruled out later. The D-dimer test was performed in all patients within 12 hours after onset of chest pain,and plasma D-dimer concentrations were compared between two groups. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of D-dimer used for diagnosing AAD were analyzed. The receiver operating characteristic (ROC) curve was also established. The statistical analysis of data was carried out by using Mann-Whitney test with SPSS 11.5 software. Results The plasma D-dimer oncentrations in AAD were significantly higher than those in controls [(5.48±7.95) vs. (0.64±0.75), P <0.0l]. Receiver operating characteristic curve analysis showed that D-dimer ( > 0.5 μg/mL) was predictive in the diagnosis of AAD, and the area under ROC curve was 0.848 ± 0.042, (95% CI: 0.766-0.930) with 87.5% sensitivity, 62.5% specificity,70% PPV and 83.3% NPV. Conclu-sions D-dimer may be a valuable biomarker in early diagnosis of AAD.