OBJECTIVE To design and synthesize of a series of novel azachalcone derivatives and study of their anti-cervical cancer activity and mechanism of action. METHODS A series of novel chalcone derivatives were designed and synthesized by using glycyrrhiza chalcone as the lead compound and VEGFR-2 and P-gp as the target sites using the active substructure splicing principle, and the structures were characterized by 1H-NMR, 13C-NMR and HR-MS. MTT, ELISA, co-dosing with cisplatin, Western blotting and molecular docking assays were used to preliminarily evaluate the proliferation inhibitory activity and mechanism of action of the target compounds on cervical cancer and cisplatin-resistant cervical cancer cells. RESULTS Compound 7h showed some antitumor activity and reversal of cisplatin resistance, and had some inhibitory effects on phosphorylation of VEGFR-2 and downstream PI3K/AKT signaling pathway proteins, with no significant differences on P-gp protein expression compared with the blank group in the concentration range of 0.5, 1.0, 1.5 μmol·L−1. CONCLUSION The anti-cervical cancer activity and reversal of cisplatin resistance of compound 7h may be related to its inhibition of VEGFR-2 and P-gp targets.

Recent data indicated a high incidence of inappropriate management of neuromuscular block, with a high rate of residual paralysis and relaxant-associated postoperative complications. These data are alarming in that the available neuromuscular monitoring, as well as myorelaxants and their antagonists basically allow well tolerated management of neuromuscular blockade. In this first European Society of Anaesthesiology and Intensive Care (ESAIC) guideline on peri-operative management of neuromuscular block, we aim to present aggregated and evidence-based recommendations to assist clinicians provide best medical care and ensure patient safety. We identified three main clinical questions: Are myorelaxants necessary to facilitate tracheal intubation in adults? Does the intensity of neuromuscular blockade influence a patient′s outcome in abdominal surgery? What are the strategies for the diagnosis and treatment of residual paralysis? On the basis of this, PICO (patient, intervention, comparator, outcome) questions were derived that guided a structured literature search. A stepwise approach was used to reduce the number of trials of the initial research ( n=24 000) to the finally relevant clinical studies ( n=88). GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was used for formulating the recommendations based on the findings of the included studies in conjunction with their methodological quality. A two-step Delphi process was used to determine the agreement of the panel members with the recommendations: R1 We recommend using a muscle relaxant to facilitate tracheal intubation (1A). R2 We recommend the use of muscle relaxants to reduce pharyngeal and/or laryngeal injury following endotracheal intubation (1C). R3 We recommend the use of a fast-acting muscle relaxant for rapid sequence induction intubation (RSII) such as succinylcholine 1 mg/kg or rocuronium 0.9 to 1.2 mg/kg (1B). R4 We recommend deepening neuromuscular blockade if surgical conditions need to be improved (1B). R5 There is insufficient evidence to recommend deep neuromuscular blockade in general to reduce postoperative pain or decrease the incidence of peri-operative complications (2C). R6 We recommend the use of ulnar nerve stimulation and quantitative neuromuscular monitoring at the adductor pollicis muscle to exclude residual paralysis (1B). R7 We recommend using sugammadex to antagonise deep, moderate and shallow neuromuscular blockade induced by aminosteroidal agents (rocuronium, vecuronium) (1A). R8 We recommend advanced spontaneous recovery (i. e. TOF ratio>0.2) before starting neostigmine-based reversal and to continue quantitative monitoring of neuromuscular blockade until a TOF ratio of more than 0.9 has been attained (1C).

Background: Heart failure (HF) biomarkers have prognostic value. The aim of this study was to combine HF biomarkers into an objective classification system for risk stratification of patients with HF. Methods: HF biomarkers were analyzed in a population of HF outpatients and expressed relative to their cut-off values (N-terminal pro-B-type natriuretic peptide [NT-proBNP] >1,000 pg/mL, soluble suppression of tumorigenesis-2 [ST2] >35 ng/mL, growth differentiation factor-15 [GDF-15] >2,000 pg/mL, and fibroblast growth factor-23 [FGF-23] >95.4 pg/mL). Biomarkers that remained significant in multivariable analysis were combined to devise the Heartmarker score. The performance of the Heartmarker score was compared to the widely used New York Heart Association (NYHA) classification based on symptoms during ordinary activity. Results: HF biomarkers of 245 patients were analyzed, 45 (18%) of whom experienced the composite endpoint of HF hospitalization, appropriate implantable cardioverter-defibrillator shock, or death. HF biomarkers were elevated more often in patients that reached the composite endpoint than in patients that did not reach the endpoint. NT-proBNP, ST2, and GDF-15 were independent predictors of the composite endpoint and were thus combined as the Heartmarker score. The event-free survival and distance covered in 6 minutes of walking decreased with an increasing Heartmarker score. Compared with the NYHA classification, the Heartmarker score was better at discriminating between different risk classes and had a comparable relationship to functional capacity. Conclusions The Heartmarker score is a reproducible and intuitive model for risk stratification of outpatients with HF, using routine biomarker measurements.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as powerful drugs that can be used to treat heart failure (HF) patients, both with preserved and reduced ejection fraction and in the presence or absence of type 2 diabetes. While the mechanisms underlying the salutary effects of SGLT2 inhibitors have not been fully elucidated, there is clear evidence for a beneficial metabolic effect of these drugs. In this review, we discuss the effects of SGLT2 inhibitors on cardiac energy provision secondary to ketone bodies, pathological ventricular remodeling, and inflammation in patients with HF. While the specific contribution of ketone bodies to the pleiotropic cardiovascular benefits of SGLT2 inhibitors requires further clarification, ketone bodies themselves may also be used as a therapy for HF.

Objective: Advances in ovarian cancer cytoreductive surgery have enabled more extensive procedures to achieve maximal cytoreduction but with a consequent increase in postoperative morbidity and mortality. The aim of this study was to evaluate factors for postoperative morbidity after extensive cytoreductive surgery for primary epithelial ovarian cancer (EOC), particularly those which may be modifiable. Methods: Electronic databases were searched. Meta-analysis was conducted using random-effects models. Results: Fifteen relevant studies, involving 15,325 ovarian cancer patients, were included in this review. Severe 30-day postoperative complications occurred in 2,357 (15.4%) patients. The postoperative mortality rate was 1.92%. Meta-analysis demonstrated that patient with following risk factors; age (p<0.001), Eastern Cooperative Oncology Group score >0 (p=0.001), albumin level <3.5 g/dL (p<0.001), presence of ascites on CT scan (p=0.013), stage IV disease (p<0.001) and extensive surgical procedure (p<0.001) has a significantly increase risk of developing postoperative complications. Surgical procedures including peritonectomy (p=0.012), splenectomy (p<0.001) and colon surgery (p<0.001) were significant predictors for postoperative complications. Moreover, we found that patients who received neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) had a lower risk of developing severe complications compared to those who underwent primary debulking surgery (PDS) (p<0.001). Conclusion Our study demonstrated that patient performance status and hypoalbuminemia were the only significant adjustable preoperative risk factors associated with postoperative complications. Patients who underwent NACT-IDS had a lower risk of developing severe complications compared to PDS.

Vaccination the pulmonary route could be an attractive alternative to parenteral administration. Research towards the best site of antigen deposition within the lungs to induce optimal immune responses has conflicting results which might be dependent on the type of vaccine and/or its physical state. Therefore, in this study, we explored whether deep lung deposition is crucial for two different vaccines, .., influenza and hepatitis B vaccine. In view of this, influenza subunit vaccine and hepatitis B surface antigen were labeled with a fluorescent dye and then spray-dried. Imaging data showed that after pulmonary administration to mice the powders were deposited in the trachea/central airways when a commercially available insufflator was used while deep lung deposition was achieved when an in-house built aerosol generator was used. Immunogenicity studies revealed that comparable immune responses were induced upon trachea/central airways or deep lung targeting of dry influenza vaccine formulations. However, for hepatitis B vaccine, no immune responses were induced by trachea/central airways deposition whereas they were considerable after deep lung deposition. Thus, we conclude that deep lung targeting is not a critical parameter for the efficacy of pulmonary administered influenza vaccine whereas for hepatitis B vaccine it is.

Objective :To explore influence of different doses of clopidogrel combined aspirin on platelet related inde—xes and safety in patients with unstable angina pectoris (UAP).Methods : A total of 92 UAP patients treated in our hospital were randomly and equally divided into large dose clopidogrel combined group (received 150mg／d clopi—dogrel combined aspirin ) and routine dose clopidogrel combined group (received 75mg／d clopidogrel combined aspi—rin) ,both groups were continuously treated for three months .Therapeutic effect , medication safety , level of thrombolytic granule membrane protein (GMP)—140 ,maximum platelet aggregation rate (LTA—PAmax ) and ADP—induced maximum platelet amplitude (MAADP ) were compared between two groups .Results : After three—month treatment ,there were no significant difference in total effective rate ,incidence rate of major adverse cardiovascular events ,GMP—140 level ,LTA—PAmax and MAADP between two groups , P＞0. 05 all.Incidence rate of severe hemor—rhage in large dose clopidogrel group was higher than that of routine dose group (6.52% vs.2. 17%) without signifi—cant difference ( P＝0.609).Conclusion : Increased dose of clopidogrel combined aspirin doesn＇t obtain significant therapeutic effect ,but may be risk of hemorrhage for unstable angina pectoris ,which calls for clinical attention

Objective: To observe the endoscopic morphology of gastric varices of patients with portal hypertension type one isolated gastric varices (IGV-1) and to explore the etiology, treatment and prognosis of portal hypertension IGV-1. Methods: From January 2006 to June 2018, at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and North Branch of Ruijin Hospital, 54 patients with portal hypertension IGV-1 were retrospectively analyzed. The varices were classified according to the endoscopic morphology and the etiology treatment, therapeutic efficacy and prognosis were also analyzed. Descriptive method was used for statistical analysis. Results: Among the 54 patients with portal hypertension IGV-1, the endoscopic morphology of varices were tuber type in 24 patients (44.4%), grape string type in nine patients (16.7%), strip type in five patients (9.3%), dendritic type in three patients (5.6%) and mixed type in 13 patients(24.1%). Etiological analysis showed that the primary disease of 34 cases (63.0%) were hepatogenic, 11 cases (20.4%) were pancreatic origin, and nine cases (16.7%) were from other diseases. As to treatment, three cases (5.6%) were treated with adhesive, two cases (3.7%) were treated with sclerotherapy, and 49 cases (90.7%) were treated with combination of adhesive and sclerotherapy. Therapeutic efficacy evaluation showed that 46 cases (85.2%) were significantly effective, eight cases were effective, 0 case was ineffective, and all the 54 cases (100.0%) were improved. The prognostic analysis showed that 35 cases (64.8%) had no bleeding in five years and eight cases (14.8%) had no bleeding in 10 years. Nine patients (16.7%) died, including six cases of pancreatic cancer, two cases of liver failure and one case of gastrointestinal bleeding. Conclusions The endoscopic morphology of IGV-1 portal hypertension in mainly tuber type. The main cause is hepatogenic and the combination of adhesive and sclerotherapy is beneficial to the regression of gastric varices.

Objective To evaluate the clinical significance of positive peritoneal cytology in patients with endometrial cancer.Methods The records of 315 patients with endometrial cancer who were operated at Cancer Hospital, Fudan University between January 1996 and December 2008 were reviewed.Peritoneal cytology were performed and diagnosed in all patients.Factors related with peritoneal cytology were analyzed by correlation analysis.Log-rank test and Cox regression test was used for the analysis of prognosis,respectively.Results (1) Peritoneal cytology were positive in 30 (9.5%) patients.Positive peritoneal cytology was associated with pathological subtype ( P = 0.013 ), stage ( P = 0.000 ), myometrial invasion ( P =0.012), lymph-vascular space invasion ( P = 0.012 ), serosal involvement ( P = 0.004 ), cervical involvement ( P = 0.016), adnexal involvement ( P = 0.000), and omental involvement ( P = 0.000), with no association with grade ( P = 0.152 ) and lymph node metastasis ( P = 0.066 ).( 2 ) Three-year overall survival (OS) and progression-free survival(PFS) were 93.0% and 85.5% ,respectively.Positive peritoneal cytology, surgical stage, pathological subtype, myometrial invasion, grade, and lymph-vascular space invasion were significantly associated with worse prognosis by univariate analysis ( P ＜ 0.05 ), while only surgical-pathology stage and myometrial invasion were independent prognostic factors by multivariate analysis ( P ＜ 0.05 ).For 30 cases with positive peritoneal cytology, the patients with no high risk factors shown significantly prognoses better than those with any risk factors.The results shown that for patients with late stage (stage Ⅲ - Ⅳ ) endometrial cancer with positive peritoneal cytology was significantly associated with the worse OS and PFS by multivariate analysis ( P = 0.006).Conclusions Positive peritoneal cytology was associated with serosal involvement, cervical involvement, adnexal involvement, omental involvement, and late stage.Therefore, peritoneal cytology should be performed and reported separately as a part of full surgical staging procedure.