Objective:To observe the influence of erythropoietin (EPO)combined adjuvant iron treatment on cardiac function,exercise capacity and anemia in patients with diastolic heart failure (DHF)complicated anemia.Methods:A total of 94 DHF + anemia patients were randomly divided into routine treatment group (n=46)and combined treatment group (n=48,received EPO combined adjuvant iron treatment based on routine treatment).Patients re-ceived 6min walking test,levels of hemoglobin (Hb)and N-terminal pro brain natriuretic peptide (NT-proBNP), transmitral early diastolic peak velocity deceleration time (DT),early diastolic peak flow velocity (E),late diastolic peak flow velocity (A)and E/A etc.were measured and compared between two groups before and after six-month treatment.Results:Compared with before treatment,after treatment,NT-proBNP and DT significantly reduced, E/A and 6min walking distance significantly rose in both groups,P <0.05 or <0.01;compared with routine treat-ment group after treatment,there were significant reductions in NT-proBNP level [(368.4±110.7)pg/ml vs.(239 ±89.7)pg/ml]and DT [(257.5±73.4)ms vs.(208.9±59.1)ms],and significant rise in Hb level [(83.3±9.2) g/L vs.(122.1±13.6)g/L],E/A [(0.87±0.3)vs.(1.07±0.27)]and 6min walking distance [(367.54±21.08) m vs.(438.63±20.35)m]in combined treatment group,P <0.05 all.Conclusion:Erythropoietin combined iron treatment can better improve heart function and exercise capacity in patients with diastolic heart failure complicated anemia.

Aim Tostudytheantidepressanteffectand mechanism of Gross saponins of Tribulus terrestris. Methods Themodelofdepressionwasestablishedby unpredictable chronic mild stress(UCMS),then open filed test (OFT)and tail suspension test (TST)were used to evaluate the behavioral changes.LC-MS/MS method was employed to measure blood neurotransmit-ters.mRNA expressions of IDO,IL-10 and IL-1βwere detected by quantitative PCR method.Hippocampus protein expression was detected by Western blot.Re-sults Comparedwithcontrolgroup,modelgroup's total distance,number of standing and tail suspension fixed time increased significantly (P <0. 05 ),Neuro-transmitter level of 5-HT in the blood was significantly decreased(P<0. 05 ).mRNA expression of IDO and IL-1βwas increased in hippocampus.Protein expres-sion of IDO was significantly increased in hippocampus (P <0. 05 ).Compared with model group,the treat-ment group was significantly decreased in total distance,number of standing and tail suspension fixedtime(P<0. 05).Neurotransmitter level of 5-HT in the blood and mRNA expression of IL-10 in hippocampus were significantly increased after treatment (P <0. 05 ).mRNA and protein expression of IDO were ob-viously down-regulated in hippocampus (P <0. 05 ). Conclusions GrosssaponinsofTribulusterrestriscan obviously improve rat behavior and show antidepressanteffect,which can increase neurotransmitter level of 5-HT in the blood,down-regulate mRNA expression of IDO and IL-1β,and obviously increase protein expres-sion levels of IDO in hippocampus(P<0. 05 ).

Purpose To optimize the preparation of NC-1900 loaded MePEG-PLA nanoparticles (NPs). Methods MePEG-PLA copolymers of different molecular weight synthesized by solvent poly-merization method were used to prepare NC-1900 loaded MePEG-PLA NPs by double emulsion/solvent evaporation method.Orthogonal experimental design and multiple regressions were used to optimize the preparation method with nanoparticle size and NC-1900 encapsulation efficiency (EE) as res-ponse variables.NPs were characterized by particle size and Zeta potential detector and transmission electron microscope.The leakage of NC-1900 from NPs was evaluated by high-performance liquid chromatography (HPLC) detection. Results MePEG3000-PLA44800 NPs prepared according to the optimized conditions had a mean diameter of (77 ± 11) nm and EE of (21.4 ± 0.1) %.Only 5% and 15% of NC-1900 were leaked in pH 7.4 PBS and blank plasma at the end of 48 h,respectively. Conc-lusions The optimized MePEG3000-PLA44800 NPs is a favorable carrier for NC-1900.

Objective: To explore change of hemoglobin (Hb) concentration, the relationship between anemia and left ventricular function and the influence of anemia on prognosis in patients with diastolic heart failure (DHF). Methods: According to NYHA classification, a total of 176 DHF patients were divided into class Ⅱ group (n=78), class Ⅲ group (n=50) and class Ⅳ group (n=48), then Hb level and morbidity rate of anemia were analyzed in each group. According to diagnostic standard of anemia, patients were divided into anemia group (n=58, , occupied 33.0%) and non anemia group (n=118, occupied 67.0% ). Left ventricular diastolic function, mortality rate and rehospitalization rate during follow-up were compared and analyzed between two groups. Results: Along with cardiac function class rose (from class Ⅱ to class Ⅳ), Hb level showed a decreasing trend [(130±6) g/L vs. (108±4) g/L vs. (96±12) g/L], while morbidity rate of anemia gradually rose (8.97% vs. 36.0% vs. 68.8%), P<0.05 all in anemia group；Compared with non-anemia group, there were significant rise in percentages of patients with coronary heart disease (55.1% vs. 65.5%), levels of creatinine [(87.6±39.2) μmol/L vs. (113.7±59.8) μmol/L] and N terminal pro B type natriuretic peptide [NT-proBNP, (578.0±136.7) pg/ml vs. (886.0±174.8) pg/ml], and early-diastolic peak velocity deceleration time [(137±15)ms vs. (196±13)ms], and significant reduction in mitral early/late diastolic peak flow velocity [E/A, (0.87±0.32) vs. (0.62±0.29)], P<0.05 all. Compared with non-anemia group, there were significant rise in mortality rate (9.3% vs. 20.7%) and rehospitalization rate (18.6% vs. 32.8%) in anemia group during follow-up, P<0.05 all. Conclusion: DHF patients often complicate with anemia. Along with heart failure aggravates, their morbidity rate of anemia rises, and anemia may aggravate cardiac diastolic dysfunction. Mortality rate and rehospitalization rate rise in DHF patients complicated with anemia.

Background Elevated intraocular pressure leads to the loss of retinal ganglion cells and vigorous reaction of retinal glial cells.The expression of nestin in retinal glial cells secondary to hypertention and its significance are unclear.ObjectiveThis study aim to investigate the expression of nestin in retinal glial cells (RGCs) in ocular hypertention rats.Methods The ocular hypertention models were established by cauterizing the limbus-draining veins in the right eyes of 42 SD rats,and a conjunctival incision in the left eyes of the rats served as the sham group.The intraocular pressure (IOP) was measured with the Tono-Pen XL tonometer.The number of RGCs in the rats with ocular hypertention was counted.The expression of the nestin protein in RGCs was semi-quantitatively analyzed using Western by immunochemistry.Double immunofluorescence was carried out to evaluate the the confocal laser scaning microscope.Results Significant differences were found in the IOP between the model group and the sham group at various time points (P＜0.05).In 1 week to 3 weeks after operation,the number of RGCs significantly declined in the model group compared with the sham group (P＜0.05).Immunochemistry showed that from 2 hours through 1 week after operation,the expression of nestin was gradually enhanced in the model group in comparison with the sham group.Western blot revealed that the expression of the nestin protein reflected a similar tendency to that of immunofluorescence.The increased introcular pressure as manifested by the induced expression of nestin.Immunoelectron microscopy also confirmed the induced expression of nestin especially at their end-feet suggests a potential neuroprotective mechanism in neuronal degeneration.Nestin may be a useful biomarker for retinal injury study.

Aim To study of the expression and distribution of four α-synuclein truncations in three cells.Method Four α-synuclein gene truncations were obtained by PCR method,followed by subcloning into the pEGFP-N1 eukaryotic expression vector.Four obtained recombination plasmids were transfected into MN9D cells,PC12 cells and SH-SY5Y cells using Lipofectamine 2000 respectively.The expression and distribution of four α-synuclein truncations were observed by Confocal.Results Distribution of four α-synuclein truncations was discrepant obviously,the truncations,with more C terminal remained,were prone to emerging in nuclei.Conclusion Localization of α-synuclein protein in cells may be related to the C terminal,and the whole C terminal plays an important role in distribution of α-synuclein into nuclei.

Objective: To evaluate the predictive value of plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) on short term prognosis in patients with acute coronary syndrome (ACS). Methods: Plasma NT-proBNP levels were measured in ACS patients within 24 h after admission with ELISA method. The 600 ACS patients were divided into two groups: event group （n=108）and no-event group （n=492）according to occurrence of cardiovascular events（including cardiac death, cardiac shock and heart failure）, The NT-proBNP levels were compared between two groups. Single factor and multiple factor Logistic regression analyses were used to evaluate if NT-proBNP was an independent predictor for short term prognosis. Results: The plasma NT-proBNP levels of event group were significantly higher than those of no-event group [1361.2 (965.3, 2088.6) pmol/L vs.605.7 (274.5, 1177.8) pmol/L, p<0.01]. Multiple factor Logistic regression analyses demonstrated that plasma NT-proBNP was an independent predictor for short term prognosis (OR=1.000, p<0.01) in ACS patients. Conclusion: Plasma NT-proBNP was an independent predictor for short term prognosis in ACS patients.

Objective:To investigate the relationship between the expression of serum exsomal miRNA-155-5p (miR-155-5p) and prognosis in patients with esophageal squamous cell carcinoma (ESCC).Methods:A total of 336 samples from ESCC patients in Fujian Provincial Cancer Hospital from October 2014 to December 2015 were collected. The relative expression levels of serum exsomal miR-155-5p were detected by using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). Cut-off value of the expression levels of serum exsomal miR-155-5p was determined by using X-tile software. Based on the optimal cut-off value, patients were divided into miR-155-5p low expression group and miR-155-5p high expression group. The survival curve was drawn by using Kaplan-Meier method and Cox proportional hazards regression model was used to make survival analysis.Results:The cut-off value of serum exsomal miR-155-5p expression level was 2.340. According to the cut-off value, patients were divided into miR-155-5p low expression group (<2.340) of 51 cases and miR-155-5p high expression group (≥2.340) of 285 cases. There were no statistical differences in age ( χ2 = 0.020, P = 0.887), gender ( χ2 = 0.283, P = 0.595), tumor location ( χ2 = 0.063, P = 0.977), differentiation grade ( P = 0.474), clinical staging ( χ2 = 3.996, P = 0.136) and surgery treatment ( χ2 = 0.941, P = 0.332) of patients in both groups. ESCC patients in serum exsomal miR-155-5p high expression had a higher risk of death compared with patients in miR-155-5p low expression group ( HR = 1.763, 95% CI 1.049-2.961, P = 0.032). Conclusion:The high expression level of serum exsomal miR-155-5p is associated with poor prognosis in ESCC patients and it could be used as a prognostic new marker in ESCC patients.

Objective:To investigate the clinical features and prognosis of patients with pancreatic metastasis from clear cell renal cell carcinoma(CCRCC).Methods:From Jan 2000 to May 2020, the clinical data of patients pathologically diagnosed as CCRCC with pancreatic metastasis and admitted in Cancer Institute and Hospital of Tianjin Medical University were analyzed retrospectively. The gender, age, metastasis time, relapse time, metastatic sites, numbers of metastatic lesions and whether metastatic pancreatic lesions should be surgerically removed were recorded and the influencing factors were analyzed.Results:Among the 20 patients, there were 12 males and 8 females. The median age of diagnosis was 50 years. There were 12 patients(60%) of left renal carcinoma and 8 patients(40%)of the other side. 12 cases(60%) had single pancreatic metastatic lesion and the other 8 cases(40%) had multiple metastatic lesions. Seven patients(35%) had other organs metastasis besides pancreatic metastasis. Two patients(10%) had simultaneous pancreatic metastasis and renal cancer, and the other eighteen patients(90%) had pancreatic metachronous metastasis after being diagnosed as renal cancer. The median time from the diagnosis of CCRCC to pancreatic metastasis was 102 months. Thirteen patients(65%)had recurrences within 10 years and the other seven patients(35%)had recurrences after 10 years. Pancreatectomy was performed in nine patients(45%) and targeted therapy was conducted in thirteen patients. The mean follow-up was 122.9 months (1-256 months). Three patients (15%) died and 17 patients (85%) survived. The median overall survival was 75.9 months, and the 5 year-survival rate was 66.7%. Simultaneous metastasis and extra-pancreatic metastasis were prognostic factors in patients with CCRCC with pancreatic metastasis.Conclusions:Pancreatic metastases from renal clear cell carcinoma were rare, but the prognosis was good, especially in patients with only pancreatic metastases several years after renal carcinoma was diagnosed.

OBJECTIVE To mine the adverse drug events （ADE） signals for gilteritinib， and provide a reference for safe drug use in clinic. METHODS ADE reports with gilteritinib as the primary suspected drug were extracted from the FDA Adverse Event Reporting System （FAERS） database from February 1st， 2018 to December 31st， 2023. Reporting odds ratio （ROR） and proportional reporting ratio （PRR） were applied to detect the risk signals from the data in the FAERS database. The classification and statistics of collected signal data were conducted by using the preferred term （PT） and systemic organ class （SOC） in ADE terminology set of the Medical Dictionary for Regulatory Activities （24.1 edition）. RESULTS Totally， 2 755 gilteritinib-related ADE reports were collected from the database， involving 676 ADE signals （95 positive signals）， 313 PTs and 25 SOCs. Among them， nine signals were not recorded in the package insert. The top 5 PTs consisted of abnormal liver function， decreased platelet count， febrile neutropenia， pneumonia and myelosuppression. The top 6 SOCs for positive signal counts were examinations， general disorders and administration site conditions， respiratory， thoracic and mediastinal disorders， infections and infestations， heart organ disorders， and nervous system disorders. ADEs not recorded in the drug package insert included pneumonia， myelosuppression， decreased blood cell count， sepsis， hemorrhage， infection （not specifically referred to）， septic shock， respiratory failure， and aspergillosis. CONCLUSIONS In addition to paying attention to common ADEs such as liver dysfunction and thrombocytopenia， it is necessary to monitor ADEs with strong signals that are not mentioned in the drug instructions when using gefitinib， such as pneumonia， bone marrow suppression， cytopenia， sepsis， bleeding， infection （not specifically referred to）， septic shock， respiratory failure， Aspergillus infection， elevated serum creatinine and interstitial lung disease.