OBJECTIVE To investigate enhanced immune function of methionine encephalin (MENK) and its anti-tumor mechanism in CT26 colon cancer mouse model. METHODS 3×106 CT26 cells were implanted subcutaneously in BALB/c mice. Four days after, MENK was peritoneally administrated at the concentration of 20 mg·kg-1 for 14 d. The percentage of MDSCs in bone marrow, spleen, blood, tumor and liver were detected by flow cytometry. Non- esterified fatty acid (NEFA), triglycerides (TG) and total cholesterol (T-CHO) in liver homogenate were tested by a NEFA test kit, a TG test kit and a T- CHO test kit respectively. qRT- PCR and Western blot were used to measure mRNA and protein levels of inflammation-, glycometabolsim- and lipometabolsim-associated indexes in liver. RESULTS MENK decreased percentages of MDSCs in bone marrow, spleen, blood and tumor in colon cancer mice. MENK-treated mice displayed elevated ratio of CD4+T and CD8+T cells in spleen as well as increased T and B lymphocytes proliferation. Meanwhile, MENK also ameliorated liver damage reflected by lower levels of GPT and GOT in serum and reduced risks of cancer- associated index including inflammation, high lipid and high glucose. Furthermore, MENK lowered down the levels of NEFA, TG and T- CHO in liver homogenate. MENK treatment decreased expression of p- STAT3, increased expression of p-AKT, IRS1 and Glut4 at protein level as well as reduced lipogenesis-associated genes and elevated glycolysis-associated genes in liver of tumor bearing mice. Also, abated expression of genes associated with MDSCs generation (M-CSF, GM-CSF, IL-6, IL-1β) and migration (S100A9, KC) was observed within shrunken subcutaneous tumor by MENK intervention. CONCLUSION MENK has the ability to strength immune function against colon cancer by reducing MDSCs and improving liver metabolism.

Objective To observe the effect of embelin on the cardiac injury in sepsis mice model, and to explore whether PPAR-participates in the mechanism of cardioprotection of embelin.Methods Male mice were randomly divided into five groups.Control group were received PBS i.p.injection.Sepsis model group were received LPS (10 mg/kg) i.p.injection.Embelin treatment groups were received LPS (10 mg/kg) i.p.injection, and after 30 min different doses of embelin were given (5, 10, and 20 mg/kg, i.p.).Results The serum cTnI level and TNF-α、NF-κB protein in low dose embelin (5 mg/kg) treatment mice was not different with that of the sepsis mice.But the serum cTnI level and TNF-α、NF-κB protein in middle and high doses embelin (10, 20 mg/kg) treatment mice was lower than that of sepsis mice, and the expression of PPAR-γ was higher(P<0.05).Conclusion Embelin could protect against sepsis-induced cardiac injury.The mechanism might be involved in the upregulation of PPAR-γ protein, inhibition of NF-κB activation,and reduction of TNF-α level.

To investigate the high-risk factors for newborn hearing loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to pass the universal newborn hearing screening (UNHS) were referred to Jinan Newborn Hearing Screening and Rehabilitation Center from 7 newborn hearing screening centers in seven cities of Shandong province. One-to-one pair-matched case-control method was employed for statistical analysis of the basic features of definitely identified cases. High-risk factors relating to the bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. Our results revealed that 721 transferred newborns who didn't pass the hearing screening received audiological and medical evaluation and 367 were confirmed to have hearing loss. Of them, 177 neonates with hearing loss who met the matching requirements were included in the study as subjects. Univariate analysis showed that high-risk factors related to hearing loss incuded age of father, education backgrounds of parents, parity, birth weight, gestational weeks, craniofacial deformity, history of receiving treatment in neonatal intensive care unit (NICU), neonatal disease, family history of otopathy and family history of congenital hearing loss. Multivariate Logistic regression analysis revealed that 4 independent risk factors were related to bilateral hearing loss, including parity (OR=16.285, 95% CI 3.379-78.481), neonatal disease (OR=34.968, 95% CI 2.720-449.534), family history of congenital hearing loss (OR=69.488, 95% CI 4.417-1093.300) and birth weight (OR=0.241, 95% CI 0.090-0.648). It is concluded that parity, neonatal disease and family history of hearing loss are the promoting factors of bilateral hearing loss in neonates and appropriate intervention measures should be taken to deal with the risk factors.

Objective To observe the therapeutic effect of ulinastatin on traumatic brain edema (TBE) accompanied by pulmonary edema due to seawater drowning in rats. Methods Thirty-two Sprague-Dawley rats were randomly divided into control group (nffi8) and ulinastatin treatment group (n=24). A rat model of moderate brain trauma was established by lateral head impact, and pulmonary edema was induced in these rats by pulmonary lavage with seawater to mimic seawater drowning. Twenty-four hours after intmperitoneal injection of ulinastatin, the changes in the cerebral and pulmonary water contents and concentrations of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in the brain, lungs and serum were measured, and the histopathological changes of the brain and lung tissues were observed. Results The cerebral and pulmonary water contents and the IL-1β and TNF-α concentrations in the serum, brain and lungs of the rats with brain trauma and pulmonary edema were markedly decreased after ulinastatin injection, which also resulted in obvious improvement of the brain and lung pathologies induced by the injuries. Conclusion Ulinastatin can alleviate traumatic brain edema in rats with pulmonary edema due to seawater drowning by inhibiting the proinflammatory cytokines.

Objective To develop a LC-MS/MS method for determination of daptomycinin human plasma.Methods The plasma samples were precipitated by acetonitrile,then the supernatant were separated on Eclipse Plus C18column (2.1 mm × 100 mm,3.5 μm) and eluted with acetonitrile-10 mmol · L-1 ammonium acetate (80∶ 20,containing 0.1％ formic acid),and the column temperature was 25 ℃.Detection of the analyte was achieved using positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode.The MS/MS ion transitions monitored were m/z 811.0→m/z 159.1 and m/z 237.1→m/z 194.1 for daptomycin and internal standard,respectively.The specificity,standard curve and lower limitation of quantitation,precision and recovery rate and stability as well as the matrix effect were investigated.Results The linear regression equation was y =1.49 × 10-2x-2.06 × 10-3 (r =0.9980) The linear range of daptomycin was 0.10-100 μg · mL-1,with the lower limit of quantitation (LLOQ) of 0.10 μg · mL-1.Accuracy was 97.1％-104.8％,Intra-day and inter -dayrelative standard deviations were both below 15％.The absolute recovery in plasma was81.9％-91.4％.The matrix effects were 90.01％-109.28％.Conclusion The established method israpid,sensitive,accurate,specific and reliable,and suitable for the determination ofdaptomycin in human plasma and pharmacokinetic study.

Increasing studies have demonstrated that interferon gamma (IFN-γ),which serves as a critical inflammatory cytokine,is essential to induce the immunosuppressive effects of mesenchymal stem cells (MSCs).However,the mechanisms underlying the enhanced immunosuppressive effects of IFN-γ-stimulated MSCs (γMSCs) are not fully understood.MSC-derived rnicrovesicles (MSC-MVs) have been viewed as potential pivotal mediators of the immunosuppressive effects of MSCs.Moreover,microRNAs (miRNAs) are important regulators of immunological processes and can be shuttled from cell to cell by MVs.The aim of our study was to analyze the the miRNA expression signature of MVs derived from γMSCs (γMSC-MVs),which may provide better understanding of the immunosuppressive property of their parent cells.Through miRNA microarray and bioinformatics analysis,we found 62 significantly differentially expressed miRNAs (DEMs) in γMSC-MVs compared with MSC-MVs.And the potential target genes and signaling pathways regulated by DEMs were predicted and analyzed.Interestingly,many DEMs and predicted signaling pathways had been.demonstrated to be involved in immunoregulation.Furthermore,the network between immunoregulation-related pathways and relevant DEMs was constructed.Collectively,our research on the miRNA repertoires of γMSC-MVs not only provides new perspectives into the mechanisms underlying the enhanced immunosuppressive property of γMSCs,but also paves the way to clinical application of these potent organelles in the future.

Objective: To retrospectively analyze the serum calcium level in sepsis patients, understand the influencing factors of abnormality calcium metabolism, and analyze the effect of serum calcium level on sepsis prognosis. Methods: From January 1, 2017 to January 31, 2018, clinical data about sepsis patients admitted hospital were collected. The patients were divided into 2 groups according the levels of serum calcium measured in patients admitted in 24 h: normal serum calcium group (serum calcium 2.03-2.67 mmol/L), and low serum calcium group (serum calcium<2.03 mmol/L). And this study did not find hypercalcemia patients. The data about laboratory test index were compared between two groups. Results: Fifty-two cases were included in this study, including 14 cases of normal serum calcium and 38 cases of hypocalcemia, and the incidence rate of hypocalcemia was 73.1%(38/52). The level of serum calcium in hypocalcemia group was (1.78 ± 0.17) mmol/L, and was (2.16 ± 0.14) mmol/L in normal serum calcium group. The main position of infections in patients with sepsis were digestive system, respiratory system and urinary system. Compared with that in the normal serum calcium group, the number of malnutrition patients in the hypocalcemia group was more. The total protein (TP), albumin (ALB), prealbumin (PAB) and total cholesterol (TCH) in the nutritional status of the patients were lower, the sequential organ failure assessment (SOFA) scores was higher, the prothrombin activity (PTA) was lower, the prothrombin time (PT) was prolonged, and international normalized ratio (INR) was increased. The differences were statistically significant (P<0.05 or <0.01). Pearson correlation test was used to screen the tests and scores related to the concentration of serum calcium. The results showed that the serum calcium concentration was negatively correlated with the level of SOFA scores, procalcitonin (PCT), PTA, thrombin time (PT), activated partial thromboplastin time (APTT) and INR (r=- 0.431, - 0.361, - 0.441, - 0.431, - 0.427, - 0.420, P<0.01 or<0.05), and the serum calcium concentration was positively correlated with TCH, TP, ALB and PAB (r=0.442, 0.475, 0.463, 0.419, P<0.01). Conclusions Hypocalcemia is related to the nutritional status of the body, and is related to coagulation function, serum protein level, PCT concentration and SOFA scores. The decrease of serum calcium indicates that multiple organ dysfunction syndrome may occur, and should be paid more attention to.

Objective To investigate the effect of full nutrition management on cancer patients with chemotherapy, and to support theory bases for the standardized clinical nutrition of cancer patients. Methods From January 2016 to December 2017, a total of 88 patients with the first chemotherapy were recruited and randomly divided into experimental group and control group, with 44 patients in each group. These patients all complied with the inclusion and exclusion criteria, and volunteered for the study. The two groups all received the same of anti-tumor treatment and the same conventional nutritional support (according to the results of nutrition screening and nutrition assessment, the nutritional support was formulated and patients′dietary guidance was given), while only patients of the experimental group were given full nutritional management, including regularly following up the patient′s condition changes, gastrointestinal reactions, and the feed. According to the five-step treatment model of malnutrition, nutritional support was improved in a timely manner, and appropriate nutritional support was provided. At the end of chemotherapy, the change of weight, albumin, prealbumin, hemoglobin was compared with that before treatment in the two groups. Results After chemotherapy, albumin, prealbumin, hemoglobin had no obvious drop compared with that before treatment in two groups (P>0.05). The patients of experimental group showed stable weight after chemotherapy: (53.39 ± 9.24) kg vs. (54.66 ± 9.41) kg, P>0.05. Weight loss in the control group after chemotherapy was statistically significant:(54.61 ± 10.76) kg vs. (56.52 ± 10.46) kg, P<0.05. Conclusions The full nutritional management can help maintain nutrition status during chemotherapy, especially can prevent the weight loss.

The expression of vascular endothelial growth factor(VEGF)in ovarian cancer tissues is closely related to the degree of malignancy of ovarian cancer,and can be an effective target for ovarian cancer treatment.Bevacizumab,as a monoclonal antibody targeting VEGF,can inhibit tumor neovascularization and tumor growth,and is used for the treatment of ovarian cancer,cervical cancer,metastatic colorectal cancer and other malignant tumors.Bevacizumab administered by intraperitoneal perfusion has good efficacy for malignant ascites in tumor patients,and can alleviate patients'clinical symptoms.In recent years,more studies have explored the clinical application method,therapeutic efficacy and related adverse effects of bevacizumab intraperitoneal instillation in the treatment of ovarian cancer,and this article is a review in this field,aiming to provide reference for the clinical treatment of ovarian cancer.

Animals ; Body Weight ; drug effects ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Hematopoietic Stem Cell Mobilization ; Injections, Subcutaneous ; Myocardial Infarction ; drug therapy ; mortality ; pathology ; Rats ; Rats, Sprague-Dawley ; Stem Cell Factor ; administration & dosage ; Ventricular Remodeling ; physiology