Obgective To analyze the demographic data,non-specific items,pathogens and antibiotic sensitivity between the children with early-onset and late-onset sepsis,in order to guide the diagnosis and treatment of neonatal sepsis.Methods Three hundred and fifty-two cases with positive blood culture were retrospectively recruited and divided into an early-onset group and a late-onset sepsis group according to the onset of sepsis.Results Of 352 cases,144 cases (40.91％) were the early-onset children while 208 cases (59.09％) were the late-onset children,and in the late-onset group,108 cases occurred due to nosocomial infection.Most neonates of the early-onset term were term infants [107/144 cases (74.31％)],while the preterm infants [77/208 cases (37.02％)] and low birth weight infants[70/208 cases(33.65％)] accounted for the majority of the late-onset group.The asphyxia,perinatal intrauterine distress,meconium-staining amniotic fluid and premature rupture of fetal membranes ≥ 18 h occurred more frequently in the early-onset group [21/144 cases (14.58％),14/144 cases (9.72％),26/144 cases (18.06％),31/144 cases (21.53％)],respectively,while those in the late-onset group were [17/208 cases (8.17％),9/208 cases(4.33％),13/208 cases(6.25％),17/208 cases(8.17％)],respectively,there were significant differences (x2 =4.622,3.886,5.950,13.345,all P ＜ 0.05) between 2 groups.In the early-onset group abnormal temperature[72/208 cases(34.62％)vs 30/144 cases(20.83％)],vomiting or abdominal distention[109/208 cases (52.40％) vs 35/144 cases (24.31％)],lethargy [79/208 cases (37.98％) vs 38/144 cases (26.39 ％)] and umbilicalitis or skin pustule [33/208 cases (15.87 ％) vs 11 / 1 44 cases (7.64 ％)] occurred more frequently in late-onset group,and there were significant differences (x2 =7.853,8.763,5.153,5.265,all P ＜ 0.05).Besides,more cases in the late-onset group had elevated immature neutrophil vs total neutrophil count ratio [27/184 cases (14.67％)] and C-reactive protein value [76/206 cases (36.89％)],compared with those in early-onset group [9/133 cases (6.77％),38/143 cases(26.57％)],and there were significant differences (x2 =4.794,4.087,allP ＜ 0.05).Compared with early-onset group,patients in the late-onset group were more likely to suffer from suppurative meningitis [17.79％ (37/208 cases) vs 8.33％ (12/144 cases);x2 =6.348,P ＜ 0.05].In terms of pathogens,the main pathogens in the early-onset group were gram negative bacteria[39.58％ (57/144 cases),including detection of Klebisella pneumoniae in 21 cases and E.coli in 20 cases] and coagulase negative staphylococcus[32.64％ (47/144 cases)].In late-onset group,the main pathogens were gram positive bacteria [58.65％ (122/208 cases)],including detection of coagulase negative staphylococcus in 90 cases(43.27％) and E.coli [17.79％ (37/208 cases)].There was no significant difference in prognosis between 2 groups(x2 =1.187,P =0.552).Conclusions Early-onset sepsis and late onset sepsis differ in the clinical manifestation and laboratory findings.Distinguishing neonatal early-onset and late onset septicemia is of clinical significance in choosing appropriate antibiotics.

Objective To investigate the possible influence of immunosuppressive therapy,including sirolimus (SRL) and calcineurin inhibitors (CNI, tacrolimus), on level of Treg in the liver allo-graft recipients, Methods Forty-seven liver transplant recipients with stable liver function were assessed for at least 2 years, and divided into two groups: one composed of 15 patients receiving SRL,and another, of those receiving CNI (32 patients with tacrolimus). Thirty-eight age-matched healthy subjects (HS) were used as normal controls. We examined the expression of CD4, CD25, and Foxp3 in peripheral blood monouclear cells. Treg of every group was analyzed using Cell Quest software.Results SRL significantly increased the prevalence of CD4+ CD25high T cells, compared with HS and CNI group. The prevalence of CD4+ CD25high T cells of CNIs group was significantly lower than that of HS. The percentage of CD4+ CD25high T cells in the total CD4+ T cells was 1.88 % (1.56 %-2. 60 %), 1. 15 % (0. 57 %-l. 48 %) and 0. 84 % (0. 46 %-1. 45 %) in SRL, NS and CNI group,respectively (P<0. 01 or P<0. 05). Foxp3 was expressed in more than 95 % of CD4 + CD25high T cells and less than 20 % of CD4+ CD25low T cells, whereas not expressed in CD4+ CD25- T cells.Conclusion Different immunosuppressive therapy (SRL or CNI) might have different roles in tolerance induction in liver transplant recipients. Namely, SRL promoted the induction of allo-antigen tolerance, but CNI hampered the progression.

Urinary sodium was measured by means of 24-hour urine collection in 186 patients with type 2 diabetes.All patients were categorized into quartiles of urinary sodium.There was a significant positive trend of association of greater carotid intima-media thickness(CIMT) with increasing urinary sodium quartile,even adjusting for age,smoking,and blood pressure (Ptrend＜0.01).Multiple linear regression analysis showed that 24-hour urinary excretion may be associated with CIMT in type 2 diabetes patients (β=0.074,P＜0.01).

PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z′-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. RESULTS: c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC₅₀ values of 297 nmol/L, 1.31 µmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. CONCLUSION: In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting it's potential antitumor activity.
Adenosine Triphosphate ; Blotting, Western ; Carcinogenesis ; Carcinoma, Non-Small-Cell Lung* ; Cell Movement ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Hepatocyte Growth Factor ; Lung Neoplasms ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Protein-Tyrosine Kinases

【Objective】 To establish and optimize a method for the determination of aluminum (Al) residue by inductively coupled plasma mass spectrometry (ICP-MS). 【Methods】 Nitric acid solution was used to treat samples and standards. The concentration of nitric acid solution and equipment parameters were optimized, and the specificity, linearity, repeatability, accuracy, detection limit, quantitative limit and intermediate precision of the optimized detection method were investigated to confirm whether it was suitable for the determination of Al residue in human serum albumin. 【Results】 The concentration of nitric acid was 5%, and digest time was 4 h. The equipment condition of ICP-MS was as follows: RF power: 1600 W, sampling depth: 10 mm, atomizer / carrier gas flow rate: 1.0 L/ min, compensation flow rate: 0.5 L/ min, experimental mode: standard mode, integration time: 0.2 s, data acquisition: 3 times. Specificity: The recoveries of Al: 92% (high concentration, RSD=3.5%), 98% (low concentration, RSD=4.9%). Linearity: In the range of (0~40) μg/L, the correlation coefficient between concentration and optical energy signal (CPS) of standard / sample were higher than 0.999 0. Accuracy/ Repeatability: The recoveries of sample (3 concentration): 108% (RSD=4.7%), 110% (RSD=4.9%) and 110% (RSD=2.8%). The detection limit was 0.006 μg/L, and the quantitation limit was 0.019 μg/L. Intermediate precision: personnel factor and date factor, P>0.05, RSD (12 times)=2%. Comparison between ICP-MS and atomic absorption spectrometry (AAS): the deviation between ICP-MS and AAS was 8%, and that of samples was 3%, with no significant difference noticed between the two methods. 【Conclusion】 After optimization, ICP-MS method has shown good performance in terms of specificity, linearity, repeatability, accuracy, detection limit, quantitative limit and intermediate precision, and is suitable for the determination of Al residue in human albumin products of our company.

【Objective】 To investigate the matrix effect on the determination of potency in Recombinant Human Coagulation Factor Ⅷ for Injection (rFⅧ). 【Methods】 Two different detection matrices were used to establish two methods for detecting the potency in Recombinant Human Coagulation Factor Ⅷ for Injection. And the matrix effect on the determination of potency was determined, including specificity, linearity, repeatability, accuracy and intermediate precision. 【Results】 As to the specificity, the recoveries of the two substrates at high vs low concentration level were 112% and 110% vs 104% and 109%, respectively. As to the linearity, in the range of (0.125-1.000) IU/mL, the correlation coefficient between concentration and coagulation time of standard/ sample was higher than 0.99. As to the accuracy/repeatability, the recoveries of two matrices was 104% and 102%, and RSD was 2.4% and 1.9%. As to the intermediate precision, personnel factor of two matrices was 0.72 and 0.23, date factor was 0.79 and 0.85, and RSD(for 12 times) was 4.2% and 3.0%. Comparison of two matrices was as follows: Deviation in test results of 6 batches of rFⅧ was all lower than 5%. There was no significant difference between two matrices. 【Conclusion】 The two matrices for potency detection show good performance including specificity, linearity, repeatability, accuracy, and intermediate precision. They are suitable for the determination of potency in rFⅧ products.

OBJECTIVE： To promote rational use of proton pump inhibitors （PPIs） during perioperative period. METHODS： PDCA （Plan， Do， Check， Action） cycle management was used， the irrational use of PPIs of 300 medical records in neurosurgery department of our hospital were collected. The reasons were analyzed， management target was formulated and measures were implemented. The effects of management were evaluated through comparing the rate of irrational drug use and ratio of irrational type of PPIs in 300 medical records of neurosurgery department during perioperative period after management. RESULTS： Through collecting related data to confirm risk factors of stress ulcer， establishing rationality evaluation criteria for perioperative prophylactic use of PPIs， conducting rational drug use training among medical staff， drawing up various management systems and strengthening supervision and management， the rate of irrational use of PPIs was decreased significantly in our hospital； the number of irrational drug use cases decreased from 240 before management to 156 after management， among which the rate of prophylactic drug use without indication decreased from 37.33％ to 29.00％ （P＜0.05）； the irrational dosage rate decreased from 11.33％ to 6.33％ （P＜0.05）； the rate of irrational dosing frequency dropped from 12.67％ to 5.00％ （P＜0.01）. CONCLUSIONS： PDCA cycle management of our hospital can standardize the prophylactic use of PPIs in neurosurgery department during perioperative period and promote rational use of PPIs.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.