OBJECTIVE To discuss the constitution and drug sensitivity of pathogens that cause pulmonary infection in NICU. METHODS Sputa were collected from patients hospitalized in NICU from Mar 2006 to Mar 2007 and analyzed for distribution and drug sensitivity of pathogenic bacteria. RESULTS All 555 strains of pathogenic bacteria were isolated. The most common pathogens were Pseudomonas aeruginosa(183 strains,33.0%),Staphylococcus aureus(114 strains,20.5%) and Klebsiella pneumoniae(56 strains,10.1%). Nearly most pathogenic bacteria were multi-resistant to commonly used antibiotics. Meticillin resistant strains of S. aureus accounted for 97.4%. The percentange of fungi strains was increasing in NICU. The main isolated strains were Candida tropicalis(5.9%),C. albicans(3.8%)and C. glabrata(3.6%). And all of the fungi were sensitive to amphotericin B. fluconazole. and ketoconazole. CONCLUSIONS Pulmonary infections in NICU are mainly caused by Gram-negative bacteria with high rate of drug resistance. It can be of great importance to make drug sensitivity tests at regular intervals to guide the use of antibiotics.

Objective To analyze distribution and drug resistance of pathogenic bacteria isolated from blood specimens of inpa-tients,so as to guiding the principle of clinical use of antibacterials and improve clinical efficacy.Methods The results of bacterial culture and drug sensitivity test of 2 125 blood specimens,from November 2012 to November 2014,in the Rizhao Hospital of Tradi-tional Chinese Medicine were retrospectively analyzed.Results A total of 233 strains of pathogens were isolated(the positive rate was 10.96%),including 57 strains of gram-positive coccus(accounted for 24.46%)and 1 74 strains of gram-negative bacilli(accoun-ted for 74.68%).The coagulase-negative staphylococci and Staphylococcus aureus were most common in gram-positive coccus,the detection rate of methicillin-resistant coagulase-negative staphylococci (MRCNS)and methicillin-resistant Staphylococcus aureus (MRSA)were 84.2% and 40.0%,respectively.The rate of drug resistance of coagulase-negative staphylococci and Staphylococcus aureus to penicillin,erythromycin and clindamycin were no less than 80.0%.The Escherichia coli,Klebsiella pneumoniae and Pseud-omonas aeruginosa were most common in gram-negative bacilli,the detection rate of extended spectrum beta-lactamases(ESBLs) producing Escherichia coli and Klebsiella pneumoniae were 35.85% and 28.13%,respectively.The sensitive rate of Escherichia coli and Klebsiella pneumoniae to imipenem were both 100.0%.Conclusion Gram-negative bacilli is the most common pathogen in this hospital and multidrug resistance is observed.Therefore,cultures of blood specimen should be timely submitted in order to guiding the rational antimicrobial application in clinic.

Objective: To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) . Methods: Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events. Results: Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51.9% (14/27) and 66.7% (18/27) respectively, including 1 sCR (3.7%) , 3 CR (11.1%) , 3 VGPR (11.1%) , and 7 PR (25.6%) . In 13 patients with prior Rd, ORR and CBR were 38.5% (5/13) and 61.5% (8/13) respectively, of which 5 patients with ≥MR carried high-risk cytogenetic[ (e.g.17p- or t (4;14) ] together with at least one of other adverse-prognostic cytogenetic (e.g.13q- and/or 1q21+) . In 24 patients with prior bortezomib-based therapy, ORR and CBR were 45.8 and 62.5%, respectively. With a median follow-up time of 14.9 (range 1.0-33.8) months, the median PFS and OS were 12.0 (95%CI 11.6-12.4) and 27.6 (95%CI 15.1-40.1) months, respectively. The BiRd regimen was well tolerated. Conclusion The BiRd regimen is an effective and safety protocol for RRMM, including those carrying high-risk cytogenetic markers.

OBJECTIVETo explore the effect of 20 (S)-ginsenoside Rg3 [20 (S)-Rg3] on the proliferation inhibition and secretion of vascular endothelial growth factor (VEGF) of multiple myeloma (MM) cell line U266.

METHODSThe proliferation inhibition rate of U266 cells after treatment with different doses of 20 (S)-Rg3 was detected by MTT method, the cell cycle and apoptosis by flow cytometry, the expression of apoptosis related proteins of caspase-3, 8 and 9 by Western blot, VEGF concentration in the culture supernatant by ELISA.

RESULTSIt showed that 20 (S)-Rg3 could inhibit the proliferation of U266 in a dose-dependent manner (P<0.05) with IC50 of (71.07 ± 2.63)μmol/L and (44.06 ± 3.98) μmol/L at 24 h and 48 h, respectively. VEGF concentration in the culture supernatant showed a dosedependent reduction (P<0.05), decreased from (419.93 ± 36.76) pg/106 cells in the control group to (314.82 ± 27.05) pg/106 cells in 80 μmol/L 20 (S)-Rg3 treated group by ELISA assay. Flow cytometry with Annexin-V/PI double staining revealed that 20(S)-Rg3 may induce U266 cells apoptosis in a concentration-dependent manner from (0.51 ± 0.05)% at control group to (8.32 ± 0.83)%, (10.72 ± 1.29)% and (15.27 ± 2.26)% at 20, 40 and 80 μmol/L treatment groups, respectively (P<0.05). Flow cytometry with PI staining showed that the ratio of cells in G0/G1 phase increased from (49.11 ± 1.71)% to (52.72 ± 7.75)%, (60.29 ± 5.76)% and (61.81 ± 3.46)%, respectively (P<0.05). Western blot analysis indicated that the expression of caspase-3, 8 and 9 declined, and that of cleaved-caspase-3, 8 and 9 significantly increased (P<0.05) with 20 (S)-Rg3 concentration increased.

CONCLUSION20(S)-Rg3 can inhibit the proliferation of U266 cells by cell cycle arrest in G1 phase and induce cell apoptosis by increasing the expressions of cleaved-caspase-3, -8 and -9. It can also inhibit VEGF secretion of U266 cells, which makes it a potential agent for multiple myeloma therapy.

Apoptosis ; drug effects ; Caspases ; metabolism ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Ginsenosides ; pharmacology ; Humans ; Multiple Myeloma ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.