Objective To investigate the relationship between nasal colonization of Staphylococcus aureus(SA) and nosocomial infection in intensive care unit(ICU), and observe the therapeutic effect of Anerdian III in nasal decolonizaion. Methods Bacterial cultures were made by means of nasal swabs among inpatients whom the occurrence of nosocomial infection were observed.Patients with SA colonization were randomly divided into two groups:control and treatment.Control group were given regular treatment, and treatment group were administered Anerdian III in addition to regular treatment.Then the clearance rate of SA and the occurrence of nosocomial infection of two groups were observed. Results A total of 751 patients were enrolled, of whom 108(14.4%) were with nosocomial infection and 85(11.3%) with SA nasal colonization. Methicillin resistant Staphylococcus aureus ( MRSA ) was detected in 33 patients (4.4%).The nosocomial infection rate of patients with MRSA colonization was 51.5%, which was significantly higher than those in patients with other bacterial colonization(P<0.05).The SA clearance rate in treatment group was significantly higher than that in control group(81.4% vs.42.8%,P<0.05).The nosocomial infection rate in treatment group was significantly lower than that in control group ( 16 .3% vs. 40.5%,P <0.05).After decolonization treatment,the nosocomial infection rate of patients with MRSA colonization was significantly lower than that in control group(25.0% vs.76.5%,P <0.05). Conclusion The incidence rate of nosocomial infection in patients with MRSA nasal colonization is markedly increased in ICU, and the decolonization treatment by Anerdian III increases the clearance rate of nasal SA and decreases the incidence rate of nosocomial infection.

OBJECTIVETo investigate effects of low-dose cyclophosphamide and prednisone (CP) metronomic chemotherapy on microvessel density of bone marrow, serum vascular endothelial growth factor (VEGF) and platelet derived growth factor BB (PDGF-BB)in multiple myeloma (MM) patients.

METHODS54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and peripheral blood of each patient were collected before and 2, 4, 6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Microvessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients.

RESULTS2, 4, 6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/HP, 24.8 ± 3.7/HP, 19.7 ± 2.1/HP respectively; the expressions of VEGF were (394 ± 57) ng/L, (268 ± 32) ng/L and (217 ± 20) ng/L respectively; the expressions of PDGF-BB were (304 ± 31) ng/L, (274 ± 31) ng/L and (196 ± 22) ng/L respectively. After CP metronomic chemotherapy, there were significantly lower of microvessel density, VEGF and PDGF-BB levels than pretreatment \[MVD 48.5 ± 5.9/HP, VEGF (517 ± 60) ng/L, PDGF-BB (484 ± 60) ng/L\]in the responders (P < 0.01). While in the non-responders, after treated by CP metronomic chemotherapy for 2 months, microvessel density, the expression of VEGF and the expression of PDGF-BB were 32.5 ± 4.7/HP, 512 ± 39 ng/L and (452 ± 39) ng/L respectively. There were no significant changes of MVD, VEGF and PDGF-BB levels compared with pretreatment \[MVD 33.2 ± 5.6/HP,VEGF (498 ± 55) ng/L, PDGF-BB (488 ± 44) ng/L\] (P > 0.05).

CONCLUSIONSOur findings suggested that continuous low-dose CP metronomic chemotherapy could decrease microvessel density of bone marrow in MM patients. Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its anti-angiogenesis in MM.

Aged ; Aged, 80 and over ; Angiogenesis Inhibitors ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; administration & dosage ; Female ; Humans ; Male ; Microvessels ; drug effects ; Middle Aged ; Multiple Myeloma ; blood ; blood supply ; drug therapy ; Prednisone ; administration & dosage ; Proto-Oncogene Proteins c-sis ; blood ; Vascular Endothelial Growth Factor A ; blood

Adult ; Asian Continental Ancestry Group ; statistics & numerical data ; China ; epidemiology ; Humans ; Hypertension ; ethnology ; Metabolic Syndrome ; ethnology

AIM:To observe the changes of autophagy-related indexes during endoplasmic reticulum stress (ERS) induced by dithiothreitol (DTT) and its effect on apoptosis in human normal hepatocytes.METHODS:LO2 cells were treated with DTT at 2.0 mmol/L for 0, 6, 12 and 24 h to induce ERS.The expression of glucose-regulated protein 78 (GRP78) , protein kinase R-like endoplasmic reticulum kinase (PERK) , activating transcription factor 4 (ATF4) , C/EBP homologous protein (CHOP) , autophagy-related gene 12 (Atg12) , autophagy-related gene 5 (Atg5) and microtubule-associated protein 1 light chain 3 (LC3) at mRNA and protein levels was determined by real-time PCR and Western blot.The apoptosis was analyzed by flow cytometry.The formation of autophagosomes was observed under transmission electron microscope.After the LO2 cells were pretreated with rapamycin at 400 nmol/L for 1 h and treated with DTT at 2.0mmol/L for 24 h, the effect of rapamycin pretreatment on the apoptosis was analyzed by flow cytometry.RESULTS:After treatment with DTT at 2.0 mmol/L for 6, 12 and 24 h, the mRNA and protein levels of GRP78, PERK, ATF4, CHOP, Atg12, Atg5 and LC3 in the LO2 cells were significantly higher than those in 0 h group (P<0.05).At the same time, the ratio of LC3Ⅱ/LC3Ⅰwas also increased after DTT treatment (P<0.05).Observation under transmission electron microscope showed that autophagosomes were found in the LO2 cells treated with DTT for 6, 12 and 24 h.After DTT treatment for 6, 12 and 24 h, the apoptosis rate of LO2 cells was significantly higher than that in DTT 0 h group, while the apoptosis induced by DTT was significantly decreased after rapamycin pretreatment (P<0.05).CONCLUSION:ERS induces autophagy and rapamycin pretreatment alleviates the apoptosis of LO2 cells to some extent.

AIM:To investigate the effect of SET7/9 (SET domain containing 7/9) -mediated endoplasmic reticulum stress (ERS) on protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway, and to explore the mechanisms of arsenic-induced hepatocyte apoptosis.METHODS:Human liver LO2 cells were divided into control group, arsenic poisoning model group, negative transfection group and SET7/9 siRNA transfection group.The apoptosis of the LO2 cells in each group was analyzed by flow cytometry.The protein levels of SET7/9, glucose-regulated protein 78 (GRP78) , PERK and p-PERK in the LO2 cells of each group were observed by Western blot.RESULTS:Inhibition of SET7/9 expression reduced the apoptotic rate of arsenic-induced LO2 cells.Arsenic exposure increased the expression of SET7/9 in the LO2 cells.Arsenic exposure increased the protein levels of GRP78 and p-PERK in the LO2 cells, but decreased the protein levels of GRP78 and p-PERK after transfection with SET7/9 siRNA (P<0.05).CONCLUSION:Arsenic exposure induces hepatocyte apoptosis by increasing SET7/9 to activate ERS by PERK signaling pathway.

OBJECTIVEThis review focuses on the state-of-the-art of CXCL12/CXCR4 signaling axis in pancreatic cancer and its role in tumor progression.

DATA SOURCESRelevant articles published in English were identified by searching in Pubmed from 1997 to 2013, with keywords "CXCL12", "CXCR4" and "pancreatic cancer". Important references from selected articles were also retrieved.

STUDY SELECTIONArticles about CXCL12/CXCR4 signaling axis in pancreatic cancer and relevant mechanisms were selected.

RESULTSPancreatic cancer has been one of the most lethal human malignancies, with median survival less than one year and overall 5-year survival only 6%. Tumor cells from pancreatic cancer express high level of CXCR4. CXCL12, the ligand for CXCR4, is extensively secreted by neighboring stromal cells and other distant organs. CXCL12 primarily binds to CXCR4, induces intracellular signaling through several divergent pathways, which are involved in progression and metastasis of pancreatic cancer.

CONCLUSIONSCXCL12/CXCR4 signaling axis may play an important role in the communication between pancreatic cancer cells and their microenvironment, which may have effect on tumor proliferation, invasion, angiogenesis, metastasis and chemoresistance. CXCL12/CXCR4 signaling axis may serves as a novel therapeutic target for pancreatic cancer.

Chemokine CXCL12 ; genetics ; metabolism ; Humans ; Pancreatic Neoplasms ; genetics ; metabolism ; Receptors, CXCR4 ; genetics ; metabolism ; Signal Transduction ; genetics ; physiology

Objective: To isolate the cross-reactive antibodies against hemagglutinin of influenza virus and identify its biological function. Methods: The antibodies gene reservoir of cross-reactive and H5N1 pseudotype particles neutralizing B cell circulating in peripheral blood of a human H5N1 case was recovered by in vitro B cell culture, screening, RT-PCR and expression vector cloning techniques. The Ab gene pairing was screened by transient transfection of human kidney 293T cells and detected using ELISA and neutralization test. The heterosubtypic antibodies were prepared and characterized. Results: We discovered the VH1-2-based heterosubtypic antibodies from two B cell lineages could neutralize GX-H5N1 pseudotype particles and have broader binding with Group 1 (including H1, H5, H6 and H9) and H7 subtype. Conclusions Cross-reactive antibodies can be induced by H5N1 infection.

OBJECTIVE: To study the expression and function of long non-coding RNA linc00467 in childhood acute myeloid leukemia (AML). METHODS: Bone marrow samples were collected from 5 children with AML who were diagnosed from May 2016 to June 2018. Normal bone marrow samples based on bone marrow examination were collected from 3 children as controls. Quantitative real-time PCR was used to measure the expression of linc00467 in the two groups. A lentivirus system was used to achieve overexpression of linc00467 in AML cells (HL-60) (linc00467 overexpression group), and empty vector expressing green fluorescent protein (GFP) was transfected into AML cells to establish a GFP control group. A lentivirus system was used to insert an interfering sequence into AML cells (sh-linc00467 interfering group), and a random sequence was inserted to establish an sh-NC control group. Cell proliferation and resistance to doxorubicin were observed for all groups. RESULTS: Compared with the normal control group, the children with AML had a significant increase in linc00467 (P=0.018). Overexpression and interference with linc00467 expression had no significant effect on cell proliferation. Compared with the GFP control group, the linc00467 overexpression group had a significant increase in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 μg/mL (P<0.05). Compared with the sh-NC control group, the sh-linc00467 interfering group had a significant reduction in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 μg/mL (P<0.05). Compared with the untreated group, the adriamycin treatment group had a significant increase in the expression of linc00467 in HL-60 cells (P<0.05). CONCLUSIONS This study reveals the biological function of linc00467 to promote the resistance to adriamycin in AML, which provides a basis for developing new therapeutic drugs for AML.
Cell Proliferation ; Child ; Drug Resistance, Neoplasm ; Humans ; Lentivirus ; Leukemia, Myeloid, Acute ; genetics ; RNA, Long Noncoding ; genetics

BACKGROUNDPatients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported.

METHODSDemographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium.

RESULTSBoth cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles -CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses.

CONCLUSIONSTwo Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy.

Aged ; Anticoagulants ; adverse effects ; Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2C9 ; Female ; Genotype ; Hemorrhage ; chemically induced ; Humans ; Male ; Middle Aged ; Mixed Function Oxygenases ; genetics ; Pharmacogenetics ; Vitamin K Epoxide Reductases ; Warfarin ; adverse effects