The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87;95％ CI:1.37-2.57;P=0.000),but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63;95％ CI:-0.45-1.72;P=0.26] and overall survival (OS) (MD=-0.67;95％ CI:-2.54-1.20;P=0.49).In the sub analysis,better ORR was obtained with the addition of EGFR (OR=1.75;95％ CI:1.20-2.56;P=0.004) and VEGFR (OR=2.5;95％ CI:1.28-4.87;P=0.007) targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS (MD=l.36;95％ CI:0.29-2.43;P=0.01).No significant differences were observed in the incidences ofneutropenia (OR=1.37;95％ CI:0.89-2.12),thrombocytopenia (OR=l.40;95％ CI:0.83-2.39),anemia (OR=l.21;95％ CI:0.62-2.38),peripheral neuropathy (OR=1.52;95％ CI:0.81-2.88),increased AST/ALT (OR=l.40;95％ CI:0.82-2.39) as well as fatigue (OR=1.65;95％ CI:0.96-2.84) in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present mcta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

OBJECTIVETo observe the therapeutic effect of moxibustion and exercise comprehensive scheme intervention for children with short stature of deficience of the kidney essence.

METHODSTwenty four cases of children in 12 to 14 years old were selected, 12 male and 12 female, they were treated with comprehensive therapy of exercise therapy and moxibustion. Running and jumping were selected as main exercise therapy, it became a suitable exercise amount when the heart rate reach to 150 to 170 times per minute, thrice each week, 35 to 45 minutes each time. After exercises they were treated with moxibustion, Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36), Dazhu (BL 11), Xuanzhong (GB 39), Geshu (BL 17) etc. were selected. After treatment for half a year, the changes of the body height, body weight, bone age(BA), growth hormone (GH), testosterone (T) and estradiol (E2) were compared before and after treatment.

RESULTSThe body height and bone age of the boys and girls were significantly higher than those before treatment (all P<0.05), the growth of body height was more than 4 cm, the growth of bone age was more than 0.5 years old in half a year; the testosterone of all children was significantly increased (all P<0.05), and there were no significant differences in body weight, GH and E2 compared to those before treatment (all P>0.05).

CONCLUSIONMoxbustion and exercise comprehensive scheme can effectively improve the children with short stature of deficience of the kidney essence, the mechanism is related to the improving of the testosterone level.

Adolescent ; Body Height ; Child ; Estradiol ; metabolism ; Exercise Therapy ; Female ; Growth Disorders ; metabolism ; physiopathology ; therapy ; Human Growth Hormone ; metabolism ; Humans ; Kidney ; physiopathology ; Male ; Moxibustion ; Testosterone ; metabolism ; Treatment Outcome

OBJECTIVETo determine the antibiotics resistance, aminoglycoside-modifying enzymes and homology of high-level gentamycin resistant enterococcus in clinical specimens.

METHODSThe high-level gentamicin resistant (HLGR) isolates were screened by the agar method and the resistance of 14 antimicrobial agents was determined by K-B method. The aminoglycoside-modifying enzyme genes were detected by polymerase chain reaction (PCR). Pulsed-field gel electrophoresis (PFGE) was used to analyze the homology of HLGR isolates.

RESULTSThe ratio of HLGR was 64.2% (68/106). Among the HLGR,there were no isolates resistant to linezolid, vancomycin and tecoplanin, and Enterococcus faecium was more resistant to beta-lactam antibiotics and quinolone than Enterococcus faecalis. The positive rate of aac(6')-Ie-aph(2')-Ia was 92.6% and 3 isolates had the resistance gene mostly similar to aph(2')-Id. And among 51 HLGR isolates from the hospitalized patients, PFGE grouped 17 E. faecalis isolates into 4 clusters (A-D), and 33 E. faecium isolates into 8 clusters (A-H) with A cluster as predominant.

CONCLUSIONHLGR has become the important antibiotic resistance bacteria which results in nosocomial infection; and aac(6')-Ie-aph(2')-Ia is the main aminoglycoside-modifying enzyme gene which causes HLGR.

Drug Resistance, Bacterial ; genetics ; Electrophoresis, Gel, Pulsed-Field ; Enterococcus ; drug effects ; genetics ; Enterococcus faecalis ; drug effects ; genetics ; Enterococcus faecium ; drug effects ; genetics ; Gentamicins ; pharmacology ; Humans ; Kanamycin Kinase ; genetics ; Microbial Sensitivity Tests

BACKGROUNDAlemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia). However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.

METHODSTwelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection) while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment) for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.

RESULTSThe numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05). Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.

CONCLUSIONSAlemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after alemtuzumab treatment.

Alemtuzumab ; Animals ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Apoptosis ; drug effects ; Flow Cytometry ; Intestines ; cytology ; Lymphocytes ; drug effects ; Macaca fascicularis ; Male ; Microscopy, Electron, Transmission

Amino Acid Sequence ; Base Sequence ; Genes, Bacterial ; Humans ; Molecular Sequence Data ; Polymerase Chain Reaction ; Staphylococcus epidermidis ; enzymology ; genetics ; beta-Lactamases ; chemistry ; genetics

Volatile organic compounds (VOCs) in ambient air can participate in photochemical reactions, which lead to the generation of secondary pollutants such as ozone and aerosol. So real-time and accurate monitoring of atmospheric VOCs plays an important role in the study of the causes of air pollution. On the basis of proton transfer reaction mass spectrometry (PTR-MS) research, a novel dipolar proton transfer reaction mass spectrometer (DP-PTR-MS) for real-time and on-line monitoring atmospheric VOCs was developed. Compared with the conventional PTR-MS with one kind of reagent ion H3O+, DP-PTR-MS had three kinds of reagent ions H3O+, OH-, (CH)2COH+, which could be switched according to the actual detection need. So DP-PTR-MS can improve the qualitative ability and expand the detection range effectively. The reagent ion H3O+can be used for detecting VOCs whose proton affinities are greater than that of H2O. The reagent ion OH-can be used to identify VOCs cooperating with the reagent ion H3O+,and can also be used for detecting some inorganic substances such as CO2. The reagent ion (CH3)2COH+can be used for accurately detecting NH3under interference elimination circumstances. The limit of detection (LOD) and sensitivity of DP-PTR-MS were measured by using six kinds of standard gases. The results showed that the LOD for detecting toluene was 7×10-12(V/V) and the sensitivity for detecting ammonia has reached 126 cps/10-9 (V/V). The ambient air in Hefei city was on-line and real-time monitored for continuous 78 hours with DP-PTR-MS. The results showed that the newly developed DP-PTR-MS could be used for long-term and real-time monitoring atmospheric VOCs with the concentration of 10-12(V/V) level. DP-PTR-MS is an important tool for the study of the causes of atmospheric pollution and the monitoring of trace VOCs emissions.

Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.
Cell Line, Tumor ; Endothelin-3 ; genetics ; Gene Silencing ; Humans ; Melanoma ; genetics ; pathology ; Osteonectin ; genetics

OBJECTIVE: To establish a novel method to isolate endothelial progenitor cells（EPC） from cryopreserved umbilical cord blood (cryoUCB), to investigate the biological characteristics of EPC and to improve the rate of EPC obtained from cryoUCB. METHODS: Twelve cryoUCB samples during 2000 to 2001 years were collected from allogeneic cord blood bank, cryoUCB was thawed rapidly in a water bath at 37 ℃, total nucleated cells (TNCs) were washed by phosphate-buffered saline (PBS). TNCs were seeded onto fibronectin-coated dishes to isolate EPC. Flow cytometry and immunofluorescence were used to identify EPC. The function of EPC was identified in vitro, such as the incorporation of Dil-Ac-LDL and FITC-UEA-I, the formation of capillary-like structure in matrigel, and the release of VEGF by ELISA. RESULTS: One to five cluster of cobble stone-like cells appeared at 2-3 weeks after seeding. Flow cytometric analysis showed that positive rates of CD31, CD34, CD144, and VEGFR (CD309) were（92.91±5.20）%, （30.0±23.27）%, （88.55±3.83）% and （67.21±12.12）% in passage 1 to passage 3 of EPC. EPC could uptake Dil-Ac-LDL and FITC-UEA-I, form capillary-like network on Matriget and release VEGF. CONCLUSION EPC had been successfully isolated from cryopreserved umbilical cord blood by this method with high stability and reproducibility. EPC can be obtained in 85% frozen umbilical cord blood. This method may lay a foundation to supply abundant EPC for clinical application.
Cell Differentiation ; Cells, Cultured ; Endothelial Progenitor Cells ; Fetal Blood ; Reproducibility of Results ; Stem Cells

OBJECTIVE: To analyze the clinical characteristics of multiple myeloma(MM) patients with early relapse. METHODS: A total of 50 MM patients with early relapse (≤12 months) and 50 matched controls with late relapse (>12 months) were selected. The time from diagnosis to relapse and related clinical data of the 100 patients were retrospectively analyzed, and the factors associated with early relapse were identified. Kaplan-Meier curve was used to analyze the overall survival (OS) time of the whole cohort. Area under the curve (AUC) was used to evaluate the effect of circulating plasma cells on early recurrence of the patients. RESULTS: The results showed that high-risk cytogenetics (FISH) (P=0.005), and ISS stage III (P=0.008) were associated with early recurrence of the patients. For patients with early relapse, high-risk FISH showed poor survival. Compared with the patients with late relapse, most of the chromosome karyotype of patients with early relapse showed quantitative and structural abnormalities. The expression of circulating plasma cells was significantly increased in patients with early recurrence group (P=0.0318). The response to initial treatment was poor in the early recurrence group (P=0.001), and the prognosis was significantly worse than those in the late recurrence group (median OS: 38 vs 81 months, P=0.002). CONCLUSION Early relapse is a marker poor prognostic in MM patients, and such patients should be focused on the improving their prognosis.
Cytogenetics ; Humans ; Multiple Myeloma/drug therapy* ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies

Programmed DNA double-strand breaks (DSBs) are necessary for meiosis in mammals. A sufficient number of DSBs ensure the normal pairing/synapsis of homologous chromosomes. Abnormal DSB repair undermines meiosis, leading to sterility in mammals. The DSBs that initiate recombination are repaired as crossovers and noncrossovers, and crossovers are required for correct chromosome separation. Thus, the placement, timing, and frequency of crossover formation must be tightly controlled. Importantly, mutations in many genes related to the formation and repair of DSB result in infertility in humans. These mutations cause nonobstructive azoospermia in men, premature ovarian insufficiency and ovarian dysgenesis in women. Here, we have illustrated the formation and repair of DSB in mammals, summarized major factors influencing the formation of DSB and the theories of crossover regulation.
Animals ; Chromosome Segregation ; DNA Breaks, Double-Stranded ; DNA Repair/physiology* ; Humans ; Mammals/genetics*