Epigenesis, Genetic ; Humans ; Rhinitis, Allergic ; therapy

Chronic Disease ; Combined Modality Therapy ; Endoscopy ; Humans ; Postoperative Period ; Rhinitis ; surgery ; therapy ; Sinusitis ; therapy

Contraindications ; Desensitization, Immunologic ; Humans

Multidrug-resistant (MDR) bacterial infections, especially those caused by Gram-negative pathogens, have emerged to be one of the world's greatest health threats. However, not only have recent decades shown a steady decline in the number of approved antimicrobial agents but a disappointing discovery also void. The development of novel antibiotics to treat MDR Gram-negative bacteria has been stagnated over the last half century. Though few compounds have shown activities in vitro, in animal models or even in clinical studies, the global antibiotic pipeline is not encouraging. There are a plethora of unexpected challenges that may arise and cannot always be solved to cause promising drugs to fail. This review intends to summarize recent research and development activities to meet the inevitable challenge in restricting the proliferation of MDR Gram-negative bacteria, with focus on compounds that have entered into clinical development stage. In addition to new analogues of existing antibiotic molecules, attention is also directed to alternative strategies to develop antibacterial agents with novel mechanisms of action.
Aminoglycosides ; pharmacology ; therapeutic use ; Animals ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Drug Discovery ; Drug Resistance, Multiple, Bacterial ; Enzyme Inhibitors ; pharmacology ; therapeutic use ; Ferrous Compounds ; pharmacology ; therapeutic use ; Gram-Negative Bacteria ; drug effects ; Gram-Negative Bacterial Infections ; drug therapy ; Humans ; Peptides ; pharmacology ; therapeutic use ; Peptidomimetics ; pharmacology ; therapeutic use ; Tetracyclines ; pharmacology ; therapeutic use ; beta-Lactamase Inhibitors ; beta-Lactams ; pharmacology ; therapeutic use

Background and purpose:Nowadays, the golden standard of diagnosis for malignant hydrothorax or ascites is exfoliocytology examination, but the missed diagnosis rate is too high. Other methods including immunologic test, telomerase activation test, conjugation of chromosome analysis with cytological examination test, and RT-PCR test. But none of them was widely used due to high cost or high false positive rate. Immunomagnetic beads (IMB) technique is a popular method all over the world in recent years. It was mainly used in isolating and purifying cells, but it was rarely used to detect cancer cells in patients with hydrothorax or ascites so far. Our aim was to fi nd an effi cient way to detect the cancer cells in patients with cancer related hydrothorax or ascites and to improve the corresponding diagnosis rate. Methods:In the experiments, both the traditional exfoliocytology examination method and IMB technique were used to detect the cancer cells in the hydrothorax or the ascites for comparison. Results:Using IMB technique and exfoliocytology method, the positive rates in 30 patients with cancers were 63.3% (19/30) and 23.3% (7/30), respectively, and the false positive rates in 30 patients without cancers were 3.3% (1/30) and 0.0% (0/30), respectively. It could be observed that the positive rate using IMB technique was much higher than that using exfoliocytology method (P0.05). Conclusions:The present study demonstrated that IMB technique is an accurate, sensitive, fast and economic method in detecting the cancer cells in patients with cancer related hydrothorax or ascites, especially for diagnosis and therapy in the early clinical stage. Due to the high effi ciency, IMB technique could be used after exfoliocytology examination to improve the diagnosis rate..

Objective To investigate the role of CTLA4-Ig and anti-CD40L monoclonal antibody in the acute rejection of pancreaticoduodenal transplantation model of rats.Methods Pancreaticoduo- denal transplantation model was established from the donor F344 rats to the Lewis recipients(diabetes models).The models were divided into 4 groups:groups A,B,C and D with 12 rats in each group. Two days after transplantation,recipients were injected intraperitoneally with saline,CTLA4-Ig(200?g),anti-CD40L monoclonal antibody(200?g),CTLA4-Ig(200?g)combined with anti-CD40L monoclonal antibody(200?g)respectively.On the day 1,4,7,10 after transplantation,the grafts were harvested for histopathological examination and RT-PCR to determine the levels of interleukin (IL)-2,interferon(IFN)-?,IL-4 and IL-10;The blood CD3~+,CD4~+and CD8~+ T cells were detected by flow cytometry.On the day 4 after transplantation,the CD4~+ CD25~+ T cells in the grafts were de- tected by flow cytometry.Results As compared with group A,the severity of the rejection of grafts in groups B,C and D were depressed;Down-regulation of IL-2 was observed in the groups B,C and D, and the levels in group D were lowest.Down-regulation of IFN-7 was detected in the groups B,C and D,but there was no significantly difference between groups D and B or groups D and C.Up-regulation of IL-4 was observed in the groups B and C,and the levels in group D were lower than in groups A,B and C.Up-regulation of IL-10 was observed in groups B and C,and there was significant difference between groups D and B or groups D and C.The CD3~+,CD4~+ and CD8~+ T cells in groups B,C and D were less,but more CID4~+ CD25~+ T ceils in transplanted pancreas were observed,more notably in group D than in group C.Conclusions Combined use of CTLA4-Ig and anti-CD40L monoclonal anti- body can remarkably diminish the severity of the rejection,which might be mediated by altering the balance in Th1/Th2 and increasing the number of CD4~+ CD25~+ regulatory T cells.Co-stimulation blockade with CTLA4-Ig and anti-CD40L monoclonal antibody induction seems to be an attractive strategy to control allograft rejection.

Objective To investigate the correlation of changes in peripheral natural killer T(NKT) cells and fatty liver disease(NAFLD).Methods Peripheral blood samples were obtained from 60 NAFLD patients and 60 age and gender matched healthy controls.The frequency of peripheral NKT cells was detected by flow cytometry.The differences of clinical presentation and laboratory data in two groups were analyzed.The risk factors of NAFLD were screened by Logistic regression analysis. Results NAFLD patients had lower frequency of peripheral NKT cells than healthy controls [median fre- quency was 1.12%(IQR0.87%～1.54%)in patients vs.1.48%(1.23%～1.98%) in controls,P

·AIM:To present a case of late onset bilateral keratectasis after laser in situ keratomileusis (LASIK) for myopia with rigid gas-permeable contact lenses with a brief review of literature on this subject.·METHODS:A 27-year-old woman underwent bilateral uneventful LASIK for moderate myopia. Preoperative cycloplegic refractions were -5.50/-0.50×50° right eye (OD) and - 4.50/-1.00×15° left eye (OS).Corneal pachymetry was 526μm OD and 541μm OS, Preoperative corneal topography was normal and did not reveal any keratoconus or forme fruste keratoconus.Following the creation of flaps with 160μm plates,ablations of 102μm OD and 86μm OS were performed,estimated to leave residual stromal beds of 264μm OD and 295μm OS.·RESULTS:Twenty-nine months postoperatively,the patient developed bilateral inferior keratectasia of -12.50/-4.00×160° OD and -6.00/- 4.25×125° OS.Visual acuity was reduced in both eyes;the central cornea had steepened; and pachymetry showed central corneal thinning.Keratectasia was diagnosed,and rigid contact lenses were fitted.Three years later,the patient achieved satisfactory visual acuity and all-day lens wear with minimal complications.·CONCLUSION:Late keratectasia may follow LASIK for low to moderate myopia despite a thorough preoperative work-up.Rigid contact lenses can offer a safe,reversible option for improving visual acuity in such patients by delaying or avoiding the need for intracorneal ring segments implanting or penetrating keratoplasty.

BACKGROUND:For patients in intensive care unit (ICU), mechanical ventilation is an effective treatment to survive from acute illness and improve survival rates. However, long periods of bed rest and restricted physical activity can result in side effects. This study aimed to investigate the feasibility of early rehabilitation therapy in patients with mechanical ventilation. METHODS:A randomized controlled trial was carried out. Sixty patients, with tracheal intubation or tracheostomy more than 48 hours and less than 72 hours, were admitted to the ICU of the Affiliated Hospital of Medical College, Qingdao University, from May 2010 to May 2012. These patients were randomly divided into a rehabilitation group and a control group. In the rehabilitation group, rehabilitation therapy was performed twice daily, and the training time and intensity were adjusted according to the condition of the patients. Early rehabilitation therapy included heading up actively, transferring from the supine position to sitting position, sitting at the edge of the bed, sitting in chair, transferring from sitting to standing, and ambulating bedside. The patient's body mass index, days to first out of bed, duration of mechanical ventilation, length of ICU stay, APACHE Ⅱ score, highest FiO2, lowest PaO2/FiO2 and hospital mortality of patients were all compared between the rehabilitation group and the control group. The differences between the two groups were compared using Student's t test. RESULTS:There was no significant difference in body mass index, APACHE Ⅱ score, highest FiO2, lowest PaO2/FiO2 and hospital mortality between the rehabilitation group and the control group (P>0.05). Patients in the rehabilitation group had shorter days to first out of bed (3.8±1.2 d vs. 7.3±2.8 d; P=0.00), duration of mechanical ventilation (5.6±2.1 d vs. 12.7±4.1 d; P=0.005) and length of ICU stay (12.7±4.1 d vs. 15.2±4.5 d; P=0.01) compared with the control group. CONCLUSION:Early rehabilitation therapy was feasible and effective in improving the outcomes of patients with mechanical ventilation.

In this study, a rapid and sensitive analytical method was developed for the determination of 10 major compounds (procyanidin B1, catechin, procyanidin B2, rutin, isoquercitrin, kaempferol-3-O-rutinoside, astragalin, quercitrin, quercetin, and kaempferol) in Tetrastigma hemsleyanum by using ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-MS/MS) in multiple-reaction monitoring (MRM) mode. UPLC-MS/MS assay with negative ion mode was performed on a Waters CORTECS C18 (2.1 mm x 100 mm, 1.6 μm) with the mobile phase consisting of acetonitrile (A) and 0.1% aqueous formic acid (B) in gradient elution at a flow rate of 0.25 mL · min(-1) and the column temperature was set at 45 °C. Under the optimized chromatographic conditions, good separation for 10 target compounds were obtained including chiral isomer procyanidins B1 and B2 were completely separated within 8.5 min. Satisfactory linearity was achieved with wide linear range and fine determination coefficient (r > 0.996 6), the overall recoveries were ranged from 95.44%-110.40% with the RSD ranging from 2.37%-8.69%. It is the first report about simultaneous analysis of 10 major flavonoids components in Tetrastigma hemsleyanum by using UPLC-MS/MS method, which affords highly sensitive, specific, speedy and efficient method for quality control of Tetrastigma hemsleyanum
Acetonitriles ; Chromatography, High Pressure Liquid ; Flavonoids ; chemistry ; Kaempferols ; Quercetin ; analogs & derivatives ; Rutin ; Tandem Mass Spectrometry ; Vitaceae ; chemistry