Objective To explore the construction of modular intervention for patients dependent on mechanical ventilation in ICU,and to conduct the clinical empirical study.Methods A total of 100 mechanical ventilation-dependent patients in ICU were enrolled and divided into two groups according to the admission order,with 50 patients in each group.Control group received routine intervention,while observation group was treated with modular intervention in addition to the treatment given to control group.The weaning success rate,weaning time,complications,rehabilitation index,blood gas analysis index,psychological state,and nutritional status were compared between two groups.Results Compared with control group,observation group had higher weaning success rate,shorter weaning time,ICU stay and general ward admission,and lower incidence of complications(P<0.05).After intervention,observation group had lower PaCO2,and higher PaO2 and PaO2/FiO2 than control group(P<0.05);the scores of SAS,SDS and APACHEⅡwere lower in observation group than in control group(P<0.05);and the serum levels of ALB,PA,TRF and TP in observation group were higher than those in control group(P<0.05).Conclusion Modular intervention for mechanical ventilation-dependent patients in ICU can increase weaning success rate,improve blood gas analysis index and nutritional status,alleviate negative emotions,reduce complications and speed recovery.

ObjectiveTo study the virulence and biofilm inhibition effect of Fufang Huangbai Fluid Paint （FFHBFP） on methicillin-resistant Staphylococcus aureus （MRSA）， and to explore the antibacterial effect of FFHBFP on MRSA， which provides a theoretical basis and reference for clinical medication. MethodFirstly， the microdilution method and time–growth curve were used to determine the minimum inhibitory concentration （MIC） of FFHBFP and vancomycin （VAN） against MRSA and the effect on bacterial growth. The effects of FFHBFP and VAN on the inhibition of MRSA virulence factor lipase and restoration of hydrogen peroxide （H₂O₂） sensitivity were detected under sub-minimum inhibitory concentration （sub-MIC）. The inhibitory effect of FFHBFP and VAN on MRSA biofilm formation and maturation was detected by the microplate method. The morphological changes of mature biofilms before and after administration were observed under a scanning electron microscope （SEM）. Real-time polymerase chain reaction （Real-time PCR） was utilized to detect the effect of 50.600 g·L^-1 concentration of FFHBFP on the expression of MRSA virulence gene crtM and biofilm-forming genes fnbA and icaA. Finally， molecular docking technology was used to predict the mechanism of potential antibacterial active ingredients of FFHBFP in inhibiting the virulence and biofilm of MRSA. ResultThe MIC of VAN was 2 mg·L^-1， and VAN below 1 mg·L^-1 exerted no effect on MRSA growth. The MIC of FFHBFP was not determined， while the 101.200-202.400 g·L^-1 original solution inhibited MRSA growth. Compared with the blank group and the VAN group， sub-MIC （25.300-50.600 g·L^-1 original solution） inhibited lipase and recovered MRSA sensitivity to H₂O₂ （P<0.01）. The results of the microplate method showed that FFHBFP （25.300-202.400 g·L^-1 original solution） inhibited biofilm formation and maturation （P<0.05， P<0.01）. The SEM exhibited that FFHBFP made the structure of biofilm loose and the size of the bacteria varied. FFHBFP at 50.600 g·L^-1 concentration can inhibit the expression of related virulence genes and biofilm-forming genes （P<0.05， P<0.01）， and molecular docking results also showed that the main antibacterial active ingredients in FFHBFP have good binding ability to the target. ConclusionFFHBFP that cannot directly kill MRSA exerts clinical efficacy by impairing virulence expression， biofilm formation， and other pathogenic properties.

OBJECTIVE: To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells. METHODS: The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP RESULTS: Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP CONCLUSION Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.
Animals ; Apoptosis/drug effects* ; Cell Cycle/drug effects* ; Cell Line, Tumor ; Humans ; Leukemia ; Mice ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Telomerase/metabolism* ; Telomere/metabolism*

Objective:To observe the effect of combination of Tanreqing injection(Tanreqing) and imipenem-cilastatin on extensively-drug resistant Pseudomonas aeruginosa (XDPA), and study the mechanism of the combination. Method:The minimum inhibitory concentrations (MICs) of Tanreqing and imipenem-cilastatin against planktonic XDPA strain isolated in clinic were determined by the broth microdilution method. The checkerboard method was used to evaluate the combination effect. The bacterial metabolic activity in mature biofilm was studied by microtiter-plate test. The destructive effect of combination drugs on dynamic biofilm was observed by using BioFlux system, and viable cells were examined by confocal laser scanning microscope (CLSM) after treatment. The scanning electron microscopy (SEM) was used for observing Pseudomonas aeruginosa and length measurement. Result:The MIC values of imipenem-cilastatin and Tanreqing were 512 mg·L^-1 and more than 16 500 mg·L^-1. The checkerboard analysis showed that Tanreqing could enhance the sensitivity of imipenem-cilastatin, while the combination drugs synergistically inhibited the growth of bacteria. Compared with the control group or the imipenem-cilastatin individual group, the combined drugs significantly reduced the amount of living bacteria in the biofilm (P<0.05,P<0.01). BioFlux results showed that the combination drugs destructed the biofilm structure and reduced the area coverage (P<0.05) by comparing with the control group or the single drug group. The results of fluorescent staining showed that the combination drug significantly inhibited the metabolic activity of bacteria in dynamic biofilm. Tanreqing inhibited bacterial division to achieve the antibacterial effect. Conclusion:Tanreqing and imipenem-cilastatin synergistically inhibit the bacterial growth in planktonic and biofilm states, and destruct biofilms.

OBJECTIVE: To investigate the distribution of airway inflammation phenotype in patients with bronchial asthma (asthma), and to analyze clinical characteristics, inflammatory cytokines, pulmonary small vessels remodeling and small airway wall remodeling in patients with neutrophilic asthma. METHODS: Sixty-three patients with asthma were enrolled from January 2015 to December 2015 in Peking University Third Hospital. Clinical data including gender, age, body mass index (BMI), pulmonary function tests (PFTs), asthma control test (ACT) were recorded. All the patients underwent sputum induction. The cellular composition of the sputum was evaluatedand the concentration of active MMP-9 in the sputum tested. Blood routine tests were done and the concentration of IgE, periostin, and TGF-beta1 levels were measured in serum by enzyme-linked immunosorbent assay (ELISA). Small airway wall remodeling was measured in computed tomography (CT) scans, as the luminal diameter, luminal area, wall thickness and wall area % adjusted by body surface area (BSA) at the end of the 6th generation airway, in which the inner diameter was less than 2 mm. Small vascular alterations were measured by cross-sectional area (CSA), and the total vessel CSA < 5 mm² was calculated using imaging software. RESULTS: The distributions of airway inflammatory phenotypes of the asthmatic patients were as follows: neutrophilic asthma (34.9%, 22/63), eosinophilic asthma (34.9%, 22/63), mixed granulocytic asthma (23.8%, 15/63), and paucigranulocytic asthma (6.3%, 4/63). The neutrophilic subtype patients had a significantly higher active MMP-9 level in sputum compared with the eosinophilic phenotypepatuents, as 179.1 (74.3, 395.5) vs. 50.5 (9.7, 225.8), P<0.05. Sputum neutrophil count was negatively correlated with FEV1%pred (r=-0.304,P<0.05), and positively correlated with active MMP-9 level in sputum (r=-0.304, P<0.05), and positive correlation trend with airway wall thickness (r=0.533, P=0.06). There was a significantly negative correlation of active MMP-9 level in sputum with FEV1%pred (r=-0.281, P<0.05), in positive correlation with small airway wall area (%)(r=0.612, P<0.05), and inpositive correlation trend with airway wall thickness (r=0.612, P=0.06). Neutrophils count in peripheral blood was positively correlated with neutrophil counts in sputum. CONCLUSION Neutrophil count in airway is related to lung function in asthmatic patients. Neutrophils may accelerate small airway wall remodeling through the release of active MMP-9. Neutrophil count in peripheral blood is related to neutrophils count in sputum, which may be used as a substitute for evaluating inflammatory phenotype.
Airway Remodeling ; Asthma/physiopathology* ; Eosinophils ; Humans ; Inflammation ; Sputum

Pharmacokinetic parameters can be significantly altered for acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO) and continuous veno-venous hemofiltration therapy (CVVH). Here we reported a case of individualized vancomycin dosing for a patient diagnosed as severe acute pancreatitis treated with concurrent ECMO and CVVH. A 65 kg 32-year-old woman was admitted to hospital presented with severe acute pancreatitis (SAP), respiratory failure, metabotropic acidosis and hyperkalemia. She was admitted to intensive care unit (ICU) on hospital day 1 and was initiated on CVVH. She progressed to multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) on ICU day 2, and veno-venous ECMO was instituted. Several catheters were inserted into the body to support ECMO, CVVH and pulse indicator continuous cardiac output (PiCCO), so vancomycin was prescribed empirically on ICU day 3 for prevention of catheter-related infection. Given the residual renal function and continuous hemofiltration intensity on day 3, vancomycin bolus of 1 000 mg was prescribed, followed by a maintenance dose of 500 mg every 8 hours. On ICU day 4, a vancomycin trough serum concentration of 14.1 mg/L was obtained before the fourth dose, which was within the target range of 10-20 mg/L. By ICU day 7, vancomycin dosage was elevated to 1.0 g every 12 hours because of aggravated infection and improved kidney function. On ICU day 14, a vancomycin trough serum concentration of 17 mg/L was obtained. Her white blood cell (WBC) and neutrophil percentage (Neut%) dropped to the normal level by ICU day 19. This vancomycin regimen was successful in providing a target attainment of trough serum concentration ranging from 10-20 mg/L quickly and in controlling infection-related symptoms and signs properly. With the help of this case report we want to call attention to the clinically significant alteration in vancomycin pharmacokinetics among critically ill patients. Individualized vancomycin dosing regimens and therapeutic drug monitoring are necessary for critically ill patients receiving CVVH and ECMO to ensure that the target serum vancomycin levels are reached to adequately treat the infection and avoid nephrotoxicity.
Adult ; Anti-Bacterial Agents/administration & dosage* ; Critical Illness ; Extracorporeal Membrane Oxygenation ; Female ; Hemofiltration ; Humans ; Pancreatitis/drug therapy* ; Vancomycin/administration & dosage*

Objective The active ingredient was used as index to optimize the extraction and enrichment process of anti-in-flammatory and analgesic active-fraction(ARF)of Dianbaizhu. Methods Methyl salicylate triglycoside-B was chosen as index com-ponent to extract and enrich methyl salicylate glycosides. Extraction and elution solvents were optimized. The HPLC fingerprint was ob-tained with Thermo Hypersil Gold C18(250 mm×4.6 mm,5μm)column and a gradient elution with the mobile phase consisting of ace-tonitrile(A)-0.2％acetic acid(B)at a flow rate of 1.0 ml/min. And the detection wavelength was set at 294 nm. Results The opti-mized extraction solvent of Dianbaizhu was the 30％ethanol and the optimized elution solvent of ARF enriched by AB-8 macroporous resins was the 35％ethanol. The methodological study on similarity and RSD in ARF HPLC fingerprint of three batches of samples cor-responded to related regulations. Conclusion The extraction and enrichment process of ARF is stable and repeatable.

OBJECTIVETo analysis the early complications of tibial fracture and its related factors, and propose a solution.

METHODSFrom December 2003 to December 2013,38 patients with early complications of tibial plateau fracture after operation were retrospectively analyzed. There were 35 males and 3 females, aged from 37 to 69 years old (averaged 42.3 years). According to Schatzker classification, 3 cases were classified as type II, 2 cases as type III, 2 cases as type IV, 19 cases as type V, 12 cases as type VI. The intervals between injury and operation ranged from 9 hours to 9 days, 26 cases within 3 days. Fifteen cases were treated with internal fixation of plates and 23 were treated by plate fixation and bone transplantation. Early complications included skin necrosis in 15 cases, infection in 6 cases, osteofascial compartment syndrome in 3 cases, common peroneal nerve injury in 2 cases, the superficial peroneal nerve injury in 3 cases, popliteal artery injury in 2 cases, loss of reduction in 7 cases.

RESULTSThe wound of 14 cases healed at the first stage and 24 cases healed delay. Hospitalization days ranged from 7 to 67 days (averaged 25.6 days). All patients were followed up for 12 to 36 months with an average of 16.4 months. The fracture healing time ranged from 3 to 9 months (averaged 6.9 months). According to Merchant knee function evaluation criteria, the results were excellent in 19 cases, good in 12, fair in 5 and poor in 2.

CONCLUSIONEarly complications of tibial fracture after operation is closely associated with the severe fracture complexity and related with preoperative preparation, surgical timing, operation incision selection and surgical technique. Early detection and timely processing reduce damage.

Adult ; Aged ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Postoperative Complications ; therapy ; Tibial Fractures ; surgery

OBJECTIVETo evaluate efficacy of adjuvant chemotherapy after D2 dissection on survival for patients with gastric cancer.

METHODSRandomized clinical trials (RCT) that compared adjuvant chemotherapy after D2 dissection with D2 dissection alone for gastric cancer were searched with Pubmed, Cochrane, Embase and CBM databases. Eligible trials published between 1990 and 2012 were included in the study. The quality of RCTs was assessed by the Jadad scale. Data synthesis and statistical analysis were performed by RevMan 5.1 software.

RESULTEight RCTs with 3633 patients were included in this study. Among them, 1824 patients received adjuvant chemotherapy and 1809 patients didn't. Adjuvant chemotherapy was associated with a significant benefit in terms of overall survival (RR = 0.76, 95% CI: 0.69-0.84), disease free survival (RR = 0.72, 95%CI: 0.66-0.80) and recurrence rate (RR = 0.69, 95% CI: 0.62-0.77).

CONCLUSIONAdjuvant chemotherapy was associated with survival benefit for gastric cancer after D2 dissection.

Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Gastrectomy ; Humans ; Male ; Neoplasm Recurrence, Local ; Prognosis ; Randomized Controlled Trials as Topic ; Stomach Neoplasms ; drug therapy ; mortality ; surgery ; Survival Rate

OBJECTIVETo study the effects of Ginkgo biloba extract 50 (GBE50) on inflammatory cytokines and glia cell injury in the prefrontal cortex and hippocampus of aging rats and its probable mechanism. Methods Totally 45 male SD rats were randomly divided into 4 groups, i.e., the normal control group (n=12), the model group (n=11), the low dose GBE50 group (n=10), and the high dose GBE50 group (n=12). The aging rat model was intraperitoneally injected with D-galactose to establish the aging model for 42 days. Starting from the 22nd day of modeling, rats in the low dose GBE50 group and the high dose GBE50 group were administered by gastrogavage with 75 mg/kg and 150 mg/kg respectively. The protein contents and mRNA expressions of IL-1beta, IL-6, and TNF-a in the prefrontal cortex and hippocampus of rats were detected by radioimmunoassay and Real-time fluorescence quantitative PCR assay respectively. The ultrastructural changes of glia cells in the hippocampal CA1 region were observed by transmission electron microscope. Results The protein contents and mRNA expressions of IL-1beta and TNF-alpha in the prefrontal cortex and the hippocampus of aging rats obviously increased when compared with the normal control group (P < 0.05, P < 0.01). The content of IL-6 in the hippocampus of aging rats obviously decreased (P < 0.01). Compared with the model group, the protein content and mRNA expression of IL-1beta in the prefrontal cortex and the hippocampus were obviously downregulated in the low and high dose GBE50 groups. The content of TNF-alpha in the prefrontal cortex was obviously downregulated in the low and high dose GBE50 groups, the content of TNF-alpha in the hippocampus was obviously downregulated in the low dose GBE50 group (P < 0.05, P < 0.01). The content of IL-6 in the prefrontal cortex of the low dose GBE50 group was up-regulated. The content of IL-6 in the hippocampus of the high dose GBE50 group was also upregulated. The mRNA expression of IL-6 in the prefrontal cortex of the low and high dose GBE50 groups obviously increased (P < 0.05, P < 0.01). Low and high dose GBE50 showed obvious recovery on the ultrastructural damage of glia cells in the hippocampal CA1 region.

CONCLUSIONSGBE50 showed inhibitive effects on the inflammatory reaction of nerves of aging rats. Its mechanism might be possibly correlated with its regulatory effects on the cytokines in the prefrontal cortex and the hippocampus, as well as the ultrastructures of glia cells in the prefrontal cortex and hippocampus to some degree.

Aging ; Animals ; Cytokines ; metabolism ; Ginkgo biloba ; Hippocampus ; cytology ; drug effects ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Male ; Neuroglia ; ultrastructure ; Plant Extracts ; pharmacology ; Prefrontal Cortex ; cytology ; drug effects ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism