Objective To unravel the relationship between Toll-like receptor 4 (TLR4) expression in platelets and the activation of platelet in thrombocytopenia (TCP) in case of sepsis. Method A total of 64 patients with sepsis were prospectively studied with control. Platelet count (PC), mean platelet volume (MPV),platelet distribution width (PDW),platelet TLR4 expression, platelet PAC-1 expression, sCD40L and TNF-α concentrations were compared between healthy control group (15 cases) and sepsis group on admission and 3 d,Sd,and 9 days after admission. The changes of MPV and PDW in TCP and non-TCP subgroups of sepsis before and after treatment were recorded. Prognostic index was analyzed. Results The PC was lower in sepsis group (P=0.006), and MPV and PDW were higher in sepsis group than those in healthy control group (P = 0.046, P =0.001). Platelet TLR4 and PAC-1 expressions, and sCD40L and TNF-α levels also increased more significantly in sepsis group (P ＜ 0.001). PAC-1 expression and TNF- level were higher in TCP group than those in non-TCP group before and after treatment (P = 0.023, P = 0.011). The sCD40L concentration and platelet TLR4 expression were significantly higher in treated TCP groups than in non-TCP group (P = 0.047, P = 0.001). Compared with non-TCP,the rate of bleeding was higher (P = 0.024) and the length of ICU stay was longer (P = 0.013).The APACHE Ⅱ score and the 28-day mortality were higher in TCP group (P ＜ 0.01, P = 0.048). Conclusions The elevation of platelet TLR4 expression in sepsis along with platelet activation is closely related to the incidence of thrombocytopenia. The occurrence of TCP is a poor prognosis sign of sepsis.

OBJECTIVETo observe the effects of Modified Liangge Powder (MLP) on the expressions of platelet toll like receptor 4 (TLR4) and the release of platelet-derived cytokines interleukin 8 (IL-8), beta platelet globulin (beta-TG), soluble CD40 ligand (sCD40L).

METHODSThe modulating effects on the release of cytokines from mice platelets by TLR4 ligand through monoclonal antibody blocking TLR4 on platelet were compared. The stimulated platelet by LPS was incubated with low (0.94 g/mL), medium (1.89 g/mL), and high (2.84 g/mL) dose of MLP contained serum. The changes of the platelet TLR4 expression and platelet-derived cytokines were observed.

RESULTSThe positive expression rate of platelet TLR4 obviously decreased (P < 0.01) and the release of sCD40L and beta-TG from platelets significantly increased (P < 0.01) after stimulated by LPS. However, the release of sCD40L and beta-TG from platelets obviously decreased by TLR4 monoclonal antibody (P < 0.05, P < 0.01). There was no statistical difference in IL-8 between before and after LPS stimulation (P > 0.05). Platelet TLR4 positive expression rate was significantly higher after incubated by medium and high doses of MLP contained serum (P < 0.01), and the releasing of sCD40L and beta-TG was lower in the serum contained groups. The inhibitory effects were enhanced in a dose-dependent manner.

CONCLUSIONSLPS induced platelet activation by TLR4 and released sCD40L and beta-TG, while the release of platelet IL-8 was not dependent on platelet TLR4-LPS pathway. MLP could inhibit LPS-stimulated sCD40L and beta-TG, inhibit the binding of platelet TLR4 and LPS in a dose-dependent manner, thus reducing the release of platelet cytokines.

Animals ; Beta-Globulins ; metabolism ; Blood Platelets ; drug effects ; metabolism ; CD40 Ligand ; metabolism ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Interleukin-8 ; metabolism ; Lipopolysaccharides ; adverse effects ; Male ; Mice ; Mice, Inbred ICR ; Serum ; Toll-Like Receptor 4 ; metabolism

AIMTo study the sodium nitrite induced DNA mutation by convolution spectrometry (CS).

METHODSThe spectra of sodium nitrite-induced mutative calf thymus DNA was compared with ego criteria based on Spectra of the primary DNA within the wavelength range from 200 to 340 nm. Distilled water served as blank and normal saline served as negative control. Any difference was quantitatively expressed by differential value (delta) of convolution spectra. Near-infrared spectroscopy was employed as the reference method.

RESULTSThe differential value was positively correlated with the increasing time and concentration of sodium nitrite. delta values increased to 1.37%, 2.41% and 5.44% respectively within 2-hour's reaction between calf thymus DNA and 0.5, 0.05 and 0.005 microgram.mL-1 sodium nitrite, while on the contrary, changes could be hardly observed on the corresponding UV absorption spectra. The results were also confirmed by their corresponding near-infrared spectra.

CONCLUSIONThe delta values can be used to represent the compound's strength of mutagenesis. Every convolution procedure takes less than one minute, so CS provides a fast, simple and inexpensive alternative method to determine chemical or medicinal DNA mutation.

Animals ; Cattle ; DNA ; chemistry ; drug effects ; In Vitro Techniques ; Mutation ; drug effects ; Sodium Nitrite ; pharmacology ; Spectrum Analysis ; methods ; Thymus Gland ; chemistry ; drug effects

ObjectiveTo make a comparison between microsurgical lumbar discectomy(MSLD) and microendoscopic discectomy(MED) in terms of methods,feathers,and effectiveness for lumbar disc herniation (LDH).MethodsA prospective clinical review was conducted.From January 2006 to December 2009,900patients with single segment lumber disc herniation were randomly divided into the MSLD group and the MED group.There were 450 patients in each group.Comparison would be made in terms of the length of skin incision,the operative time,amount of bleeding,incidence of complication,duration of hospitalization,the time of recovery to ordinary work or life,pre- and post-operative assessment based on the criteria of visual analogue scales (VAS),and the Oswestry disability index(ODI).ResultsThe mean lengths of skin incision were (3.8±1.1) cm and (2.4±0.7) cm for MSLD and MED respectively; the operative time were (51.0±14.2) min and (62.0±16.3) min; and the blood loss were (60±35) ml and (106±43) ml,which showed a significant difference(P＜0.05).There was no significant differences in terms of the hospitalization time and the time of recovery to ordinary work or life between the two groups (P＞0.05).The results of VAS and ODI of two groups also showed no significant difference at final follow-up (P＞0.05).As for the complications,the incidence of dural tear,acute hematomas of sacrospinalis,nerve roots and cauda equina injury and recurrence in MSLD group were much lower than that of MED group (P＜0.01).There was no incidence of wrong segment,greater artery injury,or postoperative infection in each group.ConclusionThe clinical effects of both minimal invasive methods are satisfactory.However,MSLD has advantages of simpler maneuvering,shorter learning curve,and less complication than MED.

OBJECTIVESTo evaluate the influence of thoracic kyphosis to sagittal alignment and balance of the lumbosacral vertebrae in thoracic adolescent idiopathic scoliosis patients.

METHODSStanding posteroanterior and lateral x-rays of a cohort of 55 patients with thoracic adolescent idiopathic scoliosis were obtained. The patients were classified according to their thoracic kyphosis, the first group TK < 10 degrees and the second group 10 degrees < or = TK < or = 40 degrees . The following parameters were measured: lumbar lordosis (LL), upper and lower arc of lumbar lordosis, sagittal vertical axis, sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT). Sagittal plane parameters were analyzed using t-test between two groups, with significance set at P < 0.05. Linear correlations between parameters were calculated using Pearson correlation coefficients, with significance set at P < 0.01.

RESULTSThere were smaller LL and upper arc of lumbar lordosis in the first group. Significant linear correlations were found between each single adjacent shape parameter. Significant correlations were also found between TK, LL and upper arc of lumbar lordosis, as well as between PT, SS and PI.

CONCLUSIONSSagittal alignment and balance of the lumbosacral vertebrae may influence the thoracic kyphosis in AIS patients. The mechanism of this influence may through the adaptation of upper arc of lumbar lordosis. This influence must be considered in thoracic adolescent idiopathic scoliosis patients who undergo selective posterior thoracic fusion.

Adolescent ; Adult ; Female ; Humans ; Kyphosis ; complications ; pathology ; Lumbar Vertebrae ; diagnostic imaging ; pathology ; Male ; Radiography ; Sacrum ; diagnostic imaging ; pathology ; Scoliosis ; complications ; pathology ; Thoracic Vertebrae ; diagnostic imaging ; pathology

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests

Objective:To observe the effect of acupuncture in regulating ubiquitin-proteasome pathway (UPP),and discuss the action of acupuncture in intervening heroin-induced brain damage.Methods:Thirty male Sprague-Dawley (SD) rats were divided into a control group,a model group and an acupuncture group by using the random number table.Rats in the model and acupuncture groups received intramuscular heroin injection for successive 8 d at a progressively increased dose.Afterwards,the injection was suspended for 5 d for withdrawal.The heroin relapse rat model was established by repeating the drug addiction and withdrawal process for 3 times.The control group followed the step of the model establishment,but was given intramuscular injection of normal saline at the stage of addiction and no intervention at the stage of withdrawal;the model group was given intramuscular heroin injection at a progressively increased dose at the addiction stage and no intervention at the withdrawal stage;the acupuncture group was dealt in the same way as the model group at the addiction stage,but received acupuncture at Baihui (GV 20) and Dazhui (GV 14) at the withdrawal stage,with the needles retained for 30 min each time,1 session a day,for successive 5 d.On the 39th day,brain tissues were extracted from the hippocampus and ventral tegmental area (VTA) of the three groups of rats.The apoptosis of brain nerve cells was detected by using terminal deoxynucleotidyl transferase-mediated nick and labeling (TUNEL).The mRNA and protein expressions of ubiquitin (Ub),ubiquitin protein ligase (E3) and 26S were examined by immunohistochemistry and quantitative real-time polymerase chain reaction (RT-qPCR).Results:Compared with the model group,rat's hippocampus and VTA in the acupuncture group showed significantly fewer cells positively stained by TUNEL staining (P＜0.01),and its mRNA and protein expressions of Ub,E3,26S were significantly lower (P＜0.01).Conclusion:Reducing nerve cell apoptosis and regulating the mRNA and protein expressions of Ub,E3 and 26S in rat's hippocampus and VTA are possibly one of the action mechanisms of acupuncture in intervening heroin-induced brain damage.

OBJECTIVETo investigate the impairment pattern and the influencing factors of pulmonary function in patients with Marfan and Marfanoid syndrome associated scoliosis (MS).

METHODSIn this retrospective study, totally 25 MS patients (aged 11 - 20 years, 11 boys and 14 girls) who received posterior instrumentation and fusion (Group A) and 38 adolescent idiopathic scoliosis (AIS) patients (Group B) (aged 10 - 19 years, 11 boys and 27 girls) were included from February 1998 to September 2007. The curve pattern was matched in both groups. The preoperative pulmonary function test (PFTs) were compared in two groups. And the parameters influencing the preoperative pulmonary function were analyzed in group A.

RESULTSIn Group A, the Cobb angle of thoracic curve was negatively correlated with the percentage of predicted pulmonary volumes (VC%, FVC% and FEV1%) (r = -0.514, -0.503, -0.464, P < 0.05). And the reduction of lung function parameters (VC%, FVC%, FEV1% and MMEF%) was more severe in Group A than in Group B with compared magnitude of thoracic curve (P < 0.05). In Group A, the extent of impairment of pulmonary function in patients with the number of vertebrae involved ≥ 8 were more severe than those involved < 8 vertebrae (P < 0.05). However, there was no significant difference of deterioration of lung function between the higher apex (T₄₋₈) subgroup and lower apex (T₉₋₁₂) subgroup. And no correlation was found between thoracic kyphosis and the degrees of impairment of respiration function.

CONCLUSIONSPatients with MS have mixed ventilation dysfunction, which is more severe than AIS patients with matched age and Cobb angle. The pulmonary dysfunction in MS patients can be influenced by the severity of thoracic curve and the number of involved vertebrae.

Adolescent ; Child ; Female ; Humans ; Lung ; physiopathology ; Male ; Marfan Syndrome ; complications ; physiopathology ; Respiratory Function Tests ; Retrospective Studies ; Scoliosis ; complications ; physiopathology ; Young Adult

Objective To investigate the intervention effect of CD147 on learning and memory ability in rat model of Alzheimer's disease. Methods A total of 60 healthy Sprague-Dawley rats were randomly divided into sham operation group, model group and CD147 group, 20 rats in each group. All of the rats were anesthetized with intraperitoneal injection of 10％chloral hydrate (0.3 g/kg). The rats in the model group and the CD147 group were injected with Aβ1-40 (10μg) in the bilateral hippocampal CA1 regions, while the rats in the sham operation group were injected with the same amount of saline at the same sites. After 48 h, the rats in CD147 group were injected with CD147 cDNA in the bilateral ventricles, while the rats in model group and sham operation group were injected the same amount of saline at the same sites. Morris water maze test was used to detect the ability of learning and memory of rats. The expressions ofβamyloid protein (Aβ) andγ-secretase were detected by Western blot assay. Results The escape latency was significantly longer in model group than that of sham operation group, while which was significantly lower in CD147 group than that of model group (P<0.05). The number of times across the platform and the time of staying on platform were significantly lower in model group than those of sham operation group, while which was significantly higher in the CD147 group than that of model group (P<0.05). The expressions of Aβandγ-secretase were increased significantly in model group compared to those of sham operation group, while which were significantly decreased in CD147 group compared with those of model group (P<0.05). Conclusion Exogenous CD147 can significantly improve the learning and memory ability of AD rats, and its specific mechanism may be related to regulating the activity ofγ-secretase and down regulating the expression of Aβ.

AIMTo study the effects of bone marrow MSCs transplantation on the apoptosis of alveolar wall cells and the expression of Bcl-2 and Bax of lung tissue in papain and Co60-induced pulmonary emphysema rats.

METHODSFemale Lewis rats were randomly divided into three groups: control group, emphysema group, emphysema + MSCs transplantation group. Rats were sacrificed at days 14 and 28 after treatment. Morphologic analysis of the lung tissue was performed. The apoptosis of the lung cells was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of Bcl-2 and Bax were determined by immunohistochemical staining.

RESULTSEmphysematous changes of the lung tissue were observed in emphysema group and emphysema + MSCs transplantation group. However, the emphysematous change in emphysema + MSCs transplantation group was improved compared with the emphysema group. There was significant difference in the number of alveolar counted per unit area (MAN), mean alveoli area (MAA) and mean linear interval(MLI) between emphysema group and emphysema + MSCs transplantation group. The apoptotic index of the alveolar wall cells in emphysema + MSCs transplantation group was less than that in the emphysema group. The percentage of Bcl-2 positive cells in emphysema + MSCs transplantation group was significantly higher than that in the emphysema group. The percentage of Bax positive cells in emphysema + MSCs transplantation group was significantly lower than that in the emphysema group. The ratio of Bcl-2/Bax of emphysema + MSCs transplantation group was significantly higher than that in the emphysema group.

CONCLUSIONBone marrow MSCs transplantation inhibits the apoptosis of alveolar wall cells, upregulates the expression of Bcl-2 and downregulates the expression of Bax. This may be part of the reason that bone marrow MSCs transplantation improves the papain and Co60-induced pulmonary emphysema.

Animals ; Apoptosis ; Bone Marrow Transplantation ; Cells, Cultured ; Cobalt Isotopes ; adverse effects ; Female ; Lung ; cytology ; Mesenchymal Stem Cell Transplantation ; Papain ; adverse effects ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pulmonary Alveoli ; drug effects ; pathology ; radiation effects ; Pulmonary Emphysema ; chemically induced ; metabolism ; pathology ; surgery ; Rats ; bcl-2-Associated X Protein ; metabolism