Activation of microglia plays a vital role in the initiation and maintenance of specific neuropathic pain states. By activating microglia in central nervous system, Toll-like receptor 4 (TLR4) can promote the release of proinflammatory cytokines and neuroactive compounds, participate in the initiation and maintenance of neuropathic pain, and trigger the opiate side effects. Therefore, TLR4 may be a potential therapeutic target for neuropathic pain. Inhibition of TLR4 has shown some biological effects in neuropathic pain models and ibudilast (the TLR4 pathway-inhibiting agent) has been approved for for phase 2 clinical trials. This article briefly reviews the structure, function, and mechanism of TLR4 as well as the development of TLR4-targeted drugs.
Humans ; Neuralgia ; drug therapy ; physiopathology ; Toll-Like Receptor 4 ; antagonists & inhibitors ; physiology

Objective To survey the arsenic content of drinking water in Jingzhou City, to provide basis for prevention and control of endemic arsenic disease. Methods According to historical data, the .arsenic content of water was detected in 357 villages from 6 counties of Jianglin, Songzi, Gongan, Shishou, Jianli, Honghushi in Jinzhou City in 2007 and 2008, The past have been found to have high arsenic water villages, villages known to have high concentration of arsenic were put into census. Villages not found to have high-arsenic wells were sampled 10 percent of the whole water resources at five directions of east, west, south, north and the center. Using sampling investigation, water arsenic was determined by half -quantitative fast reagent kit. All samples of water with arsenic exceeding the standard were re-determined using silver diethyl dithiocarbamate using silver diethyl dithiocarbamate colorimetric mothod. Survey on the disease was carried out in the villages with arsenic exeeeding the standard. Results All 6074 water samples was inspected. Arsenic in 210 samples outnumbered 0.05 mg/L, 51 natural villages were high arsenic areas;The maximum level of arsenic content in drinking water was 0.7 mg/L 3.2% (152/4784) of the wells no deeper that 30 meters and 4.9%(58/1184) between 30 to 100 m had arsenic exceeding the standard The water arsenic content was normal when the wells was deeper that 100 m. The abnormal percentages of water arsenic was related with the depth of wells with a significant difference(χ2 = 12.29,P < 0.01). Medical examination 84 064 residents in 51 villages having high arsenic water 31 neighboring villages was made, No Patients was found suffering from endemic arsenic poisoning. Conclusions High arsenic source has been found in Jingzhou City ,but no endemic arsenic poisoning patient in Jingzhou City. It is suggested that necessary preventive measures should be taken in high arsenic area, low-arsenic water should be spotted or high arsenic water improved. Moreover, wells should be drilled for more than 100 meters or more in depth.

The paper is to report the study of pharmacokinetics of transdermal administered nicotine in the brain of freely moving rat by using microdialysis with stable labeled isotope as internal standard. The pharmacokinetic behavior of nicotine in Sprague Dawley rat brain was investigated after intranasal administration (3.75 mg). Brain fluid samples were collected by intracerebral microdialysis with DL-nicotine as internal standard. Concentrations of nicotine and DL-nicotine in the sample were measured by HPLC-MS/MS. Main pharmacokinetic parameters were calculated and analyzed by Das 2.0 pharmacokinetic software. The recovery of nicotine and the delivery of DL-nicotine were the same. The fate of absorption and distribution was two compartment model and the values of t1/2alpha was 170.31 min, t1/2beta was 263.30 min and the AUC(0-infinity) was 2.75 x 10(5) microg x L(-1) min separately. DL-nicotine can be used to calibrate the recovery of nicotine, and the new method of stable isotope microdialysis can be used to study the pharmacokinetics of freely moving rat. It will make sense for the treatment of addiction of tobacco and provide a new thought for the research of pharmacokinetics-pharmacodynamic combination.
Administration, Cutaneous ; Administration, Intranasal ; Animals ; Area Under Curve ; Brain ; metabolism ; Chromatography, High Pressure Liquid ; Deuterium ; Female ; Isotope Labeling ; methods ; Male ; Microdialysis ; methods ; Nicotine ; administration & dosage ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

AIMTo establish the methods for determining the activity of sphingosine kinase(SPK) and the content of sphingosine 1-phosphate (S1P) in biological samples.

METHODSThe ECV304 cells were transfected with pcDNA3 vector encoding Flag-labeled SPK gene. The expression of SPK was measured by Western blot assay and the activity of SPK was determined by enzymatic reaction, isotope incorporation and thin-layer chromatography methods. The S1P in biological samples was extracted, digested by alkaline phosphatase and then catalyzed by SPK. The S1P contents were determined according to the amounts of products.

RESULTSSPK gene transfection could enhance the expression and activity of SPK in cells markedly, and the cellular S1P was also increased obviously. HGF stimulation could increase the activity of SPK and cellular S1P in ECV304 cells.

CONCLUSIONMethods for determining the activity of SPK and the content of SPK in biological samples were established.

Cell Line ; Cytophotometry ; Humans ; Isotope Labeling ; Lysophospholipids ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; metabolism ; Sphingosine ; analogs & derivatives ; metabolism

Acute Disease ; Adult ; Altitude Sickness ; blood ; enzymology ; Glutathione ; blood ; Glutathione Peroxidase ; blood ; Humans ; Lipid Peroxidation ; Male ; Military Personnel ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Oxidoreductases ; metabolism ; Superoxide Dismutase ; blood

OBJECTIVETo investigate the cell viabilities of vascular smooth muscle cells and vascular endothelial cells stimulated by cigarette smoke extract(CSE) .

METHODSThe CSE was prepared by smoke-bubbled phosphate buffered saline(PBS) generation.After culturing cells with different concentrations of CSE, we used the cell counting kit-8 to determine the cell viability.The expression levels of c-jun and cyclinD1 were analyzed through Western blot.The c-jun plasmid was transfected to detect the change of cyclinD1 expression.

RESULTSThe smooth muscle cell viability increased when the CSE concentration ranged 0.625%-10%, whereas the endothelial cells viability decreased when exposed to the CSE concentration. After exposure to CSE for 48 hours, there was no difference in c-jun expression between toxin group and PBS group;however, the expression of p-c-jun in the smooth muscle cells significantly increased in the toxin groups than in the PBS group(P<0.05) and the expression of p-c-jun in the vascular endothelial cells significantly decreased(P<0.05) . The level of cyclinD1 significantly increased after exposed to CSE, and its expression level also increased in respond to the c-jun overexpression.

CONCLUSIONCSE can enhance the proliferation of vascular smooth muscle cells and decrease in the activity of endothelial cells proliferation, which may be explained by the phosphorylation of c-jun and the expression of cyclinD1.

Cell Proliferation ; drug effects ; Cell Survival ; Cells, Cultured ; Cyclin D1 ; metabolism ; Endothelial Cells ; drug effects ; metabolism ; Humans ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Proto-Oncogene Proteins c-jun ; metabolism ; Tobacco ; adverse effects

OBJECTIVETo evaluate the risk factors of lateral lymph node metastasis in advanced lower rectal cancer and its correlation with local recurrence and prognosis.

METHODSData from 96 consecutive patients with advanced lower rectal cancer underwent curative surgery with lateral dissection were retrospectively analyzed. The correlations of lateral lymph node metastasis with clinicopathologic characteristics, local recurrence and prognosis were investigated.

RESULTSLateral lymph node metastasis was observed in 14.6 (14/96) of the cases. In 40 patients with tumor diameter > or = 5 cm, 10 (25.0%) patients were found with lateral lymph node metastasis; while in the other 56 patients, only 4 (7.1%) cases were found with lateral lymph node metastasis (P < 0.05). Lateral lymph node metastasis was more frequent in patients whose tumor infiltrated full range of the intestinal wall (70%) than patients with 3/4, 2/4 and 1/4 intestinal wall was infiltrated (12.0%, 6.7% and 6.3%, respectively) (P < 0.05). Lateral lymph node metastasis rate of poorly differentiated carcinomas was significantly higher than those of moderate and well-differentiated ones (30% vs. 9.1% and 4.5%, P < 0.05). Local recurrence occurred in 18.8% (18 of 96 cases) of patients. Local recurrence in patients with positive lateral lymph node metastasis was 64.3%, while 11.0% in those without lateral lymph node metastasis (P < 0.05). Kaplan-Meier survival analysis showed significant improvements in median survival for patients with negative lateral lymph node metastasis over patients with lateral lymph node metastasis (80.9 +/- 2.1 vs. 38 +/- 6.7 months, log-rank P < 0.05).

CONCLUSIONSTumor diameter, degree of tumor infiltration and histological differentiation are significant risk factors of lateral lymph node metastasis in advanced lower rectal cancer. Lateral lymph node metastasis is an important predictor of local recurrence and prognosis of patients.

Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prognosis ; Rectal Neoplasms ; pathology ; surgery ; Retrospective Studies

OBJECTIVETo study the molecular mechanism of exercise to improve cardiovascular health, and exploring the effect of different intensity exercise on AMP activated protein kinase (AMPK) protein expression and phosphorylation of vascular endothelial cells in rat.

METHODSForty-eight Wistar rats were divided into control group (group C), model group (group AS), low intensity exercise model group (ASL) and high intensity exercise model group (ASH). The serum inflammatory factor concentrations such as IL-6, TNF-alpha, CRP were studied, and the endothelial cell total AMPK and p-AMPK protein were checked by means of Western blot.

RESULTS(1) The level of IL-6 between AS group and control group had no significant difference, the value of ASH group was markedly increased and had significant difference compared with that of the control group or AS group. The serum TNF-alpha levels of AS group and ASL group were significantly higher than those in control group, but the value of ASH and ASL was significantly lower than that in AS group. The serum concentration of CRP after the AS molding was significantly higher than that of the control group, there was no statistical difference between that of ASL and ASH groups. (2) The total AMPK protein content of ASL and ASH groups was significantly higher than that in control group. When compared between the two groups, there was statistical significance. (3) The value of p-AMPK protein of ASL and ASH groups was significantly higher than that of AS group, the value of p-AMPK protein of ASH group was significantly higher than that of the control group at the same time.

CONCLUSIONExercise can reduce the serum levels of inflammatory factors in atherosclerosis rat, and increase AMPK protein expression and phosphorylation level in endothelial cell.

AMP-Activated Protein Kinases ; metabolism ; Animals ; Atherosclerosis ; metabolism ; C-Reactive Protein ; metabolism ; Endothelial Cells ; metabolism ; Interleukin-6 ; blood ; Male ; Phosphorylation ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood

Objective To improve the voltage regulator for the traditional X-ray machine to provide heating voltage and current to X-ray tube filament heating circuit.Methods The circuits included the ones for regulator output voltage sampling,desired voltage generation,control voltage generation,synchronous pulse triangular signal generation,phase control,siliconcontrolled rectifier (SCR) and regulator input voltage sampling.Negative feedback control was executed by the sampling,detection and comparison of the regulator output voltage,and the comparison was carried out with the synchronous pulse triangular signal to generate the signal for controlling SCR.The regulator output voltage was kept stable by regulating the modes of SCR conduction angle.Results Installing and debugging of designed circuit for domestic power frequency X-ray machine contributed to realizing voltage regulation for the filament heating circuit.The test also measured voltage waveform distortion in AC circuits,and this kind of adverse effect did not affect the filament heating circuit.Conclusion The improved system has small volume,low heat,little noise and high performance,which can replace the traditional MSVR.

ObjectiveTo introduction of perforator flaps,muscle flaps pedicled by descending branch of lateral circumflex femoral artery,method and their clinical application that multiple soft tissue defects of hand are repaire by muliplefoliated tissue flap only branch lateral circumflex femoral artery.MethodsFifteen patients with multiple soft tissue defects of hand were repaired muliplefoliated tissue flap only pedicled bydescending branch lateral circumflex femoral artery.At first,the anterolateral thigh perforator flap was designed and harvested according to the soft tissue defects of hand, then the descending branch lateral circumflex femoral artery was dissected at the same time the segmented perforator flap,fascia lata flap,rectus femoris muscle flap, vastus lateralis muscle flap, vastus intermedius muscle flap and distal spatium intermusculare flap were harvested in need according to distance among soft tissue defects.The muliplefoliated tissue flap was harvested only pedicled by descending branch lateral circumflex femoral artery, at last muscle flaps and fascia lata flaps were covered by skin graft, so the multiple soft tissue defects of hand were repaired in one time.ResultsNo vascular crisis happened. All skin grafts survived well, the contour of all repaired soft tissue defects was good and protective feeling was recovered by skin grafts of all flaps. All cases were got follow-up and the range was from 6 to 20 months(the average was 8.7 months).Wound of donor site healed well, muscle strength of quadriceps and motion of knee were normal. Three cases were excellent,nine cases were well and 3 cases were good, according to upper extremity function evaluation criteria of Chinese Medical Society for the Surgery of the Hand, the rate of good was 80 percent.ConclusionMultiple soft tissue defects of hand can be repaired by muliplefoliated flap only pedicled by descending branch of lateral circumflex femoral artery. Its advantages included reduction of operation time and treatment, good recovery of hand contour and function. It is a good method to repair multiple soft tissue defects of hand.