Aim To study the analgesic effect of geraniol on neuropathic pain and to explore the possible mechanism.Method A neuropathic pain rat model of Spared Nerve Injury(SNI) was established to measure changes in the threshold of paw withdrawal before and after i.p.administration of geraniol.Patch clamp whole-cell recording was performed to measure activity of sodium channels using ipsilateral L3/L4/L5 dorsal root ganglion(DRG) cells isolated from the SNI rats.In addition, HEK 293 cells expressing hNav1.7 and hTRPA1 channels were used for measuring the changes in channel activities with or without geraniol by whole-cell patch clamp.Results Geraniol had a fast analgesic effect on hypersensitivity of mechanical pain in the SNI model.It significantly inhibited sodium channels on DRGs isolated from SNI rats and hNav1.7 but not hTRPA1 channels expressed by HEK293 cells.However, high concentrations of geraniol facilitated the activation of HTRPA1 channel stimulated by AITC.Conclusion Geraniol may abirritate hypersensitivity of mechanical pain in the SNI model by specifically inhibiting Nav1.7 channel activity on the DRG cells.

Objective To explore the clinical efficacy of anatomic liver resection in treatment of hepatocellular carcinoma (HCC) with microvascular invasion (MVI).Methods The retrospective cohort and case-control study was conducted.The clinical data of 150 HCC patients with MVI who were admitted to the Anhui Medical University Affiliated Provincial Hospital from June 2007 to June 2012 were collected.Sixty patients undergoing anatomic liver resection were allocated into the AR group and 90 undergoing non-anatomic liver resection in the NR group.Patients in the AR group underwent anatomic liver resection according to results of preoperative ICG R15 test,and patients in the NR group underwent non-anatomic liver resection.Observation indicators:(1) operation situations:operation time,volume of intraoperative blood loss,number of patients with blood transfusion;(2) postoperative recovery situations:time of drainage-tube removal,duration of hospital stay,Clavein grade of complication within 30 days postoperatively,number of patients with hepatic failure within 30 days postoperatively and number of death within 30 days postoperatively;(3) follow-up:postoperative median survival time,5-year overall survival rate and 5-year tumor-free survival rate;(4) prognostic factors analysis of 150 HCC patients with MVI.Measurement data with normal distribution were represented as-x±s and comparison between groups was analyzed using the independent-sample t test.Count data were represented as the chi-square test or Fisher exact probability.The survival rate was calculated using the Kaplan-Meier method and survival analysis was done using Log-rank test.The univariate analysis and multivariate analysis were done using the COX regression model.Results (1) Operation situations:all the 150 patients received successful radical resection of HCC.Operation time,numbers of patients with volume of intraoperative blood loss ≥ 500 mL and with volume of intraoperative blood loss ＜ 500 mL and number of patients with blood transfusion were (165±39) minutes,12,48,15 in the AR group and (136±30)minutes,34,56,38 in the NR group,respectively,with statistically significant differences between the 2 groups (t =29.172,x2=5.351,4.673,P＜0.05).(2) Postoperative recovery situations:time of drainage-tube removal and duration of hospital stay were (2.7± 1.1)days and (5.2± 1.3) days in the AR group,(3.8±1.6)days and (7.1±2.3)days in the NR group,respectively,with statistically significant differences between the 2 groups (t =4.641,5.812,P＜0.05).Numbers of patients with grade Ⅰ-Ⅱ of Clavein grade and with grade Ⅲ-Ⅳ and number of death within 30 days postoperatively were 45,15,1 in the AR group and 61,29,2 in the NR group,respectively,with no statistically significant difference between the 2 groups (x2 =0.906,P＞0.05).Number of patients with hepatic failure within 30 days postoperatively in the AR and NR group were respectively 4 and 17,with a statistically significant difference (x2=4.467,P＜0.05).(3) Follow-up:all the 150 patients were followed up for 1-106 months,with a median time of 26 months.The postoperative median survival time,5-year overall survival rate and 5-year tumor-free survival rate were 46 months,33.3％,21.7％ in the AR group and 18 months,15.6％,2.2％ in the NR group,respectively,with statistically significant differences in overall survival and tumor-free survival between the 2 groups (x2=23.718,63.932,P＜ 0.05).(4) Prognostic factors analysis of 150 HCC patients with MVI:result of univariate analysis showed that maximum diameter of tumor,tumor capsule,TNM stage,Edmondson grade and surgical procedures were relative factors affecting overall survival and tumor-free survival of HCC patients with MVI,with statistically significant differences (x2=5.519,2.790,13.639,8.321,42.470,31.057,15.963,19.594,23.718,63.932,P＜ 0.05).Result of multivariate analysis showed that missing tumor capsule,stage Ⅲ-Ⅳ of TNM stage,grade Ⅲ-Ⅳ of Edmondson grade and non-anatomic liver resection were independent factors affecting poor overall survival and tumor-free survival of HCC patients with MVI,and maximum diameter of tumor ＞5 cm was an independent factor affecting poor overall survival of HCC patients with MVI,with a statistically significant difference [HR =0.527,0.683,0.333,0.522,0.576,0.514,0.523,0.268,95％ confidence interval (CI):0.355-0.782,0.475-0.983,0.219-0.504,0.361-0.755,0.389-0.852,0.358-0.737,0.342-0.800,0.174-0.413;HR=0.559,95％CI:0.370-0.845,P＜0.05].Conclusions Anatomic liver resection in the treatment of HCC patients with MVI is safe and effective,with good short-term and long-term outcomes,and it can also improve prognosis of patients.Missing tumor capsule,stage Ⅲ-Ⅳ of TNM stage,grade Ⅲ-Ⅳ of Edmondson grade and non-anatomic liver resection are independent factors affecting poor overall survival and tumor-free survival of HCC patients with MVI,and maximum diameter of tumor ＞5 cm is an independent factor affecting poor overall survival of HCC patients with MVI.

Objective To evaluate the effect of endemic disease prevention in Shaanxi province caused by earthquake and supply a scientific basis for making decision regarding restoration and reconstruction after the earthquake.Methods Forty different drinking water samples were collected respectively from Mianxian county and Chencang district the earthquakes'most severely hit areas in Shaanxi province with drinking-water-borne fluorosis.The contents of fluorine and arsenic in the water was detected by Fluoride ion-selective electrode and hydride generation atomic fluorescence spectrometry,respectively.Two hundreds iodized salt and urine samples were collected from affected household women aged 18-45 in severely hit Ningqiang and Lveyang countie with iodine deficiency disorders.The contents of iodine in the salt was detected by semi-quantitative and of urinary iodine of household women was determined by AsⅢ-Ce4+ catalytic spectrophotometry.Two hundred children aged 7-12 were detected by clinical and X-ray examination from Ningqiang and Lveyang counties of Kashin-Beck disease prevailing areas.Hair and food samples from 20 children were collected.The contents of selenium were determined by 2,3-Diamino naphthalene fluorescence spectrophotometry and of T-2 toxin in the food was detected by ELISA.Results No incidents of serious hydrologieM or geological damage were found.Fluoride content in one of eighty water samples was beyond 1.5 mg/L,accounting for 1.25%;five samples were between 1.0 mg/L and 1.5 mg/L,accounting for 6.25%:the arsenic content of all samples were below 0.01 mg/L;all the salt samples from the home of household aged 18-45 were iodine salt,the median of urine iodine of household wonlen Was 303.03μg/L (21.40-1133.54 μg/L) and 325.21 μg/L(27.61 - 1191.46 μg,/L) in Ningqiang and Lveyang counties, respectively.No clinical and X-ray patients were found in the children aged 7 - 12, the average content of selenium in hair was (0.2638 ± 0.0875)mg/kg; the content of T-2 toxin in the forty food samples was below 100 μg/kg. Conclusions The prevention of the endemic disease in the four counties has been moderately affected by the earthquake, but the situation of endemic disease is stable and there is no evidence of the endemic disease.

One hundred and fifty ASA Ⅰ-Ⅱ infants scheduled to undergo surgery on unilateral inguinal region,were randomly assigned to 3 groups with 50 in each group.In groups Ⅰ and Ⅱ puncture was performed at traversus abdominis plane under ultrasound-guidance,0.4 or 0.5/kg of 0.25％ ropivacaine was injected respectively.In group Ⅲ the triangle of Petit was positioned through palpating and then 0.5 ml/kg of 0.25％ ropivacaine was injected.HR,RR,SpO2,PETCO2,expired sevoflurane concentration and BIS value at the time of entering the operation room (T1),incision of skin (T2),pulling hernia sac (T3),ending the surgery (T4),waking (T5),the number of pressing the analgesia pump after operation were recorded.The results showed that HR at T2 and T3 of groups Ⅰ and Ⅱ was lower than group Ⅲ (P ＜ 0.05).The were significant differences in case numbers of insufficient intraoperative analgesia among 3 groups(x2 =10.500,P =0.005).The CHEOPS scores and the number of pressing analgesia pump after operation in groups Ⅰ and Ⅱ were lower than those in group Ⅲ (x2 =7.230,P =0.027).Results indicate that ultrasound-guided transversus abdominis plane block is safer and more effective than conventional method for operations of inguinal region in infants; it may reduce dose of local anesthetics and postoperative use of analgesics.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC₅₀ value of 7, 9, 6 and 6 nmol·L^-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.

Background The integration of segregated pathways from the two eyes first appears in V1 neurons,where it not only plays a critical role in the generation of a three-dimensional visual representation.Abnormal visual experiences in critical period usually lead to amblyopia and binocular integration defects.Objective Present study was to investigate how neurons of kitten coordinate their activity patterns in response to synchronous dichoptic stimulus inputs in striate cortex.Methods Spike rate and local field potential(LFP) gamma band(20-90Hz) power of three kitten(1-1.2Kg,8-10 weeks old) to monocular and synchronous dichoptic presented gratings were assessed for 28 binocular neurons in V1 of kitten by in vivo extracellular record method under anaesthesia and paralysis.Ocular dominance index(ODI) and binocular integration index(BII) were assessed and the correlation between these two indexes were analyzed.Results In 28 cells with binocular characteristic,the absolute value of spike-ODI was significant larger than that of LFP-ODI(t=2.606,P=0.021).A positive linear correlation between the ocular preferences of spike and LFP was found(R2=0.513,F=27.423,P=0.003).In dichotic trails,binocular facilitation with BII for spike was 2.348±0.996,showing a significant reduce in comparison with BII for LFP(3.678±1.974)(t=2.671,P=0.019).Binocular integration index for two signals were greater when monocular responses of both eyes were similar(P=0.035 and P=0.124,respectively).Conclusion Both spike rate and gamma band power of LFP exhibited binocular facilitation to synchronous presented dichotic stimuli with significant facilitation induced by balanced monocular responses.Spiking activity and LFP reflect neural activities of different spatial scales and source components.

Objective:To observe the effects of different moxibustion time on cartilage morphology,tumor necrosis factor(TNF)-α and interleukin(IL)-10 of the knee joint in rats with knee osteoarthritis(KOA),and to explore the best treatment time of moxibustion for KOA.Methods:Healthy male Wistar rats were randomly divided into a blank group,a model group,a 15-minute-moxibustion group,a 30-minute-moxibustion group,and a 60-minute-moxibustion group,with 10 rats in each group.Except for the blank group,the KOA model was established in all groups by injecting sodium iodoacetate solution into the knee joint cavity of rats.Rats in the 15-minute-moxibustion group,the 30-minute-moxibustion group,and the 60-minute-moxibustion group were all treated with mild moxibustion intervention for 15 min,30 min,and 60 min,respectively at Neixiyan(EX-LE4)and Dubi(ST35)points near the patella,3 times a week for 4 weeks,12 times in total.Rats in the blank group and the model group were fixed for 30 min without moxibustion intervention.Macroscopic observation for the smoothness of knee cartilage surface was performed after the intervention.Hematoxylin-eosin staining,toluidine blue staining,and Mankin score were used to evaluate the pathological changes in the cartilage.The expression levels of TNF-α and IL-10 in the serum were detected by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the articular cartilage surface in the model group was rough,the chondrocyte arrangement was irregular,the Mankin score and the serum TNF-α expression were significantly increased(P＜0.05),while the expression of serum IL-10 was significantly decreased(P＜0.05).Compared with the model group,the articular cartilage surface was smoother,the chondrocytes were arranged neatly,the Mankin score and serum TNF-α expression level were significantly lower in the three moxibustion intervention groups(P＜0.05);the serum IL-10 level in the 30-minute-moxibustion group and the 60-minute-moxibustion group was increased significantly(P＜0.05).Compared with the 15-minute-moxibustion group,the articular cartilage surface in the 30-minute-moxibustion group and the 60-minute-moxibustion group was smoother,the chondrocyte arrangement was more regular,the Mankin score and the serum TNF-α level were decreased significantly(P＜0.05),and the serum IL-10 level was increased(P＜0.05).There was no significant difference in the serum TNF-α or IL-10 level between the 30-minute-moxibustion group and the 60-minute-moxibustion group(P＞0.05).Conclusion:Moxibustion can obviously improve the morphology and structure of KOA articular cartilage,protect articular cartilage,inhibit cartilage inflammation,and delay KOA cartilage degeneration.Moxibustion's effect is closely related to moxibustion time;the therapeutic effect of the 30-minute-moxibustion and the 60-minute-moxibustion is better than that of the 15-minute-moxibustion.

To determine the relationship between the intercellular adhesion operon (ica) and the biofilm production in Staphylococcus epidennidis isolates from nosocomial infection, and the affection of ica on the antibiotic susceptibility of the isolates, we collected 106 strains, epidermidis isolates from nosocomial infection specimen to detect their biofilm production by quantitative and qualitative method and investigate the existence of ica operon by PCR. The minimal inhibitory concentration (MIC) to erythromycin, ampicillin, cefoxitin, ceftriaxone, teco-planin, ciprofloxacin, tetracycline, trimethoprim-sulfamethoxazole and vancomycin were tested. Among the isolates, 33 (31. 1% ) of them were detected out carrying ica operon. The rate of biofilm production of the ica-posi-tive isolates was higher than that of the ica-negative (P =0. 001) . By adding glucose and NaCl into the culture the detection rate of biofilm production could be increased. The antibiotic susceptibility of the plankton cells of ica-positive isolates to erythromycin, cefoxitin and ceftriaxone , except ampicillin, ciprofloxacin, tetracycline and tremethoprim-sulfamethoxazole, were lower than those of ica-negative isolates. This study showed that the existence of ica operon was close related to the biofilm formation in 5. epidermidis isolates from nosocomial infection. However, the mechanism of antibiotic resistance of the strains inside the biofilm still needed to be illustrated.

Objective To determine the genotypes and their epidermiology of microlide, lincosamide and streptogramin B(MLS_B)resistant S.epidermidis isolates causing nosocomial infection.Method 126 isolates were collected from inpatients in three hospitals in Beijing from 2003-2004 for testing the antibiotic susceptibility to the macrolide erythromycin,the lincosamide clindamycin.The resistance phenotypes of erythromycin-resistant isolates were determined by the double-disc test with erythromycin and clindamycin.The presence of the relative genes(ermA,ermB,ermC and msrA)to MLS_B resistance was identified by PCR and the similarity of the isolates was analyzed by PFGE.Result The isolates were mostly resistant to macrolide and lincosamide.In the constitutive phenotype cMLS_B isolates,the methicillin resistant S.epidermidis(MRSE)proportion appeared high(78.5%),whereas high methicillin susceptible S.epidermidis(MSSE)proportion was found in the inducible MLS_B phenotype(iMLS_B) (69.2%).ermC was shown as the most frequent determinant to the resistance,not only in MRSE and MSSE (70.8% and 6.8%),but also in iMLS_B and cMLS_B(76.9% and 90.3%).No specific endemic strain was found by PFGE analysis.The same resistance phenotype pattern was not clustered together and distributed into type A～F at the similarity of 60%.Among the phenotypes(cMLS_B,iMLS_B and MS phenotype),no significant difference was shown in the PFGE genotype distribution.Conclusion Our results indicate that the MLS_B resistance in S.epidermidis causing nosocomial infection is prevalent in the hospital and MLS_B antibiotics should be used iudiciously,ermC was shown as the most frequent determinant to the resistance.

Objective To investigate the effects of fentanyl and remifentanil on the viability of human adenocarcinoma cell line A549.Methods Human adenocarcinoma A549 cells cultured in logarithmic growth phase were seeded in 75 ml culture bottles or 96-well plates.After being cultured for 24 h,the cells were randomly divided into 9 groups (n =30 each):4 fentanyl groups (groups F1-4 ),4 remifentanil groups (groups RF1-4 ) and control group (group C).Groups F1-4 were exposed to fentanyl with the final concentrations of 0.5,5.0,50.0 and 500.0 ng/ml respectively.Groups RF1-4 were exposed to remifentanil with the final concentrations of 0.5,5.0,50.0 and 500.0 ng/ml respectively.The viability of the cells was determined by methyl thiazolyl tetrazolium assay after being incubated for 24,48 and 72 h.The cell cycle progression and apoptosis were determined by flow cytometry after being incubated for 24 h.Results Compared with group C,the viability of A549 cells were gradually decreased at 72 h of incubation,the proportion of the cells in S phase was gradually decreased at 24 h of incubation,and the proportion of the cells in G2/M phase and apoptotic rate were gradually increased in groups F2-4 and in groups RF2-4 ( P ＜ 0.05).Conclusion Fentanyl and remifentanil with the final concentration ≥5 ng/ml can inhibit the viability of human adenocarcinoma cell line A549 in a dose-independent manner by inducing cell apoptosis and cell cycle arrest in G2/M phase.