AIM: To study the pharmacokinetics of ligustilide in the volatile oil from Angelica Sinensis(Oliv.) Diels in the rabbit. METHODS: HPLC method for ligustilide determination in the blood was developed.The HPLC system consisted of C_(18) column using MeOH-H_2O(65∶35,v/v) as mobile phase at a flow rate of 1.0 mL/min and UV detection at 236 nm. RESULTS: Linear calibration curves were obtained over the concentration range of 0.40 ?g?mL~(-1)～10.00 ?g?mL~(-1) for ligustilide.The minimum limit detection was 0.40 ?g?mL~(-1).The recovery of ligusitilide in blood was 90.90% with RSD 2.74%. CONCLUSION: After oral administration of volatile oil,intracorporal process of ligustilide in rabbit accords with 2-compartment model with 1 st order absorption,(2.6638) h and 108.88 h are obtained as t_(1/2?) and t_(1/2?) respectively.

Objective To study the correlation between genetic polymorphisms of interleukin (IL)-1A/1B and susceptibility to tuberculosis (TB).Methods Genetic polymorphisms of IL-1A and IL1 B in 1032 TB patients and 1008 non-TB patients were analyzed using PCR-MassARRAY method.The correlation between genetic polymorphisms of IL-1A/1B and susceptibility to TB was statistically analyzed.Results Two tag SNPs of IL-1A and three tag SNPs of IL-1B were screened for the study.There were differences in the allele frequencies of rs2853550 and rs3783526 between TB group and non-TB group (P=0.047and P =0.034,respectively).IL-1 B SNP1 rs2853550 (P =0.025,OR =1.302,95 ％ CI =1.034-1.640,TC vs.CC) was found to be highly associated with TB,while the other SNPs showed no significant correlations with TB.Furthermore,IL-1B SNP1 rs2853550 [P=0.019,OR=1.308,95％ CI=1.045-1.638 for (TC+TT) vs.CC] in the dominant model conferred significant risk for TB,but IL-1A SNP2 rs3783526 [P=0.000,OR=0.764,95％ CI =0.591-0.988 for GG vs.(AA+GA)] in the recessive model showed protective effects against TB.The haplotype ‘TG’ in the IL-1B block showed a higher risk for TB compared with the common ‘ CA’ haplotype (P=0.032,OR=1.265,95％ CI=1.020-1.567).The diplotypes containing ‘ GA’ haplotype in IL-1A block and ‘ TG’ haplotype in IL-1B block were major risk factors for TB (for onecopy,adjusted P=0.014,OR=1.403 and 95％ CI=1.072-1.836; adjusted P=0.013,OR=1.339 and 95％ CI=1.063-1.688,respectively),but the diplotype with ‘CG’ in IL-1B block played a protective effect against TB (for two-copy,P=0.006,OR=0.664 and95％ CI=0.494-0.891).Conclusion The genetic polymorphisms of IL-1B rs2853550 might be closely associated with TB,but the GG genotype of IL1 A SNP rs3783526 might have the characteristic of anti-TB.

Objective To find out an effective therapeutic method for and observe whether there is any synergistic action or not between fetal spinal cord transplantation (FST) and methylprednisolone (MP).Methods Fifty male adult SD rats were randomly divided into group A,B,C,D and E,10 in each group.Group A was treated with both large dosage of MP and FST,group B with MP only, grop C with FST only and group D without any treatment.Group E served as blank control.Fetal spinal cord was obtained from 14-day pregnant rats .Spinal cord Somatosensory evoked potential (SSEP) examination and behavior observation were performed in 24 hours and in 8 months after treatment By the way of reduced silver staining, the condition of nerve plerosis and regeneration could be observed.Results There were significant differences in the latent period and amplitude of N1 wave in SSEP between group A and group B,C and D (P＜0.05).No obvious behavior changes were found except partial sensory recovery in the left lower limbs in Group A.Histologically,more nerve fibers contacting with branches at injury area could be found in Group A than in Group B,C and D.Conclusion The combination of large dosage of MP and FST can produce synergistic effect in the recovery of the injured spinal cord.

Objective:To optimize the formula composition of rutin self-microemulsifying drug delivery system by pseudo-ternary phase diagram.Methods:The oil, surfactant and co-surfactant were chosen by the solubility test , and the formula of rutin self-microe-mulsifying drug delivery system was optimized by pseudo-ternary phase diagram .Results: The formula of rutin self-microemulsifying drug delivery system was with the mass ratio of oleic acid , Cremopher RH40 and absolute ethyl alcohol of 23∶36∶12 .The microemul-sion was clear transparent liquid .Conclusion:The prepared rutin self-microemulsifying drug delivery system using the optimized for-mula screened by pseudo-ternary phase diagram can increase the solubility of rutin significantly .

Objective To evaluate the value of blood coagulation biomarkers in orthopaedic traumatic patients after surgery and analyze its diagnostic values for venous thrombosis embolism.Methods In thiscase control study, we consecutive enrolled 108 traumatic patients after surgery.54 patients have thrombosis and other 54 patients have no thrombosis.Blood was taken 3 -4 days after surgery.Routine coagulation screening test , FDP(fibrinogen/fibrin degradation products) , D dimer and new item such as TM( thrombomodulin) , TAT( thrombin-anti-thrombin complex) , t-PAIC( tissue-type plasminogen activator-plasminogen activator inhibitor complex),PIC(plasmin-anti-plasmin complex) were tested.The difference between groups of these biomarkers was compared, and then the receiver operation curve ( ROC) was drew to determine the diagnostic cut-off point and diagnostic performance.Results ALL blood coagulation biomarkers in orthopaedic traumatic patients after surgery were significantly increased.The group of patients with thrombosis have higher TM(9.04 ±2.06) IU/ml,t-PAIC(10.15 ±4.23) ng/ml, PIC(1.15 ±0.70)μg/ml, D dimer(5.31 ±5.10) ng/ml than group without thrombosis TM(7.50 ±1.70) IU/ml, t-PAIC (6.97 ±2.56)ng/ml, PIC(0.93 ±0.84)μg/ml,D dimer(2.35 ±2.12)ng/ml,and P=0.000 2,<0.000 1,<0.000 1,<0.000 1, respectively.However, TAT(4.79 ±4.32)ng/ml, (6.51 ±5.92)ng/ml, FDP (8.87 ±7.68 )μg/ml, ( 4.91 ±4.67 )μg/ml showed no difference between thrombosis groupand no thrombosis group, (P=0.212 3,0.050 8; respectively).The area under the ROC curve of TM, t-PAIC, PIC and D-dimer were 0.718 5,0.741 6,0.648 0,0.670 0, respectively; P values were <0.000 1,<0.000 1, 0.009 3,0.004 1, respectively; cut-off values were 11.15 IU/ml, 10.65 ng/ml, 1.36 μg/ml, 7.69 ng/ml, respectively;positive likelihood ratios were 9.00,11.29,3.66,14.60, respectively;specificity were 98.15%,96.23%, 90.20%, 97.96%, respectively; the diagnostic rates were 20.3%, 46.3%, 35.8%, 25.9%, respectively.Conclusions There were coagulation and fibrinolysis system activated in orthopaedic traumatic patients after surgery.TM, t-PAIC, PIC, D dimer were good biomarkers for the diagnosis of thrombosis after trauma surgery.TAT was not fit for screening thrombosis after surgery because of influence of anti-coagulation.

Using syringaldehyde as raw material, the phosphine ylide intermediate was efficiently synthesized through acetylated hydroxyl protection, aldehyde group reduction, chlorination and reaction with triphenylphosphine. On this basis, moscatilin (MST) and its 12 analogs (MST-1-MST-12) were synthesized by wittig reaction, deacetylation and double bond reduction. All the structures were confirmed by 1H NMR, 13C NMR and ESI-MS. Bacterial lipopolysaccharide-induced mouse macrophage RAW264.7 inflammation model was used to conduct preliminary anti-inflammatory activity tests in vitro for the target compounds. Results showed that all compounds could inhibit the production of inflammatory factor NO, and that MST-5 exhibited the strongest anti-inflammatory activity (IC50= 0.428 μmol/L).Further exploration is expected for the study of the anti-inflammatory mechanism of MST-5.

Objective:To optimize the preparation technology of rutin nanoemulsion. Methods:The pseudoternary phase diagram of rutin nanoemulsion under the condition of different Kmwas drawn. With the drug loading and the particle size as the independent var-iables,and the percent of oil and the weight ratio of surfactant to cosurfactant as the dependent variables, the blank formula of rutin nanoemulsion was optimized by central composite design-response surface method. Results:The optimal formula was as follows:the ra-tio of ethyl oleate, cremopher RH40,1,2-propanediol and water was 7: 13: 5: 25. The average particle size of the prepared rutin nanoemulsion was 26.51 nm,and the drug loading was 8.97 mg·ml-1. Conclusion:The central composite design-response surface method can obtain a good formula of rutin nanoemulison,and the model has a good predictive function.

Objective: To evaluate the changes of molecular markers of thrombosis in patients with deep venous thrombosis of lower extremities and analyze their value in the detection of venous thrombosis and evaluate the therapeutic effects. Methods: In case-control study, we selected traumatic patients after surgery from Beijing Jishuitan Hospital during December 2018 to May 2019. A total of 64 patients with thrombosis were in DVT group, 39 patients without thrombosis were in non-DVT group, and 28 healthy subjects in the same period were in healthy control group. Venous blood samples were taken from all these people. Coagulation parameters thrombin-antithrombin complexes (TAT), plasmin-α2-plasmin inhibitor complexes (PIC) and tissue-type plasminogen activator-inhibitor complexes (t-PAIC) were detected at first diagnosis and one month after rivaroxaban anticoagulation therapy beginning. The differences of the markers between these groups were compared. Results: The coagulation markers of the patients with lower extremity deep venous thrombosis increased significantly at diagnosis. The levels of plasma TAT, PIC, t-PAIC and sTM in DVT group were significantly higher than those in non-DVT group (P＜0.05). The levels of plasma TAT, PIC and t-PAIC in DVT group were higher than those in healthy control group (P＜0.05). There was no significant difference in sTM level between DVT group and healthy control group (P＞0.05). The results and changes of TAT, PIC, t-PAIC in the patients before and after one month of anticoagulation therapy were statistically different (P＜0.05) in comparison. Conclusion The molecular markers of thrombosis, TAT, PIC and t-PAIC, could effectively detect deep venous thrombosis of lower extremities and showed significant efficacy in evaluating the efficacy of anticoagulation therapy.

Objective:To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence.Methods:Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results:With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval o F>12 months had a lower sLR rate. Patients with recurrence interval o F>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60 Gy vs.>60 Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%( P=0.061) with tumor bed dose ≤60 Gy and>60 Gy, respectively. Conclusions:Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60 Gy, and it should be above 60 Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.

Objective:To analyze the prognosis of patients with isolated regional recurrence (RR) after mastectomy, and evaluate the efficacy of radiotherapy and identify the optimal radiation target volumes.Methods:Clinical data of 144 patients with first isolated RR after mastectomy between 2001 and 2018 were retrospectively analyzed. All patients had not received post-mastectomy radiotherapy. The primary endpoints consisted of the subsequent locoregional recurrence (sLRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS).Results:With a median follow-up of 82.5 months after RR, the 5-year sLRR, DM, PFS and OS rates for the entire group were 42.1%, 71.9%, 22.9% and 62.6%, respectively. Local plus systemic therapy was an independent favorable prognostic factor for sLRR ( P<0.001) and PFS ( P=0.013). The sLRR rate in the surgery plus radiotherapy group was the lowest ( P<0.001). Surgery plus radiotherapy significantly reduced the 5-year risk of recurrence within the initially involved nodal regions ( P<0.001). Patients with chest wall irradiation obtained the 5-year subsequent chest wall recurrence rate of 12.1% compared to 14.8%( P=0.873) for those without chest wall irradiation. The subsequent supraclavicular recurrence rate was lower in patients with prophylactic supraclavicular irradiation than that without prophylactic supraclavicular irradiation (9.9% vs. 23.8%, P=0.206). The incidence rates of initially uninvolved axillary and internal mammary nodal recurrence were below 10% regardless of prophylactic irradiation or not. Conclusions:Patients with RR alone have an optimistic 5-year OS in the contemporary era. Comprehensive locoregional treatment including surgery and radiotherapy combined with systemic therapy is recommended. The chest wall, axillary and internal mammary nodal prophylactic irradiation should not be routinely performed for all patients with RR. The value of supraclavicular prophylactic irradiation remains to be evaluated.