Objective To investigate the relationship between lipocalintype prostaglandin dsynthase(L-PGDS) and visfatin in the lower extremity atherosclerotic plaque. Methods Collected from February 2014 to February 2016 in vascular surgery of our hospital 40 cases of femoral artery atherosclerotic plaque intima specimens (observation group), 20 cases of splenic artery, superior mesenteric artery samples (control group), the expression of visfatin and L-PGDS protein were detected by immunohistochemical staining, and the expression of visfatin and L-PGDS mRNA were determined by RT-PCR. Results The observation group visfatin protein expression was (121.42±11.07), significantly higher than the control group (72.07±12.81), and L-PGDS protein expression was (87.93±9.73), significantly lower than the control group (107.04±10.58), the difference was statistically significant (P<0.05). The relative expression of visfatin mRNA in the observation group was (0.321±0.024), which was significant higher than that of the control group (0.217±0.031), while L-PGDS mRNA was (0.203±0.018), significantly lower than the control group (0.314±0.029), the difference was statistically significant (P<0.05); The expression of L-PGDS protein was negatively correlated with the expression of visfatin protein in the plaque tissue (r=-0.617, P<0.05), visfatin mRNA and L-PGDS mRNA were negatively correlated (r=-0.645, P< 0.05). Conclusion Visfatin and L-PGDS in lower extremity atherosclerosis occurrence and development have an important relationship, both of them may play an antagonistic role.

This study is to establish a cell-based model targeting to neuraminidase (NA) of the 2009 H1N1 influenza A virus. NA is an influenza virus structural protein with enzymatic activity of the cleavage of HA-sialic acid interaction to release new viral particles from cells. A model of HIV-1 (pNL4-3.Luc.R(-)E(-)) based pseudovirions packed with HA [hemagglutinin, A/VietNam/1203/2004 (H5N1)] and NA [A/California/04/2009 (H1N1)] was established to evaluate compounds activities on NA function. The viral release can be blocked by neuraminidase inhibitors, oseltamivir and oseltamivir carboxylate, with IC50 of (61 +/- 31) nmol L(-1) and (5.5 +/- 2.9) nmol L(-1) respectively. A point mutation of H275Y on NA leads oseltamivir-resistance. This corresponding mutation was introduced into the system which was also confirmed by oseltamivir and oseltamivir carboxylate.

Objective To establish an HPLC method for the determination of metoclopramide (MCP) and its related substances in MCP nasal spray .Methods Chromatographic separation was performed on an Agilent TC-C18 column (250 mm ×4.6 mm,5 μm) using acetonitrile and phosphate buffer solution (0.05 mol/L potassium dihydrogen phosphate solution, added with 5 ml of triethylamine and adjusted to pH 4.0 with phosphoric acid)(19∶81) as the mobile phase at 1.0 ml/min.The detection wavelength was 275 nm and the column temperature was set at 30℃.Results and Conclusion Related substances were completely separated from MCP .For MCP,the linearity of determination was over the range of 10-200 μg/ml and the recovery of the method ranged from 100.3%to 101.6%.The relative standard deviation was 0.68%(n=9).The method is accurate, reliable, repeatable, and could be readily utilized as a quality control method for MSP nasal spray .

Objective To explore the relation between lower extremity deep venous thrombosis and knee injury.Methods 100 knee injury patients were operated on in our department.The difference of incidence rates of DVT,the thrombus location and incidence rates of DVT before and after operation in the two groups was compared.There were no fatal pulmonary embolism occurring in either group.Results The incidence rate of DVT in tibial plateau fracture group was 52％,that in patellar fracture was 30％ (P ＜ 0.05).DVT incidence rate of popliteal,pretibial,posterior tibial vein thrombosis in group of tibial plateau fracture was higher than that in group of patellar fracture (P ＜ 0.05),while there was no significant difference in postoperative thrombosis between the two groups(P ＞ 0.05).Conclusions There is a high incidence rate of DVT in knee joint injury.Which is closely related to the position of fracture and limb immobilization.

CC chemokine receptor 4 (CCR4) is a kind of G-protein-coupled receptor, which plays a pivotal role in allergic inflammation. The interaction between 2-(2-(4-chloro-phenyl)-5-{[(naphthalen-1-ylmethyl)-carbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-N-(3-morpholin-4-yl-propyl)-acetamide (S009) and the N-terminal extracellular tail (ML40) of CCR4 has been validated to be high affinity by capillary zone electrophoresis (CZE). The S009 is a known CCR4 antagonist. Now, a series of new thiourea derivatives have been synthesized. Compared with positive control S009, they were screened using ML40 as target by CZE to find some new drugs for allergic inflammation diseases. The synthesized compounds XJH-5, XJH-4, XJH-17 and XJH-1 displayed the interaction with ML40, but XJH-9, XJH-10, XJH-11, XJH-12, XJH-13, XJH-14, XJH-3, XJH-8, XJH-6, XJH-7, XJH-15, XJH-16 and XJH-2 did not bind to ML40.Both qualification and quantification characterizations of the binding were determined. The affinity of the four compounds was valued by the binding constant, which was similar with the results of chemotactic experiments. The established CEZ method is capable of sensitive and fast screening for a series of lactam analogs in the drug discovery for allergic inflammation diseases.

Objective To explore the impact of arterial injury on distal limb blood supply in lower limb trauma. Meth?ods Retrospective analysis of 93 patients with different levels of lower limb arterial injury admitted to our hospital from June 2014 to August 2017. There were 84 males and 9 females aged 43.54±9.90 years (ranging 25-65 years). Revascularization was performed through open reduction. Patients were divided into three groups according to their arterial injury locations. Proximal ves?sels were along the superficial femoral artery, from its beginning to the point where it was divided into the descending genicular ar?tery and direct periosteal branches. Intermediate vessels were from the dividing point on the superficial femoral artery to the popli?teal artery before it was divided into the medial inferior genicular artery. Distal vessels were from the dividing point on the poplite?al artery to the distal end of the peroneal artery. The duration from injury to revascularization in the three groups were 13.67±5.99 h, 11.15±4.43 h, and 11.92±5.48 h, respectively. There was no significant difference between groups (F=1.564, P=0.215). ISS in the three groups were 13.00±3.74, 12.77±3.81, and 11.50±3.99, respectively. There was no significant difference between groups (F=1.445, P=0.241). The following items were compared among the three groups, postoperative creatine kinase, arterial blood lac?tate and limb compartment cut. Results Creatine kinase of the intermediate vascular group was 8 743.15±6 968.48 u/L, proximal vascular group 1 467.67±1 810.27 u/L, distal vascular group 2 893.51±1 304.56 u/L. The data of intermediate vascular group were higher than those of proximal and distal vascular groups with significant difference among the groups (F=22.587,P=0.000). The lactate of the intermediate vascular group was 3.20 ± 1.51 mmol/L, proximal vascular group 1.63 ± 0.46 mmol/L, distal vascular group 1.85±0.69 mmol/L with significant difference among the groups (F=20.612,P=0.000). The compartment cut of the intermedi?ate vascular group was incised in 24, but not in 15. The proximal vascular group was not incised in 18, while 15 was incised and 21 not incised in distal vascular group. The rates of compartment cut were 61.5%, 0 and 41.7%, respectively with significant differ? ences (χ2=19.156, P=0.000). Conclusion In lower limb injuries, the intermediate vascular (from the superficial femoral artery after it is divided into the descending genicular artery and direct periosteal branches to the popliteal artery before it is divided into the medial inferior genicular artery) injury leads to the most severe distal limb ischemia.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.