Tryptophan-kynurenine metabolic pathways are involved in a series of enzymatic reactions,generate a variety of bioactive compounds and participate in some complex pathophysiological processes.In recent years,studies have shown that kynurenine metabolic pathways may be associated with the pathogenesis of migraine and treatment.This article reviews the advances in research on the relationship between tryptophankynurenine metabolic pathways and migraines.

Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent inherited white matter disorders in childhood,and it′s the only known hereditary human disease due to the direct defects in protein synthesis process,with the gene defects in EIF2B1-5,encoding the five subunits of eukaryotic translation initiation factor(eIF2B ?,?,?,? and ?) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2? and eIF2B? is an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological condition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open reading frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms of VWM are far from well understood.It′s suggested that level of AFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological condition,which makes the mutant cells more susceptible to endoplasmic reticulum(ER) stress and unfolded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle of UPR activation,which may underlie the neurological aggravation in VWM patients after minor stress,a specific cli-nical feature of VWM.Elucidating the pathogenesis of VWM will be helpful to further understand the protein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treatment strategies in the future.Abstract:SUMM ARY Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent in-herited white matter d isorders in childhood,and i′ts the only known hered itary human d isease due to the d irect defects in protein synthesis process,with the gene defects inEIF2B1-5,encod ing the five sub-units of eukaryotic translation initiation factor(eIF2B?,?,?,?and?) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2?and eIF2B?is an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological cond ition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open read ing frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms ofVWM are far from well understood.I′ts sugges-ted that level ofAFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological cond ition,which makes the mutant cellsmore susceptible to endoplasm ic reticulum(ER) stress and un-folded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle ofUPR activa-tion,which may underlie the neurological aggravation in VWM patients afterm inor stress,a specific cli-nical feature ofVWM.E lucidating the pathogenesis ofVWM will be helpful to further understand the pro-tein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treat-ment strategies in the future.

Objective To evaluate the efficacy of transarterial chemoembolization (TACE) and percutaneous cryosurgery sequential therapy for unresectable hepatocellular carcinoma (HCC).Methods Four hundred and twenty patients with unresectable HCC were divided into sequential TACE-cryosurgery sequential (sequential) group (n=290) and cryosurgery alone (cryoalone) group (n = 130). TACE was performed with the routine operation; the percutaneous cryosurgery was conducted 2 to 4 weeks after TACE. The patients were followed up at the first month and once every 2 to 3 month later. Liver ultrasound or both computer tomography and alpha fetal protein were examined during follow-up. Results During a mean follow-up of (42±17) months (range from 24 to 70 months), the local recurrence rate of ablated lesion was 17% for all the patients, 11% and 24% for patients in sequential group and cryoalone groups respectively (P=0. 001). The overall 1-, 2-, 3-, 4-and 5-year survival rate was 72%, 57%, 47%, 39% and 31%, respectively. The 1- and 2-year survival rates (71% and 61 % ) in sequential group were similar to those (73 % and 54 % ) in cryo-alone group (P=0.69 and 0. 147), while the 4- and 5-year survival rates were higher in sequential group (49 % and 39 % ) than those (29 % and 23 % ) in cryo-alone group (P= 0.001). Eighteen patients with large HCC (＞5 cm in diameter) in sequential group survived for more than 5 years while no one in cryo-alone group. Complication rate was 24% in all patients, 21% and 26% for the sequential and cryo-alone groups respectively (P=0. 06). The incidence of hepatic bleeding was higher in cryo-alone group than in sequential group (P=0. 02). Liver crack occurred in two patients of the cryoalone group. Conclusions Pre-cryosurgical TACE increased the cryoablation efficacy and decrease its complications, especially hepatic bleeding. TACE and cryosurgery sequential therapy may be a better treatment for unresectable HCC, especially for large HCC.

Objective To investigate the changes ofcalcitonin gene-related peptide (CGRP) and regional cerebral blood flow (rCBF) and their correlation in patients with migraine.Methods Thirty-eight patients with acute migraineurs,collected in our hospital from May 2010 to May 2012,and 20 healthy controls were enrolled;their clinical data were retrospectively analyzed;brain SPECT examination was performed and CGRP was determined;14 patients in the intermission of migraine (after treatment) were reexamined.The rCBF and plasma concentration of CGRP were analyzed and the correlation was compared.Results (1) The rCBF was decreased during migraine attacks;statistical significances were noted between patients during migraine attacks and healthy controls (the left frontal lobe:0.97±0.03 vs.1.02±0.04,the right one:0.96±0.04 vs.1.00±0.02;the left temporal lobe:0.89±0.04 vs.0.98±0.06,the right temporal lobe:0.90±0.07 vs.1.02±0.09,P＜0.05);(2) The rCBF was increased in the 14 intermittent patients (after treatment);statistical significances were noted between intermittent patients and attack patients (before treatment) (left frontal lobe:1.00±0.03 vs.0.98±0.03,left temporal lobe:0.93±0.05 vs.0.90±0.05,right temporal lobe:0.98±0.04 vs.0.92±0.06,right occipital lobe:1.02± 0.02 vs.1.00±0.03,P＜0.05);(3) The plasma concentrations of CGRP (63.37±5.70,51.39±7.33) during migraine attacks and intermission were statistically higher than healthy controls (46.09±6.67,P＜0.05);(4) Pearson correlation coefficient between plasma concentration of CGRP and rCBF of two hemisphere during migraine attacks was noted (r=-0.375,P=0.020),while no correlation was noted in patients at intermission period (r=0.436,P=0.119) and healthy controls (r=0.112,P=0.638).Conclusion The rCBF is low and the plasma concentration of CGRP is high during migraine attacks,and there is correlation between the two factors.

Objective To explore value of CT features in diagnosis of traumatic diaphragmatic rupture.Methods A retrospective analysis was performed on totally 256 patients with suspected traumatic diaphragmatic rupture,among them 128 were confirmed after surgery.All patients underwent CT scan before surgery.The prevalence of CT findings were recorded,including diaphragm discontinuity or segmental non-recognition of diaphragm," collar" sign," intrathoracic herniation of abdominal contents" sign," dependent viscera" sign," dangling diaphragm" sign and " thickness of the diaphragm" sign.The sensitivity and specificity of each sign were calculated.Results The sensitivity of diaphragm discontinuity or segmental non-recognition of diaphragm,"collar" sign,"intrathoracic herniation of abdominal contents" sign,"dependent viscera" sign,"dangling diaphragm" sign and "thickness of the diaphragm" sign of diaphragmatic rupture was 75.00％ (96/128),84.37％ (108/128),78.13％ (100/128),76.56％ (98/128),54.68％ (70/128) and 46.87％ (60/128),respectively.The specificity was 93.75％ (120/128),98.43％ (126/128),98.43％ (126/128),99.21％ (127/128),93.75％ (120/128) and 84.38％ (108/128),respectively.The sensitivity and specificity of overall MSCT signs was 92.18％ and 100％,respectively.Conclusion CT features have high value in diagnosis of traumatic diaphragmatic rupture.