Since the development of molecular biology,the treatment of advanced non-small cell cancer is shifting from traditional chemotherapy into molecular targeted therapy with genotyping as a guide′s help.The most widely used is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).With the appli-cation of EGFR-TKIs,the resistances to EGFR inhibitors are paid more and more attention,in recent years. The main mechanisms of acquired resistances are as follows:secondary mutation of the EGFR gene,amplifica-tion of c-MET,Her2 and other target genes,histological transformation,activation of the bypass mechanisms, loss of p53,the relief of negative feedback loops,overlap of mechanisms,etc.

Objective To compare the treatment effects of catheter directed thrombolysis and thrombetomy for acute ar?terial ischemia of the lower extremity. Methods Patients who visited Tianjin Medical University General Hospital from 2011 to 2013 and were attacked by acute ischemic disease of lower extremities within 3 days (n=66) were investigated. Thrombetomy and thrombolysis treatment had been performed to 32 cases and 34 cases respectively according to patients’ own willingness. Postoperative symptom remission rate, limb salvage rate, fatality rate, reperfusion injury rate (including re?nal inadequacy, heart failure, muscle fascia compartment syndrome), bleeding rate and limb dysfunction rate were compared between these two groups. Results There was no statistical difference on the rate of symptom remission (93.8% vs 94.1%), limb salvage(96.9%vs 100%), case fatality rate(3.1%vs 0), bleeding rate(0 vs 8.8%)and limb dysfunction rate (0 vs 5.9%)between these two groups. However, the incidence of reperfusion injury was higher in the group of thrombectomy (37.5%vs 2.9%, P<0.05)compared to that of the other group. Conclusion Similar effect of treatment and less reperfusion injury, especially renal injury, had been achieved by CDT compared with thrombetomy.

Objective:To summarize the characteristics of methylmalonic acidemia(MMA) with thrombotic microangiopathy as the prominent manifestation.Methods:Clinical data was collected from MMA patients with thrombotic microangiopathy as the prominent manifestation, who were treated at Shengjing Hospital of China Medical University from September 2014 to December 2019.The clinical manifestations, laboratory results, imaging results, histopathological examination, treatment and prognosis were analyzed.Results:Six children aged 1 month to 7 years old were included in our study, including 5 males and 1 female.Six cases were all MMA complicated hyperhomocysteinemia.All patients had a history of prodromal infection before admission.All cases had edema.Five patients were hypertenson and 4 patients accompanied neurologic presentation.One patient had a family history.All patients were treated with Vitamin B 12, levocarnitine, folic acid and betaine.Three patients′ psychiatric symptoms and renal function were improved and hemolysis were controlled.Two of them were similar with the same age children in intelligence and motor development, with normal renal function, good blood pressure control and normal urine protein.The third one was significantly improved in intelligence development, but still slightly worse than that of the children with the same age.He had no convulsions occurred in recent one year with antiepileptic drugs in oral.His blood pressure was maintained between 135/90-160/110 mmHg(1 mmHg=0.133 kPa), 24-hour urine volume was about 2 000 mL, creatinine was maintained at about 150 μmol/L, ionic level was normal, and urinary protein was 2 + .One case discharged from hospital.Two patients died of multiple organ failure. Conclusion:An early screening of metabolic diseases should be achieved for thrombotic microangiopathy of unknown etiology.Early screening of homocysteine is important for early detection and treatment.

Adolescent ; Depression ; complications ; diagnosis ; drug therapy ; Humans ; Male ; Tourette Syndrome ; complications ; diagnosis ; drug therapy ; Treatment Outcome

Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.
Drug Design ; Drug Discovery ; Small Molecule Libraries

China is entering into an aging society, and the incidence of hypertension and atherosclerosis were increased year by year. The incidence of transient ischemic attack (TIA) patients with carotid stenosis increased year by year. Carotid artery stenosis or occlusion can cause reduction of local brain tissue perfusion resulting from TIA. CT cerebral perfusion imaging and SPECT could detect earlier the chronic hyper fusion of carotid stenosis TIA, forecast risk coefficient and intervention and prevent the occurrence of cerebral infarction, to evaluate effect of carotid endarterectomy and carotid s carotid artery stenting. It is very important to monitor cerebral hemodynamic changes. The technology has the features of blood infusion situation, advantages, curative effect evaluation and development trend in carotid stenosis TIA reviewed by CT perfusion imaging and SPECT.

To improve and optimize marine antimicrobial peptide R-1 production by a newly isolated Brevibacillus laterosporus Lh-1, Plackett-Burman (PB) design and response surface methodology (RSM) using central composite design was adopted in culture conditions. MINITAB 15.0 was used for planning the experiments, data analysis, contour diagrams and response optimizations. In this study, PB design was undertaken to evaluate the effects of the fifteen factors. By the statistical regression analysis, the significant factors affecting the novel antimicrobial peptide R-1 in submerged fermentation by Br. laterosporus Lh-1 were determined as follows: glucose, peptone and CaCl2. Then a RSM was used to optimize the above critical internal factors, and the optical concentration of the variables were deter-mined as: 15.72 g/L glucose, 6.01 g/L peptone and 3.29 g/L CaCl2. The content of R-1 was increased from 82.15 kU/mL to 116.27 kU/mL.

Objective To investigate the levels of interleukin-1?,interleukin-6,tumor necro- sis factor-? in preterm labor with intraamniotic infection(IAI).Methods Plasma and amniotic fluid were sampled from 30 women with preterm labor(Group A),31 women with term labor(Group B) and 46 women without labor but after 37 weeks(Group C).Interleukin-6 in blood,interleukin-1?, interleukin-6 and tumor necrosis factor-? in amniotic fluid were examined.IAI were diagnosed accord- ing to clinical criteria or bacterial culture or pathology.Results 1.The levels of IL-6 in blood in Group A were higher than in Group Band C(46.34 vs 20.53,6.67pg/ml,P

This paper presented the effects of experimental hyperinsulinemia on the main apolipoproteins (At, B) and on tbe process of reverse cholesterol transport in rabbit, which consisted of 1) uptake of cholesterol from peripheral tissue by HDL; 2) cholesterol esterification and 3) cholesterol ester transfer. The results showed that insulin could significantly decrease both serum and lymph Apo A1 levels and inhibit all the three steps of reverse cholesterol transport. The larger the dose of insulin, the greater the effects. Apo B did not seem to be influenced by insulin. It was further demonstrated by a series of statistical analyses that insulin had both direct and indirect inhibitory actions, to different extent, on each of the three main steps of reverse cholesterol transport.

Objective To observe the efficacy of lipoic acid combined with mosapride in the treatment of diabetic neurogenic bladder.Methods 30 patients with type 2 diabetes complicated with diabatic neurogenic bladder were treated with lipoic acid and mosapride for three weeks,on the base of good controlling of blood glucose,blood lipids,and other metabolic indicators.The residual urine volume of bladder and urodynamic indicators were compared before and after treatment.Results The residual urine volume of bladder and urodynamic indicators after treatment for three weeks and withdrawal for four weeks were (62.5 ± 27.8) ml and (61.3 ± 21.6) ml,(8.3 ± 1.9) ml/s and (7.9 ±2.1)ml/s,(10.7 ± 1.8)ml/s and (10.3 ± 1.6) ml/s,(25.6 ±2.7)cm H2O and (24.5 ±2.3)cm H2O,which were significiantly better than those before treatment [(128.3 ± 72.5) ml,(5.2 ± 1.3) ml/s,(8.4 ± 1.2) ml/s,(18.1 ±1.2)cm H2O](t=4.01,4.21,3.45,3.52,3.68,3.47,3.33,3.24,all P ＜0.01).Conclusion Lipoic acid combined with mosapride has good effect in the treatment of diabetic neurogenic bladder.