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

Objective To investigate the effect of penehyclidine (PHCD) on Toll-like receptor 4 (TLR4)mRNA and Toll-like receptor 2 (TLR2) mRNA expression in the lung tissue in rats with acute lung injury induced by lipopolysaccharide (LPS) .Methods Sixty healthy SD rats of both sexes weighing 200-220 g were randomly divided into 5 groups ( n = 12 each) :control group (group C) , LPS group and P1-3 groups. Acute lung injury was induced by intraperitoneal (IP) LPS 8 mg/kg in LPS and P1-3 groups. PHCD 0.3, 1.0 and 3.0 mg/kg were given IP after LPS administration in P1-3 groups. The animals were anesthetized at 6 h after IP LPS. Blood samples were collected for determination of serum TNF-α and IL-6 concentrations ( by ELISA) and then sacrificed, the lungs were immediately removed for determination of TLR4 mRNA and TLR2 mRNA expression (by RT-PCR), and microscopic examination. Results LPS significantly increased TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and IL-6 concentrations. PHCD 1.0 or 3.0 mg/kg significantly inhibited LPS-induced increase in TLR4 mRNA and TLR2 mRNA expression in the lung tissue and serum TNF-α and ILr6 concentrations.The lung histopathologic damage was significantly ameliorated in P2 and P3 groups as compared with group LPS.Conclusion PHCD can protect the lungs against LPS-induced acute lung injury through inhibiting TLR4 mRNA and TLR2 mRNA expression in the lung tissue and reducing the inflammatory response.

Objective To compare the results of manually -tested speech recognition threshold (SRT ) with automatically software -recorded SRT in the trial of Mandarin disyllabic test ,exploring the significance to the clini-cal applying .Methods 128 normal people of different ages without hearing loss and 57 workers exposed to noise in an automobile manufacturing was selected .These two group of volunteers speak mainly Mandarin in their daily life . MADSEN Conera (Danmark) clinical audiometr was applied .A group of double syllable word list with the same dif-ficulty of equivalence was used as test material .The initial presentation level was 20 dB HL higher than PTA .Then compared the results of manually -tested SRT with automatically software -recorded SRT .Results In the normal group ,the automatic value SRT was 7 .84 ± 3 .98 dB HL ,the manual value was 9 .19 ± 4 .47 dB HL ,and the average value of speech frequency threshold was 7 .63 ± 5 .78 dB HL .In the noise group ,the automatic value SRT was 6 .10 ± 8 .40 dB HL ,the manual value was 18 .81 ± 9 .52 dB HL ,and the average value of language frequency threshold was 27 .18 ± 19 .13 dB HL .There was significant difference between the values of SRT tested manually and recorded automatically (P<0 .01) .Conclusion There are differences between SRT valued manually and automatically .The SRT in people with normal hearing can be tested using automatic -recorded method .This method is convenient for screening in people without hearing loss .To exam in people with hearing loss ,the manual test is more appropriate .

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 explore the significance and the ultrastructural changes of platelets in patients with acute cerebral infarction.Methods Changes of platelets in 20 patients with acute cerebral infarction were observed by transmission electron microscope.Results The ultrastructural changes of platelets within 24 hours after the onset were significant,including more pseudopodium,aggregation and fusion;there were remarkable fewer alpha granules and mitochondria,the remain of mitochondria swelled and more disruption of platelet membrance were found.The degree of platelet changes consisted with the severity and sizes of cerebral infarction.The ultrastructural change of platelets was obviously restored after 2 weeks,but no restoration was found in 3 patients with large area infarction.Conclusion Ultrastructural changes of platelets in acute period of cerebral infarction were remarkable,especially a lack of alpha granules,this might be regarded as an objective index in the judgment of severity and prognosis of cerebral infarction.

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.