ABSTRACT
Objective The aim of the study is to investigate the therapeutic efficacy of next-generation anaplastic lynphoma kinase-tyrosine kinase inhibitor (ALK-TKI) in advanced non-small cell lung cancer (NSCLC).Methods The clinical data and outcomes of 22 patients with advanced non-small cell lung cancer who received the next generation of ALK-TKI from 2014 to 2017 in our hospital were retrospectively analyzed.Results 22 patients were included for survival analysis with 15 males and 7 females.The median age was 48 and all of them were adenocarcinoma patients.There were 12,2,7 and 1 patients received ceritinib,alectinib,brigatinib and lorlatinib,respectively.A total of 14 patients could be evaluated,including complete response (CR) in 2 cases,partial response (PR) in 3 cases,stable disease (SD) in 6 cases,progressive disease (PD) in 3 cases.The ORR and DCR were 35.7％ and 78.6％,respectively.The median progression free survival (PFS) of the 22 NSCLC patients was 8.7 months.Progression pattern can be analyzed in 17 patients.Among them,10 patients underwent primary progression (lung),occurring at the leading frequency (accounting for 58.8％) and followed by central nerve system (CNS) progression (accounting for 29.4％).Conclusions Next-generation ALK-TKI provide a reasonable choice for crizotinib-resistant patients.Primary progression (lung) is the leading cause for treatment failure.Multi-disciplinary integration may provide a potential choice for prolonging administration of next-generation ALK-TKI.
ABSTRACT
Da perspectiva histórica, todos os elementos que envolvem uma doença, desde sua nomeação até a carga de significado que lhe é atribuída, resultam de "negociações" elaboradas por múltiplos atores sociais. No caso da lepra, a descoberta das sulfonas, em 1941, contribuiu de forma significativa para a transformação do entendimento dessa enfermidade, gerando um questionamento acerca das ações utilizadas para o seu controle/combate, sobretudo o isolamento compulsório dos doentes. Com base nesses pressupostos, este artigo analisa o debate que se constituiu acerca do processo de substituição das antigas práticas profiláticas para o controle da lepra, em um importante periódico de circulação nacional, Arquivos Mineiros de Leprologia, na década de 1950.
From a historical viewpoint, all the elements surrounding a disease, from its name to the weight of meaning attached to it, are the result of "negotiations" in which many sections of society are participants. In the case of leprosy, the discovery of sulfones in 1941 made a significant contribution towards transforming our understanding of this disease, leading to questions being raised as to the measures adopted for its prevention and control, particularly the compulsory isolation of sufferers. On the basis of these assumptions, this article examines the debate which took place regarding the process whereby the old prophylactic procedures for the control of leprosy were replaced, in an important national journal, Arquivos Mineiros de Leprologia, in the 1950s.
Subject(s)
Humans , History, 20th Century , Leprosy/history , Patient Isolation/history , Sulfones/history , Leprosy/drug therapy , Leprosy/prevention & control , Quarantine/history , Sulfones/therapeutic useABSTRACT
Objective To use Ex-Rad as a lead compound to design and synthesize aryl benzyl sulfones derivatives with protein tyrosine kinase’(PTK) inhibitory activity. Methods 2-Naphthol was used as a raw material to synthesize intermediates 3a-3f. The target compounds 4a, 4d, and 5a-5f were synthesized by oxidizing 3a-3f in acetic acid with H202. Enzyme-linked immunosorbent assay’ELISA) was used and inhibition rate was calculated to screen out the compounds with PTK inhibitory activitity. Results Eight compounds containing a sulfone or sulfoxide group were synthesized and the structures were confirmed by 1H NMR. Preliminary evaluation of the 8 compounds demonstrated that the PTK inhibitory activity of 5c was much stronger than that of the lead compound. Conclusion The synthetic method is simple, and the materials are cheap and readily available. 5c shows strong PTK inhibitory activity by ELISA.
ABSTRACT
Objective To use Ex-Rad as a lead compound to design and synthesize aryl benzyl sulfones derivatives with protein tyrosine kinases(PTK) inhibitory activity. Methods 2-Naphthol was used as a raw material to synthesize intermediates 3a-3f. The target compounds 4a, 4d, and 5a-5f were synthesized by oxidizing 3a-3f in acetic acid with H2O2. Enzyme-linked immunosorbent assay(ELISA) was used and inhibition rate was calculated to screen out the compounds with PTK inhibitory activitity. Results Eight compounds containing a sulfone or sulfoxide group were synthesized and the structures were confirmed by 1H NMR. Preliminary evaluation of the 8 compounds demonstrated that the PTK inhibitory activity of 5c was much stronger than that of the lead compound. Conclusion The synthetic method is simple, and the materials are cheap and readily available. 5c shows strong PTK inhibitory activity by ELISA.
ABSTRACT
Objective To explored the effect of sildenafil in treatment of pregnant women with pulmonary arterial hypertension.Methods From January 2012 to November 2013,64 pregnant women with pulmonary arterial hypertension (PAH) were randomly divided into group and control group.Control group:16 cases with mild and 16 cases with moderate PAH.To treatment with low-flow oxygen,low-salt diet therapy,cardiac,etc.sildenafil group:15 cases were mild pulmonary hypertension,and 17 cases moderate PAH.Treatment sildenafil 25 mg,rid in this study.Then the variation of the blood oxygen saturation,pulmonary artery systolic pressure,hemodynamic parameters and pregnancy outcome,including delivery modes,neonatal weight,morbidity of mother and fetus were compared.Results (1) Cardiac function and pulmonary hypertension:control group:the proportion of cardiac functional class Ⅰ-Ⅱ reduced from 81％ (26/32) to 56％ (18/32) significantly after treatment (P ＜ 0.05).Sildenafil group:the proportion of cardiac functional class Ⅰ-Ⅱ increased from 75％ (24/32) to 84％ (27/32) significantly after treatment (P ＜ 0.05).Between two groups,the proportion of mild and moderate turning to server PAH patients were significant differentce (P ＜ 0.05).(2) The pregnancy outcome of two group:the premature birth rate,low birth weight rate and cesarean section rate of 9％ (3/32),9％ (3/32)and 69％ (22/32)in sildenafil group were significantly lower than 16％ (5/32),19％ (6/32) and 81％ (26/32) in control group (P ＜0.05).The rate of vaginal delivery,term pregnancy and neonatal weight of 31％ (10/32),91％ (29/32) and (3 214 ±306) g in sildenafil group were different with 19％ (6/32),84％ (27/32) and (3 004 ±458) g in control group (P ＜ 0.05).(3) Hemodynamic parameters:in control group,arterial partial pressure of oxygen,oxygen saturation and left ventricular ejection fraction,pulmonary systolic pression were (80 ± 5) ％ to (72 ±8)％,(87 ±8) to(83±9) mmHg(1 mmHg=0.133 kPa),0.77 ±0.24 to 0.70 ±0.38 and (63 ±9) to (69 ± 12) mmHg before and after treatment,which showed remarkable decreased trends(P ＜ 0.05).The other parameter were not significantly different (P ＞ 0.05).In sildenafil group,arterial partial pressure of oxygen,oxygen saturation and left ventricular ejection fraction,pulmonary systolic pression showed increased trend before and after treatment,which were (80 ± 9) ％ to (88 ± 9) ％,(84 ± 3) to (89 ± 7) mmHg,0.70 ± 0.32 to 0.79 ± 0.27 (P ＜ 0.05),in the mean time,pulmonary systolic pression showed decreased trend from (65 ± 18) to (60 ± 13) mmHg (P ＜0.05).The other parameter did not show significant different (P ＞ 0.05).Conclusions Sildenafil treatment can significantly improve the clinical symptoms,cardiac function and hemodynamic parameters.It also could significantly improve pregnancy outcomes,reduce premature delivery,the incidence of low birth weight children,and cesarean section rate.
ABSTRACT
Objective To explore the mechanism of inhibitory effect of dimethyl sulfoxide (DMSO) on the hyperplasia of the fibrous capsule around the tissue expander. Methods The experimental model was established in rats as follows: after implanting the expander on the back of rats, 30 % DMSO or normal saline was injected into the expander. The former was classified as experimental group, and the latter as control group. The cystic wall was resected after the skin and soft tissues were expanded. In situ hybridization and the immunohistochemical staining were used to determine the expression of typesⅠand Ⅲ of collagen and procollagen mRNA in the cystic walls. Results It was found that both the typeⅠand Ⅲ of collagen content and the expressing quantity of mRNA of procollagen in the cystic wall of the experimental group were less than those of control group. Conclusion The results imply that the mechanism that DMSO inhibits the expression of typesⅠand Ⅲ of collagen in the fibrous cystic wall may be achieved through down-regulating the genetic expression of procollagen in the fibroblasts.
ABSTRACT
Objective To investigate the cerebral CT appearances of toxic encephalopathy of tetramine and improve the recognition on this disease. Methods Four cases of toxic encephalopathy of tetramine were collected and their cerebral CT appearances were retrospectively analyzed. Results Cerebral CT appearances in acute phase (within 8 days): (1) cerebral edema in different degree. CT abnormalities consisted of cortical hypodensities and complete loss of gray-white matter differentiation. The CT value were in 11-13 HU, and to be watery density in serious case,(2)subarachnoid hemorrhage. It demonstrated the signs of poisoning hypoxic ischemic encephalopathy in chronic phase. Conclusion The cerebral CT appearances of toxic encephalopathy of tetramine had some character in acute phase and it can predict the serious degree of intoxication, but there was no characteristic findings in chronic phase.