RESUMO
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the key to the treatment of advanced non-small cell lung cancer (NSCLC),but there are various drug-resistant mutations in the latter stage.The first and second generation of EGFR-TKIs significantly prolong the survival of patients with EGFR-activated mutant tumors.The third generation of EGFR-TKIs effectively inhibit the progress of T790M mutant tumors.The fourth generation of EGFR-TKIs inhibit both L858R,T790M and L858R,T790M,C797S mutant tumors.Using circulating tumor DNA and exogenous RNA can effectively detect the mutation types of EGFR,and choose EGFR-TKIs therapy or combined chemotherapy according to the mutation types.
RESUMO
Reversible posterior leukoencephalopathy syndrome (RPLS) is a critical maternal complication in some pre-eclampsia (PE) and nearly all eclampsia patients; RPLS is associated with high blood pressure (BP). However, the effect of BP on RPLS and the different characteristics of RPLS in PE or eclampsia are largely unknown. We consecutively collected data from 69 patients who were diagnosed with RPLS in PE or eclampsia between 2013 and 2017. The BP and biochemical indicators at onset and post onset of RPLS were examined to explore their likely correlation with RPLS. We grouped patients into PE (n=40) and eclampsia (n=29) groups according to whether a seizure had occurred. Information regarding BP, clinical symptoms and imaging features was collected retrospectively to explore the differences between groups. BP measurements (moderate and severe hypertension, systolic pressure (SBP), diastolic pressure (DBP) and mean arterial pressure (MAP) levels) and biochemical indicators (uric acid, lactate dehydrogenase (LDH), C-reactive protein and WBC) were higher at the onset of RPLS than post-onset of RPLS (P<0.001), whereas normal BP and serum albumin levels were lower (P<0.001). Moreover, the BP values (SBP, DBP and MAP) and LDH levels were significantly correlated with the degree of edema (Spearman's correlation, P<0.01). These results suggest that hypertension and LDH are likely factors in the development of RPLS in PE or eclampsia. Moreover, BP and LDH were closely related to the degree of brain edema, However, no significant differences were found between the PE and eclampsia groups with the exception of age and consciousness impairment.
Assuntos
Pressão Sanguínea , Eclampsia/fisiopatologia , Síndrome da Leucoencefalopatia Posterior/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Adulto , Fatores Etários , Biomarcadores/sangue , Biomarcadores/urina , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Edema Encefálico/fisiopatologia , Transtornos da Consciência/etiologia , Eclampsia/diagnóstico por imagem , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , L-Lactato Desidrogenase/sangue , Imageamento por Ressonância Magnética , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/etiologia , Pré-Eclâmpsia/diagnóstico por imagem , Gravidez , Estudos RetrospectivosRESUMO
Objective To observe the effect of febuxostat on epithelial-to-mesenchymal transition (EMT) of kidney tubules and the levels of serum IL-6 nad transforming growth factor (TGF) β1 in hyperuricemic rats.Methods Forty male SD rats were divided into 4 groups:normal control group (NC group),oteracil potassium group (OP group),oteracil potassium with febuxostat group (OF group) and oteracil potassium with benzbromarone group (OB group).Each group had 10 rats and balanced in body weights.To induce hyperuricemia,rats were given oteracil potassium by gastric garage once a day for eight weeks.Rats in OF group and OB group were given either febuxostat or benbromarone starting with oteracil potassium,and rats in NC group was given saline only.Blood samples were taken before,and at the end of 4 and 8 weeks of the treatments and serum uric acid,creatinine,blood usea nitrogen (BUN),IL-6 and TGFβ1 contents were measured at each time point.Renal pathological changes were observed via HE and Masson staining,and the expression of α-SMA and E-cadherin were detected by immunohistochemistry.Results Compared with those in NC group,the levels of serum uric acid,creatinine,BUN,IL-6 and TGFβ1 in the another three groups were increased significantly (all P < 0.01).However,the IL-6 and TGFβ1 contents in OF group were much lower than those in OP group (P <0.01).HE and Masson staining showed that OF group had less damage and tubulointerstitial fibrosis than OP group and OB group (P <0.01).Moreover,the expression of α-SMA was significantly down-regulated (P < 0.01) and that of E-cadherin was significantly up-regulated in OF group compared with those in OP group.Conclusion Febuxostat treatment significantly inhibited EMT and reduced the levels of IL-6 and TGFβ1 in hyperuricemia rats.
RESUMO
Objective To study the effect of liquid extracts from leaves of Canarium pimela Leenh on myo-cardial ischemia-reperfusion injury in rats. Methods The langendorff isolated perfused heart system was applied in this study. Ligating of the left descending anterior for 35 min,followed with 100 min or 50 min reperfusing to set up the cardiac ischemia-reperfusion injury model (I/R). After perfusing the effective pharmacological extracts of leaves of Canarium pimela Leenh(CPL)to the isolated heart,we monitored the cardiac parameters of left ventricu-lar systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP)and left ventricular maximal rise/fall of left ventricular pressure(±dp/dtmax)in the following assays with or without 10 min CPL pretreatment. 1. the cardiac parameters,2. the cardiac parameters in 35 min ischemia,followed with 10 min or 50 min reperfusion,3. the incidence of ventricular fibrillation or ventricular tachycardia after 10 min reperfusion,4. the activity of creatine kinase(CK)and lactate dehydrogenase(LDH)in the coronary effluent after 10 min reperfusion,5. pathological analysis in the I/R,CPL and VER group after reperfusion. Results CPL pretreatment improved functions of normal left heart. Furthermore,it significantly reduced LVEDP and +dp/dtmax,the incidence of ventricular fibrillation or ventricular tachycardia,as well as the activities of CK and LDH in coronary effluent induced by ischemia-reperfusion compared with the I/R model. Moreover,CPL pretreatment markedly alleivated the pathological changes of ischemia-reperfusion. Conclusions The liquid extracts of leaves of Canarium pimela Leenh can effectively relieve the myocardial ischemia-reperfusion injury in rats.
RESUMO
Objective To investigate the risk factors of reversible posterior leukoencephalopathy syndrome (RPLS) in pre-eclampsia or eclampsia gravida. Methods This study was conducted in the Third Affiliated Hospital of Guangzhou Medical University between January 2013 and March 2016. A total of 100 patients who had no severe neurological diseases and were diagnosed pre-eclampsia or eclampsia, and underwent brain MRI were collected retrospectively. They were divided into 2 groups according to the MRI results, the RPLS group (n=49) and the non-RPLS group (n=51). The medical history, clinical symptoms and the results of laboratory examination were analyzed by the logistic regression, in order to explore the risk factors.Results In single factor analysis, HELLP syndrome, pregnancy associated with other diseases, poor prenatal care, grade 3 hypertension, elevated systolic blood pressure or diastolic blood pressure, elevated WBC, aspartate transaminase (AST), alanine aminotransferase (ALT), uric acid (UA) and lactate dehydrogenase (LDH), decreased platelet (PLT), headache, visual changes, seizures and conscious disturbance were more frequent in the RPLS group than those in the non-RPLS group (all P<0.05). According to the multivariate logistic regression analysis, the elevated WBC (OR=1.291, 95%CI:1.058-1.575, P=0.012), UA (OR=1.008,95%CI:1.001-1.016,P=0.032) and headache (OR=18.260, 95%CI:3.562- 93.607, P=0.000) were the independent risk factors.Conclusions Maternal history, clinical symptoms and some laboratory examinations might help in the early diagnosis of RPLS in pre-eclampsia or eclampsia gravida. Headache, the elevation of WBC and UA were the most significant factors.
RESUMO
We reviewed the diagnosis and treatment of three patients with fulminant type 1 diabetes mellitus (FT1D) in our hospital.And then we discussed the clinical characteristics of a total of 24 cases of FT1D from published reports.Among them,14 patients presented with gastrointestinal symptoms.Close attention is needed as FT1D is characterized by acute onset,rapid progression and poor prognosis.
RESUMO
ObjectiveToinvestigatetheriskfactorsforunfavorableoutcomeinpatientswithminor ischemic stroke. Methods Patients with minor ischemic stroke were enroled prospectively. The modified Rankin Scale ( mRS ) w as used to assess the clinical outcome at day 90 after onset, and mRS 0-2 w as defined as favorable outcome. The demographic data, vascular risk factors, clinical data, imaging data, stroke etiologic subtypes, laboratory test results, and treatment methods in the favorable outcome group and unfavorable outcome group w ere compared. Multivariate logistic regression analysis w as used to identify the independent risk factors for early poor outcome in patients w ith minor ischemic stroke. Results A total of 516 patients with minor ischemic stroke were enroled. At day 90 after onset, 90 patients (17.44%) had unfavorable outcome and 426 (82.56%) had favorable outcome. Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.045, 95% confidence interval [CI] 1.017-1.074; P=0.002), heart diseases (OR 2.021, 95%CI 1.063-3.841; P=0.032), baseline National Institutes of Health Stroke Scale (NIHSS) score (OR 1.662, 95%CI 1.177-2.347; P=0.004), limb movement disorder ( OR 2.430, 95%CI 1.010-5.850; P=0.048), ataxia (OR 2.929, 95%CI 1.188-7.221;P=0.020), early neurological deterioration ( OR 50.994, 95%CI 17.659-147.258; P<0.001), infarct diameter ( OR 1.279, 95%CI 1.075-1.521; P=0.005), non-responsible vascular stenosis ( OR 2.518, 95%CI 1.145-5.536;P=0.022), and large artery atherosclerotic stroke ( OR 2.010, 95%CI 1.009-4.003; P=0.047) w ere the independent risk factors for unfavorable outcome in minor ischemic stroke. Conclusions The early poor outcome of minor ischemic stroke is closely associated w ith age, heart diseases, baseline NIHSS score, limb movement disorder, ataxia, early neurological deterioration, infarct diameter, non-responsible vascular stenosis, and large artery atherosclerotic stroke. The relevant examinations need to be improved early, the etiologic subtype should be identified, and the correct clinical treatment should be guided.
RESUMO
Objective To investigate clinical and radiological characteristics of reversible posterior leukoencephalopathy syndromes(RPLS) in preeclampsia/eclampsia and to summarize prognosis of patients and fetus in order to provide the basis for early diagnosis and early treatment.Methods Clinical and radiological characteristics, and treatments and outcomes of 33 pregnant women with RPLS in preeclampsia/eclampsia were analyzed retrospectively.All patients were treated in Guangzhou Medical Center for Critical Pregnant Women during January 2013 and July 2015.Results Clinical symptoms :23 of 33 patients were with headache, 19 cases with visual changes, 15 with seizures, and 12 cases with conscious or mental disorder besides 3 cases with nausea and vomiting, and 4 cases with chest tightness and shortness of breath symptoms.Imaging features: 33 cases were all checked with radiological examination in acute period, which suggests edema of white matter.It involved the most common parts of occipital lobe(24 cases), 13 cases in the parietal lobe,9 cases in temporal lobe and basal ganglia,and 6 cases in frontal lobe.Moreover, the common parts involving the brain stem occurred in 4 cases, and 2 cases of cerebellum.Clinical outcomes: 33 cases of pregnant women in prenatal emergency termination of pregnancy include 31 cases of cesarean section, and 1 case of natural delivery.After active treatment, the prognosis was good, except 1 case complicated with systemic lupus erythematosus (SLE) died, the rest were good.Fetal prognosis : stillbirths occurred in 8 cases, the rest were good.Conclusions The clinical presentations of RPLS in patients with eclampsia or preeclampsia are typical, including headache, epileptic seizures, visual changes, conscious, or mental disorder.The imaging features which involved the most common parts are occipital lobe and parietal lobe.The early diagnosis and timely intervention lead to a sound prognosis.
RESUMO
Objective To evaluate the influence of ultrasound-mediated contrast agent microbubbles carrying kallidinogenase targeted therapy on neurogenesis and angiogenesis after experimental acute cerebral infarction.Methods Kallidinogenase-loaded microbubbles were prepared using mechanical shaking method.Middle cerebral artery occlusion (MCAO) model was established in male Wistar rats by sutureoccluded method.MCAO rats (n =120) were randomly divided into 5 groups:ultrasound-mediated kallidinogenase-loaded microbubbles group (group 1),ultrasound-mediated microbubbles group (group 2),ultrasound-mediated saline group (group 3),kallidinogenase group (group 4),saline group (group 5).Medication was given through tail vein daily for 2-6 consecutive days starting 24 h after MCAO.Ultrasound groups (groups 1,2 and 3) were given 2 MHz pulse ultrasonic irradiation on the ischemia lateral skull for 10 min after injection.Cell proliferation was examined using 5'-bromo-2'-deoxyuridine (BrdU,50 mg/kg).Infarction volume and neurological function were evaluated on the 3rd,7th day after MCAO respectively.Doublecortin (DCX) + cells in the subventricular zone and laminin + in the peri-infarction region were observed at the same time.Results The number of DCX + cells in the subventricular zone (under 20 × ocular) of groups 1-5 was 251.8 ± 13.1,125.7 ± 11.6,130.2 ± 13.7,234.5 ± 12.4 and 123.7 ± 10.0 respectively.The percentage of laminin + cells in the peri-infarction region (× 10 objective) of groups 1-5 was 10.0% ± 0.8%,5.2% ± 0.7%,5.0% ± 1.0%,8.0% ± 1.8% and 5.0% ± 0.9% respectively.The number of DCX + cells in the subventricular zone and laminin + cells in the peri-infarction region of the group 1 and the group 4 was significantly more on the 7th day after MCAO compared with those of the other three groups (DCX:t values of group 1 vs groups 2,3,5 were 17.88,17.17 and 18.16,all P < 0.01 ; t values of group 4 vs groups 2,3,5 were 15.42,14.78 and 15.70,all P <0.01.Laminin:t values of group 1 vs groups 2,3,5 were 7.01,6.71 and 7.11,all P < 0.01 ; t values of group 4 vs groups 2,3,5 were 4.23,3.94 and 4.33,all P <0.01).Moreover,the number of DCX+ cells in the subventricular zone (t =2.46,P < 0.05) and laminin + cells in the peri-infarction region (t =2.78,P < 0.05) of the group 1 was much more than those of the group 4.Neurologic scores on the 7th day of groups 1-5 were 1.00 (0.75,1.25),2.0 (2.00,3.00),2.0 (1.00,2.00),1.5 (0.75,2.00),2.0 (2.00,2.50).Compared with other four groups,group 1 showed better functional improvement after stroke (U values of group 1 vs groups 2-5 were 2.0,4.0,7.5 and 2.5,all P < 0.05).While there was no significant difference in infarction volume among five groups at all the time points after MCAO.Conclusions Our study demonstrates ultrasound-mediated kallidinogenase-loaded contrast agent microbubbles targeted therapy promotes neuroblasts proliferation and vascular regeneration compared with mediated and non-medicine-loaded microbubbles therapy,which attributes to functional improvement after MCAO.Therefore,ultrasound-mediated ultrasound contrast agent microbubbles carrying drugs targeted therapy may have a perspective on ischemic stroke.
RESUMO
Problem-based learning (PBL) teaching method can improve students' ability of study,analysis and problem-solving.Network platform based PBL teaching mode combines the network education and PBL teaching mode; it has clear superiority in information acquisition,communication and transmission.Furthermore,it can also solve the problem of inadequate teaching sources.Network platform based PBL teaching mode was applied in neurology teaching to investigate the best scheme and form for teaching plan compilation,network platform building-up and teaching process implementation.At the same time,teaching effect was evaluated and summarized in an aim to improving neurology teaching quality and speeding up the reform of network-based PBL teaching.
RESUMO
The synapsins are a family of neuron specific phosphoproteins associated with the membranes of synaptic vesicles. The synapsins play important roles in the neurotransmitter release and during the early neuronal development. In this review, we focus on the family members, gene location, distribution, structure and function of the synapsins.
RESUMO
Oxidative stress is one of the important pathogenesis of diabetic nephropathy.In recent years,the role of oxidized low-density lipoprotein(Ox-LDL) in the occurrence and progress of diabetic nephropathy has been more and more concerned about,and becomes a hot spot once again.This paper makes a review of the formation and metabolic mechanism of Ox-LDL,the changes of Ox-LDL in the progress of diabetic nephropathy and its clinical significance,and a number of new treatments for Ox-LDL in recent years to further understand the role of Ox-LDL in the occurrence and progress of diabetic nephropathy,then to provide new ideas for effective clinical treatment of diabetic nephropathy. Abstract:Summ ary:Oxidative stress is one of the important pathogenesis of d iabetic nephropathy.In recent years,the role of oxi-d ized low-density lipoprote in(Ox-LDL) in the occurrence and progress of d iabetic nephropathy has been more and more concerned about,and becom es a hot spot once again.Th is paperm akes a review of the form ation and m etabolic m echan ism of Ox-LDL,the changes of Ox-LDL in the progress of d iabetic nephropathy and its c lin ical sign ificance,and a number of new treatm ents forOx-LDL in recent years to further understand the role ofOx-LDL in the occurrence and progress of d ia-betic nephropathy,then to provide new ideas for effective c lin ical treatm ent of d iabetic nephropathy.
RESUMO
Objective To investigate the dynamic changes of ATP content in rat cerebral cortex after transient ischemia followed by reperfusion and the relationship between the change of energy and the recovery of neural function.Methods The rats were subjected to 10 min of middle cerebral artery occlusion (MCAO). At the time point of 0 h, 1 h, 3 h, 6 h, 12 h, 24 h and 72 h after reperfusion, ATP contents of frontal and parietal cortex were measured by capillary zone electrophoresis.Results At the end of 10 min ischemia, ATP content fell dramatically to less than 20% of the control level. After reperfusion, ATP content recovered gradually. After 1 h, 3 h, 6 h and 12 h of reperfusion, ATP content returned to 70.5%, 65.7%, 84.8% and 86.9% of the control level ( P=0.052, 0.030, 0.332 and 0.491). From 24 h on until 72 h after reperfusion, ATP content decreased again, reaching half of the control level ( P=0.003 and P=0.023). After 10 min ischemia, limb function recovered gradually and completely at last. From 24 h on until 72 h after reperfusion, unwillingness of action and eating was found.Conclusions The recovery of cellular energy system function is delayed even though the reperfusion is in time after transient cerebral ischemia. Furthermore, secondary failure of cellular energy system function occurrs with the reperfusion proceeding. These phenomena are probably responsible for the delayed recovery of neural function after cerebral ischemia in spite of reperfusion.