人肺鳞癌类器官三维培养体系的建立

目的：探索构建人肺鳞癌体外类器官培养的实验方法,并对成功建立的类器官模型进行组织层面评估。方法：收集早期肺鳞癌患者手术切除的新鲜原位肿瘤标本,在以基质胶凝固液滴为基础的培养基中进行体外类器官培养,倒置显微镜观察类器官生长情况;将培养的类器官用Histogel包埋并制成石蜡标本,切片进行HE染色及免疫组化染色。结果：成功建立了肺鳞癌类器官的体外培养方法,HE染色提示细胞核浆比高,核异型性符合肺鳞癌细胞特征;免疫组化显示细胞P63阳性,TTF-1阴性,与肺鳞癌分子病理特征相符。结论：本实验初步建立了人肺鳞癌患者的体外类器官培养平台,将为肺鳞癌的基础研究和靶向药物的筛选提供新模型。     

Clustering of cardiovascular risk factors and stroke: a prospective cohort study in Inner Mongolia

Objective: This study aimed to evaluate the effect of clustering of cardiovascular risk factors (CVRF) on stroke incidence and find some high predictive clusters among Inner Mongolians in China.

Methods: A prospective cohort study was conducted among 2589 participants aged 20 and older from Inner Mongolia, China. The participants were divided into four groups according to the number of CVRFs and followed up from June 2002 to July 2012. Cox proportional hazards model was used to evaluate the clustering of CVRFs on the incidence of stroke. Area under curve was used to compare the effect of every cluster on stroke and find those having higher predictive value.

Results: A total of 124 stroke occurred during the follow-up period. The incident stroke cases tended to be older and male; had higher prevalence of smoking, drinking, and family history of cardiovascular diseases (FHCVD); had greater waist circumference, higher systolic and diastolic blood pressure, and C-reactive protein levels at baseline compared with those who did not experience stroke. Unadjusted hazard ratio (HR) (95% confidence interval) of stroke in the participants with at least three CVRFs was 5.230 (2.646–10.336), compared with those without CVRF. After multiple adjustments, the result remained statistically significant (HR, 3.388; 95% confidence interval: 1.678–6.840). On the basis of FHCVD, clustering of hypertension with other CVRFs and clustering of diabetes with tachycardia had higher predictive value than other clustering.

Conclusion: The clustering of CVRFs increased the risk of stroke. On the basis of FHCVD, the clustering of hypertension with other CVRFs and the clustering of diabetes with tachycardia had higher predictive value for stroke than other cluster.     

Post-stroke cognitive impairment and the risk of stroke recurrence and death in patients with insulin resistance

ObjectivePost-stroke cognitive impairment (PSCI) is associated with etiology, severity, and functional outcome of stroke. The risks of recurrent stroke and death in patients with PSCI and insulin resistance (IR) is unknown. The goal of this study was to determine whether global and domain-specific cognitive impairment after stroke in patients with IR was associated with recurrent stroke and death.Materials and MethodsWe studied patients with recent stroke or transient ischemic attack (TIA) and IR with a baseline Modified Mini-Mental State Examination (3MS) cognitive exam at median of 79 days after stroke. We considered a baseline score of ≤ 88 on the 3MS to indicate global cognitive impairment, and domain-specific summary scores in the lowest quartile to indicate language, attention, orientation, memory and visuospatial impairments. The primary endpoint was fatal or non-fatal recurrent stroke, and the secondary endpoints were all-cause mortality, and fatal or non-fatal myocardial infarction (MI).ResultsAmong studied n = 3,338 patients 13.6% had global cognitive impairment. During the median 4.96 years of follow-up, 7.4% patients experienced recurrent stroke, 3.5% MI, and 7.3% died. In the fully adjusted model, impairment in language (HR 1.35; 95% CI 1.01—1.81) and orientation (HR 1.41; 95% CI: 1.06—1.87) were associated with a higher risk of recurrent stroke, while attention impairment was associated with all-cause mortality (HR 1.34; 95% CI: 1.01—1.78).Discussion/ConclusionIn patients with recent stroke/TIA and IR, post-stroke language and orientation impairments independently predicted recurrent stroke, while attention deficit was associated with increased risk of all-cause mortality.     

Use of cyproheptadine hydrochloride (HCl) to reduce neuromuscular hypertonicity in stroke survivors: A Randomized Trial: Reducing Hypertonicity in Stroke

ObjectivesThe goal of this study was to examine how the administration and dosing of the anti-serotonergic medication cyproheptadine hydrochloride (HCl) affects involuntary muscle hypertonicity of the spastic and paretic hands of stroke survivors.Materials and MethodsA randomized, double-blinded, placebo-controlled longitudinal intervention study was performed as a component of a larger clinical trial. 94 stroke survivors with chronic, severe hand impairment, rated as levels 2 or 3 on the Chedoke-McMaster Stroke Assessment Stage of Hand (CMSA-H), were block randomized to groups receiving doses of cyproheptadine HCl or matched doses of placebo. Doses were increased from 4 mg BID to 8 mg TID over 3 weeks. Outcomes were assessed at baseline and after each of the three weeks of intervention. Primary outcome measure was grip termination time; other measures included muscle strength, spasticity, coactivation of the long finger flexors, and recording of potential adverse effects such as sleepiness and depression.Results89 participants (receiving cyproheptadine HCl: 44, receiving placebo: 45) completed the study. The Cyproheptadine group displayed significant reduction in grip termination time, in comparison with the Placebo group (p<0.05). Significant change in the Cyproheptadine group (45% time reduction) was observed after only one week at the 4mg BID dosage. The effect was pronounced for those participants in the Cyproheptadine group with more severe hand impairment (CMSA-H level 2) at baseline. Conversely, no significant effect of Group * Session interaction was observed for spasticity (p=0.6) or coactivation (p=0.53). There were no significant changes in strength (p=0.234) or depression (p=0.441) during the trial.ConclusionsUse of cyproheptadine HCl was associated with a significant reduction in relaxation time of finger flexor muscles, without adversely affecting voluntary strength, although spasticity and coactivation were unchanged. Decreasing the duration of involuntary flexor activity can facilitate object release and repeated prehensile task performance.RegistrationClinical Trial number: NCT02418949     

Preoperative Microvascular Invasion Prediction to Assist in Surgical Plan for Single Hepatocellular Carcinoma: Better Together with Radiomics

Annals of Surgical Oncology - Prediction models with or without radiomic analysis for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) have been reported, but the potential for...     

Protective mechanisms of coenzyme-Q10 may involve up-regulation of testicular P-glycoprotein in doxorubicin-induced toxicity

The anticancer drug; doxorubicin (DOX), causes testicular toxicity as an adverse effect. P-glycoprotein (P-gp) is a multidrug resistance efflux transporter expressed in blood-testis barrier, which extrudes DOX from the testis. We investigated whether DOX-induced gonadal injury could be prevented by the use of antioxidant; coenzyme-Q10 (CoQ10). The involvement of P-gp expression, as a possible protective mechanism, was also investigated. CoQ10 was administered orally for 8 days, and DOX toxicity was induced via a single i.p. dose of 15 mg/kg at day 4. Concomitant administration of CoQ10 with DOX significantly restored testicular oxidative stress parameters and the distorted histopathological picture, reduced the up-regulation of caspase 3 caused by DOX, and increased P-gp expression. We show for the first time that CoQ10 up-regulates P-gp as a novel mechanism for gonadal protection. In conclusion, CoQ10 protects against DOX-induced testicular toxicity in rats via ameliorating oxidative stress, reducing apoptosis and up-regulating testicular P-gp.     

Combined effects of oxytetracycline and Pb on earthworm Eisenia fetida

Combined effects of oxytetracycline (OTC) and Pb on lysosomal membrane stability and coelomocyte apoptosis of earthworm were studied in the paper. Compared with control, the lysosomal membrane stability decreased and coelomocyte apoptosis increased in the treatments of single OTC and Pb contamination. As for compound pollution, combined effect of (5 mg/kg OTC + 50 mg/kg Pb) treatment on earthworm lysosomal was synergistic (except 28 d). However, it was antagonistic at higher concentration of (10 mg/kg OTC + 50 mg/kg Pb) and (20 mg/kg OTC + 50 mg/kg Pb) treatment. In addition, coelomocyte apoptosis of earthworm decreased significantly compared with single OTC, indicating an antagonistic reaction. And joint toxicity of OTC and Pb decreased significantly with the increasing OTC concentration.     

Betaine supplementation protects against renal injury induced by cadmium intoxication in rats: Role of oxidative stress and caspase-3

Cadmium (Cd) is an environmental and industrial pollutant that can induce a broad spectrum of toxicological effects that affect various organs in humans and experimental animals. This study aims to investigate the effect of betaine supplementation on cadmium-induced oxidative impairment in rat kidney. The animals were divided into four groups (n = 10 per group): control, cadmium, betaine and betaine + cadmium (1) saline control group; (2) cadmium group in which cadmium chloride (CdCl₂) was given orally at a daily dose of 5 mg/kg body weight for four weeks; (3) betaine group, in which betaine was given to rats at a dose of 250 mg/kg/day, orally via gavage for six weeks; (4) cadmium + betaine group in which betaine was given at a dose of 250 mg/kg/day, orally via gavage for two weeks prior to cadmium administration and concurrently during cadmium administration for four weeks. Cadmium nephrotoxicity was indicated by elevated blood urea nitrogen (BUN) and serum creatinine levels. Kidneys from cadmium-treated rats showed an increase in lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) concentration and reductions in total antioxidant status (TAS), reduced glutathione (GSH) content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase concentration (SOD) and catalase activity. Caspase-3 activity, a marker of DNA damage was also elevated in renal tissues of cadmium-treated rats. Pre-treatment of rats with betaine substantially attenuated the increase in BUN and serum creatinine levels. Betaine also inhibited the increase in TBARS concentration and reversed the cadmium-induced depletion in total antioxidant status, GSH, GSH-Px, SOD and catalase concentrations in renal tissues. Renal caspase-3 activity was also reduced with betaine supplementation. These data emphasize the importance of oxidative stress and caspase signaling cascade in cadmium nephrotoxicity and suggest that betaine pretreatment reduces severity of cadmium nephrotoxicity probably via antioxidant action and suppression of apoptosis.