RESUMO
PURPOSE: This study aimed to assess pathogen distributions and antimicrobial sensitivity characteristics in patients with non-small cell lung cancer (NSCLC) with severe radiation pneumonitis (SRP) and secondary infections. METHODS AND MATERIALS: Data from 1746 patients with NSCLC and SRP after thoracic radiation therapy from January 2009 to December 2020 were retrospectively analyzed. Pneumonia incidence, causative pathogens, and antibiotic resistance characteristics in patients with secondary lung infections were analyzed. Risk factors associated with mortality were identified through univariate and multivariate analyses. Antifungal drug efficacy and duration-related effects were assessed with Forest plots and receiver operating characteristic curves. RESULTS: Overall, 44.5% of patients with NSCLC and SRP (777 of 1746 patients) were diagnosed with secondary lung infections. In total, 899 bacterial strains were isolated from these patients, with Acinetobacter baumannii (n = 206; 27%), Klebsiella pneumonia (n = 200; 26.2%), and Pseudomonas aeruginosa (n = 104; 13.6%) being the most common. Carbapenem and cefoperazone-sulbactam resistance rates of 52.7% and 32.2%, 28.8% and 26.4%, and 23.7% and 20.2% were observed for these isolates, respectively. Infection-related deaths occurred in 22.4% of patients with SRP. Independent risk factors for infection-related death included poor performance status scores, inappropriate empirical antimicrobial treatment, bacteria/fungal coinfection, and lack of empirical antifungal treatment. Receiver operating characteristic curves showed that the cutoff value of empirical antifungal treatment duration was 9 (area under the curve: 0.819). CONCLUSIONS: For patients with SRP and secondary lung infections, appropriate empirical antimicrobial treatment could decrease infection-related mortality, and cefoperazone-sulbactam may be an appropriate antibacterial drug. Empirical antifungal treatment for a minimum of 9 days might contribute to better outcomes. Although this represents a promising treatment approach for patients with SRP and secondary lung infections before antibacterial susceptibility testing, further prospective validation is essential.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Coinfecção , Neoplasias Pulmonares , Pneumonite por Radiação , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Coinfecção/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Testes de Sensibilidade Microbiana , Pneumonite por Radiação/tratamento farmacológico , Estudos RetrospectivosRESUMO
The aim of the present study is to evaluate the vasodilation effects of Tongmai Yangxin Pills (TMYX) on rat mesenteric artery as well as its mechanism of action. The relaxation effects of TMYX extracts with different concentrations were determined on isolated rat mesenteric artery in normal condition as well as pretreating by phenylephrine and KCl. Vascular relaxation effects of TMTX were also determined in mesenteric artery preincubated with L-ANME and indomethacin or in endothelium denuded mesenteric artery. Moreover, effects of TMYX by 50 mg·L⻹ on NO secretion and the phosphorylation of eNOS in a cellular model of human umbilical vein endothelial cell (HUVEC) pretreated with or without L-NAME were also observed. The experimental results showed that TMYX has no obvious effect on vasodilation of arteries in normal or KCl pretreated condition, while it can dose-dependently relax the rat mesenteric artery with intact endothelium stimulated with phenylephrine at a maximal diastolic rate of (64.71±10.03)%. After preincubating with L-NAME for 15 min or removal of mesenteric artery endothelium, the maximal diastolic rate was decreased to (35.77±8.93)% and (25.85±10.84)% respectively. However, preincubating with indomethacin had no inhibitory effect on TMYX induced vascular relaxation. Meanwhile, TMYX at 50 mg·L⻹ could increase the expression of P-eNOS and the secretion of NO in HUVEC. L-NAME significantly inhibited NO release and phosphorylation of eNOS induced by TMYX. The results suggested TMYX exerted endothelium-dependent relaxation effects against PE-induced contractions of isolated rat mesenteric artery through NO-cGMP signaling pathway.
Assuntos
Artérias Mesentéricas , Vasodilatação , Animais , Endotélio Vascular , Humanos , RatosRESUMO
Deafening elicits a deterioration of learned vocalization, in both humans and songbirds. In songbirds, learned vocal plasticity has been shown to depend on the basal ganglia-cortical circuit, but the underlying cellular basis remains to be clarified. Using confocal imaging and electron microscopy, we examined the effect of deafening on dendritic spines in avian vocal motor cortex, the robust nucleus of the arcopallium (RA), and investigated the role of the basal ganglia circuit in motor cortex plasticity. We found rapid structural changes to RA dendritic spines in response to hearing loss, accompanied by learned song degradation. In particular, the morphological characters of RA spine synaptic contacts between 2 major pathways were altered differently. However, experimental disruption of the basal ganglia circuit, through lesions in song-specialized basal ganglia nucleus Area X, largely prevented both the observed changes to RA dendritic spines and the song deterioration after hearing loss. Our results provide cellular evidence to highlight a key role of the basal ganglia circuit in the motor cortical plasticity that underlies learned vocal plasticity.
Assuntos
Vias Auditivas/fisiopatologia , Gânglios da Base/fisiologia , Surdez/patologia , Espinhas Dendríticas/fisiologia , Córtex Motor/patologia , Vocalização Animal , Análise de Variância , Animais , Biotina/análogos & derivados , Surdez/etiologia , Espinhas Dendríticas/ultraestrutura , Dextranos , Modelos Animais de Doenças , Eletrólise/efeitos adversos , Tentilhões , Centro Vocal Superior/fisiopatologia , Masculino , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Córtex Motor/ultraestrutura , Sinapses/patologia , Sinapses/ultraestruturaRESUMO
PURPOSE: To investigate the effects of bilberry extract, Difrarel, on form-deprivation myopia in guinea pigs. METHOD: Thirty healthy pigmented guinea pigs, at the age of 3 weeks, were randomly assigned to 3 groups: 2 groups receiving daily orally administered Difrarel (300 mg/kg) either from the outset for 4 or 2 weeks after form deprivation and a control group. Form deprivation was induced with translucent eye patches on the right eye and lasted for 4 weeks. Another 12 guinea pigs without the form deprivation were assigned into 2 groups for oral administration of Difrarel and saline for 4 weeks. The refractive errors and axial length were measured in both eyes, and the posterior sclera was removed and assayed to evaluate the expressions of matrix metalloproteinase 2 (MMP2) and collagen I by a quantitative polymerase chain reaction and Western blot. RESULTS: Oral administration of Difrarel for 4 weeks was found to inhibit the axial elongation and decrease the myopic shift of refractive errors in the form-deprived eye. Upregulation of MMP2 and degradation of collagen I in the sclera of form-deprived eye were observed, and these were prevented by orally administered Difrarel. Moreover, oral administration of Difrarel had no effects on axial length, refractive errors, and the expression of MMP2 in the normal eye. CONCLUSION: This work demonstrates that orally administered Difrarel has an effect against form-deprivation myopia and raises the possibility that bilberry extracts or specific components might represent a useful treatment for preventing the progression of myopia in clinical practice.