RESUMEN
Background: The efficacy of perioperative chemotherapy (PC) in pulmonary sarcomatoid carcinoma (PSC) is controversial. We conducted this study to investigate the effect of different histological subtypes on the efficacy of PC in PSC patients. Methods: Clinicopathological data of 811 PSC patients of different histological subtypes were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method and log-rank test were used to evaluate the effects of PC on the overall survival (OS) and cancer-specific survival (CSS) in different subtypes of PSC patients. Propensity score matching (PSM) was used to reduce potential confounding effects. Subgroup analyses were conducted to further investigate the efficacy of PC in patients with different characteristics. Results: A total of 210 (25.89%) enrolled PSC patients received PC. PC was not associated with OS or CSS benefit in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients, neither before nor after matching. But survival benefit of PC was observed in carcinosarcoma patients both before (5-year OS: 48.79% vs. 38.75%, P=0.01) and after (5-year OS: 51.29% vs. 17.54%, P=0.003) matching. Subgroup analyses showed that in patients whose tumor larger than 4 cm, PC was still associated with improved survival in carcinosarcoma, but not in the other histological subtypes of PSC. Conclusions: The efficacy of PC varies between different subtypes of PSC. Survival benefit of PC was only observed in carcinosarcoma patients, but not in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients. Histological subtype should be considered when treating PSC patients with PC.
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Severe corneal injury can lead to blindness even after prompt treatment. 14-3-3zeta, a member of an adaptor protein family, contributes to tissue repair by enhancing cellular viability and inhibiting fibrosis and inflammation in renal disease or arthritis. However, its role in corneal regeneration is less studied. In this study, filter disc of 2-mm diameter soaked in sodium hydroxide with a concentration of 0.5 N was placed at the center of the cornea for 30 s to establish a mouse model of corneal alkali injury. We found that 14-3-3zeta, which is mainly expressed in the epithelial layer, was upregulated following injury. Overexpression of 14-3-3zeta in ocular tissues via adeno-associated virus-mediated subconjunctival delivery promoted corneal wound healing, showing improved corneal structure and transparency. In vitro studies on human corneal epithelial cells showed that 14-3-3zeta was critical for cell proliferation and migration. mRNA-sequencing in conjunction with KEGG analysis and validation experiments revealed that 14-3-3zeta regulated the mRNA levels of ITGB1, PIK3R1, FGF5, PRKAA1 and the phosphorylation level of Akt, suggesting the involvement of the PI3K-Akt pathway in 14-3-3zeta-mediated tissue repair. 14-3-3zeta is a potential novel therapeutic candidate for treating severe corneal injury.
Asunto(s)
Proteínas 14-3-3 , Quemaduras Químicas , Lesiones de la Cornea , Cicatrización de Heridas , Animales , Humanos , Masculino , Ratones , Proteínas 14-3-3/metabolismo , Proteínas 14-3-3/genética , Proteínas 14-3-3/biosíntesis , Western Blotting , Quemaduras Químicas/metabolismo , Quemaduras Químicas/patología , Quemaduras Químicas/tratamiento farmacológico , Movimiento Celular , Proliferación Celular , Células Cultivadas , Lesiones de la Cornea/metabolismo , Lesiones de la Cornea/patología , Lesiones de la Cornea/genética , Modelos Animales de Enfermedad , Epitelio Corneal/metabolismo , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/lesiones , Quemaduras Oculares/inducido químicamente , Regulación de la Expresión Génica , Homeostasis , Ratones Endogámicos C57BL , Hidróxido de Sodio , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiologíaRESUMEN
Introduction: Functional dyspepsia (FD), also known as non-ulcerative dyspepsia, is a common digestive system disorder. Methods: In this study, an FD model was established using hunger and satiety disorders combined with an intraperitoneal injection of L-arginine. Indices used to evaluate the efficacy of hawthorn in FD mice include small intestinal propulsion rate, gastric residual rate, general condition, food intake, amount of drinking water, gastric histopathological examination, and serum nitric oxide (NO) and gastrin levels. Based on the intestinal flora and their metabolites, short-chain fatty acids (SCFAs), the mechanism of action of Crataegi Fructus (hawthorn) on FD was studied. The fecal microbiota transplantation test was used to verify whether hawthorn altered the structure of the intestinal flora. Results: The results showed that hawthorn improved FD by significantly reducing the gastric residual rate, increasing the intestinal propulsion rate, the intake of food and drinking water, and the levels of gastrointestinal hormones. Simultaneously, hawthorn elevated substance P and 5-hydroxytryptamine expression in the duodenum, reduced serum NO levels, and increased vasoactive intestinal peptide expression in the duodenum. Notably, hawthorn increased the abundance of beneficial bacteria and SCFA-producing bacteria in the intestines of FD mice, decreased the abundance of conditional pathogenic bacteria, and significantly increased the SCFA content in feces. Discussion: The mechanism by which hawthorn improves FD may be related to the regulation of intestinal flora structure and the production of SCFAs.