Search

Background Prolonged air leak (PAL) remains one of the most frequent postoperative complications after pulmonary resection. This study aimed to develop a predictive nomogram to estimate the risk of PAL for individual patients after minimally invasive pulmonary resection. Methods Patients who underwent minimally invasive pulmonary resection for either benign or malignant lung tumors between January 2020 and December 2021 were included. All eligible patients were randomly assigned to the training cohort or validation cohort at a 3:1 ratio. Univariate and multivariate logistic regression were performed to identify independent risk factors. All independent risk factors were incorporated to establish a predictive model and nomogram, and a web-based dynamic nomogram was then built based on the logistic regression model. Nomogram discrimination was assessed using the receiver operating characteristic (ROC) curve. The calibration power was evaluated using the Hosmer-Lemeshow test and calibration curves. The nomogram was also evaluated for clinical utility by the decision curve analysis (DCA). Results A total of 2213 patients were finally enrolled in this study, among whom, 341 cases (15.4%) were confirmed to have PAL. The following eight independent risk factors were identified through logistic regression: age, body mass index (BMI), smoking history, percentage of the predicted value for forced expiratory volume in 1 second (FEV1% predicted), surgical procedure, surgical range, operation side, operation duration. The area under the ROC curve (AUC) was 0.7315 [95% confidence interval (CI): 0.6979–0.7651] for the training cohort and 0.7325 (95% CI: 0.6743–0.7906) for the validation cohort. The P values of the Hosmer-Lemeshow test were 0.388 and 0.577 for the training and validation cohorts, respectively, with well-fitted calibration curves. The DCA demonstrated that the nomogram was clinically useful. An operation interface on a web page (https://lirongyangql.shinyapps.io/PAL_DynNom/) was built to improve the clinical utility of the nomogram. Conclusion The nomogram achieved good predictive performance for PAL after minimally invasive pulmonary resection. Patients at high risk of PAL could be identified using this nomogram, and thus some preventive measures could be adopted in advance.

DDRGK domain-containing protein 1 (DDRGK1) is an important component of the newly discovered ufmylation system and its absence has been reported to induce extensive endoplasmic reticulum (ER) stress. Recently, emerging evidence indicates that the ufmylation system is correlated with autophagy, although the exact mechanism remains largely unknown. To explore the regulation mechanism of DDRGK1 on autophagy, in this study, we established an immortalized mouse embryonic fibroblast (MEF) cell lines harvested from the DDRGK1F/F:ROSA26-CreERT2 mice, in which DDRGK1 depletion can be induced by 4-hydroxytamoxifen (4-OHT) treatment. Here, we show that DDRGK1 deficiency in MEFs has a dual effect on autophagy, which leads to a significant accumulation of autophagosomes. On one hand, it promotes autophagy induction by impairing mTOR signaling; on the other hand, it blocks autophagy degradation by inhibiting autophagosome–lysosome fusion. This dual effect of DDRGK1 depletion on autophagy ultimately aggravates apoptosis in MEFs. Further studies reveal that DDRGK1 loss is correlated with suppressed lysosomal function, including impaired Cathepsin D (CTSD) expression, aberrant lysosomal pH, and v-ATPase accumulation, which might be a potential trigger for impairment in autophagy process. Hence, this study confirms a crucial role of DDRGK1 as an autophagy regulator by controlling lysosomal function. It may provide a theoretical basis for the treatment strategies of various physiological diseases caused by DDRGK1 deficiency.

Chicken blastodermal cells (BCs) are pluripotent stem cells derived from early embryos and may be easily obtained and manipulated. However, in vitro cultured BCs have extremely low germline capacity, which may limit their applications. Research on the germ cell differentiation of mammalian pluripotent cells using chemical-inducing agents has gained popularity, and tremendous achievements have been made. Whether chemical-inducing agents allow acquirement of germline competence in BCs is, however, questionable. In this study, retinoic acid (RA) and bone morphogenetic protein 4 (BMP4) promoted the expression of germline-specific genes and restored the germline competence of in vitro cultured BCs. Moreover, BCs induced with RA and BMP4 could efficiently produce gonadal chimeric chick embryos. These results may greatly enhance the potential applications of BCs in biotechnology and basic research.

Background Producing transgenic chickens with chicken blastodermal cells (cBCs) is inefficient due to the extremely low germline transmission capacity of cBCs. As chicken primordial germ cells (PGCs) have been reported as an efficient method for producing transgenic chickens, the inefficiency of cBCs could potentially be resolved by inducing them to differentiate into germ cells. However, whether chemical inducers are able to enhance cBCs germline competence in vitro is unknown and the molecular mechanisms of differentiation of chicken pluripotent cells into germ cells are poorly understood. Results We cultured cBCs with a monolayer morphology in E8 medium, a xeno- and feeder-free medium. We showed that retinoic acid (RA) treatment increased expression of germ cell-specific genes in cBCs. Using western blot, we determined that RA stimulated Smad1/5 phosphorylation. Moreover, Smad1/5 activation regulates the expression of germ cell-specific genes, as co-treatment with a Smad1/5 phosphorylation inhibitor or activator alters expression of these genes. We also demonstrate that Smad1/5 is required for RA-induced differentiation by RNA interference knockdown. Conclusion Our results demonstrated that E8 medium is able to maintain cBC growth for weeks and RA treatment induced germ cell differentiation of cBCs through the BMP-Smad1/5 signaling pathway. Electronic supplementary material The online version of this article (doi:10.1186/s12896-017-0332-y) contains supplementary material, which is available to authorized users.