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Purpose: Venous thromboembolism (VTE) is a common postoperative complication in patients with lung cancer that seriously affects prognosis and quality of life. This study aimed to establish a nomogram for predicting the probability of postoperative VTE risk in patients with stage IA non-small cell lung cancer (NSCLC).Methods: 452 patients with stage IA NSCLC from January 2017 to January 2022 were retrospectively analyzed and randomly divided into a training set and a validation set at a ratio of 7:3.Independent risk factors were identified by univariate and multivariate logistic regression analyses, and a nomogram was established based on the results and internally validated. The predictive power of the nomogram was evaluated by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).Results: The nomogram included three risk factors: age, preoperative D-dimer, and intermuscular vein dilatation. The areas under the ROC curve of this model were 0.832 (95% CI: 0.732-0.924) and 0.791 (95% CI: 0.668-0.930) in the training and validation sets, respectively, showing good discriminative power. In addition, the probability of postoperative VTE occurrence predicted by the nomogram was consistent with the actual occurrence probability. In the decision curve, the nomogram had a better net clinical benefit at a threshold probability of 5%-90%.Conclusion: This study is the first to develop a nomogram for predicting the risk of postoperative VTE in patients with stage IA NSCLC; this nomogram can accurately and intuitively evaluate the probability of VTE in these patients and help clinicians make decisions on prevention and treatment.

Background Cervical mediastinoscopy is useful for diagnosing lung and mediastinal disease. Ultrasound is a safe real‐time diagnostic tool widely employed in many surgical fields. Ultrasound was used in cervical mediastinoscopy in our cohort with satisfactory results. This study investigated the safety, feasibility, and availability of video‐assisted mediastinoscopy (VAM) combined with ultrasound for mediastinal lymph node biopsy. Methods A total of 87 cases involving cervical mediastinal lymph node biopsy performed from November 2015 to May 2020, with complete clinical and pathological information, were retrospectively analyzed in the Department of Thoracic Surgery at Beijing Chaoyang Hospital. The cohort was divided into two groups: ultrasound‐guided biopsy under video‐assisted mediastinoscopy (UVAM) (44 cases) and routine VAM (43 cases). Operation time, biopsy number and nodal stations, postoperative complications, pathological conditions, and surgical difficulty were compared between the two nodal stations. Results UVAM was significantly shorter and more lymph node specimens were obtained than with VAM. There was one case of fatal bleeding and two cases of right recurrent laryngeal nerve injury in the VAM group, and no postoperative complications in the UVAM group. Conclusions When used with cervical VAM, ultrasound guidance assists physicians assess the space between lymph nodes, surrounding tissues, and large vessels systematically, making biopsy safer and easier, improving lymph node sampling, and decreasing postoperative complications. Furthermore, surgeons can easily learn and master this method. Key points Significant findings of the study: Ultrasound was used in combination with cervical mediastinoscopy and the results showed that ultrasound guidance makes biopsy in patients safer and easier, improves lymph node sampling, and decreases postoperative complications. What this study adds: Surgeons can easily learn and master this method., Ultrasound was used in combination with cervical mediastinoscopy and the results showed that ultrasound guidance makes biopsy in patients safer and easier, improves lymph node sampling, and decreases postoperative complications. Furthermore, surgeons can easily learn and master this method.

Ethanol affects the nervous system of animals to cause a boost of feeding, sexual, verbal, and locomotor behaviors. To understand the neural mechanisms of these ethanol-induced behaviors, we investigated a neural pathway of ethanol-induced feeding behavior by guanylate cyclases and serotonin signals in C. elegans. We recorded the intracellular calcium signaling of seven sensory neurons in response to ethanol, and only found a significant increase of calcium signaling in BAG among the seven sensor neurons. And both guanylate cyclases GCY-31 and GCY-33 were crucial signaling protein of calcium response in BAG neurons. In addition, serotonin, released from NSM motor neurons, promoted feeding behavior under ethanol stimulation. And the rescue experiment of double mutant indicated the guanylate cyclases and serotonin in the same signaling pathway. So BAG neurons respond to alcohol through the promotion of intracellular calcium signaling, and then the downstream motor neurons NSM release serotonin to regulate the feeding behavior in C. elegans. These findings revealed a neural circuit to understand how the nervous system responds to ethanol and generates corresponding behavior.

Oligosaccharides analysis is crucial for brewing technology. Herein, we reported a rapid and highly reproducible method for profiling of oligosaccharides in beer using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) by employing a reasonably designed reactive-matrix, 2-phenyl-3-(p-aminophenyl) acrylonitrile (PAPAN). The PAPAN enhanced ionization efficiency of oligosaccharides and improved reproducibility comparing to the use of conventional matrix, 2,5-dihydroxybenzoic acid (DHB). After optimization of sample dilution factor and cationization agents, the distributions of maltooligosaccharides in different brands of beers were unambiguously identified. Since the PAPAN selectively reacts with the reducing end of oligosaccharides, the interferences from matrixes are effectively eliminated. Therefore, the method shows potentials for analysis of oligosaccharides in other foods.

Background: The long-term success of lung transplantation is limited by the development of chronic lung allograft dysfunction (CLAD) in which IL-17 plays an important role. Direct evidence of IL-17-mediated allograft rejection has been observed when T-bet is absent. However, lack of T-bet also leads to failure in production of IFN-γ which is required for tolerance induction and allograft acceptance, as T-bet deficiency results in IL-17-expressing CD8+ T cells mediated costimulation blockade-resistant allograft rejection. Our previous research demonstrated that additional STAT6 deficiency to T-bet deficiency resulted in Th17-dominant immune responses, and importantly, restored IFN-γ production. Here we investigated whether T-bet/STAT6 double knout-out (DKO) mice as allograft recipients could provide a useful model to study IL-17 and Th17 in lung transplantation. Methods: Murine orthotopic allogeneic lung transplants were performed in C57BL/6 wild type (WT) or T-bet/STAT6 DKO (C57BL/6 background) mice using MHC fully mismatched BALB/c donors. Syngeneic transplants were also performed in WT C57BL/6 mice using C57BL/6 donors. At day 10, histopathologic characteristics and rejection status of transplanted grafts were assessed; graft-infiltrating cells were isolated and real-time RT-PCR was performed for IL-17, IFN-γ and IL-4 expressions. Results: Isografts showed no apparent rejection as anticipated. Allografts of both WT and DKO recipients displayed vigorous acute rejection and expressed comparable levels of IFN-γ; while T-bet/STAT6 double deficiency resulted in much more IL-17 and less IL-4 production. Histopathologic examination demonstrated that allografts of both WT and DKO recipients have marked inflammatory cell infiltration and pulmonary parenchyma lesion. In contrast to lymphocyte-predominant inflammation observed in WT recipients, allografts of DKO recipients displayed obvious polymorphonuclear cell infiltration and severer obliterative airway inflammation. Compared to WT recipients, the ratio of graft-infiltrating CD8+ versus CD4+ T cells increased significantly with much higher numbers of neutrophils in allografts of DKO recipients. Conclusions: T-bet/STAT6 DKO recipients of lung allografts result in IL-17-dominant transplant immunity, retain IFN-γ responses, and develop neutrophilia, obliterative airway inflammation and acute transplant rejection. Our results indicate that T-bet/STAT6 DKO mice serving as allograft recipient could be utilized as a new viable model to study the roles of IL-17 in lung transplantation.

BACKGROUND The rationality of selective mediastinal lymph node dissection based on lobe-specific metastasis is still controversial. The correlation of lymph node metastasis in lobe-specific lymphatic drainage regions (LSDRs) and non-LSDRs has not been widely reported. The purpose of this study was to investigate the variables affecting nodal metastasis in non-LSDRs and to further evaluate the rationality of selective lymphadenectomy in clinical stage IA non-small cell lung cancer (NSCLC) patients. METHODS The clinicopathological information of 316 patients with clinical stage IA NSCLC who underwent lobectomy with systematic lymph node dissection between June 2014 and June 2018 was retrospectively collected for analysis. RESULTS The overall lymph node metastasis rate was 19.3%. For 35 patients with positive LSDR lymph nodes, the non-LSDR lymph node metastasis rate was 31.4%. Only one patient (0.4%) among 281 patients with negative LSDR lymph nodes had nodal spread in non-LSDRs. Univariate analysis identified that solid consistency, worse differentiation, and positive status in LSDRs were unfavorable predictive variables of lymph node metastasis in non-LSDRs. Multivariate analysis showed that nodal metastasis in LSDRs was the only independent predictor of nodal involvement in non-LSDRs (P

Surgical treatment with complete resection is the standard of care in the management of thymic tumors. Although minimally invasive surgery is not routinely recommended due to the lack of long-term oncologic data according to NCCN guideline, video-assisted thoracic surgery (VATS) technique has been proved to be promising alternative to open approach in the surgical treatment of early-stage thymoma by previous studies (1). Postoperative chylothorax can occur in every cardiothoracic surgical procedure, especially esophagectomy, but it is a rare complication accompanied by thoracoscopic extended thymectomy.

Background: The high incidence of venous thromboembolism (VTE) has been perceived in post thoracic surgery patients. However, the significance of perioperative coagulation and fibrinolysis related parameters after lung surgery for VTE predicting is not clear. To investigate that, we conducted a prospective single center study. Methods: A total of 111 patients undergoing lung surgery were enrolled in this study, included 52 primary lung cancer patients and 59 benign lung disease patients from July 2016 to March 2017. Preoperative and postoperative days 1, 3, and 5 coagulation and fibrinolysis related parameters were tested, including antithrombin (AT), fibrinogen degradation product (FDP), prothrombin time (PT), prothrombin time activity (PA), prothrombin time ratio (PR), international normalized ratio (INR), activated partial thromboplastin time (APTT), plasma fibrinogen (FBG), thrombin time (TT) and D-Dimer. The Doppler ultrasonography was performed before and after surgery for deep venous thrombosis (DVT) confirmation. Patients with new postoperative DVT, unexplained dyspnea, hemoptysis, chest pain, or high Caprini score (≥9) were received further computer tomography pulmonary angiography (CTPA) for pulmonary embolism (PE). We used the area under receiver-operating-characteristic (ROC) curve to discriminate patients between those who developed VTE and those who did not. Single factor analysis was utilized to define risk factors associated with VTE. Results: The overall incidence of VTE was 16.2% (18/111). The incidence of VTE in primary lung cancer patients was 23.1% (12/52), much higher than that in benign lung diseases 10.2% (6/59), but did not reach statistical significance (P=0.066). Among 18 VTE patients, 83.3% was DVT, 16.7% was DVT + PE and 72.2% was muscular veins of the calf thrombosis. D-Dimer was much higher in VTE group than that in non-VTE group preoperatively and at postoperative days 1, 3 (0.64±0.24 vs . 0.33±0.06, P=0.007; 3.14±0.75 vs . 1.51±0.09, P=0.005, and 1.88±0.53 vs . 0.76±0.05, P=0.001, respectively). And the ROC curve areas of preoperative and postoperative days 1, 3 of D-Dimer were 0.70, 0.71 and 0.74, respectively. And FDP was much higher in VTE group than that in non-VTE group at postoperative day 3 (6.78±1.43 vs . 3.79±0.15, P=0.004). But AT, PT, PA, PR, INR, APTT, FBG and TT there were no significantly difference. Conclusions: The overall incidence of VTE after lung surgery was 16.2%. The patients with preoperative high D-Dimer should receive VTE prophylaxis.

[This corrects the article DOI: 10.21037/jtd.2018.03.174.].

The cellular and molecular mechanisms underlying lung allograft rejection remain poorly understood. We investigated the potential role of interleukin (IL)-17A in lung transplant rejection in a mouse model, because previous studies in clinical and rodent models have implicated IL-17A in both acute and chronic rejection.To generate an orthotopic lung transplantation model, lungs from C57BL/6 or BALB/c mice were transplanted into C57BL/6 mice (isograft and allograft models, respectively). The effects of anti-IL-17A treatment in allograft recipients were investigated. The histological features and rejection status of isografts and allografts were assessed at 3, 7, and 28 days after transplantation, and differences in graft infiltrating cells and mRNA expression of relevant cytokines were quantified at 3 and 7 days after transplantation.As expected, isografts showed no obvious signs of rejection, whereas allografts exhibited minimal-to-mild rejection (grade A1-A2) by day 3 and moderate-to-severe rejection (grade A3-A4) by day 7, without evidence of obliterative bronchiolitis (OB). However, by 28 days, evidence of OB was observed in 67% (2/3) of allografts and severe rejection (grade A4) was observed in all. IL-17 mRNA expression in allografts was increased with rejection, and interferon (IFN)-γ and IL-6 mRNA expression levels followed a similar pattern. In contrast, IL-22 expression in allografts was only slightly increased. Antibody (Ab) neutralization of IL-17A diminished the signs of acute rejection at 7 days after transplantation in allografts, and this early protection was accompanied by a decrease in cellular stress according to histological evaluation, suggesting the involvement of IL-17A in the development of early post-transplantation lesions.Our data indicate that IL-17A is important in the pathophysiology of allograft rejection, and neutralization of IL-17A is a potential therapeutic strategy to preventing lung transplant rejection.

Gangliosides are critical in many functions of mammalian cells but present as a minor lipid component with many molecular species of subtle differences. Conventional strategies for profiling gangliosides suffer from poor reproducibility, low sensitivity, and low-throughput capacity. Prior separation of gangliosides by thin-layer chromatography and/or high-performance liquid chromatography not only was laborious and tedious but also could introduce uneven losses of molecular species. We developed a new strategy of using electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to profile gangliosides with high-throughput potential. This strategy involves three new findings: (i) collision-induced fragmentation of gangliosides gave rise to a common ion of m/z 290, a derivative of N-acetylneuraminic acid; (ii) phospholipids exert a profound suppression of ganglioside detection in ESI-MS/MS to prevent a direct detection in total cellular lipid extracts; and (iii) enrichment of gangliosides in the aqueous phase from total cellular lipid extracts eliminates the damping effect of phospholipids and permits direct precursor scan.

The long-term success of lung transplantation is mainly limited by the development of obliterative bronchiolitis (OB) in which IL-17 plays a critical role. However, murine orthotopic allogeneic lung transplant model in wild type recipients develops IFNγ-dominant acute allograft rejection. Our previous research demonstrated that additional STAT6 deficiency to T-bet deficiency resulted in Th17-dominant immune responses, and also restored CD4 T cells to produce IFNγ which is essential to immunosuppression and immunological tolerance. In this study, murine orthotopic lung transplants were performed in C57BL/6 wild type or T-bet/STAT6 double knout-out (DKO) mice using BALB/c donors. Vigorous allograft rejection was observed in T-bet/STAT6 DKO recipients with much higher levels of IL-17 but comparable levels of IFNγ expression to that in wild type recipients. Analysis of the graft-infiltrating cells displayed a significantly decreased CD4:CD8 ratio in T-bet/STAT6 DKO recipients compared to wild type recipients, but not as extremely as that observed in T-bet KO recipients, demonstrating more balanced CD4 and CD8 responses in DKO recipients. Our results indicate T-bet and STAT6 double deficient recipients of lung allografts develop obliterative airway inflammation that is mediated by both CD4 and CD8 responses, more closely resembling OB pathogenesis, and provide a new viable model to study lung transplant rejection.

Development of obliterative bronchiolitis (OB) is the biggest obstacle that limits long-term allograft survival and clinical application of lung transplantation. Mouse orthotopic trachea or lung transplantations were utilized to examine roles of Th17 and Th1 during OB pathogenesis after transplantation. Allografts of wild type recipients displayed elevated levels of Th1 and Th17 cytokines IFNγ, IL-6 and IL-17 expression. Recipients deficient in Th1 key transcriptional factor T-bet resulted in decreased cell infiltration and improved airway integrity in orthotopic transplanted trachea grafts; Lack of Th2 transcriptional factor Stat6 had little effect; While absence of Th17 master transcriptional factor RORγt had striking effects in abolishing airway epithelial injury, a leading factor of OB pathogenesis. Administering anti-IL-6 or anti-IL-17 but not anti-IFNγ mAbs restored normal airway epithelial morphology. Furthermore, we found that anti-CD40L treatment resulted in increased FoxP3 and regulatory T cells, and decreased IFNγ expression; However it had very limited effect on IL-17 suppression and airway epithelial protection. While CTLA4-Ig treatment significantly inhibit IL-17 expression and reduced epithelial injury, and the combination of CTLA4-Ig and anti-CD40L markedly restored airway morphology of grafts. Together, our findings provide new insights for understanding Th17 and Th1 responses during OB pathogenesis and demonstrate the critical importance of suppressing Th17 for OB development after transplantation.

In cultured mammalian cells, both normal and transformed, cell–cell contact was shown to alter the detergent extractability of nuclear and plasma membranes detected using immunocytochemistry of fixed cells. This alteration occurred in each cell individually, occurred in less than 1 hour after altered cell–cell contact, and did not involve new protein or mRNA synthesis. These results indicate that composition of cellular membranes is highly affected by cell–cell contact and culture density. This suggests a possible role for alterations in membrane composition in the regulation of normal cell behavior, including signaling of contact inhibition of growth and movement, behaviors that are not effectively regulated by cell–cell contact in malignantly transformed cells. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc.

Nonhuman primates used in these studies had been fed for 5 years diets enriched with cholesterol and one of three classes of fatty acids: saturated, monounsaturated, or polyunsaturated fatty acids. Atherosclerotic iliac artery lipid extracts were quantitatively analyzed for cholesterol, cholesteryl esters, fatty acid composition, and a marker of lipid oxidation, the F(2)-isoprostanes. There was no significant difference in the mean accumulation of F(2)-isoprostanes among the different diet groups. To account for the small, individual variation in the arachidonate concentration the F(2)-isoprostane mass from each sample was normalized by dividing by arachidonate mass: F(2)-isoprostane mass/(mass arachidonate). At lower levels of cholesterol accumulation, the F(2)-isoprostane mass/(mass arachidonate) ratio was greater in lipids from POLY arteries compared to SAT arteries, but the reverse was true at high levels of cholesterol. F(2)-isoprostane/(mass arachidonate) increased with mole fraction linoleate for the SAT group, but decreased for the POLY group. In summary, these studies demonstrated that there is no simple explanation of how F(2)-isoprostane accumulation did not depend on the concentration of oxidizable lipids that promote free-radical lipid oxidation.

The red sensitivity of dichromated cellulose triacetate holographic recording material without any dye sensitization is reported. We suggest that the sensitivity is due to the absorption at 590 nm of the intermediate Cr(V) formed in the reducing process of chromium from Cr(VI) to Cr(III). In the experiment, the real-time transmission gratings are recorded with 632.8-nm irradiation from a He-Ne laser.