ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity.

BACKGROUND: The role of Acyl-CoA dehydrogenase long chain (ACADL) in different tumor types had different inhibiting or promoting effect. However, its role in non-small cell lung cancer (NSCLC) carcinogenicity is not clear. METHOD: In this study, we utilized The Cancer Genome Atlas (TCGA) database to analyze ACADL expression in NSCLC and its correlation with overall survival. Furthermore, we investigated the function of ACADL on cellular proliferation, invasion, colony, apoptosis, cell cycle in vitro with NSCLC cells. Mechanistically, we evaluated the regulatory effect of ACADL expression on its downstream factor yes-associated protein (YAP) by assessing YAP phosphorylation levels and its cellular localization. Finally, we verified the tumorigenic effect of ACADL on NSCLC cells through xenograft experiments in vivo. RESULTS: Compared to adjacent non-cancerous samples, ACADL significantly down-regulated in NSCLC. Overexpression of ACADL, effectively reduced the proliferative, colony, and invasive capabilities of NSCLC cells, while promoting apoptosis and inducing cell cycle arrest. Moreover, ACADL overexpression significantly enhanced YAP phosphorylation and hindered its nuclear translocation. However, the inhibitory effect of the overexpression of ACADL in NSCLC cells mentioned above can be partially counteracted by YAP activator XMU-MP-1 application both in vitro and in vivo. CONCLUSION: The findings suggest that ACADL overexpression could suppress NSCLC development by modulating YAP phosphorylation and limiting its nuclear shift. This role of ACADL-YAP axis provided novel insights into NSCLC carcinogenicity and potential therapeutic strategies.

Ensemble inference of unobserved infections in networks using partial observations.

Undetected infections fuel the dissemination of many infectious agents. However, identification of unobserved infectious individuals remains challenging due to limited observations of infections and imperfect knowledge of key transmission parameters. Here, we use an ensemble Bayesian inference method to infer unobserved infections using partial observations. The ensemble inference method can represent uncertainty in model parameters and update model states using all ensemble members collectively. We perform extensive experiments in both model-generated and real-world networks in which individuals have differential but unknown transmission rates. The ensemble method outperforms several alternative approaches for a variety of network structures and observation rates, despite that the model is mis-specified. Additionally, the computational complexity of this algorithm scales almost linearly with the number of nodes in the network and the number of observations, respectively, exhibiting the potential to apply to large-scale networks. The inference method may support decision-making under uncertainty and be adapted for use for other dynamical models in networks.

Influence maximization based on threshold models in hypergraphs.

Influence maximization problem has received significant attention in recent years due to its application in various domains, such as product recommendation, public opinion dissemination, and disease propagation. This paper proposes a theoretical analysis framework for collective influence in hypergraphs, focusing on identifying a set of seeds that maximize influence in threshold models. First, we extend the message passing method from pairwise networks to hypergraphs to accurately describe the activation process in threshold models. Then, we introduce the concept of hypergraph collective influence (HCI) to measure the influence of nodes. Subsequently, we design an algorithm, HCI-TM, to select the influence maximization set, taking into account both node and hyperedge activation. Numerical simulations demonstrate that HCI-TM outperforms several competing algorithms in synthetic and real-world hypergraphs. Furthermore, we find that HCI can be used as a tool to predict the occurrence of cascading phenomena. Notably, we find that the HCI-TM algorithm works better for larger average hyperdegrees in Erdös-Rényi hypergraphs and smaller power-law exponents in scale-free hypergraphs.

IGF2BP1 facilitates non-small cell lung cancer progression by regulating the KIF2A-mediated Wnt/ß-catenin pathway.

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are crucially implicated in the cancer progression. The current study intends to excavate and clarify the mechanisms of the key IGF2BPs in non-small cell lung cancer (NSCLC). The expression of IGF2BPs and kinesin family member 2A (KIF2A) was examined using immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot in NSCLC tissue samples or cell lines. NSCLC cell viability was examined using a cell counting kit-8 assay. Cell apoptotic rate was assessed using flow cytometry analysis. The migration and invasion of H1299 cells were subject to scratch test and Transwell assays, respectively. Starbase 2.0 was used to detect the downstream factors of the IGF2BP1 protein. The binding of IGF2BP with KIF2A was detected using RNA binding protein immunoprecipitation assays. Ki-67 immunohistochemistry assay and TUNEL assays were applied for the evaluation of proliferation and apoptosis in vivo, respectively. IGF2BP1 was upregulated in NSCLC tissue samples and cells. Functionally, IGF2BP1 overexpression promoted the proliferative ability, migration, and invasiveness of H1299 cells, while inhibiting cell apoptosis in vitro. In vivo studies revealed that overexpression of IGF2BP1 promoted tumor growth of NSCLC. Mechanistically, IGF2BP1 was involved in KIF2A mRNA stabilization. KIF2A exerted the same functions as IGF2BP1 via the Wnt/ß-catenin signaling. In conclusion, IGF2BP1 enhances NSCLC malignant progression by stabilizing KIF2A to modulate the Wnt/ß-catenin pathway.

Transcription factor ZEB1 regulates PLK1-mediated SKA3 phosphorylation to promote lung cancer cell proliferation, migration and cell cycle.

Lung cancer (LC) is one of the most common malignancies worldwide with low 5-year survival rate. The mechanism of spindle and kinetochore-associated complex subunit 3 (SKA3) in LC tumorgenesis remains largely unclear. The expression of SKA3 in LC cells was detected by quantitative PCR. Cell proliferation, migration and cell cycle were evaluated by functional assays including 5-ethynyl-2'-deoxyuridine, wound healing, transwell assays and flow cytometry analysis. Bioinformatics analysis, chromatin immunoprecipitation, luciferase reporter, co-immunoprecipitation and in vitro phosphorylation assays were applied to explore the interactions between zinc finger E-box binding homeobox 1 (ZEB1) and SKA3/polo-like kinase 1 (PLK1). SKA3 is highly expressed in LC cell lines and drives LC cell proliferation, migration and cell cycle. PLK1 also enhances the malignancy of LC cells. PLK1 can mediate SKA3 phosphorylation and enhance the stability of SKA3 protein, thus promoting LC progression. Besides, we found that transcription factor ZEB1 transcriptionally activates SKA3/PLK1 expression, contributing to LC cell malignancy. This study demonstrated that transcription factor ZEB1 modulates PLK1-mediated SKA3 phosphorylation to accelerate LC cell growth, migration and cycle, which might offer novel insight into LC treatment.

Evaluating the impact of stay-at-home and quarantine measures on COVID-19 spread.

BACKGROUND: During the early stage of the COVID-19 pandemic, many countries implemented non-pharmaceutical interventions (NPIs) to control the transmission of SARS-CoV-2, the causative pathogen of COVID-19. Among those NPIs, stay-at-home and quarantine measures were widely adopted and enforced. Understanding the effectiveness of stay-at-home and quarantine measures can inform decision-making and control planning during the ongoing COVID-19 pandemic and for future disease outbreaks. METHODS: In this study, we use mathematical models to evaluate the impact of stay-at-home and quarantine measures on COVID-19 spread in four cities that experienced large-scale outbreaks in the spring of 2020: Wuhan, New York, Milan, and London. We develop a susceptible-exposed-infected-removed (SEIR)-type model with components of self-isolation and quarantine and couple this disease transmission model with a data assimilation method. By calibrating the model to case data, we estimate key epidemiological parameters before lockdown in each city. We further examine the impact of stay-at-home and quarantine rates on COVID-19 spread after lockdown using counterfactual model simulations. RESULTS: Results indicate that self-isolation of susceptible population is necessary to contain the outbreak. At a given rate, self-isolation of susceptible population induced by stay-at-home orders is more effective than quarantine of SARS-CoV-2 contacts in reducing effective reproductive numbers [Formula: see text]. Variation in self-isolation and quarantine rates can also considerably affect the duration of outbreaks, attack rates and peak timing. We generate counterfactual simulations to estimate effectiveness of stay-at-home and quarantine measures. Without these two measures, the cumulative confirmed cases could be much higher than reported numbers within 40 days after lockdown in Wuhan, New York, Milan, and London. CONCLUSIONS: Our findings underscore the essential role of stay-at-home orders and quarantine of SARS-CoV-2 contacts during the early phase of the pandemic.

LncRNA PTPRG-AS1 facilitates glycolysis and stemness properties of esophageal squamous cell carcinoma cells through miR-599/PDK1 axis.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is the most significant subtype of esophageal cancer featured with high occurrence. Long noncoding RNAs (lncRNAs) have been proved to modulate the biological properties of cancer cells, including cell proliferation, invasion, migration, and apoptosis. LncRNA protein tyrosine phosphatase receptor type G-antisense RNA 1 (PTPRG-AS1) has been reported to play as an oncogene in diverse cancers. However, the detailed function PTPRG-AS1 may exert in ESCC is unclear. METHODS: PTPRG-AS1 expression in ESCC cells was investigated via quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The effects of PTPRG-AS1 on ESCC cell proliferation, migration, glycolysis, and stemness were verified through functional assays. Mechanism assays including RIP assay, RNA pull down assay, and luciferase reporter assays were performed to verify the molecular mechanism of PTPRG-AS1. RESULTS: PTPRG-AS1 silencing hindered the proliferation, migration, glycolysis and stemness of ESCC cells. PTPRG-AS1 regulated pyruvate dehydrogenase kinase 1 (PDK1) expression via sponging miR-599. The PTPRG-AS1/miR-599/PDK1 axis was further verified to aggravate the progression of ESCC cells. CONCLUSION: PTPRG-AS1 sponged miR-599 to up-regulate PDK1 expression, thereby promoting the proliferation and migration as well as glycolysis and stemness properties of ESCC cells.

Laparoscopic gastric dissociation using a two-port approach in minimally invasive esophagectomy.

BACKGROUND: A new approach for laparoscopic gastric dissociation in minimally invasive esophagectomy (MIE) was attempted. This study aimed to evaluate the short-term outcomes, safety, and efficacy of two-port laparoscopy using the McKeown procedure. METHODS: This retrospective study included 206 consecutive patients with esophageal cancer who underwent a modified two-port laparoscopic or the traditional five-port McKeown procedure at our institution from August 2019 to August 2021. Surgical outcomes of the two methods were compared. RESULTS: Of the 206 patients, 106 (51.46%) underwent the modified two-port procedure, whereas 100 (48.54%) underwent the traditional five-port procedure. Subsequently, 182 propensity score-matched patients were compared. No significant differences were observed in laparoscopic operative time, blood loss during laparoscopic surgery, number of dissected lymph nodes, and pain score on postoperative day 1 between the two groups. The rate of complication and postoperative length of hospital stay did not differ significantly between the two groups. The total hospitalization cost also did not differ significantly between the two groups (p = 0.325). No postoperative deaths occurred in either group. CONCLUSIONS: Our findings demonstrate that laparoscopic gastric dissociation using the two-port approach in MIE is a safe and effective procedure, with short-term outcomes comparable to those of the traditional five-port procedure in patients with esophageal cancer. Larger studies with longer follow-up duration are warranted.

E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell lung cancer cells through mediating the ubiquitination of Smad4.

Lung cancer is the leading cause of cancer-related death globally. Ubiquitin modification plays a crucial role in the regulation of gene expression, and is closely associated with cancer pathogenesis. The aim of our study was to clarify the role and mechanisms of action for HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1 (HECW1) in non-small cell lung cancer (NSCLC). Herein, we demonstrate that the expression of HECW1 was significantly increased in NSCLC cell lines and tissues. Upregulation of HECW1 markedly enhanced the proliferation of NSCLC cells, whereas downregulation of HECW1 significantly inhibited proliferation. Moreover, the expression levels of HECW1 positively correlated with the migration and invasiveness of NSCLC cells. Upregulation or downregulation of HECW1 only affected the protein expression levels of SMAD family member 4 (Smad4), but had no effect on the mRNA expression levels. Furthermore, after treatment with MG-132, the relative protein level of Smad4 significantly increased in NSCLC cells. HECW1 promoted the proliferation, migration, and invasiveness of NSCLC cells by inducing the ubiquitination and degradation of Smad4, thus our data provide a novel target for NSCLC treatment.

On the stability of multilayer Boolean networks under targeted immunization.

In this paper, we study targeted immunization in a multilayer Boolean network model for genetic regulatory networks. Given a specific set of nodes immune to perturbations, we find that the stability of a multilayer Boolean network is determined by the largest eigenvalue of the weighted non-backtracking matrix of corresponding aggregated network. Aimed to minimize this largest eigenvalue, we developed the metric of multilayer collective influence (MCI) to quantify the impact of immunizing individual nodes on the stability of the system. Compared with other competing heuristics, immunizing nodes with high MCI scores can stabilize an unstable multilayer network with higher efficiency on both synthetic and real-world networks. Moreover, despite that coupling nodes can exert direct influence across multiple layers, they are found to exhibit less importance as measured by the MCI score. Our work reveals the mechanism of maintaining the stability of multilayer Boolean networks and provides an efficient targeted immunization strategy, which can be potentially applied to the location of pathogenesis of diseases and the development of targeted therapy.

Dynamic range maximization in excitable networks.

We study the strategy to optimally maximize the dynamic range of excitable networks by removing the minimal number of links. A network of excitable elements can distinguish a broad range of stimulus intensities and has its dynamic range maximized at criticality. In this study, we formulate the activation propagation in excitable networks as a message passing process in which a critical state is reached when the largest eigenvalue of the weighted non-backtracking matrix is close to one. By considering the impact of single link removal on the largest eigenvalue, we develop an efficient algorithm that aims to identify the optimal set of links whose removal will drive the system to the critical state. Comparisons with other competing heuristics on both synthetic and real-world networks indicate that the proposed method can maximize the dynamic range by removing the smallest number of links, and at the same time maintaining the largest size of the giant connected component.

Surgical Method, Postoperative Complications, and Gastrointestinal Motility of Thoraco-Laparoscopy 3-Field Esophagectomy in Treatment of Esophageal Cancer.

BACKGROUND The aim of this study was to investigate the surgical method, postoperative complications, and gastrointestinal motility of thoraco-laparoscopic esophagectomy in the treatment of esophageal cancer. MATERIAL AND METHODS Using random sampling method, we selected 132 esophageal cancer patients who were treated in our hospital from January 2012 to December 2014; these patients were regarded as the study group and underwent thoraco-laparoscopy 3-field surgery treatment. Another 108 esophageal cancer patients admitted to our hospital over the same period were regarded as the control group and underwent traditional open McKeown esophagectomy. RESULTS The amount of blood loss and postoperative drainage of pleural fluid in the study group were significantly lower (P<0.05) and the time to removal of the chest tube and hospital stay were significantly shorter (P<0.05). The incidence of anastomotic fistula, vocal cord paralysis, chylothorax, and arrhythmia were significantly lower in the study group than in the control group (P<0.05). However, no significant differences in the incidence of pneumonia, atelectasis, or acute respiratory distress were detected (P>0.05). For postoperative gastrointestinal motility, first flatus time, first defecation time, and bowel tone recovery time after the operation, as well as the total amount of gastric juice draining, were reduced in the thoraco-laparoscopic esophagectomy group (P<0.05). The postoperative MTL and NO levels were higher but VIP level was lower in the thoraco-laparoscopic group (P<0.05). CONCLUSIONS Thoraco-laparoscopic esophagectomy was technically feasible and safe; it was associated with lower incidence of certain postoperative complications and had less effect on postoperative gastrointestinal motility. Skilled technique and cooperation could further shorten the operation time and might lead to better patient outcomes.

Insufficient radiofrequency ablation promotes the growth of non-small cell lung cancer cells through PI3K/Akt/HIF-1α signals.

Accelerated progression of residual non-small cell lung cancer (NSCLC) after incomplete radiofrequency ablation (RFA) has frequently been reported. In this study, NSCLC cells A549, CCL-185, and H358 were treated using a water bath at 47°C for 5, 10, 15, 20, and 25 min gradually to establish the sublines A549-H, CCL-185-H, and H358-H, respectively. A549-H, CCL-185-H, and H358-H cells showed a significant increase in proliferation rate when compared with their corresponding parental cellsin vitro The expression of hypoxia-inducible factor-1α (HIF-1α) was obviously upregulated in both A549-H and CCL-185-H cells. Silencing of HIF-1α abolished the insufficient RFA-induced proliferation in A549-H and CCL-185-H cells. Furthermore, insufficient RFA treatment markedly elevated the phosphorylation of ERK1/2 and Akt, but not of p38 MAPK or JNK, in A549-H and CCL-185-H cells. The inhibitor of Akt, LY294002, but not the inhibitor of ERK1/2, PD98059, suppressed the upregulation of HIF-1α and the proliferation of A549-H and CCL-185-H cellsin vitro Thein vivoresults confirmed that insufficient RFA could trigger the tumor growth, upregulate the HIF-1α expression, and activate Akt in A549 xenograft tumors. Our data suggest that insufficient RFA can promote thein vitroandin vivogrowth of NSCLC via upregulating HIF-1α through the PI3K/Akt signals.

[3-D fluorescence properties of river with great flow rate].

In the present study, the three-dimensional fluorescence spectra of River A with great flow rate were investigated. The results showed that there existed three unambiguous peaks in the excitation-emission matrix of River A at lambda(ex)/lambda(em) of around 230/340, 280/320 and 250/450 nm respectively. The fluorescence intensity varied significantly and had sharp fluctuation sometimes. But the COD(Mn) of the samples remained quite stable. This study indicated that fluorescence technique could demonstrate the pollution in the water bodies with great flow rate and furthermore make up for the deficiency of the conventional parameters related to organic pollution, i. e. invalidation to exhibit the components of pollutants. It is a good tool for the early-warning of the water quality.

Genome-edited rabbits: Unleashing the potential of a promising experimental animal model across diverse diseases.

Animal models are extensively used in all aspects of biomedical research, with substantial contributions to our understanding of diseases, the development of pharmaceuticals, and the exploration of gene functions. The field of genome modification in rabbits has progressed slowly. However, recent advancements, particularly in CRISPR/Cas9-related technologies, have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases, including cardiovascular disorders, immunodeficiencies, aging-related ailments, neurological diseases, and ophthalmic pathologies. These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice. This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine, underscoring their impact and future potential in translational medicine.

Impact of Body Composition on Clinical Outcomes in Patients with Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Immunotherapy Plus Chemotherapy.

AIM: Some studies have reported that body composition profiles affect clinical outcomes of multidisciplinary treatments in several types of cancers; however, a paucity of data exists on the association in neoadjuvant immunotherapy. In the present study, we aimed to investigate the effect of body composition on the clinical outcomes of patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy plus chemotherapy (nICT). METHODS: Clinicopathological data and computed tomography (CT) images of 85 patients with locally advanced ESCC who underwent esophagectomy after nICT were collected. At diagnosis and before surgery, the CT scan of the third lumbar vertebra was chosen to evaluate the skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), the subcutaneous and the visceral adiposity index. The relationships between body composition and tumor response after nICT and postoperative complications were analyzed. RESULTS: The clinical stage (Odds Ratio (OR) 0.345, 95% confidence interval (CI) 0.141-0.844, p = 0.020) and change in SMI (∆SMI, OR 1.394, 95% CI 1.061-1.832, p = 0.017) were associated with tumor remission after nICT. Moreover, the multivariate logistic analysis revealed that ∆SMI (OR 0.598, 95% CI 0.433-0.828, p = 0.002) was associated with the incidence of postoperative complications. Patients with ∆SMI <-1 had a higher rate of postoperative complications (56% vs 15%, p < 0.001). CONCLUSIONS: For ESCC, ∆SMI is associated with the pathological response after nICT and postoperative complications. Further analysis is needed to clarify whether nutritional intervention during neoadjuvant therapy increases SMI and thus improves clinical outcomes.

Two-year outcomes of clinical N2-3 esophageal squamous cell carcinoma after neoadjuvant chemotherapy and immunotherapy from the phase 2 NICE study.

OBJECTIVE: This study aims to report the 2-year outcomes of patients with clinical stage N2-3 esophageal squamous cell carcinoma who received neoadjuvant chemotherapy and immunotherapy followed by surgery from a phase 2 NICE trial. METHODS: Eligible patients with clinical stage N2-3 esophageal squamous cell carcinoma were screened and enrolled, then treated with regimen of nab-paclitaxel (100 mg/m2, days 1, 8, 15), carboplatin (area under the curve = 5, day 1), camrelizumab (200 mg, day 1) of two 21-day cycles and esophagectomy 4 to 6 weeks after the last chemotherapy. Oncologic outcomes, recurrence patterns, overall survival (OS), and recurrence-free survival (RFS) were explored. RESULTS: From November 20, 2019, to December 22, 2020, 60 patients were recruited. After a median follow-up of 27.4 months, disease recurrence was observed in 19 (37.3%) patients, with 5 (9.8%) locoregional recurrence, 9 (17.6%) distant metastasis, and 5 (9.8%) combined recurrence. Lung was the most commonly involved metastatic site. The median time to recurrence was 10.8 months (interquartile range, 7.5-12.7 months). The 2-year OS and RFS rates were 78.1% and 67.9%, respectively. Patients who achieved major pathologic response (MPR) had a significantly greater 2-year OS rate (91.4% vs 47.7%; P < .001) and RFS rate (77.1% vs 45.9%; P = .003). On multivariable analysis, MPR was indicated as an independent prognostic factor for disease recurrence (hazard ratio, 0.39; 95% confidence interval, 0.21-0.82; P = .029). CONCLUSIONS: In patients receiving neoadjuvant chemotherapy and immunotherapy, distant metastasis remains the predominant recurrence pattern. MPR is associated with lower recurrence and better survival. Long-term results derived from randomized controlled trials are further required. TRIAL REGISTRATION NUMBER: ChiCTR1900026240.

Analysis of complication risk factors in preoperative computed tomography-guided hookwire location of pulmonary nodules.

BACKGROUND: This study aimed to explore the efficacy of hookwire for computed tomography (CT)-guided pulmonary nodule (PN) localization before video-assisted thoracoscopic surgery (VATS) resection and determine the risk factors for localization-related complications. METHODS: We enrolled 193 patients who underwent preoperative CT-guided PN hookwire localization. The patients were categorized into groups A (103 patients had no complications) and B (90 patients had complications) according to CT and VATS. Uni- and multivariate logistic regression analyses were used to identify risk factors for localization-related complications. A numerical rating scale was used to evaluate hookwire localization-induced pain. RESULTS: We successfully performed localization in 173 (89.6%) patients. Pneumothorax was the main complication in 82 patients (42.5%). Patient gender, age, body mass index, tumor diameter, consolidation tumor ratio, pathologic diagnosis, position adjustment during location, lesion location, waiting time for surgery, and pleural adhesions were not significantly different between the two groups. The number of nodules, number of punctures, scapular rest position, and depth of insertion within the lung parenchyma were significant factors for successful localization. Multivariate regression analysis further validated the number of nodules, scapular rest position, and depth of insertion within the lung parenchyma as risk factors for hookwire-localization-related complications. Hookwire localization-induced pain is mainly mild or moderate pre- and postoperatively, and some patients still experience pain 7 days postoperatively. CONCLUSIONS: Hookwire preoperative PN localization has a high success rate, but some complications remain. Thus, clinicians should be vigilant and look forward to further improvement.

Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

Comparative outcomes of video-assisted thoracoscopic surgery versus open surgery for bronchogenic cysts in adults: a retrospective cohort study.

Background: Open thoracotomy has been the traditional surgical approach for patients with bronchogenic cysts (BCs). This study aimed to evaluate the safety and efficacy of video-assisted thoracoscopic surgery (VATS) compared to open surgery for the treatment of BCs in adults. Methods: This single-institution, retrospective cohort study included 117 consecutive adult patients who underwent VATS (group A) or open surgery (group B) for BC resection between February 2019 and January 2023. Data regarding clinical history, operation duration, length of hospital stay, 30-day mortality, and recurrence during follow-up were collected and analyzed. Results: Of the total cohort, 103 (88.0%) patients underwent VATS, while 14 (12.0%) patients underwent open surgery. Patients' age in group B were much older than group A (P=0.014), and no significant differences in other demographic and baseline clinical characteristics were observed between the groups. The VATS group had shorter median operation duration (96 vs. 149.5 min, P<0.001) and shorter mean length of hospital stay (5.0±5.5 vs. 8.6±4.0 days, P<0.001). One death occurred in the open surgery group. During a median follow-up of 34 (interquartile range, 20.8-42.5) months, no instances of BC recurrence were observed in either group. Conclusions: Compared to open surgery, VATS is also a safe and efficacious approach for treating BCs in adults. What's more, VATS offered shorter operative times and hospital stays. Considering the minimally invasive, VATS may be a better choice in most patients with bronchial cysts.