USP14 Modulates Cell Pyroptosis and Ameliorates Doxorubicin-Induced Cardiotoxicity by Deubiquitinating and Stabilizing SIRT3.

This study investigates the role of the deubiquitinating enzyme USP14 in alleviating doxorubicin (DOX)-induced cardiotoxicity(DIC), particularly concerning its mechanism of regulating pyroptosis through the stabilization of the mitochondrial protein SIRT3. Using in vivo and in vitro models, the research demonstrated that USP14 overexpression protects against DOX-induced cardiac damage by modulating pyroptosis. Silencing SIRT3 via siRNA revealed that SIRT3 is a key intermediary molecule in USP14-mediated regulation of pyroptosis. Notably, DOX exposure resulted in decreased USP14 expression, while its overexpression preserved mitochondrial function and reduced oxidative stress by stabilizing SIRT3. Immunoprecipitation confirmed that USP14 stabilizes SIRT3 through deubiquitination. These findings position USP14 as a promising therapeutic target for mitigating DOX-induced cardiotoxicity by stabilizing SIRT3 and maintaining mitochondrial integrity, suggesting potential novel strategies for cardio-protection in chemotherapy.

Decreased Serum CTRP3 level was associated with connective tissue diseases.

Objective: Complement C1q tumor necrosis factor-related protein 3 (CTRP3) and 9 (CTRP9) are two of the most extensively studied adipokines, known for their diverse biological functions. However, it remains unclear whether serum levels of CTRP3 or CTRP9 are associated with connective tissue diseases (CTD). Methods: Serum CTRP3 and CTRP9 levels were measured by enzyme-linked immune sorbent assay (ELISA) and analyzed in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS), ankylosing spondylitis (AS), undifferentiated connective tissue disease (UCTD), as well as in healthy controls (HCs). Results: Serum CTRP3 levels were all significantly lower in patients with RA, SLE, pSS and AS compared with HCs. However, there were no significant differences in serum CTRP9 levels between patients with RA, SLE, pSS, or AS and HCs. In pSS patients, CTRP3 showed a weak correlation with blood glucose, creatinine, and urine acid in pSS patients, while no correlations were observed between serum CTRP3 levels and clinical or laboratory indices in RA, SLE or AS patients. Stable associations between CTRP3 and RA, SLE, pSS and AS were evaluated using multivariate logistics regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluated CTRP3 as a marker for RA, SLE, pSS and AS, yielding area under curve (AUC) values of 0.691, 0.727, 0.658 and 0.694, respectively. Conclusion: Decreased serum CTRP3 levels were associated with RA, SLE, pSS and AS.

Perioperative and mid-term outcomes of robotic-assisted versus video-assisted minimally invasive esophagectomy for esophageal cancer: a retrospective propensity-matched analysis of 842 patients.

Aim: Comparing the safety, effectiveness, and mid-term survival rates of robot-assisted minimally invasive esophagectomy (RAMIE) and video-assisted minimally invasive esophagectomy (VAMIE). Methods: A total of 842 patients undergoing minimally invasive esophagectomy were analyzed, including 694 patients in VAMIE group and 148 in RAMIE group. PSM analysis was applied to generate matched pairs for further comparison. Operative outcomes, postoperative complications and Mid-term outcomes were compared between all patients in matched groups. Results: After 1:4 PSM, 148 patients in the RAMIE and 592 patients in the VAMIE. Compared to VAMIE, RAMIE exhibited earlier removal of chest and neck drainage tubes, shorter postoperative hospital stays, and a higher number of lymph node dissections. However, the surgical duration of RAMIE was longer than that of VAMIE. Postoperative complications were no statistically significant between the RAMIE and VAMIE groups. There was no statistically significant difference in the 3-year OS and DFS between the two groups. Conclusion: Compared to VAMIE, RAMIE emerges as a viable and safe surgical approach and suggests RAMIE as a potential alternative to minimally invasive esophagectomy.

Jejunostomy feeding plus oral feeding versus intravenous nutrition plus oral feeding after esophageal cancer resection: a comparative retrospective cohort study.

Background: There are multiple choices for the nutritional management mode after esophageal cancer surgery. Currently, there is still controversy regarding which nutritional management mode has an impact on the postoperative recovery and overall survival (OS) of patients. This study aims to compare the differences between two commonly used clinical nutritional management modes: jejunostomy feeding plus oral intake (JF plus OI) and intravenous nutrition plus oral intake (IN plus OI), in terms of short-term efficacy and 3-year OS, in order to further explore the optimal mode of enteral nutrition management after esophageal cancer surgery. Methods: We evaluated esophageal cancer patients who underwent radical surgery at Union Hospital of Fujian Medical University between January 1, 2010 and January 1, 2020. The purpose of this analysis was to compare the perioperative complications, Nutritional Risk Screening 2002 (NRS2002) nutritional scores at 1 week, 2 weeks, 1 month, and 3 months after surgery, as well as the 3-year OS rates, between two different nutritional management approaches: JF plus OI and IN plus OI following esophageal cancer surgery. Results: Among the 822 patients included, 668 and 154 patients belonged to JF plus OI and IN plus OI groups, respectively. After propensity score matching, 149 patients per group were evaluated. The amount of gastric drainage fluid was higher in the IN plus OI group (P<0.05), and the incidence of postoperative gastrointestinal emptying disorder and intestinal obstruction was significantly higher in the JF plus OI group (P<0.05). The IN plus OI group had a higher incidence of perioperative hypoproteinemia (P<0.05), and a higher risk of malnutrition in 2 weeks after surgery (P<0.05). The 3-year OS was not significantly different (P>0.05). Conclusions: JF plus OI may be the preferable nutritional management approach after esophageal cancer resection as it can potentially reduce perioperative nutritional deficiency. However, attention should be paid to the risk of gastrointestinal emptying and intestinal obstruction associated with JF.

Application of predictive model based on CT radiomics and machine learning in diagnosis for occult locally advanced esophageal squamous cell carcinoma before treatment: A two-center study.

PURPOSE: Development and validation of a radiomics model for predicting occult locally advanced esophageal squamous cell carcinoma (LA-ESCC) on computed tomography (CT) radiomic features before implementation of treatment. METHODS: The study retrospectively collected 574 patients with esophageal squamous cell carcinoma (ESCC) from two medical centers, which were divided into three cohorts for training, internal and external validation. After delineating volume of interest (VOI), radiomics features were extracted and subjected to feature selection using three robust methods. Subsequently, 10 machine learning models were constructed, among which the optimal model was utilized to establish a radiomics signature. Furthermore, a predictive nomogram incorporating both clinical and radiomics signatures was developed. The performance of these models was evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis as well as measures including accuracy, sensitivity, and specificity. RESULTS: A total of 19 radiomics features were selected. The multilayer perceptron (MLP), which was found to be optimal, achieved an AUC of 0.919, 0.864 and 0.882 in the training, internal and external validation cohorts, respectively. Similarly, MLP showed good accuracy in distinguish occult LA-ESCC in subgroup of cT1-2N0M0 diagnosed by clinicians with 0.803 and 0.789 in two validation cohorts respectively. By incorporating the radiomics signature with clinical signature, a predictive nomogram demonstrated superior prediction performance with an AUC of 0.877 and accuracy of 0.85 in external validation cohort. CONCLUSION: The radiomics and machine learning model can offers improved accuracy in prediction of occult LA-ESCC, providing valuable assistance to clinicians when choosing treatment plans.

Identification of a novel prognostic cuproptosis-associated LncRNA signature for predicting prognosis and immunotherapy response in patients with esophageal cancer.

Nowadays, effective prognostic models for esophageal cancer (ESCA) are still lacking. Long noncoding RNAs (lncRNAs) are commonly utilized as indicators for diagnosing cancer and forecasting patient outcomes. Cuproptosis is regulated by multiple genes and is crucial to the progression of ESCA. However, it is not yet clear what role the cuproptosis-associated lncRNAs (CuALs) play in ESCA. To tackle this problem, a prognostic signature incorporating three CuALs was created. This signature was constructed by the use of the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression. Subsequently, the signature effectively stratified ESCA samples into a high-risk group and a low-risk group. Those in the low-risk group demonstrated extended overall survival (OS), as well as increased infiltration of T cells, macrophages, and NK cells, suggesting a potentially enhanced response to immunotherapy. The ROC curve analysis demonstrated that this prognostic signature outperformed conventional clinical factors in predicting patient prognosis (AUC = 0.708). K-M survival analysis and correlation analysis identified UGDH-AS1 (a CuAL) as a protective factor positively associated with patient prognosis. The results of RT-qPCR and wound healing assays indicated that UGDH-AS1 is overexpressed in ESCA and could inhibit cancer cell migration. In general, the prognostic signature of CuALs demonstrated a robust capability in forecasting the immune environment and patient prognosis, highlighting its potential as a tool for enhancing personalized treatment strategies in ESCA.

Association between triglyceride-glucose index trajectories and radiofrequency ablation outcomes in patients with stage 3D atrial fibrillation.

BACKGROUND: This study investigates the relationship between triglyceride-glucose (TyG) index trajectories and the results of ablation in patients with stage 3D atrial fibrillation (AF). METHODS: A retrospective cohort study was carried out on patients who underwent AF Radiofrequency Catheter Ablation (RFCA) at the Cardiology Department of the Fourth Affiliated Hospital of Zhejiang University and Taizhou Hospital of Zhejiang Province from January 2016 to December 2022. The main clinical endpoint was determined as the occurrence of atrial arrhythmia for at least 30 s following a 3-month period after ablation. Using a latent class trajectory model, different trajectory groups were identified based on TyG levels. The relationship between TyG trajectory and the outcome of AF recurrence in patients was assessed through Kaplan-Meier survival curve analysis and multivariable Cox proportional hazards regression model. RESULTS: The study included 997 participants, with an average age of 63.21 ± 9.84 years, of whom 630 were males (63.19%). The mean follow-up period for the participants was 30.43 ± 17.75 months, during which 200 individuals experienced AF recurrence. Utilizing the minimum Bayesian Information Criterion (BIC) and the maximum Entropy principle, TyG levels post-AF RFCA were divided into three groups: Locus 1 low-low group (n = 791), Locus 2 low-high-low group (n = 14), and Locus 3 high-high group (n = 192). Significant differences in survival rates among the different trajectories were observed through the Kaplan-Meier curve (P < 0.001). Multivariate Cox regression analysis showed a significant association between baseline TyG level and AF recurrence outcomes (HR = 1.255, 95% CI: 1.087-1.448). Patients with TyG levels above 9.37 had a higher risk of adverse outcomes compared to those with levels below 8.67 (HR = 2.056, 95% CI: 1.335-3.166). Furthermore, individuals in Locus 3 had a higher incidence of outcomes compared to those in Locus 1 (HR = 1.580, 95% CI: 1.146-2). CONCLUSION: The TyG trajectories in patients with stage 3D AF are significantly linked to the outcomes of AF recurrence. Continuous monitoring of TyG levels during follow-up may help in identifying patients at high risk of AF recurrence, enabling the early application of effective interventions.

Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer: A meta-analysis.

BACKGROUND: The effectiveness of neoadjuvant therapy in esophageal cancer (EC) treatment is still a subject of debate. AIM: To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) for locally advanced EC (LAEC). METHODS: A comprehensive search was conducted using multiple databases, including PubMed, EMBASE, MEDLINE, Science Direct, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Journal Database, and Chinese Biomedical Literature Database Article. Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected. RESULTS: The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival. The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate (OSR) [odds ratio (OR) = 0.95], complete response rate (OR = 3.15), and R0 clearance rate (CR) (OR = 2.25). However, nCT demonstrated a better 5-year OSR (OR = 1.02) than nCRT. Moreover, when compared to nCRT, nCT showed reduced risks of cardiac complications (OR = 1.15) and pulmonary complications (OR = 1.30). CONCLUSION: Overall, both nCRT and nCT were effective in terms of survival outcomes for LAEC. However, nCT exhibited better performance in terms of postoperative complications.

Molecular insights into the mechanisms of a leaf color mutant in Anoectochilus roxburghii by gene mapping and transcriptome profiling based on PacBio Sequel II.

Plants with partial or complete loss of chlorophylls and other pigments are frequently occurring in nature but not commonly found. In the present study, we characterize a leaf color mutant 'arly01' with an albino stripe in the middle of the leaf, which is an uncommon ornamental trait in Anoectochilus roxburghii. The albino "mutant" middle portion and green "normal" leaf parts were observed by transmission electron microscopy (TEM), and their pigment contents were determined. The mutant portion exhibited underdevelopment of plastids and had reduced chlorophyll and other pigment (carotenoid, anthocyanin, and flavonoid) content compared to the normal portion. Meanwhile, comparative transcript analysis and metabolic pathways mapping showed that a total of 599 differentially expressed genes were mapped to 78 KEGG pathways, most of which were down-regulated in the mutant portion. The five most affected metabolic pathways were determined to be oxidative phosphorylation, photosynthesis system, carbon fixation & starch and sucrose metabolism, porphyrin and chlorophyll metabolism, and flavonoid biosynthesis. Our findings suggested that the mutant 'arly01' was a partial albinism of A. roxburghii, characterized by the underdevelopment of chloroplasts, low contents of photosynthetic and other color pigments, and a number of down-regulated genes and metabolites. With the emergence of ornamental A. roxburghii in southern China, 'arly01' could become a popular cultivar due to its unique aesthetics.

Antimicrobial peptides in Dendrobium officinale: Genomic parameters, peptide structures, and gene expression patterns.

A weak codon usage bias was found in Dendrobium catenatum (D. officiale) antimicrobial peptides (AMPs), after the analysis of relative synonymous codon usage, GC contents, and the effective number of codons. The codon usage preference was mainly influenced by natural selection pressure. The self-optimized prediction method and SWISS-MODEL were applied for peptide structural and domain analyses, and some typical antimicrobial domains were found in D. officinale AMP amino sequences, such as knot1 domain, gibberellins-stimulated domain, cupin_1 domain, defensin_like domain, and SLR1-BP (S locus-related glycoprotein 1 binding pollen coat protein) domain. To investigate the AMPs gene expression pattern, abiotic stresses, such as salt stress, drought stress, salicylic acid (SA), and methyl jasmonate (JA), were applied and the gene expression levels were detected by the real-time fluorescent quantitative polymerase chain reaction. Results showed that, even though the basic AMPs gene expressions were low, some AMPs can still be induced by salt dress, while the drought dress did not show the same impact. The SA and JA signaling pathways might be involved in most of the AMPs expressions. The natural selection of the D. officinale AMPs and thus forming diverse types of AMPs enhanced the plant's innate immunity and disease resistance capability, which would lead to a better understanding of the molecular mechanism for D. officinale adapting to the environment. The finding that salt stress, SA, and JA signaling pathways can induce AMP expression lays a foundation for the further development and functional verification of D. officinale AMPs.

Perioperative outcomes of neoadjuvant immunotherapy plus chemotherapy and neoadjuvant chemoradiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective comparative cohort study.

Background: Neoadjuvant chemoradiotherapy (nCRT) is recommended as the preferred treatment for locally advanced esophageal squamous cell carcinoma. Recent studies have shown that immune checkpoint inhibitors are beneficial in treating advanced esophageal cancer. Therefore, a growing number of clinical centers are conducting trials of neoadjuvant immunotherapy or neoadjuvant immunotherapy plus chemotherapy (nICT) in patients with locally advanced resectable esophageal cancer. Immunocheckpoint inhibitors are expected to play a role in neoadjuvant therapy for esophageal cancer. However, there were few studies comparing nICT with nCRT. This study compared the efficacy and safety of nICT with that of nCRT administered prior to esophagectomy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Methods: The study included patients with locally advanced resectable ESCC who were scheduled to receive neoadjuvant therapy at Gaozhou People's Hospital from January 1, 2019, to September 1, 2022. The enrolled patients were divided into 2 groups (nCRT or nICT) according to their neoadjuvant therapy regimen. The 2 groups were compared for their baseline data, the incidence of adverse events during neoadjuvant therapy, the clinical evaluation after neoadjuvant therapy, perioperative indicators, and the incidence of postoperative complications and postoperative pathological remission. Results: A total of 44 patients were enrolled; 23 in the nCRT group and 21 in the nICT group. There were no significant differences between the 2 groups in the baseline data. In the nCRT group, leukopenia occurred more often than in the nICT group, and hemoglobin-decreasing events were rarer (P=0.03<0.05). A significantly higher proportion of patients in the nICT group experienced erythema following neoadjuvant therapy compared to the nCRT group (23.81% vs. 0%; P=0.01<0.05). Neoadjuvant therapy showed no significant difference between the 2 groups for adverse event rates, surgery-related indicators, postoperative pathological remission rates, and postoperative complications. Conclusions: nICT was a safe and feasible treatment for locally advanced ESCC and it may be a potential new treatment modality.

Characterization of the Roles of Suppressor of Cytokine Signaling-3 in Esophageal Carcinoma.

This study was aimed to analyze the diagnostic, therapeutic, and prognostic value of the suppressor of cytokine signaling 3 (SOCS3) in pancancer, especially in esophageal carcinoma (ESCA), and investigate the role of SOCS3 in the tumorigenesis and progression of ESCA. We used a variety of bioinformatics methods to explore the expression of SOCS3 in 33 kinds of cancers and evaluate its potential role in the pathogenesis, prognosis, immune microenvironment, immune evasion, and therapeutic response of cancers. The results indicated that SOCS3 was upregulated in 10 cancers, downregulated in 12 cancers, and upregulated in ESCA. Mutation and amplification were the main causes of abnormal expression of SOCS3 in pancancer. In ESCA, expression of SOCS3 was negatively correlated with methylation. The analysis showed that ESCA patients with low SOCS3 levels had better overall survival. Furthermore, the SOCS3 level was positively related to the ESTIMATE score, immune score, stromal score, and negatively related to tumor purity. In ESCA, a significant association was found between SOCS3 and several immune checkpoint genes. In addition, SOCS3 was associated with sensitivity to 59 drugs. Next, the role of SOCS3 in ESCA was investigated in ECA109, EC9706 cells, and in xenografted mouse model. SOCS3 was confirmed to be upregulated in ESCA cells. Knockdown of SOCS3 decreased the proliferation, migration, and invasion of ESCA cells while increasing apoptosis. Meanwhile, downregulation of SOCS3 activated the nuclear factor kappa-B signaling pathway and inhibited ESCA tumorigenesis in vivo. In conclusion, high SOCS3 expression is closely related to the occurrence and progression of ESCA and can be used as a therapeutic target and prognostic biomarker for ESCA.

Efficacy of sternocleidomastoid muscle flap in reducing anastomotic mediastinal/pleural cavity leak.

BACKGROUND: Anastomotic mediastinal/pleural cavity leak (AMPCL) is a life-threatening postoperative complication after esophagectomy. The objective of this study was to find a safe and effective surgical method to reduce the incidence of AMPCL. METHODS: A total of 223 patients who underwent surgery in Fujian Medical University Union Hospital from May 2020 to October 2021 were enrolled in this study. Data for preoperative and postoperative test indices, postoperative complications, perioperative treatment were collected. After using 1:1 propensity score matching (PSM) to match two cohort (caliper = 0.1), the relationship between various factors and the incidence of AMPCL were analyzed. RESULTS: 209 patients were included for further analysis in the end. There were 95 patients in the sternocleidomastoid muscle flap embedding group (intervention group) and 114 in the routine operation group (control group). There was a significant difference in mean age between two groups. Gender, age, body mass index, diabetes, American society of anesthesiologists score, preoperative neoadjuvant therapy, pathological stage were included in performing 1:1 PSM, and there were no significant differences between two groups. Median operative time was significantly less in intervention group. Anastomotic leak (AL) did not present significant difference between two groups (8 [8.6] vs. 13 [14.0], p = 0.247), however, the AMPCL in intervention group was significantly lower than control group (0 [0] vs. 6 [6.5], p = 0.029). CONCLUSIONS: The sternocleidomastoid muscle flap embedding could significantly reduce the incidence of AMPCL. This additional procedure is safe, and effective without increase in the occurrence of postoperative complications and hospital expenses.

LncRNA C9orf139 can regulate the progression of esophageal squamous carcinoma by mediating the miR-661/HDAC11 axis.

Increasing evidence has indicated that long non-coding RNAs (LncRNAs) play multiple functions in the development of cancer and function as indicators of diagnosis and prognosis. This aim of this study was to investigate the roles LncRNA C9orF139 had in the progression of esophageal squamous carcinoma (ESCC). We found C9orf139 was highly expressed in ESCC and knock down the expression of C9orf139 significantly suppressed cell proliferation, promoted apoptosis, and inhibited migration and invasion. C9orf139 was able to negatively regulate miR-661 expression. At the same time, HDAC11 expression was negatively regulated by miR-661. The C9orf139/miR-661/HDAC11 axis was further involved in regulating the expression of the NF-κB signaling pathway. The association between the C9orf139 knockdown and the reduced tumor growth and size was observed during in vivo study. C9orf139 is highly expressed in ESCC, and is thus qualified to be used as a potential diagnostic and prognostic marker for ESCC. Its promotion of ESCC progression is achieved by mediating the miR-661/HDAC11 axis.

A nomogram to predict the recurrence-free survival and analyze the utility of chemotherapy in stage IB non-small cell lung cancer.

BACKGROUND: Large part of patients of stage IB non-small cell lung cancer (IB NSCLC) may suffer recurrence after surgery. This study is to determine risk factors and establish a nomogram for postoperative recurrence and to provide a reference for adjuvant chemotherapy selection in patients with stage IB NSCLC. METHODS: A total of 394 patients with postoperative stage IB NSCLC who visited Fujian Medical University Union Hospital between January 2010 and June 2016 were selected. Patients were divided into training and validation cohorts based on the time of diagnosis. Independent risk factors were identified using a Cox proportional hazards regression model. A nomogram was created to predict recurrence-free survival (RFS) and was validated with an independent cohort. The predictive ability of the nomogram was evaluated using the concordance index (C-index) and calibration curve. RFS between the high- and low-risk groups was determined using Kaplan-Meier curves, and subgroup analysis of chemotherapy was performed. RESULTS: Visceral pleura invasion, micropapillary structures, tumor size, preoperative serum carcinoembryonic antigen (CEA) level, preoperative serum cytokeratin-19 fragments (Cyfra21-1) level, and postoperative histology were identified as independent risk factors for stage IB NSCLC recurrence. Discrimination of the nomogram showed good prognostic accuracy and clinical applicability, with a C-index of 0.827 and 0.866 in the training and validation cohorts, respectively. The difference in RFS between the high- and low-risk groups in both cohorts was significant (P<0.05). Finally, a significant difference was observed on whether high-risk group should accept postoperative chemotherapy (P<0.05). CONCLUSIONS: This nomogram can predict postoperative recurrence probability in patients with stage IB NSCLC, and can select patients with risk factors who need adjuvant chemotherapy.

Crucial Genes in Aortic Dissection Identified by Weighted Gene Coexpression Network Analysis.

BACKGROUND: Aortic dissection (AD) is a lethal vascular disease with high mortality and morbidity. Though AD clinical pathology is well understood, its molecular mechanisms remain unclear. Specifically, gene expression profiling helps illustrate the potential mechanism of aortic dissection in terms of gene regulation and its modification by risk factors. This study was aimed at identifying the genes and molecular mechanisms in aortic dissection through bioinformatics analysis. METHOD: Nine patients with AD and 10 healthy controls were enrolled. The gene expression in peripheral mononuclear cells was profiled through next-generation RNA sequencing. Analyses including differential expressed gene (DEG) via DEGseq, weighted gene coexpression network (WGCNA), and VisANT were performed to identify crucial genes associated with AD. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was also utilized to analyze Gene Ontology (GO). RESULTS: DEG analysis revealed that 1,113 genes were associated with AD. Of these, 812 genes were markedly reduced, whereas 301 genes were highly expressed, in AD patients. DEGs were rich in certain categories such as MHC class II receptor activity, MHC class II protein complex, and immune response genes. Gene coexpression networks via WGCNA identified 3 gene hub modules, with one positively and 2 negatively correlated with AD, respectively. Specifically, module 37 was the most strongly positively correlated with AD with a correlation coefficient of 0.72. Within module 37, five hub genes (AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D) displayed high connectivity and may have clinical significance in the pathogenesis of AD. CONCLUSION: Our analysis provides the possible association of specific genes and gene modules for the involvement of the immune system in aortic dissection. AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D in module M37 were highly connected and strongly linked with AD, suggesting that these genes may help understand the pathogenesis of aortic dissection.

Safety and feasibility of esophagectomy following combined neoadjuvant immunotherapy and chemotherapy for locally advanced esophageal cancer: a propensity score matching.

OBJECTIVES: This study aims to investigate the efficacy and feasibility of esophagectomy following combined neoadjuvant immunotherapy and chemotherapy for locally advanced esophageal cancer. METHODS: We retrospectively identified patients who were treated with neoadjuvant immunotherapy and chemotherapy (NICT, n = 27) or chemotherapy alone (NCT, n = 95) at our institution between January, 2017 and April, 2021. The primary end point was 30-day complications. Major complications were defined as Clavien-Dindo classification grade ≥ 3. Secondary end points were interval to surgery, operation time, postoperative thoracic drainage, thoracic drainage tube stay, 30-day readmission rate, and 30-day mortality. Propensity score matching (PSM) was used to reduce bias caused by potential confounding. RESULTS: All patients included successfully completed neoadjuvant therapy and underwent McKeown minimally invasive esophagectomy negative margins. Out of 122 eligible patients, 26 patients in NICT group and 52 patients in NCT group were identified by 1:2 PSM. After PSM, the clinical stage was matched and demographic characteristics of the two groups were well balanced, including age, gender, BMI, ASA status, age-adjusted Charlson index, smoking, drinking, chemotherapy regimens, neoadjuvant cycle, tumor location, lymphadenectomy, pathological stage, histologic sub-type, anastomotic position, route of gastric conduit, procedure type, and operative approach were comparable between groups after PSM. Although NICT group had a higher incidence of pneumonia and pleural effusion, however, the CCI index, other complication and major complications were comparable between the two groups. There were no significant differences in operation time, intraoperative blood loss, thoracic drainage tube stays, thoracic drainage volume, ICU stay, postoperative hospital stay and hospital cost. Furthermore, 30-day mortality, 30-day readmission, ICU readmission were similar in both groups. CONCLUSIONS: Based on our preliminary experience, esophagectomy is safe and feasible following combined neoadjuvant immunotherapy with chemotherapy for locally advanced esophageal cancer.

Outcomes of minimally invasive total mesoesophageal excision: a propensity score-matched analysis.

BACKGROUND: This study aimed to investigate the safety and efficacy of minimally invasive total mesoesophageal excision (TME) for esophageal cancer. METHODS: We retrospectively collected data from patients with esophageal cancer who underwent esophagectomy at our center between January 2011 and June 2017. Among 611 eligible patients, 302 underwent minimally invasive total mesoesophageal excision (the TME group) and 309 underwent non-total mesoesophageal excision (the NME group). Outcomes were compared after 1-to-1 propensity score matching, and subgroup analyses were performed for cases involving pT1-2 or pT3-4a disease. RESULTS: The propensity score matching produced 249 pairs of patients. The TME group had a shorter operative time (P < 0.001), lower intraoperative bleeding (P < 0.001), and a shorter postoperative hospital stay (P < 0.001). There were no significant differences between the two groups in the number of removed lymph nodes, 30-day mortality, or postoperative complications. In addition, both groups had similar 3-year rates of overall survival (OS) and disease-free survival (DFS). However, the 3-year recurrence rate in the esophageal bed was significantly lower in the TME group (P = 0.033). Furthermore, among patients with pT3-4a disease, the TME group had better 3-year rates of OS, DFS, and recurrence. CONCLUSION: Minimally invasive total mesoesophageal excision appears to be a safe technique that can reduce tumor recurrence in the esophageal bed. Furthermore, this technique provided survival benefits for patients with pT3-4a disease.

Neoadjuvant sintilimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, single-center, phase 2 trial (ESONICT-1).

BACKGROUND: To investigate the safety and feasibility of combining neoadjuvant sintilimab (Innovent Biologics, Suzhou, China) and chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: The study was an investigator-initiated, open-label, non-randomized, single-arm, single-center phase 2 trial. Patients aged between 18 to 75 years with locally advanced ESCC were eligible for neoadjuvant immunochemotherapy (nICT). The nICT included cisplatin (60 mg/m2) on day 1, albumin-bound paclitaxel (125 mg/m2) on days 1 and 8, and sintilimab (200 mg) on day 1 of each 21-day cycle. Clinical evaluation was conducted after 2 cycles of nICT. Within 4-6 weeks after nICT, patients underwent esophagectomy. The primary end points were pathological complete response (pCR) and adverse events (AEs). Secondary endpoints included major pathological response (MPR), R0 resection rate, interval to surgery, and 30-day complications. This trial was registered at chictr.org.cn, ChiCTR2100045659. RESULTS: From July 2020 to June 2021, 30 patients were enrolled. All patients successfully completed 2 cycles of nICT. AEs were common during nICT, and the most common AE was anorexia (20/30, 67%). However, only one patient with grade 3 ESCC had increased transaminase. According to radiologic evaluations, the objective response rate (ORR) was 67% (20/30) and the disease control rate 97% (29/30). Twenty-three patients underwent McKeown minimally invasive esophagectomy (MIE). The pCR rate of the primary tumor was 21.7%, and the MPR rate of the primary tumor was 52.2%. The median interval to surgery was 40 days, and no patients delayed surgery due to AEs. Pneumonia was the most common major 30-day postoperative complication (9/23, 39%). Anastomotic leakage (AL) occurred in two patients during the hospital stay, and one patient was readmitted due to AL. There was no treatment- or surgery-related deaths. CONCLUSIONS: Neoadjuvant sintilimab plus chemotherapy for locally advanced ESCC appears to be safe and feasible with limited AEs, high R0 resection rate, promising pCR rate, and manageable postoperative complications. Long-term follow-up is required. A multicenter, randomized, phase III clinical trial assessing the efficacy and safety of sintilimab versus placebo in combination with chemotherapy in locally advanced ESCC is warranted to confirm these results.