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1.
Heliyon ; 10(9): e30277, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707466

ABSTRACT

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.

2.
Cardiovasc Diabetol ; 23(1): 121, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38581024

ABSTRACT

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.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Male , Humans , Middle Aged , Aged , Female , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Atrial Fibrillation/etiology , Retrospective Studies , Bayes Theorem , Treatment Outcome , Risk Factors , Catheter Ablation/adverse effects , Catheter Ablation/methods , Recurrence
3.
World J Gastrointest Oncol ; 16(1): 214-233, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38292844

ABSTRACT

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.

4.
Sci Rep ; 13(1): 22751, 2023 12 20.
Article in English | MEDLINE | ID: mdl-38123722

ABSTRACT

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.


Subject(s)
Chlorophyll , Gene Expression Profiling , Chlorophyll/metabolism , Chromosome Mapping , Flavonoids/metabolism , Plant Leaves/metabolism , Transcriptome , Gene Expression Regulation, Plant , Color
5.
Plant Genome ; 16(3): e20348, 2023 09.
Article in English | MEDLINE | ID: mdl-37194434

ABSTRACT

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.


Subject(s)
Dendrobium , Dendrobium/genetics , Dendrobium/metabolism , Antimicrobial Peptides , Genes, Plant , Genomics , Salicylic Acid/metabolism , Gene Expression
6.
J Thorac Dis ; 15(3): 1279-1288, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37065590

ABSTRACT

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.

7.
Hum Gene Ther ; 34(11-12): 495-517, 2023 06.
Article in English | MEDLINE | ID: mdl-36932739

ABSTRACT

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.


Subject(s)
Carcinoma , Suppressor of Cytokine Signaling Proteins , Animals , Mice , Carcinogenesis , Carcinoma/genetics , Cytokines/metabolism , Signal Transduction , Suppressor of Cytokine Signaling Proteins/genetics , Suppressor of Cytokine Signaling Proteins/metabolism , Tumor Microenvironment/genetics , Humans
8.
Esophagus ; 20(1): 89-98, 2023 01.
Article in English | MEDLINE | ID: mdl-35900684

ABSTRACT

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.


Subject(s)
Anastomotic Leak , Esophageal Neoplasms , Humans , Anastomotic Leak/etiology , Pleural Cavity , Esophageal Neoplasms/surgery , Postoperative Complications/prevention & control , Muscles
9.
Transl Oncol ; 24: 101487, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35917643

ABSTRACT

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.

10.
Transl Lung Cancer Res ; 11(1): 75-86, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35242629

ABSTRACT

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.

11.
J Immunol Res ; 2022: 7585149, 2022.
Article in English | MEDLINE | ID: mdl-35178459

ABSTRACT

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.


Subject(s)
Aortic Dissection/genetics , Computational Biology , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Gene Regulatory Networks , Humans , Microarray Analysis
12.
Esophagus ; 19(2): 224-232, 2022 04.
Article in English | MEDLINE | ID: mdl-34988773

ABSTRACT

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.


Subject(s)
Esophageal Neoplasms , Esophagectomy , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Esophagectomy/methods , Feasibility Studies , Humans , Immunotherapy/adverse effects , Neoadjuvant Therapy/adverse effects , Postoperative Complications/etiology , Propensity Score , Retrospective Studies
13.
Surg Endosc ; 36(5): 3234-3245, 2022 05.
Article in English | MEDLINE | ID: mdl-34845550

ABSTRACT

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.


Subject(s)
Esophageal Neoplasms , Laparoscopy , Esophageal Neoplasms/pathology , Esophagectomy/methods , Humans , Laparoscopy/methods , Lymph Node Excision/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Propensity Score , Retrospective Studies , Treatment Outcome
14.
Ann Transl Med ; 9(21): 1623, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34926667

ABSTRACT

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.

15.
Medicine (Baltimore) ; 100(27): e26428, 2021 Jul 09.
Article in English | MEDLINE | ID: mdl-34232175

ABSTRACT

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common human malignancy worldwide. The tumorigenesis mechanism in ESCC is unclear. MATERIALS AND METHODS: To explore potential therapeutic targets for ESCC, we analyzed 3 microarray datasets (GSE20347, GSE38129, and GSE67269) derived from the gene expression omnibus (GEO) database. Then, the GEO2R tool was used to screen out differently expressed genes (DEGs) between ESCC and normal tissue. Gene ontology function and kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the database for annotation, visualization and integrated discovery to identify the pathways and functional annotation of DEGs. Protein-protein interaction of these DEGs was analyzed based on the search tool for the retrieval of interacting genes database and visualized by Cytoscape software. In addition, we used encyclopedia of RNA interactomes (ENCORI), gene expression profiling interactive analysis (GEPIA), and the human protein atlas to confirm the expression of hub genes in ESCC. Finally, GEPIA was used to evaluate the prognostic value of hub genes expression in ESCC patients and we estimated the associations between hub genes expression and immune cell populations (B Cell, CD8+ T Cell, CD4+ T Cell, Macrophage, Neutrophil, and Dendritic Cell) in esophageal carcinoma (ESCA) using tumor immune estimation resource (TIMER). RESULTS: In this study, 707 DEGs (including 385 upregulated genes and 322 downregulated genes) and 6 hub genes (cyclin B1 [CCNB1], cyclin dependent kinase 1 [CDK1], aurora kinase A [AURKA], ubiquitin conjugating enzyme E2C [UBE2C], cyclin A2 [CCNA2], and cell division cycle 20 [CDC20]) were identified. All of the 6 hub genes were highly expressed in ESCC tissues. Among of them, only CCNB1 and CDC20 were associated with stage of ESCC and all of them were not associated with survival time of patients. CONCLUSION: DEGs and hub genes were confirmed in our study, providing a thorough, scientific and comprehensive research goals for the pathogenesis of ESCC.


Subject(s)
Computational Biology/methods , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/metabolism , Humans , Protein Interaction Maps/genetics
16.
Biol Trace Elem Res ; 199(2): 513-526, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32557106

ABSTRACT

It remains obscure whether circulating aortic zinc (Zn) and copper (Cu) levels are associated with the progress of human abdominal aortic aneurysms (AAA). Therefore, we conducted a meta-analysis to explore this relationship. A literature search on circulating and aortic zinc and copper levels and AAA patients was conducted using online databases including PubMed, Embase, and Cochrane up to March 20, 2019. To compare Zn and Cu concentrations in AAA patients with those in aortic occlusive disease (AOD) patients or healthy aorta donors or healthy blood donors, pooled weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated. Subgroup analysis, sensitivity analysis, and meta-regression analysis were applied to explain the heterogeneity and evaluate the robustness of combined results. A total of 10 cross-sectional studies, including 252 cases and 304 controls, were used for meta-analysis. We found that circulating zinc and Zn/Cu ratio in AAA patients were significantly lower [WMD (95%CI): - 2.23 (- 4.10, - 0.36); - 0.18 (- 0.31, - 0.05), respectively] than those in non-AAA patients. Similarly, aneurysmal aorta had significantly lower zinc levels and Zn/Cu ratio [WMD (95%CI): - 9.22 (- 15.37, - 3.07); - 6.46 (- 10.14, - 2.77), respectively] than those in control group. No difference in circulating or aortic copper levels was noted between AAA patients and control group [WMD (95%CI): - 0.24 (- 2.09, 1.61); 0.30 (- 0.01, 0.61) , respectively]. Our meta-analysis suggests that zinc levels and Zn-Cu ratio, but not copper levels, may influence aneurysmal progress of AAA.


Subject(s)
Aortic Aneurysm, Abdominal , Copper , Aorta , Cross-Sectional Studies , Humans , Zinc
17.
J Cell Mol Med ; 25(1): 309-322, 2021 01.
Article in English | MEDLINE | ID: mdl-33237626

ABSTRACT

Long non-coding RNAs (lncRNAs), which are non-protein-coding transcripts, are emerging as novel biomarkers for cancer diagnosis. Their dysregulation is increasingly recognized to contribute to the development and progression of human cancers, including lung cancer. Linc00485 is a newly discovered cancer-related lncRNA; however, little is known about its role in lung cancer progression. In this study, we found that the expression of Linc00485 was significantly increased in human lung cancer tissue and associated with malignant phenotypes, including tumour-node-metastasis (TNM) stage, metastasis and relapse. Furthermore, the proliferative, migratory and invasive abilities of lung cancer cells in vitro were significantly enhanced by overexpression of Linc00485 but inhibited by its silencing. Mechanistically, Linc00485 regulated the expression of c-Myc by directly binding to miR-298; the effects of Linc00485 overexpression could be significantly reversed by a c-Myc inhibitor or small interfering RNA. Xenotransplantation experiments showed that Linc00485 silencing significantly weakened the proliferation potential of A549 cells in vivo. Overall, these findings indicate that Linc00485 overexpression down-regulates miR-298, resulting in the up-regulation of c-Myc and thereby promoting the development of lung cancer.


Subject(s)
Lung Neoplasms/metabolism , MicroRNAs/metabolism , Proto-Oncogene Proteins c-myb/metabolism , Proto-Oncogene Proteins c-myc/metabolism , A549 Cells , Female , Flow Cytometry , Gene Expression Regulation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic/physiology , Humans , Ki-67 Antigen/genetics , Ki-67 Antigen/metabolism , Lung Neoplasms/genetics , Male , MicroRNAs/genetics , Middle Aged , Neoplasm Recurrence, Local , Proto-Oncogene Proteins c-myb/genetics , Proto-Oncogene Proteins c-myc/genetics , Transplantation, Heterologous
18.
Medicine (Baltimore) ; 99(41): e22263, 2020 Oct 09.
Article in English | MEDLINE | ID: mdl-33031267

ABSTRACT

BACKGROUND: Oesophageal cancer is one of the most common malignant tumors and has been identified as one of the leading causes of cancer death worldwide. Surgery is considered to be the optimal treatment for patients with resectable oesophageal cancer. Oesophagectomy for oesophageal cancer can significantly extend the survival period of patients and provide a potential opportunity for a cure. However, there is still controversy regarding application of neck anastomotic muscle flap embedded. This systematic review and meta-analysis will be performed to determine whether the application of neck anastomotic muscle flap embedded would benefit patients more. METHODS: We will search PubMed, Web of Science, Embase, Cancerlit, the Cochrane Central Register of Controlled Trials, and Google Scholar databases for relevant clinical trials published in any language before October 1, 2020. Randomized controlled trials (RCTs), quasi-RCTs, propensity score-matched comparative studies, and prospective cohort studies of interest, published or unpublished, that meet the inclusion criteria will be included. Subgroup analysis of the type of operation, tumor pathological stage, and ethnicity will be performed. INPLASY registration number: INPLASY202080059. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: As far as we know, this study will be the first meta-analysis to compare the efficacy of the application of neck anastomotic muscle flap embedded in 3-incision radical resection of oesophageal carcinoma. Due to the nature of the disease and intervention methods, RCTs may be inadequate, and we will carefully consider inclusion in high-quality, non-RCTs, but this may result in high heterogeneity and affect the reliability of the results.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Neck Muscles/transplantation , Research Design , Surgical Flaps , Anastomosis, Surgical , Humans , Meta-Analysis as Topic , Systematic Reviews as Topic
19.
Medicine (Baltimore) ; 99(43): e22349, 2020 Oct 23.
Article in English | MEDLINE | ID: mdl-33120735

ABSTRACT

BACKGROUND: Lung cancer is one of the most common malignant tumors. Non-small cell Lung cancer (NSCLC) accounts for about 85% of the total lung cancer. For patients with resectable early NSCLC, conventional postoperative adjuvant therapy can significantly prolong the overall survival of patients and reduce the risk of tumor recurrence. With the emergence and maturity of molecular targeted therapy and immunotherapy, the strategy of postoperative chemotherapy for lung cancer patients has changed greatly. To evaluate the efficacy of postoperative chemotherapy (platinum based chemotherapy and immunotherapy) with or without radiotherapy for NSCLC patients, we will conduct a systematic review and meta-analysis of published or unpublished randomized controlled trials. METHODS: We will search Pubmed (Medline), Embase, Google Scholar, Cancerlit, and the Cochrane Central Register of Controlled Trials for related studies published without language restrictions before June 20, 2021. Two review authors will search and assess relevant studies independently. Randomized controlled trials and quasi-randomized controlled trials studies will be included. we will perform subgroup analysis in different methods of postoperative adjuvant therapy for patients with resectable early NSCLC. Because this study will be based on published or unpublished records and studies, there is no need for ethics approval. INPLASY registration number: INPLASY202080064. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will compare the efficacy of platinum chemotherapy and immunotherapy in patients with resectable early NSCLC. Since the large sample randomized trials that meet the inclusion criteria of this study may be inadequate, we will consider incorporating some high quality small sample related tests, which may lead to heterogeneity and affect the reliability of the results.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Immunotherapy , Lung Neoplasms/therapy , Platinum Compounds/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Humans , Meta-Analysis as Topic , Molecular Targeted Therapy , Research Design , Systematic Reviews as Topic
20.
Medicine (Baltimore) ; 99(36): e21453, 2020 Sep 04.
Article in English | MEDLINE | ID: mdl-32898994

ABSTRACT

To analyze the relationship between pathologic subtype and lymph node metastasis for lung adenocarcinomas of ≤3 cm diameter.We retrospectively studied 384 patients with operable lung adenocarcinomas of ≤3 cm diameter that had been radically resected by lobectomy or anatomic segmentectomy with systematic nodal dissection, at the Fujian Medical University Union Hospital between March 2014 and March 2016.Lymph node metastasis pN1 + pN2 (pN+) was found in 2 of 104 (1.9%) patients with tumor diameter ≤1.0 cm, 12 of 159 (7.5%) patients with tumor diameter >1.0 cm but ≤2.0 cm, and 35 of 121 (28.9%) patients with tumor size >2.0 cm but ≤3.0 cm (P < .01). Lymph node metastasis pN+ was found in 19 of 53 (35.8%) patients with visceral invasion pleural (VIP) and 30 of 331 (9.0%) patients without VIP (P < .05). It was also found in 16 of 51 (31.3%) patients with high serum CEA concentrations and 28 of 297 (9.4%) patients with normal concentrations (P < .05). In a multivariate analysis, tumor diameter, VIP, high serum CEA concentration, and pathologic subtype were significant risk factors. The prevalences of lymph node metastasis pN+ were: 0.0% (0/2), 0.0% (0/89), 3.2% (1/31), 16.2% (34/209), 7.7% (1/13), 46.7% (7/15), 100% (4/4), and 11.8% (2/17) for adenocarcinoma in situ (AIS); minimally invasive adenocarcinoma (MIA); predominantly lepidic (LEP), acinar (ACI), papillary, solid (SOL), and micropapillary (MIP) tumors; and variants of invasive adenocarcinoma, respectively (P < .05). For predominant SOL and MIP tumors, the prevalences of lymph node involvement were significantly higher than for the other subtypes.We have shown that lymph node metastasis in patients with tumor diameter ≤3 cm differs according to lung adenocarcinoma subtype. AIS and MIA were not associated with lymph node metastasis; therefore, systematic nodal dissection may be unnecessary. The prevalence of lymph node metastasis rate was low for LEP, suggesting that systemic lymph node sampling is sufficient. In contrast, for other pathologic subtypes, including SOL and MIP, systematic lymph node dissection should be performed.


Subject(s)
Adenocarcinoma of Lung/pathology , Lung Neoplasms/pathology , Lymphatic Metastasis/pathology , Adenocarcinoma of Lung/surgery , Female , Humans , Lung Neoplasms/surgery , Lymph Node Excision , Male , Middle Aged , Retrospective Studies
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