Exceptionally Fast Separation of Xylene Isomers with Zeolitic Nanotube Array Membranes.

The separation of xylene isomers is of vital importance in chemical industry but remains challenging due to their similar structure and overlapping physiochemical properties. Membrane-based separations using the zeolite MFI, graphene oxide, and metal-organic frameworks have been intensively studied for this application, but the performance is limited by the well-known rule that the filtrate permeance scales inversely with the membrane thickness. We propose a novel membrane design that is capable of breaking this rule, based on an array of recently discovered zeolite nanotubes. Each zeolite nanotube possesses a 3.6-nm-wide central channel, connecting to dense, uniform 0.8-nm-wide holes on its wall that act as selective pores. Comprehensive molecular dynamics simulations show that this membrane exhibits permeance exceeding current state-of-the-art membranes by at least an order of magnitude while simultaneously maintaining an acceptable selectivity. In particular, a thicker membrane featuring longer zeolite nanotubes exhibits a higher permeance due to the presence of more selective pores. The proposed membrane design is expected to be broadly applied to other gas separations and even desalination as long as zeolitic nanotubes with customized pores are available.

A Comparison of Clinicopathologic Outcomes and Patterns of Lymphatic Spread Across Neoadjuvant Chemotherapy, Neoadjuvant Chemoradiotherapy, and Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) is recommended as the treatment standard for locally advanced esophageal squamous cell carcinoma (ESCC). The use of immunotherapy in the neoadjuvant setting has gained attention. Multiple, clinical trials have explored the efficacy and safety of neoadjuvant immunochemotherapy (NICT). We evaluated the differences in clinicopathologic outcomes and the patterns of lymphatic spread among patients receiving neoadjuvant chemotherapy (NCT), NCRT, and NICT before esophagectomy for locally advanced ESCC. METHODS: A total of 702 patients with ESCC who completed transthoracic esophagectomy followed neoadjuvant therapy were included. Pathological characteristics, including pathologic complete response (pCR), tumor regression grade (TRG) score and patterns of lymphatic spread, were evaluated. RESULTS: Compared with the NCT group, the NCRT group and NICT group had an advantage in pathological response (P < 0.05). The pCR rate was 8.1% in the NCT group, 29.9% in the NCRT group, and 23.6% in the NICT group. The TRG score (P < 0.05) and pathologic T stage (P < 0.05) in the NCT group were significantly higher. Compared with NICT, NCRT can significantly reduce the rate of lymph node metastasis rate in station 1R (0 vs. 3.4%, P < 0.05) and 2R (1.1% vs. 6.8%, P < 0.05). Subgroup analysis according to the tumor location distribution showed that NICT group had higher lymph node metastasis rate in station 2R (9.1%) in middle thoracic cases (P < 0.05) and in station 18 (7.5%) (P < 0.05) in lower thoracic cases. CONCLUSIONS: NCRT or NICT followed by surgery may result in a promising pCR rate and show a better performance in therapeutic response of primary lesion. For patients with lymph node metastasis in station 1R and 2R, NCRT should be the optimal preoperative treatment strategy.

Proton Coulomb Blockade Effect Involving Covalent Oxygen-Hydrogen Bond Switching.

Instead of the canonical Grotthuss mechanism, we show that a knock-on proton transport process is preferred between organic functional groups (e.g., -COOH and -OH) and adjacent water molecules in biological proton channel and synthetic nanopores through comprehensive quantum and classical molecular dynamics simulations. The knock-on process is accomplished by the switching of covalent O─H bonds of the functional group under externally applied electric fields. The proton transport through the synthetic nanopore exhibits nonlinear current-voltage characteristics, suggesting an unprecedented proton Coulomb blockade effect. These findings not only enhance the understanding of proton transport in nanoconfined systems but also pave the way for the design of a variety of proton-based nanofluidic devices.

Probing ion binding in the selectivity filter of the Cav1.1 channel with molecular dynamics.

Cav1.1 is the voltage-gated calcium channel essential for the contraction of skeletal muscles upon membrane potential changes. Structural determination of the Cav1.1 channel opens the avenue toward understanding of the structure-function relationship of voltage-gated calcium channels. Here, we show that there exist two Ca2+-binding sites, termed S1 and S2, within the selectivity filter of Cav1.1 through extensive molecular dynamics simulations on various initial ion arrangement configurations. The formation of both binding sites is associated with the four Glu residues (Glu292/614/1014/1323) that constitute the so-called EEEE locus. At the S1 site near the extracellular side, the Ca2+ ion is coordinated with the negatively charged carboxylic groups of these Glu residues and of the Asp615 residue either in a direct way or via an intermediate water molecule. At the S2 site, Ca2+ binding shows two distinct states: an upper state involving two out of the four Glu residues in the EEEE locus and a lower state involving only one Glu residue. In addition, there exist two recruitment sites for Ca2+ above the entrance of the filter. These findings promote the understanding of mechanism for ion permeation and selectivity in calcium channels.

Field-Induced Hydration Shell Reorganization Enables Electro-osmotic Flow in Nanochannels.

Electro-osmotic flow is the motion of fluid driven by an applied electric field, for which an electric double layer near a charged surface is deemed essential. Here, we find that electro-osmotic flow can occur in electrically neutral nanochannels in the absence of definable electric double layers through extensive molecular dynamics simulations. An applied electric field is shown to cause an intrinsic channel selectivity between cations and anions, by reorienting the hydration shells of these confined ions. The ion selectivity then results in a net charge density in the channel that induces the unconventional electro-osmotic flow. The flow direction is amenable to manipulation by the field strength and the channel size, which will inform ongoing efforts to develop highly integrated nanofluidic systems capable of complex flow control.

Changes in esophagus interstitial cells of Cajal in response to acute stress.

BACKGROUND: Thoracic trauma is common, and traffic accident-related traumatic injury can cause acute stress leading to esophageal motility disorders. Interstitial cells of Cajal (ICCs) are regarded as gastrointestinal pacemaker cells. AIM: This study explored the mechanism underlying changes in lower esophagus ICCs under acute stress conditions. METHODS: Fifty adult rabbits, randomly divided into one healthy control and four study groups, were subjected to right chest puncture using a Hopkinson bar. Thereafter, one group was immediately subjected to lower esophagectomy, whereas the other three groups were maintained for 24, 48 and 72 h after puncture and subjected to lower esophagectomy. Immunohistochemistry was used to detect ICC distribution, morphology and density, and TUNEL assays were used to determine ICC apoptosis. Enzyme-linked immunosorbent assays (ELISAs) were used to measure cortisol, epinephrine, dopamine, IL-9, cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). Western blotting and RT-PCR were performed to detect changes in SCF/c-kit and nNOS pathways. RESULTS: After puncture, lung tissue was hemorrhaged, alveoli in puncture areas were destroyed, esophageal pH was decreased, and serum cortisol, epinephrine and dopamine levels increased. ICC numbers increased and apoptotic ICCs decreased in all stress groups after puncture (all p < .01). IL-9, CCK and VIP levels in lower esophagus tissue were increased after puncture (all p < .01). Moreover, SCF/c-kit and nNOS pathways were upregulated in response to stress (all p < .01). CONCLUSIONS: Acute stress promotes increases in lower esophageal ICCs that might affect esophagus ICC functions and esophageal motility.

Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation.

OBJECTIVE: Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma (ESCC), but local recurrence is the main cause of treatment failure. The changes in apoptosis and autophagy in recurrent tumors of patients with ESCC following dCRT have been poorly estimated. Thus, this study aimed to investigate the expressions of key regulators of apoptosis and autophagy in matched paired samples of primary and recurrent ESCC. METHODS: The medical records of patients with locally advanced ESCC who developed local recurrence after dCRT were reviewed, and the expression profiling of apoptosis-related genes, cell apoptosis, autophagy and autophagy-related proteins were detected in normal esophageal squamous epithelium and paired samples of primary and recurrent ESCC. RESULTS: A total of 126 patients were enrolled, and 52.4% of them had stage III disease. The 1-, 3- and 5-year local recurrence-free survival (LRFS) rates were 54.8, 19.8 and 14.3%, respectively, with a median LRFS of 13.0 months. Patients with T2 tumor or stage II disease showed a significantly prolonged LRFS compared with that of patients with T3-4 tumor or stage III disease. The Apoptotic Machinery key genes expression profiling identified 5 upregulated and 7 downregulated apoptosis-related genes in recurrent tumors compared with their expression levels in the matched primary ESCC tumors. High expression of CD40, TRAF4 and BCL2A1, and low expression of CARD6 and TNFRSF21 were associated with increased risk of early local recurrence after dCRT. No differences in apoptotic index between primary and recurrent samples were detected. However, typical morphological features of autophagosomes and elevated LC3-II protein expression were detected in recurrent tumor samples, and positive LC3-II expression was correlated with increased risk of early local recurrence. CONCLUSION: Our findings indicated that apoptosis and autophagy dysfunction correlated with early local recurrence in patients with locally advanced ESCC receiving dCRT. Further studies are necessary to understand the biology of tumor recurrence in esophageal cancer.

Edge premelting of two-dimensional ices.

The surface of a three-dimensional ice crystal naturally has a quasi-liquid layer (QLL) at temperatures below its bulk melting point, due to a phenomenon called surface premelting. Here, we show that the edges of a two-dimensional (2D) bilayer hexagonal ice adsorbed on solid surfaces undergo premelting as well, resulting in the formation of quasi-liquid bands (QLBs) at the edges. Our extensive molecular dynamics simulations show that the QLB exhibits structure and dynamics indistinguishable from the bilayer liquid phase, acting as a lower-dimensional analog of the QLL on the bulk ice. We further find that at low temperatures, the width of the QLBs at armchair-type edges of the 2D ice is almost identical to that at zigzag-type edges but becomes far greater than the latter at temperatures near the melting point. The chirality-dependent edge premelting of 2D ices should add an important new ingredient to the heterogeneity of premelting.

The impact of acute stress disorder on gallbladder interstitial cells of Cajal.

Physical and psychological stress exerts a substantial effect on gastrointestinal motility disorders, where trauma enhances symptoms of digestive dysfunction. Interstitial cells of Cajal (ICCs) act as pacemakers for gastrointestinal motility regulation and are likely important in stress-associated gastrointestinal motility disorders. This study explored the mechanisms underlying gallbladder ICCs function under acute stress conditions using a rabbit chest puncture and cholecystectomy model. The stem cell factor (SCF)/c-kit pathway is essential for the development of ICCs, and gene expression was investigated to identify stress-induced transcriptional alterations. Immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling assays were used to determine ICCs apoptosis, whereas western blot analysis and reverse-transcription polymerase chain reaction were used to detect changes in the SCF/c-kit signaling pathway. These methods revealed a reduction in ICCs via apoptosis following stress, and ICCs increased over time after stressor removal. Therefore, this study demonstrates the impact of stress on ICCs development and survival and further confirms the link between stress and gastrointestinal motility.

Neutrophils injure gallbladder interstitial Cajal-like cells in a guinea pig model of acute cholecystitis.

Acute cholecystitis is a common disease with gallbladder dysmotility. Disease pathogenesis involves immune cell infiltration as well as changes in gallbladder interstitial Cajal-like cells (ICLCs). However, it remains unclear if or how the immune cells affect ICLC morphology, density, distribution, and function in gallbladder tissue during acute cholecystitis. In this study, we explored the acute cholecystitis-related alterations in gallbladder ICLCs in a guinea pig model, focusing on the effects of neighboring neutrophils. Adult guinea pigs were randomly divided into four groups (control, 24 hr common bile duct ligation [CBDL], 48-hr CBDL, and antipolymorphonuclear neutrophil [PMN] treated) and analyzed using methylene blue staining and immunofluorescence. Gallbladder contractility was also monitored. To culture gallbladder ICLCs, collagenase digestion was performed on tissue from 10- to 15-day-old guinea pigs. Neutrophils isolated from the peripheral blood of experimental animals 48-hr postsurgery were also cocultured with the gallbladder ICLCs. Intracellular calcium was detected with Fluo-4 AM dye. Our results showed that gallbladder ICLC density significantly declined during acute cholecystitis and was accompanied by shortening of the cellular processes and damage to their network-like structure. However, pretreatment with anti-PMN partially prevented these changes. Gallbladder contraction was also significantly decreased during acute cholecystitis, and this appeared to be mediated by the neutrophils. Moreover, ICLCs cocultured with neutrophils also had shortened and reduced processes and impaired network-like structure formation. Intracellular calcium transient was less sensitive to contraction agonists and inhibitors when cocultured with neutrophils. Taken together, neutrophils greatly affect gallbladder ICLCs and dysmotility during acute cholecystitis.

Identification of Essential Sensitive Regions of the Aerolysin Nanopore for Single Oligonucleotide Analysis.

The aerolysin nanopore channel is one of the confined spaces for single molecule analysis which displays high spatial and temporal resolution for the discrimination of single nucleotides, identification of DNA base modification, and analyzing the structural transition of DNAs. However, to overcome the challenge of achieving the ultimate goal of the widespread real analytical application, it is urgent to probe the sensing regions of the aerolysin to further improve the sensitivity. In this paper, we explore the sensing regions of the aerolysin nanopore by a series of well-designed mutant nanopore experiments combined with molecular dynamics simulations-based electrostatic analysis. The positively charged lumen-exposed Lys-238, identified as one of the key sensing sites due to the presence of a deep valley in the electrostatic potentials, was replaced by different charged and sized amino acids. The results show that the translocation time of oligonucleotides through the nanopore can be readily modulated by the choice of the target amino acid at the 238 site. In particular, a 7-fold slower translocation at a voltage bias of +120 mV is observed with respect to the wild-type aerolysin, which provides a high resolution for methylated cytosine discrimination. We further determine that both the electrostatic properties and geometrical structure of the aerolysin nanopore are crucial to its sensing ability. These insights open ways for rationally designing the sensing mechanism of the aerolysin nanopore, thus providing a novel paradigm for nanopore sensing.

Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis.

BACKGROUND/AIMS: Acute cholecystitis is a common gastrointestinal disorder, often characterized by acute cholecystitis with gallbladder motility disorder. Interstitial cells of Cajal (ICCs) are the pacemaker cells of gut motility in the gastrointestinal tract. Disruption of ICC function is related to motility disorders. The aim of this study was to explore the cellular and molecular mechanisms of ICCs in acute cholecystitis and after the resolution of acute inflammation. MATERIALS AND METHODS: Fifty adult guinea pigs were randomly divided into five groups: a sham-administered group (control group); two groups that were intraperitoneally administered an anti-polyclonal neutrophil (PMN) antibody 24 h before common bile duct ligation (CBDL); and two groups of guinea pigs that were subjected to CBDL without receiving the PMN antibody. Guinea pigs that underwent CBDL were held for 24 h or 48 h after surgery before being subjected to laparotomy and cholecystectomy. Immunohistochemistry, TUNEL assays, western blotting, and real-time PCR were performed to determine ICC morphology and density, to detect ICC apoptosis, and to examine stem cell factor (SCF) and c-kit protein expression and SCF and c-kit mRNA levels, respectively. RESULTS: Both hematoxylin-eosin staining and histological inflammation scores in the PMN groups were lower than those in the control groups (P < 0.01). No differences were observed in ICC morphology between groups. During acute cholecystitis, ICCs numbers were reduced. Conversely, the density of ICCs increased after inflammation was relieved (P < 0.01). In addition, SCF and c-kit protein and mRNA expression levels decreased during acute cholecystitis (P < 0.05) and increased after inflammation was relieved (P < 0.05). Furthermore, ICC apoptosis increased during acute cholecystitis and decreased after resolution of acute cholecystitis (P < 0.01). CONCLUSIONS: In acute cholecystitis, ICC injury may be related to gallbladder motility disorder.

Geometrical Effect in 2D Nanopores.

A long-standing problem in the application of solid-state nanopores is the lack of the precise control over the geometry of artificially formed pores compared to the well-defined geometry in their biological counterpart, that is, protein nanopores. To date, experimentally investigated solid-state nanopores have been shown to adopt an approximately circular shape. In this Letter, we investigate the geometrical effect of the nanopore shape on ionic blockage induced by DNA translocation using triangular h-BN nanopores and approximately circular molybdenum disulfide (MoS2) nanopores. We observe a striking geometry-dependent ion scattering effect, which is further corroborated by a modified ionic blockage model. The well-acknowledged ionic blockage model is derived from uniform ion permeability through the 2D nanopore plane and hemisphere like access region in the nanopore vicinity. On the basis of our experimental results, we propose a modified ionic blockage model, which is highly related to the ionic profile caused by geometrical variations. Our findings shed light on the rational design of 2D nanopores and should be applicable to arbitrary nanopore shapes.

Insertion of Neurotransmitters into a Lipid Bilayer Membrane and Its Implication on Membrane Stability: A†Molecular Dynamics Study.

The signaling molecules in neurons, called neurotransmitters, play an essential role in the transportation of neural signals, during which the neurotransmitters interact with not only specific receptors, but also cytomembranes, such as synaptic vesicle membranes and postsynaptic membranes. Through extensive molecular dynamics simulations, the atomic-scale insertion dynamics of typical neurotransmitters, including methionine enkephalin (ME), leucine enkephalin (LE), dopamine (DA), acetylcholine (ACh), and aspartic acid (ASP), into lipid bilayers is investigated. The results show that the first three neurotransmitters (ME, LE, and DA) are able to diffuse freely into both 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) membranes, and are guided by the aromatic residues Tyr and Phe. Only a limited number of these neurotransmitters are allowed to penetrate into the membrane, which suggests an intrinsic mechanism by which the membrane is protected from being destroyed by excessive inserted neurotransmitters. After spontaneous insertion, the neurotransmitters disturb the surrounding phospholipids in the membrane, as indicated by the altered distribution of components in lipid leaflets and the disordered lipid tails. In contrast, the last two neurotransmitters (ACh and ASP) cannot enter the membrane, but instead always diffuse freely in solution. These findings provide an understanding at the atomic level of how neurotransmitters interact with the surrounding cytomembrane, as well as their impact on membrane behavior.

Effect of Neutrophils on Gallbladder Interstitial Cajal-Like Cells in Guinea Pig Model of Acute Cholecystitis.

BACKGROUND: Acute cholecystitis is a common condition in gallbladder motility disorder. Interstitial Cajal-like cells (ICLCs) in the gallbladder are known as one of the players in the complex motility mechanisms affecting gallbladder motility. AIM: This study explored morphological symptoms and molecular mechanisms underlying gallbladder ICLC changes induced by acute cholecystitis. MATERIALS AND METHODS: Fifteen adult guinea pigs were randomly divided into 3 groups: sham-operated group (healthy controls) and 2 experimental groups wherein these guinea pigs were subjected to common bile duct ligation to induce acute cholecystitis. Neutrophils were isolated from the peripheral blood of sham-operated animals and from the experimental animals at 24 and 48 h after surgery, and co-cultured with gallbladder ICLCs. The morphology of gallbladder ICLCs was examined by laser confocal immunofluorescence microscopy, TUNEL assay was used to detect apoptosis, and western blot and real-time PCR were performed to detect stem cell factor (SCF) and c-kit protein and mRNA expression, respectively. RESULTS: No morphological differences in the gallbladder ICLCs were observed between single-culture and co-culture with healthy control neutrophil groups. However, the ICLCs in all co-culture groups with acute inflammation were impaired. In the co-culture groups, the rate of ICLC apoptosis was significantly higher than that in the single-culture group. SCF and c-kit protein and mRNA expression levels decreased in all co-culture groups as well. CONCLUSION: We demonstrated that the neutrophils are involved in gallbladder ICLC injury in acute cholecystitis cases and associated with gallbladder motility disorder.

The Role of Interstitial Cells of Cajal in Acute Cholecystitis in Guinea Pig Gallbladder.

BACKGROUND/AIMS: Acute cholecystitis is common in gallbladder motility disorder. Interstitial cells of Cajal (ICCs) in the gallbladder are involved in the regulation of gallbladder motility. The aim of this study was to explore the change of gallbladder ICCs in acute cholecystitis. METHODS: Thirty adult guinea pigs were randomly divided into 3 groups: a sham-operated group (healthy controls) and 2 study groups. The animals in the study group were subjected to bile duct ligation and then to laparotomy and cholecystectomy at 24 and 48 hours after surgery. Immunohistochemistry, immunohistofluorescence, and laser confocal microscopy were performed to observe the shape, size, morphology, and density of gallbladder ICCs. Western blot and real-time PCR were performed to detect stem cell factor and c-kit protein and mRNA expression, respectively. RESULTS: There were no differences in the shape, size, and morphology of the gallbladder ICCs in the control and the two acute cholecystitis groups. Density of gallbladder ICCs, SCF level, and c-kit protein and mRNA expression all decreased in the acute cholecystitis groups. Further, SCF level and c-kit protein and mRNA expression decreased with progress of acute cholecystitis (all P < 0.05). CONCLUSION: Acute cholecystitis can decrease ICCs through repression of SCF and c-kit expression and that ICCs loss play a role in acute cholecystitis.

Intrinsic Stepwise Translocation of Stretched ssDNA in Graphene Nanopores.

We investigate by means of molecular dynamics simulations stretch-induced stepwise translocation of single-stranded DNA (ssDNA) through graphene nanopores. The intrinsic stepwise DNA motion, found to be largely independent of size and shape of the graphene nanopore, is brought about through alternating conformational changes between spontaneous adhesion of DNA bases to the rim of the graphene nanopore and unbinding due to mechanical force or electric field. The adhesion reduces the DNA bases' vertical conformational fluctuations, facilitating base detection and recognition. A graphene membrane shaped as a quantum point contact permits, by means of transverse electronic conductance measurement, detection of the stepwise translocation of the DNA as predicted through quantum mechanical Green's function-based transport calculations. The measurement scheme described opens a route to enhance the signal-to-noise ratio not only by slowing down DNA translocation to provide sufficient time for base recognition but also by stabilizing single DNA bases and, thereby, reducing thermal noise.

High-Resolution and Low-Noise Single-Molecule Sensing with Bio-Inspired Solid-State Nanopores.

Solid-state nanopores have been extensively explored as single-molecule sensors, bearing the potential for the sequencing of DNA. Although they offer advantages in terms of high mechanical robustness, tunable geometry, and compatibility with existing semiconductor fabrication techniques in comparison with their biological counterparts, efforts to sequence DNA with these nanopores have been hampered by insufficient spatial resolution and high noise in the measured ionic current signal. Here we show that these limitations can be overcome by the use of solid-state nanopores featuring a thin, narrow constriction as the sensing region, inspired by biological protein nanopores that have achieved notable success in DNA sequencing. Our extensive molecular dynamics simulations show that these bio-inspired nanopores can provide high spatial resolution equivalent to 2D material nanopores and, meanwhile, significantly inhibit noise levels. A theoretical model is also provided to assess the performance of the bio-inspired nanopore, which could guide its design and optimization.

Comparison of long-term survival of neoadjuvant therapy plus surgery versus upfront surgery and the role of adjuvant therapy for T1b-2N0-1 esophageal cancer: a population study of the SEER database and Chinese cohort.

BACKGROUND: For stage T1b-2N0-1 esophageal cancer, the impact of neoadjuvant therapy plus surgery (NS), surgery alone (SA), and surgery plus adjuvant therapy (ST) on cancer-specific survival (CSS) and overall survival (OS) is uncertain. METHODS: Stage T1b-2N0-1 esophageal cancer patients from the SEER database and two Chinese cancer centers were included in this study. The Kaplan-Meier method was used to plot survival curves, which were compared using the log-rank test. Propensity score matching was used to equalize differences between the groups. Cox proportional hazards regression models were used to analyze prognostic factors. A nomogram for OS was developed after screening the variables using the Cox proportional hazards regression model and the least absolute shrinkage and selection operator. The performance of the nomogram was assessed by the Harrell concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic curve, calibration plots, and decision curve analysis. RESULTS: After propensity score matching analysis, the 3-year CSS and OS rates in the NS group compared to the SA group were 80.3% versus 62.1% (P=0.016) and 75.8% versus 55.5% (P=0.006), the 3-year CSS and OS rates in the NS group compared to the ST group were 71.3% versus 68.3% (P=0.560) and 69.8% versus 62.9% (P=0.330), the 3-year CSS and OS rates in the SA group compared to the ST group were 54.6% versus 66.7% (P=0.220) and 50.2% versus 57.9% (P=0.290), respectively. The predictive nomogram for OS in T1b-2N0-1 patients ultimately incorporated five clinicopathological variables: T stage, N stage, age, examined lymph nodes , and therapy modality. The nomogram C-index for predicting OS was 0.648, 0.663, and 0.666 in the training group, external validation group-1, and external validation group-2, respectively. The 1-, 3-, and 5-year predicted AUC values of the OS prediction model were 0.659, 0.639, and 0.612 for the training group, and 0.786, 0.758, and 0.692 for validation group-1, and 0.805, 0.760, and 0.693 for validation group-2, respectively. CONCLUSION: For patients with stage T1b-2N0-1 esophageal cancer, neoadjuvant therapy significantly improves prognosis compared to surgery alone, those presenting with positive lymph nodes after upfront surgery can achieve survival benefits from adjuvant therapy.