Modified Sistrunk Procedure in 391 Pediatric Thyroglossal Duct Cyst Cases: Clinical Analysis of Efficacy and Recurrence Risk.

Objectives: The study aims to retrospectively summarize the clinical features of pediatric thyroglossal duct cyst (TGDC), investigate the efficacy of the modified Sistrunk (mSis) procedure, and analyze the recurrence risks. Methods: The clinical data of 391 children with TGDC admitted to Beijing Children's Hospital affiliated Capital Medical University and Baoding Children's Hospital from March 2012 to December 2021 were retrospectively analyzed. All patients underwent cervical ultrasound for preoperative evaluation. Twenty cases had magnetic resonance imaging and 8 cases had computed tomography for further evaluation. All patients underwent the standard mSis procedure, and clinical manifestations information, surgical information, complications, and prognosis were analyzed. Results: Among the 391 TGDC cases, 118 (30.2%) had a history of recurrent neck infection and 36 (9.2%) had undergone previous neck cyst and fistula resection surgeries, initially diagnosed as neck cyst (22 cases), TGDC (12 cases), or branchial fistula (2 cases), with only 6 cases having undergone partial hyoid bone resection in the previous operation. During the 15 to 156 months of follow-up, 10 children experienced local wound infection, but no other complications were reported. The recurrence rate was 2.30%, and the recurrence time ranged from 0.5 to 34 (average, 7.2) months post surgery. In the Poisson regression model examining factors related to recurrence, the P values of the 3 factors were <.05: clearness of the lesion boundary, surgical history, and maximum diameter and the relative risk (RR) values corresponding to the 3 risk factors, such as Exp (B), were 27.918, 10.054, and 6.606, respectively. Conclusions: The mSis procedure demonstrated safety and efficacy with fewer complications and a low recurrence rate of 2.30% in the study. Furthermore, the indistinct lesion boundary, surgical history, and large lesion diameter (>2 cm) were independent risk factors for recurrence in pediatric TGDC.Level of Evidence: IV.

Corrosion Behavior of Nacre-Inspired (TiBw-TiB2)/Al Composites Fabricated by Freeze Casting.

Nacre-inspired metal matrix composites have received much attention due to their excellent deformation coordination ability, which can achieve the synergy of strength and ductility. The preparation of nacre-like Al matrix composites by freeze casting has been a promising application, but the continuous ceramic-rich layer affects the corrosion resistance of the composites, facing complex corrosion problems during service. In this work, the microstructure and corrosion behavior of the nacre-inspired (TiBw-TiB2)/Al composites fabricated by freeze casting and squeeze casting were systematically studied. The results indicated that the Al layers and ceramic-rich layers had little change, about 35 µm and 31 µm, respectively, with an increasing ratio of the Ti/TiB2. Meanwhile, a high Ti/TiB2 ratio resulted in an increase in the Fe-Ti intermetallic phases, which was detrimental to the corrosion performance of the composites and was prone to pitting. The electrochemical test results showed that the 3Ti7TiB2 composite had the lowest corrosion current density (15.9 µA) and intergranular corrosion depth (231 µm), indicating that it had the best corrosion resistance, which can be attributable to its stable and dense passivation film. Two different corrosion phenomena during the intergranular corrosion test existed in the present nacre-inspired (TiBw-TiB2)/Al composites: intergranular corrosion in the Al matrix layer and pitting corrosion in the ceramic-rich layer. Among all the composites, the corrosion depth of the 3Ti7TiB2 composite was the smallest and significantly less than that of the 2024Al alloy. In addition, the continuous ceramic-rich layer acted as a corrosion channel during corrosion, significantly degrading the corrosion resistance of the nacre-like Al composites.

Strength-Plasticity Relationship and Intragranular Nanophase Distribution of Hybrid (GNS + SiCnp)/Al Composites Based on Heat Treatment.

The distribution of reinforcements and interfacial bonding state with the metal matrix are crucial factors in achieving excellent comprehensive mechanical properties for aluminum (Al) matrix composites. Normally, after heat treatment, graphene nanosheets (GNSs)/Al composites experience a significant loss of strength. Here, better performance of GNS/Al was explored with a hybrid strategy by introducing 0.9 vol.% silicon carbide nanoparticles (SiCnp) into the composite. Pre-ball milling of Al powders and 0.9 vol.% SiCnp gained Al flakes that provided a large dispersion area for 3.0 vol.% GNS during the shift speed ball milling process, leading to uniformly dispersed GNS for both as-sintered and as-extruded (0.9 vol.% SiCnp + 3.0 vol.% GNS)/Al. High-temperature heat treatment at 600 °C for 60 min was performed on the as-extruded composite, giving rise to intragranular distribution of SiCnp due to recrystallization and grain growth of the Al matrix. Meanwhile, nanoscale Al4C3, which can act as an additional reinforcing nanoparticle, was generated because of an appropriate interfacial reaction between GNS and Al. The intragranular distribution of both nanoparticles improves the Al matrix continuity of composites and plays a key role in ensuring the plasticity of composites. As a result, the work hardening ability of the heat-treated hybrid (0.9 vol.% SiCnp + 3.0 vol.% GNS)/Al composite was well improved, and the tensile elongation increased by 42.7% with little loss of the strength. The present work provides a new strategy in achieving coordination on strength-plasticity of Al matrix composites.

Lipid Deficiency Contributes to Impaired Alveolar Progenitor Cell Function in Aging and Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated interstitial lung disease resulting from repeated epithelial injury and inadequate epithelial repair. Alveolar type II cells (AEC2) are progenitor cells that maintain epithelial homeostasis and repair the lung after injury. In the current study, we assessed lipid metabolism in AEC2s from human lungs of IPF patients and healthy donors, as well as AEC2s from bleomycin-injured young and old mice. Through single cell RNA sequencing (scRNA-seq), we observed that lipid metabolism-related genes were downregulated in IPF AEC2s and bleomycin-injured mouse AEC2s. Aging aggravated this decrease and hindered recovery of lipid metabolism gene expression in AEC2s after bleomycin injury. Pathway analyses revealed down-regulation of genes related to lipid biosynthesis and fatty acid -oxidation in AEC2s from IPF lungs and bleomycin-injured, aged mouse lungs compared to the respective controls. We confirmed decreased cellular lipid content in AEC2s from IPF lungs and bleomycin-injured, aged mouse lungs using immunofluorescence staining and flow cytometry. We further show that lipid metabolism was associated with AEC2 progenitor function. Lipid supplementation and peroxisome proliferator activated receptor gamma (PPARγ) activation promoted progenitor renewal capacity of both human and mouse AEC2s in 3D organoid cultures. Lipid supplementation also increased AEC2 proliferation and expression of SFTPC in AEC2s. In summary, we identified a lipid metabolism deficiency in AEC2s from lungs of patients with IPF and bleomycin-injured aged mice. Restoration of lipid metabolism homeostasis in AEC2s might promote AEC2 progenitor function and offer new opportunities for therapeutic approaches to IPF. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Transcriptomics Analysis Identifies the Decline in the AT2 Stem Cell Niche in Aged Human Lungs.

Aging poses a global public health challenge, which is linked to the rise of age-related lung diseases. The precise understanding of the molecular and genetic changes in the aging lung that elevate the risk of acute and chronic lung diseases remains incomplete. Alveolar type II (AT2) cells are stem cells that maintain epithelial homeostasis and repair the lung after injury. AT2 progenitor function decreases with aging. The maintenance of AT2 function requires niche support from other cell types, but little has been done to characterize alveolar alterations with aging in the AT2 niche. To systematically profile the genetic changes associated with age, we present a single-cell transcriptional atlas comprising nearly half a million cells from the healthy lungs of human subjects spanning various ages, sexes, and smoking statuses. Most annotated cell lineages in aged lungs exhibit dysregulated genetic programs. Specifically, the aged alveolar epithelial (AT2) cells demonstrate loss of epithelial identities, heightened inflammaging characterized by increased expression of AP-1 transcription factor and chemokine genes, and significantly increased cellular senescence. Furthermore, the aged mesenchymal cells display a remarkable decrease in Collagen and Elastin transcription and a loss of support to epithelial cell stemness. The decline of the AT2 niche is further exacerbated by a dysregulated genetic program in macrophages and dysregulated communications between AT2 and macrophages in aged human lungs. These findings highlight the dysregulations observed in both AT2 stem cells and their supportive niche cells, potentially contributing to the increased susceptibility of aged populations to lung diseases. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). For commercial usage and reprints please contact Diane Gern (dgern@thoracic.org).

Clinical Analysis of 76 Cases of Second Branchial Cleft Fistula.

Objective: To provide the experience of diagnosis and treatment of second branchial cleft fistula in children. Methods: The clinical data of 76 children with second branchial cleft fistulas admitted to Beijing Children's Hospital affiliated with Capital Medical University from January 2016 to December 2020 were retrospectively analyzed. All patients underwent cervical ultrasonography and resection of the second branchial cleft fistula, and their clinical manifestations, surgical methods, complications, recurrence condition, and lesion appearance of the patients were analyzed. Results: Among the 76 cases, the lesions of 43 cases were on the right side, 20 were on the left side, and 13 were bilateral, for a total of 89 lesions. There were 49 type I lesions, 28 type II lesions, 8 type III lesions, and 4 type IV lesions. Type I and type II cases underwent complete excision of the fistula through a small incision in the neck; 2 cases of type III branchial cleft fistulas were treated with trapezoidal incision; 2 cases of type III branchial cleft fistulas underwent single transverse incisions; single small incision-assisted endoscopic resection was adopted in 4 cases of type III and 4 cases of type IV branchial cleft fistulas. During the follow-up period of 6 to 60 months, only 3 cases developed postoperative infection, the others had no postoperative complications, and no cases had recurrence during postoperative follow-up. Conclusion: The incision of the second branchial fistula should be selected according to imaging examination to achieve removal of the fistula while maintaining esthetics.

Effect of Particle Strength on SiCp/Al Composite Properties with Network Architecture Design.

Recent works have experimentally proven that metal matrix composites (MMCs) with network architecture present improved strength-ductility match. It is envisaged that the performance of architecturally designed composites is particularly sensitive to reinforcement strength. Here, reinforcing particles with various fracture strengths were introduced in numerical models of composites with network particle distribution. The results revealed that a low particle strength (1 GPa) led to early-stage failure and brittle fracture. Nevertheless, a high particle strength (5 GPa) delayed the failure behavior and led to ductile fracture at the SiC/Al-Al macro-interface areas. Therefore, the ultimate tensile strengths (UTS) of the network SiC/Al composites increased from 290 to 385 MPa, with rising particle strength from 1 to 5 GPa. Based on the composite property, different particle fracture threshold strengths existed for homogeneous (~2.7 GPa) and network (~3.7 GPa) composites. The higher threshold strength in network composites was related to the increased stress concentration induced by network architecture. Unfortunately, the real fracture strength of the commercial SiC particle is 1-2 GPa, implying that it is possible to select a high-strength particle necessary for efficient network architecture design.

Large Cyclability of Elastocaloric Effect in Highly Porous Ni-Fe-Ga Foams.

Solid-state refrigeration based on elastocaloric materials (eCMs) requires reversibility and repeatability. However, the intrinsic intergranular brittleness of ferromagnetic shape memory alloys (FMSMAs) limits fatigue life and, thus, is the crucial bottleneck for its industrial applications. Significant cyclic stability of elastocaloric effects (eCE) via 53% porosity in Ni-Fe-Ga FMSMA has already been proven. Here, Ni-Fe-Ga foams (single-/hierarchical pores) with high porosity of 64% and 73% via tailoring the material's architecture to optimize the eCE performances are studied. A completely reversible superelastic behavior at room temperature (297 K) is demonstrated in high porosity (64-73%) Ni-Fe-Ga foams with small stress hysteresis, which is greatly conducive to durable fatigue life. Consequentially, hierarchical pore foam with 64% porosity exhibits a maximum reversible ∆Tad of 2.0 K at much lower stress of 45 MPa with a large COPmat of 34. Moreover, it shows stable elastocaloric behavior (ΔTad = 2.0 K) over >300 superelastic cycles with no significant deterioration. The enhanced eCE cyclability can be attributed to the pore hierarchies, which remarkably reduce the grain boundary constraints and/or limit the propagation of cracks to induce multiple stress-induced martensitic transformations (MTs). Therefore, this work paves the way for designing durable fatigue life FMSMAs as promising eCMs by manipulating the material architectures.

Accelerated First-Principles Calculations Based on Machine Learning for Interfacial Modification Element Screening of SiCp/Al Composites.

SiCp/Al composites offer the advantages of lightweight construction, high strength, and corrosion resistance, rendering them extensively applicable across various domains such as aerospace and precision instrumentation. Nonetheless, the interfacial reaction between SiC and Al under high temperatures leads to degradation in material properties. In this study, the interface segregation energy and interface binding energy subsequent to the inclusion of alloying elements were computed through a first-principle methodology, serving as a dataset for machine learning. Feature descriptors for machine learning undergo refinement via feature engineering. Leveraging the theory of machine-learning-accelerated first-principle computation, six machine learning models-RBF, SVM, BPNN, ENS, ANN, and RF-were developed to train the dataset, with the ANN model selected based on R2 and MSE metrics. Through this model, the accelerated computation of interface segregation energy and interface binding energy was achieved for 89 elements. The results indicate that elements including B, Si, Fe, Co, Ni, Cu, Zn, Ga, and Ge exhibit dual functionality, inhibiting interfacial reactions while bolstering interfacial binding. Furthermore, the atomic-scale mechanism elucidates the interfacial modulation of these elements. This investigation furnishes a theoretical framework for the compositional design of SiCp/Al composites.

Treatment of nasolabial fold rhabdomyosarcoma in children: A single-institution experience.

OBJECTIVES: To summarize the clinical characteristics and prognosis of children with nasolabial fold rhabdomyosarcoma (RMS). METHODS: Retrospective review of children treated for nasolabial fold RMS from January 2014 to September 2019. RESULTS: Of 21 patients with nasolabial fold RMS, 90.48% were alveolar subtype, in which PAX3/7-FOXO1 fusion positive accounted for 87.5%. Ten patients (47.62%) had nodals invasion. Almost all patients received comprehensive treatment (chemotherapy [100%], radiation therapy [100%], and surgery [95.24%]). The median follow-up time was 34.3 months. The 3-year overall survival (OS) and event-free survival (EFS) was 67.7% ± 14.1% and 42.1% ± 13.5%, respectively. Four patients had regional lymph node relapse (NR), all in the ipsilateral submandibular lymph node region. CONCLUSION: Majority of the patients with RMS in the nasolabial fold area were alveolar subtype and had positive PAX3/7-FOXO1 gene fusion. In addition, the nasolabial fold RMS had a high probability of regional lymph node metastasis in the submandibular area. To maintain the facial aesthetics and functions, the surgical area for nasolabial fold RMS is often very conservative and restricted. This could be one of the contributors for the poor prognosis of nasolabial fold RMS beside its worse pathological subtype and gene fusion.

Toughening of Ni-Mn-Based Polycrystalline Ferromagnetic Shape Memory Alloys.

Solid-state refrigeration technology is expected to replace conventional gas compression refrigeration technology because it is environmentally friendly and highly efficient. Among various solid-state magnetocaloric materials, Ni-Mn-based ferromagnetic shape memory alloys (SMAs) have attracted widespread attention due to their multifunctional properties, such as their magnetocaloric effect, elastocaloric effect, barocaloric effect, magnetoresistance, magnetic field-induced strain, etc. Recently, a series of in-depth studies on the thermal effects of Ni-Mn-based magnetic SMAs have been carried out, and numerous research results have been obtained. It has been found that poor toughness and cyclic stability greatly limit the practical application of magnetic SMAs in solid-state refrigeration. In this review, the influences of element doping, microstructure design, and the size effect on the strength and toughness of Ni-Mn-based ferromagnetic SMAs and their underlying mechanisms are systematically summarized. The pros and cons of different methods in enhancing the toughness of Ni-Mn-based SMAs are compared, and the unresolved issues are analyzed. The main research directions of Ni-Mn-based ferromagnetic SMAs are proposed and discussed, which are of scientific and technological significance and could promote the application of Ni-Mn-based ferromagnetic SMAs in various fields.

A transcriptional cell atlas identifies the decline in the AT2 niche in aged human lungs.

Aging poses a global public health challenge, associated with molecular and physiological changes in the lungs. It increases susceptibility to acute and chronic lung diseases, yet the underlying molecular and cellular drivers in aged populations are not fully appreciated. To systematically profile the genetic changes associated with age, we present a single-cell transcriptional atlas comprising nearly half a million cells from the healthy lungs of human subjects spanning various ages, sexes, and smoking statuses. Most annotated cell lineages in aged lungs exhibit dysregulated genetic programs. Specifically, the aged alveolar epithelial cells, including both alveolar type II (AT2) and type I (AT1) cells, demonstrate loss of epithelial identities, heightened inflammaging characterized by increased expression of AP-1 transcription factor and chemokine genes, and significantly increased cellular senescence. Furthermore, the aged mesenchymal cells display a remarkable decrease in Collagen and Elastin transcription. The decline of the AT2 niche is further exacerbated by a weakened endothelial cell phenotype and a dysregulated genetic program in macrophages. These findings highlight the dysregulation observed in both AT2 stem cells and their supportive niche cells, potentially contributing to the increased susceptibility of aged populations to lung diseases.

Myositis Ossificans of the Trapezius Muscle: A Case Report and Literature Review.

Myositis ossificans (MO) is a benign, self-limiting, and nonneoplastic lesion involving the skeletal muscle or soft tissue, rarely occurring in the head and neck. It is relatively rare in clinical practice, and it is difficult to distinguish specific cases from musculoskeletal conditions, which poses unique challenges for clinical diagnosis and treatment. We reported that a 9-year-old boy suffered from local and nontraumatic MO of the trapezius muscle. Given the rarity of this case, the present article detailed the diagnosis and treatment of this rare case and reviewed the relevant literature on MO, focusing on the clinical, pathological, and radiographic characteristics of MO. Notably, these investigations aimed to enhance clinicians' understanding of the disease and improve diagnostic accuracy.

Differences in Efficacy and Safety of Sirolimus and Sildenafil in Pediatric Lymphatic Malformations.

OBJECTIVES: To explore the differences in the efficacy and safety of oral sirolimus and sildenafil in the treatment of pediatric intractable lymphatic malformations (LMs). METHODS: From January 2014 to May 2022, we retrospectively enrolled children with intractable LMs treated with oral drugs (sirolimus or sildenafil) and divided the patients into sirolimus and sildenafil groups from Beijing Children's Hospital (BCH). Clinical features, treatment, and follow-up data were collected and analyzed. The indicators were the ratio of reduction in lesion volume pre and posttreatment, the number of patients with improved clinical symptoms, and adverse reactions to the two drugs. RESULTS: Twenty-four children in the sildenafil group and 31 children in the sirolimus group were included in the present study. The effective rate in the sildenafil group was 54.2% (13/24), with a median lesion volume reduction ratio of 0.32 (-0.23, 0.89) and clinical symptoms improved in 19 patients (79.2%). On the contrary, the effective rate in the sirolimus group was 93.5% (29/31), with a median lesion volume reduction ratio of 0.68 (0.34, 0.96), and clinical symptoms improved in 30 patients (96.8%). There were significant differences (p < 0.05) between the two groups. Regarding safety, four patients in the sildenafil group and 23 patients in the sirolimus group with mild adverse reactions were reported. CONCLUSION: Both sildenafil and sirolimus can reduce the volume of LMs and improve clinical symptoms in partial patients with intractable LMs. Sirolimus is more effective than sildenafil and the adverse reactions associated with both drugs are mild and controllable. LEVEL OF EVIDENCE: III Laryngoscope, 133:3192-3199, 2023.

Multiple Fibroblast Subtypes Contribute to Matrix Deposition in Pulmonary Fibrosis.

Progressive pulmonary fibrosis results from a dysfunctional tissue repair response and is characterized by fibroblast proliferation, activation, and invasion and extracellular matrix accumulation. Lung fibroblast heterogeneity is well recognized. With single-cell RNA sequencing, fibroblast subtypes have been reported by recent studies. However, the roles of fibroblast subtypes in effector functions in lung fibrosis are not well understood. In this study, we incorporated the recently published single-cell RNA-sequencing datasets on murine lung samples of fibrosis models and human lung samples of fibrotic diseases and analyzed fibroblast gene signatures. We identified and confirmed the novel fibroblast subtypes we reported recently across all samples of both mouse models and human lung fibrotic diseases, including idiopathic pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, and coronavirus disease (COVID-19). Furthermore, we identified specific cell surface proteins for each fibroblast subtype through differential gene expression analysis, which enabled us to isolate primary cells representing distinct fibroblast subtypes by flow cytometry sorting. We compared matrix production, including fibronectin, collagen, and hyaluronan, after profibrotic factor stimulation and assessed the invasive capacity of each fibroblast subtype. Our results suggest that in addition to myofibroblasts, lipofibroblasts and Ebf1+ (Ebf transcription factor 1+) fibroblasts are two important fibroblast subtypes that contribute to matrix deposition and also have enhanced invasive, proliferative, and contraction phenotypes. The histological locations of fibroblast subtypes are identified in healthy and fibrotic lungs by these cell surface proteins. This study provides new insights to inform approaches to targeting lung fibroblast subtypes to promote the development of therapeutics for lung fibrosis.

Effect of intercalated molybdenum atoms on structure and electrochemical properties of Mo1+xS2synthesized by hydrothermal method.

As an alternative anode to graphene, molybdenum disulfide (MoS2) has attracted much attention due to its layered structure and high specific capacity. Moreover, MoS2can be synthesized by hydrothermal method with low cost and the size of its layer spacing can be controlled. In this work, the results of experiment and calculation proved that the presence of intercalated Mo atoms, leading to the expansion of MoS2layer spacing and weakening of Mo-S bonding. For the electrochemical properties, the presence of intercalated Mo atoms causes the lower reduction potentials for the Li+intercalation and Li2S formation. In addition, the effective reduction of diffusion resistance and charge transfer resistance in Mo1+xS2leads to the acquisition of high specific capacity for battery applications.

Realization of thousand-second improved confinement plasma with Super I-mode in Tokamak EAST.

Mastering nuclear fusion, which is an abundant, safe, and environmentally competitive energy, is a great challenge for humanity. Tokamak represents one of the most promising paths toward controlled fusion. Obtaining a high-performance, steady-state, and long-pulse plasma regime remains a critical issue. Recently, a big breakthrough in steady-state operation was made on the Experimental Advanced Superconducting Tokamak (EAST). A steady-state plasma with a world-record pulse length of 1056 s was obtained, where the density and the divertor peak heat flux were well controlled, with no core impurity accumulation, and a new high-confinement and self-organizing regime (Super I-mode = I-mode + e-ITB) was discovered and demonstrated. These achievements contribute to the integration of fusion plasma technology and physics, which is essential to operate next-step devices.

Surgical Experiences of Pediatric Cervical Bronchogenic Cysts: A Case Series of 6 Patients.

OBJECTIVES: Bronchogenic cyst is a rare congenital disease which occurs especially in the neck region. This report presents 6 cases of bronchogenic cysts and discusses the diagnosis and surgical experience of this anomaly. METHODS: A retrospective study of 6 pediatric patients with cervical bronchogenic cysts treated in our hospital during 2016 to 2019 was performed. We recorded and analyzed the clinical data of the patients, including age, symptoms, imaging findings, surgical procedure, and complications. RESULTS: All patients underwent surgical excision. The chondroid tissues were found at the base of cysts which clung to the trachea in 5 patients and completely removed by surgery without recurrence. One patient showed recurrence due to residual cartilage after the first surgery, and the second surgery was required to resect the remaining cartilage. During the surgery, the recurrent laryngeal nerve (RLN) detector was used, which confirmed that all the RLNs clung to the side wall of cysts. All cases were cured without complications. CONCLUSIONS: Although rare, bronchogenic cysts should be considered in the differential diagnosis of peritracheal masses in children. Complete resection of the bronchogenic cysts, including the cartilages at the base, is vital in preventing recurrence. The RLN must be protected during the surgery.

Molecular features and evolutionary trajectory of ASCL1+ and NEUROD1+ SCLC cells.

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer without recognised morphologic or genetic heterogeneity. Based on the expression of four transcription factors, ASCL1, NEUROD1, POU2F3, and YAP1, SCLCs are classified into four subtypes. However, biological functions of these different subtypes are largely uncharacterised. METHODS: We studied intratumoural heterogeneity of resected human primary SCLC tissues using single-cell RNA-Seq. In addition, we undertook a series of in vitro and in vivo functional studies to reveal the distinct features of SCLC subtypes. RESULTS: We identify the coexistence of ASCL1+ and NEUROD1+ SCLC cells within the same human primary SCLC tissue. Compared with ASCL1+ SCLC cells, NEUROD1+ SCLC cells show reduced epithelial features and lack EPCAM expression. Thus, EPCAM can be considered as a cell surface marker to distinguish ASCL1+ SCLC cells from NEUROD1+ SCLC cells. We further demonstrate that NEUROD1+ SCLC cells exhibit higher metastatic capability than ASCL1+ SCLC cells and can be derived from ASCL1+ SCLC cells. CONCLUSIONS: Our studies unveil the biology and evolutionary trajectory of ASCL1+ and NEUROD1+ SCLC cells, shedding light on SCLC tumourigenesis and progression.