Electrospun L-Lysine/Amorphous Calcium Phosphate Loaded Core-Sheath Nanofibers for Managing Oral Biofilm Infections and Promoting Periodontal Tissue Repairment.

Introduction: Periodontitis, a chronic inflammatory disease prevalent worldwide, is primarily treated through GTR for tissue regeneration. The efficacy of GTR, however, remains uncertain due to potential infections and the intricate microenvironment of periodontal tissue. Herein, We developed a novel core-shell structure multifunctional membrane using a dual-drug-loaded coaxial electrospinning technique (Lys/ACP-CNF), contains L-lysine in the outer layer to aid in controlling biofilms after GTR regenerative surgery, and ACP in the inner layer to enhance osteogenic performance for accelerating alveolar bone repair. Methods: The biocompatibility and cell adhesion were evaluated through CCK-8 and fluorescence imaging, respectively. The antibacterial activity was assessed using a plate counting assay. ALP, ARS, and RT-qPCR were used to examine osteogenic differentiation. Additionally, an in vivo experiment was conducted on a rat model with acute periodontal defect and infection. Micro-CT and histological analysis were utilized to analyze the in vivo alveolar bone regeneration. Results: Structural and physicochemical characterization confirmed the successful construction of the core-shell fibrous structure. Additionally, the Lys/ACP-CNF showed strong antibacterial coaggregation effects and induced osteogenic differentiation of PDLSCs in vitro. The in vivo experiment confirmed that Lys/ACP-CNF promotes new bone formation. Conclusion: Lys/ACP-CNF rapidly exhibited excellent antibacterial activity, protected PDLSCs from infection, and was conducive to osteogenesis, demonstrating its potential application for clinical periodontal GTR surgery.

GLP1R boosts survival, migration and invasion of endometrial cancer cells and protects against ferroptotic cell death.

BACKGROUND: Despite the strong evidence concerning carcinogenic roles of glucagon-like peptide 1 receptor (GLP1R), the role of this gene in endometrial cancer (EC) remains elusive. This study investigated the properties of GLP1R on EC in vitro. METHODS: The expression of GLP1R in EC was detected by RT-qPCR, immunohistochemistry, and western blotting. Cell viability, cell cycle, apoptosis, migration, invasion and ferroptosis were assessed through CCK-8, flow cytometry, wound healing, transwell, DCFH-DA and western blotting, respectively. RESULTS: We found that GLP1R was up-regulated in EC than normal specimens. It had the highest expression in AN3CA cells. Cell viability, migration and invasion were significantly reduced, while cell cycle arrest and apoptosis were induced following GLP1R knockdown. The malignant biological behaviours of AN3CA cells were investigated when treated with exendin-4 (GLP1R agonist). Moreover, GLP1R lowered intracellular ROS level and expression of SLC7A11, and FTH1, but mitigated GPX4 expression in AN3CA cells. CONCLUSION: In a word, GLP1R was up-regulated in EC and its up-regulation facilitated the proliferative and metastatic potentials, and protected cells from ferroptosis, thereby accelerating EC progression. These data emphasised the potency of GLP1R as a therapeutic agent against EC.

Endometrial cancer (EC) is the second most common form of gynaecologic malignancy, with over 189,000 new cases and about 45,000 deaths worldwide per annum. The effects of glucagon-like peptide 1 receptor (GLP1R) in cancers such as colon and pancreatic cancers have been uncovered. However, whether GLP1R affects EC progression especially ferroptosis process remains elusive. In this study, up-regulation of GLP1R promotes the proliferative and metastatic potentials of EC cells, and protects EC cells from ferroptosis. The opposite results are observed in GLP1R knocking-down. Our study found that GLP1R may exert an oncogene function in EC cells, which can affect proliferative, migrated as well as invasive capacities of EC cells. Moreover, it protected EC cells from ferroptosis. Thus, our results expanded the understanding of the function of GLP1R protein and offered insights into the targeted treatment strategies against EC.

Differences in rice component distribution across layers and their relationship with taste.

BACKGROUND: Rice taste is closely associated with endosperm composition, which varies among different rice layers. Although clarifying the relationship between this difference and nutritional taste can guide rice breeding and cultivation practices, research on this topic is limited. RESULTS: Here, typical rice varieties having excellent and poor taste characteristics were selected to analyze the distribution characteristics and differences of their components. The varieties with excellent taste exhibited lower apparent amylose content (AAC) and protein content (PC), lesser short-chain (Fa) and long-chain (Fb3 ) amylopectin (AP) and more medium-chain (Fb1+2 ) AP, higher long-to-short chain ratio (Fa:Fb3 ), and higher nitrogen (N), magnesium (Mg) and calcium (Ca) content in layer 1 (L1) than the varieties with poor taste. Layer 2 (L2) played a key role in AAC and PC regulation in the varieties with excellent taste by reducing AAC and appropriately increasing PC, consequently improving rice taste. AP structure in layer 3 (L3) substantially affected the taste of the two types of varieties. The mineral content was the highest in L1, and increased potassium (K), Ca, and Mg content improved taste in all varieties. CONCLUSION: AAC in each layer contributes to rice taste. PC and minerals primarily act on L1 and L2, whereas AP acts on L2 and L3. Therefore, the endosperm formation process should be exploited for improving rice taste. Furthermore, key resources and cultivation should be identified and regulated, respectively, to improve rice taste. © 2023 Society of Chemical Industry.

Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10.

Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.

Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing.

Despite intensive studies in modeling neuropsychiatric disorders especially autism spectrum disorder (ASD) in animals, many challenges remain. Genetic mutant mice have contributed substantially to the current understanding of the molecular and neural circuit mechanisms underlying ASD. However, the translational value of ASD mouse models in preclinical studies is limited to certain aspects of the disease due to the apparent differences in brain and behavior between rodents and humans. Non-human primates have been used to model ASD in recent years. However, a low reproduction rate due to a long reproductive cycle and a single birth per pregnancy, and an extremely high cost prohibit a wide use of them in preclinical studies. Canine model is an appealing alternative because of its complex and effective dog-human social interactions. In contrast to non-human primates, dog has comparable drug metabolism as humans and a high reproduction rate. In this study, we aimed to model ASD in experimental dogs by manipulating the Shank3 gene as SHANK3 mutations are one of most replicated genetic defects identified from ASD patients. Using CRISPR/Cas9 gene editing, we successfully generated and characterized multiple lines of Beagle Shank3 (bShank3) mutants that have been propagated for a few generations. We developed and validated a battery of behavioral assays that can be used in controlled experimental setting for mutant dogs. bShank3 mutants exhibited distinct and robust social behavior deficits including social withdrawal and reduced social interactions with humans, and heightened anxiety in different experimental settings (n = 27 for wild-type controls and n = 44 for mutants). We demonstrate the feasibility of producing a large number of mutant animals in a reasonable time frame. The robust and unique behavioral findings support the validity and value of a canine model to investigate the pathophysiology and develop treatments for ASD and potentially other psychiatric disorders.

Identification of glycogen phosphorylase L as a potential target for lung cancer.

Traditional Chinese medicine (TCM) has been widely used for cancer treatment. Identification of anti-cancer targets of TCM is the first and principal step in discovering molecular mechanisms of TCM as well as obtaining novel targets for cancer therapy. In this study, glycogen phosphorylase L (PYGL) was identified as one of the targeted proteins for several TCMs and was upregulated in various cancer types. The expression level of PYGL was positively correlated with the stage of lung cancer and the poor prognosis of patients. Meanwhile, knockdown of PYGL significantly inhibited proliferation and migration in lung cancer cells. In addition, PYGL was associated with spindle, kinetochore, and microtubule, the cellular components that are closely related to mitosis, in lung cancer. Moreover, PYGL was more susceptible to be upregulated by 144 mutated genes. Taken together, PYGL is a potential target for lung cancer treatment and its molecular mechanism probably influences the mitotic function of cells by regulating energy metabolism.

First human case report of Crohn's disease with coexistent acute appendicitis treated by endoscopic retrograde appendicitis therapy.

Background: The coexistence of Crohn's disease (CD) and acute appendicitis (AA) is rare. In this situation, therapeutic experience is lacking and the strategy is paradoxical and intractable. Appendectomy is the gold standard for the treatment of AA whereas a nonsurgical approach is recommended for CD. Case summary: A 17-year-old boy was hospitalized for right lower abdominal pain with fever of 3 days. He had the CD for 8 years. Two years ago, he underwent surgery for anal fistula with the complication of CD. His temperature was elevated at 38.3°C at admission. On physical examination, there was McBurney tenderness with mild rebound tenderness. Abdominal ultrasonography showed that the appendix was notably enlarged and dilated at 6.34 cm long and 2.76 cm wide. These findings were suggestive of uncomplicated AA in this patient with active CD. Endoscopic retrograde appendicitis therapy (ERAT) was performed. The patient had complete pain relief immediately after the procedure without tenderness in the right lower abdomen. During 18 mo follow-up, he had no more attacks in his right lower abdomen. Conclusion: ERAT was effective and safe in a CD patient with coexisting AA. Such cases can avoid surgery and its-related complications.

Erianin inhibits the growth and metastasis through autophagy-dependent ferroptosis in KRASG13D colorectal cancer.

Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Approximately 40% of CRC patients are KRAS sequence variation, including KRAS G13D mutation (KRASG13D) CRC patients, accounting for approximately 8% of all KRAS mutations in CRC patients and showing little benefit from anti-EGFR therapy. Therefore, there is an urgent need for new and effective anticancer agents in patients with KRASG13D CRC. Here, we identified a natural product, erianin, that directly interacted with purified recombinant human KRASG13D with a Kd of 1.1163 µM, which also significantly improve the thermal stability of KRASG13D. The cell viability assay showed that KRASG13D cells were more sensitive to erianin than KRASWT or KRASG12V cells. In vitro, results showed that erianin suppressed the migration, invasion and epithelial-mesenchymal transition (EMT) of KRASG13D CRC cells. Furthermore, erianin induced ferroptosis, as evidenced by the accumulation of Fe2+ and reactive oxygen species (ROS), lipid peroxidation, and changes in the mitochondrial morphology of KRASG13D CRC cells. Interestingly, we also found that erianin-induced ferroptosis was accompanied by autophagy. Moreover, the occurrence of erianin-induced ferroptosis is reversed by autophagy inhibitors (NH4Cl and Bafilomycin A1) and ATG5 knockdown, suggesting that erianin-induced ferroptosis is autophagy-dependent. In addition, we evaluated the inhibition of tumor growth and metastasis by erianin in vivo using a subcutaneous tumor model and a spleen-liver metastasis model, respectively. Collectively, these data provide novel insights into the anticancer activity of erianin, which is valuable for the further discussion and investigation of the use of erianin in clinical anticancer chemotherapy for KRASG13D CRC.

Modern thromboprophylaxis protocol based on guidelines applied in a respiratory intensive care unit: a single-center prospective cohort study.

BACKGROUND: Critically ill patients in intensive care units (ICUs) are at high risk of venous thromboembolism (VTE). This study aimed to explore the prophylaxis effect under a guideline-based thromboprophylaxis protocol among critically ill patients in a respiratory ICU. METHODS: For this single-center prospective cohort study, we followed the thromboprophylaxis protocol, which was drawn up based on relevant guidelines and Chinese experts' advice. Clinical data were entered into an electronic case report form and analyzed. Multivariate logistic regression was conducted to explore independent risk factors of VTE event under this protocol. RESULTS: From August 1, 2014, to December 31, 2020, 884 patients underwent thromboprophylaxis according to this protocol; 10.5% of them received mechanical prophylaxis, 43.8% received pharmacological prophylaxis, and 45.7% received pharmacological combined with mechanical prophylaxis. The proportion of VTE events was 14.3% for patients who received the thromboprophylaxis protocol, of which 0.1% had pulmonary thromboembolism (PTE), 2.0% had proximal deep vein thrombosis (DVT), and 12.1% had isolated distal DVT. There was no significant difference between different thromboprophylaxis measures. Cirrhosis (OR 5.789, 95% CI [1.402, 23.894], P = 0.015), acute asthma exacerbation (OR 39.999, 95% CI [4.704, 340.083], P = 0.001), and extracorporeal membrane oxygenation treatment (OR 22.237, 95%CI [4.824, 102.502], P < 0.001) were independent risk factors for proximal DVT under thromboprophylaxis. CONCLUSIONS: The thromboprophylaxis protocol based on guidelines applied in the ICU was practicable and could help decrease the proportion of PTE and proximal DVT events. The risk factors of VTE events happening under the thromboprophylaxis protocol require more attention. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02213978.

Exploring the Relationship Between Hospital Service Quality, Patient Trust, and Loyalty From a Service Encounter Perspective in Elderly With Chronic Diseases.

Based on the service encounter perspective, this study combines theoretical foundations for such factors as service quality and the characteristics of the hospital service industry to develop a research model scale to investigate whether the quality of hospital services affects patients' perceptions of health service encounters, trust, and loyalty. Nowadays, with the advancement of medical technology, patients pay more attention to the quality of medical services and good service encounters provided by healthcare professionals in order to establish positive patient relationships; hospitals need to improve their own service quality and establish good patient trust relationships so that doctor-patient satisfaction and loyalty can be improved. In a review of related literature, this study found that most past studies focused on issues related of quality of medical services and patient satisfaction, but ignored those related to the relationship between medical service encounters and patient trust and loyalty, as well as the lack of scientific measurement markers for service encounters in the Chinese medical service industry. Therefore, this study uses the Service Encounter Perspective and Service Quality Theory Development Research Scale to collect and analyze data for a typical case of a Chinese tertiary hospital. Finally, this study explores the relationship between the four variables of service quality, service encounter, trust, and loyalty by means of a questionnaire and statistical analysis of the data. Finally, it is concluded that the higher the service quality of the hospital, the higher the customer trust, the higher the service encounter, and in the greater the doctor-patient loyalty.

Deep-subwavelength gap modes in all-dielectric metasurfaces for high-efficiency and large-angle wavefront bending.

All-dielectric, phase-gradient metasurfaces manipulate light via a judiciously designed planar distribution of high and low refractive indices. In the established design approaches, the high-index elements play a dominant role, while the electromagnetic field existing between these elements is routinely viewed as either an incidental by-product or detrimental crosstalk. Here we propose an alternative approach that concentrates on exploring the low-index materials for wavefront shaping. In our Si metasurface, the low-index air gap between adjacent Si fins is judiciously tuned, while the high-index Si fins only have a single size across the whole metasurface. These gap modes provide the full 2π phase coverage, as well as high and relatively uniform transmission, at the deep-subwavelength scale. These characteristics are ideal for mapping a steep phase gradient, consequently suitable for high-efficiency and large-angle wavefront bending. This light manipulation capability is exemplified with numerical simulation in PW-SW (freely propagating wave to surface wave) conversion, where the wavefront is deflected by an angle of 90°. In the gap-mode meta-converters, the average unit size can be only 1/60 of free-space wavelength, an order of magnitude smaller than that of conventional all-dielectric metasurfaces. Their conversion efficiency can reach 68%, the highest value reported for any all-dielectric gradient metasurface THz converter.

Successful Non-Operative Treatment of Enterovesical and Enterocutaneous Fistulas Due to Crohn's Disease.

Background: The incidences of enterovesical and enterocutaneous fistulas are extremely low, and enterovesical and enterocutaneous fistulas are difficult to treat in patients with Crohn's disease. Case Summary: In this case, the patient had recurrent abdominal pain and diarrhea for more than 2 years, with fecal residue in the urine for 6 days. Pelvic magnetic resonance imaging and colonoscopy showed intestinal infection with a rectal fistula, and the initial diagnosis was severely active Crohn's disease with an enterovesical fistula. The patient had multiple internal fistulas and infections, and strongly refused surgical conditions. The patient was given an intravenous infusion of ustekinumab and somatostatin, with anti-infective treatment, nutritional support and regulation of the intestinal flora. Drainage and debridement of the cutaneous fistula were performed. After comprehensive treatment and management, the patient's condition achieved significant clinical remission. Conclusion: This patient achieved clinical response and will receive follow-up for another dose of ustekinumab after 12 weeks. The patient developed enterovesical and enterocutaneous fistulas, the incidence of multiple fistulas which are low in patients with CD and are difficult to cure and prone to relapse. Only few patients achieve complete remission. At present, there is no standard and effective treatment for CD with multiple fistulas. Usually, surgery is performed for treatment. Drug therapy, especially with biological agents, should be selected as the first-line pre-operative treatment. Clinicians, especially gastroenterologists, need to improve their knowledge of these conditions and update the treatment consensus guidelines in a timely manner. Clinicians need to take into account the patient's condition and willingness when developing an effective treatment plan.

m6A modification: recent advances, anticancer targeted drug discovery and beyond.

Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs. Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.

Endoscopic retrograde appendicitis therapy in the management of chronic fecalith appendicitis in a patient with ulcerative colitis: The first human case report.

To assess the effectiveness of endoscopic retrograde appendicitis therapy (ERAT) as a new technique and method for chronic fecalith appendicitis complicated by active ulcerative colitis. A 46-year-old male patient was admitted with right iliac fossa pain, tenderness, and raised inflammatory markers. A computed tomography (CT) scan of his abdomen confirmed a dilated appendix, which is considered chronic fecalith appendicitis combined with active ulcerative colitis. He was treated with an endoscopic retrograde appendicitis therapy procedure. The patient recovered well after the ERAT procedure and was discharged from the hospital in two days. On follow-up one year later, there was no recurrence of pain in his abdomen. In conclusion, ERAT could be seen as a different approach and be favored as a safer and more effective option in treating UC patients with appendicitis, especially those who are later in the course of the disease. Because of the ERAT procedure, such cases can avoid surgery and surgery-related complications. More research and issues must be addressed to demonstrate the efficacy and effectiveness of ERAT in appendicitis combined with UC.

Directional conversion of a THz propagating wave into surface waves in deformable metagratings.

Controllable conversion between propagating light waves and surface waves (SWs) has recently attracted significant research interests. This paper demonstrates, via numerical simulation, for the first time all-dielectric SW converters that possess a tunable and directional SW conversion efficiency. The SW converters contain multiple metagratings of Si pillars embedded in a deformable substrate. In the analysis, an infinitely large, bi-periodic metagrating under the illumination of linearly polarized light is considered first. The SW conversion efficiency of this metagrating can be modulated between 4.3% and 51.0% for incident light frequency at 0.8 THz by stretching the deformable substrate along the direction of SW propagation. Subsequently, two SW converters under circularly polarized light illumination are analyzed, where a similar level of efficiency modulation is retained in finite-sized metagratings. In these converters, only the metagrating channels along the stretch direction have a strong SW conversion efficiency, which can reach 40.4% after normalization against the effective grating area. The directivity, a parameter defined here to reveal the energy contrast among the output channels, reaches 38.6 in one of the converters. Due to its high tunability, high directivity and compact size, the SW converters may be used as tunable optical sensors and light couplers in the THz regime.

A case report of aggressive course of CD30+ primary cutaneous anaplastic large cell lymphoma.

INTRODUCTION: CD30+ primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a rare T-cell neoplasm, and has been reported to present with an indolent behavior. The PC-ALCL with aggressive behavior has not been reported in the literature. PATIENT CONCERNS: We treated a patient with PC-ALCL that exhibited indolent behavior in the past 2 years and aggressive behavior within the last 3 months before presentation. DIAGNOSIS: Aggressive CD30+ primary cutaneous anaplastic large cell lymphoma. INTERVENTIONS: The radiotherapy regimen was individualized in terms of the target volume delineation and dose prescription, and the dose-response relationship was evaluated. OUTCOMES: The mean distance of microscopic infiltration was 14.1 mm in depth and 14.3 mm circumferentially. The lesion completely regressed after the delivery of 40 Gy in 20 fractions over 4 weeks. The tumor did not recur over the next year. CONCLUSION: An aggressive disease course is rare for indolent CD30+ PC-ALCL, which has similar histopathological characteristics as indolent PC-ALCL. The radiotherapy strategy should be individualized with curative intent.

Nomogram predictive model of post-operative recurrence in non-functioning pituitary adenoma.

BACKGROUND: To analyze and predict the possibility of post-operative recurrence in non-functioning pituitary adenoma (NFPA) patients, we investigated the clinical factors leading to tumor recurrence and built a nomogram predictive model based on these risk factors. METHODS: A single-center retrospective study was performed. A total of 145 NFPA patients who underwent surgical treatment at Shenzhen People's Hospital from September 2013 to January 2019 were selected. Among them, 52 patients were diagnosed with recurrence of NFPA according to follow-up investigations. Binary logistic regression analysis was used to determine the significant risk factors. A nomogram model was then built to predict recurrence using these factors. RESULTS: The univariate analysis and the binary logistic regression analysis showed that age, tumor size, cavernous invasion, sphenoid sinus invasion, and surgical extension were significant factors affecting tumor recurrence. We then built a nomogram model to predict post-operative recurrence in NFPA patients using these factors. The correlation analysis indicated that sphenoid sinus invasion [hazard ratio (HR) =13.14, 95% confidence interval (CI): 7.03-24.58, P<0.0001], cavernous sinus invasion (HR =7.53, 95% CI: 4.27-13.28, P<0.0001), and tumor size (HR =11.06, 95% CI: 6.11-20.03, P<0.0001) could promote the recurrence of NFPA. In contrast, advanced age (HR =0.50, 95% CI: 0.28-0.86, P<0.0001) and gross total resection (HR =0.12, 95% CI: 0.07-0.22, P<0.0001) could effectively inhibit recurrence. CONCLUSIONS: In this study, we developed a nomogram predictive model based on the significant recurrence-associated factors for NFPA. This nomogram may aid neurosurgeons in the post-operative prediction of recurrence, and may facilitate tailored counseling of individual patients.

Gene mutations of esophageal squamous cell carcinoma based on next-generation sequencing.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore potential molecular targets in ESCC, we quantified the mutation spectrum and explored the relationship between gene mutation and clinicopathological characteristics and programmed death-ligand 1 (PD-L1) expression. METHODS: Between 2015 and 2019, 29 surgically resected ESCC tissues and adjacent normal tissues from the Fourth Hospital of Hebei Medical University were subjected to targeted next-generation sequencing. The expression levels of PD-L1 were detected by immunohistochemistry. Mutational signatures were extracted from the mutation count matrix by using non-negative matrix factorization. The relationship between detected genomic alterations and clinicopathological characteristics and PD-L1 expression was estimated by Spearman rank correlation analysis. RESULTS: The most frequently mutated gene was TP53 (96.6%, 28/29), followed by NOTCH1 (27.6%, 8/29), EP300 (17.2%, 5/29), and KMT2C (17.2%, 5/29). The most frequently copy number amplified and deleted genes were CCND1/FGF3/FGF4/FGF19 (41.4%, 12/29) and CDKN2A/2B (10.3%, 3/29). By quantifying the contribution of the mutational signatures to the mutation spectrum, we found that the contribution of signature 1, signature 2, signature 10, signature 12, signature 13, and signature 17 was relatively high. Further analysis revealed genetic variants associated with cell cycle, chromatin modification, Notch, and Janus kinase-signal transducer and activator of transcription signaling pathways, which may be key pathways in the development and progression of ESCC. Evaluation of PD-L1 expression in samples showed that 13.8% (4/29) of samples had tumor proportion score ≥1%. 17.2% (5/29) of patients had tumor mutation burden (TMB) above 10 mut/Mb. All samples exhibited microsatellite stability. TMB was significantly associated with lymph node metastasis (r = 0.468, P = 0.010), but not significantly associated with PD-L1 expression (r = 0.246, P = 0.198). There was no significant correlation between PD-L1 expression and detected gene mutations (all P > 0.05). CONCLUSION: Our research initially constructed gene mutation profile related to surgically resected ESCC in high-incidence areas to explore the mechanism underlying ESCC development and potential therapeutic targets.