KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Spatial analysis of stromal signatures identifies invasive front carcinoma-associated fibroblasts as suppressors of anti-tumor immune response in esophageal cancer.

BACKGROUND: Increasing evidence indicates that the tumor microenvironment (TME) is a crucial determinant of cancer progression. However, the clinical and pathobiological significance of stromal signatures in the TME, as a complex dynamic entity, is still unclear in esophageal squamous cell carcinoma (ESCC). METHODS: Herein, we used single-cell transcriptome sequencing data, imaging mass cytometry (IMC) and multiplex immunofluorescence staining to characterize the stromal signatures in ESCC and evaluate their prognostic values in this aggressive disease. An automated quantitative pathology imaging system determined the locations of the lamina propria, stroma, and invasive front. Subsequently, IMC spatial analyses further uncovered spatial interaction and distribution. Additionally, bioinformatics analysis was performed to explore the TME remodeling mechanism in ESCC. To define a new molecular prognostic model, we calculated the risk score of each patient based on their TME signatures and pTNM stages. RESULTS: We demonstrate that the presence of fibroblasts at the tumor invasive front was associated with the invasive depth and poor prognosis. Furthermore, the amount of α-smooth muscle actin (α-SMA)+ fibroblasts at the tumor invasive front positively correlated with the number of macrophages (MØs), but negatively correlated with that of tumor-infiltrating granzyme B+ immune cells, and CD4+ and CD8+ T cells. Spatial analyses uncovered a significant spatial interaction between α-SMA+ fibroblasts and CD163+ MØs in the TME, which resulted in spatially exclusive interactions to anti-tumor immune cells. We further validated the laminin and collagen signaling network contributions to TME remodeling. Moreover, compared with pTNM staging, a molecular prognostic model, based on expression of α-SMA+ fibroblasts at the invasive front, and CD163+ MØs, showed higher accuracy in predicting survival or recurrence in ESCC patients. Regression analysis confirmed this model is an independent predictor for survival, which also identifies a high-risk group of ESCC patients that can benefit from adjuvant therapy. CONCLUSIONS: Our newly defined biomarker signature may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for reversing the fibroblast-mediated immunosuppressive microenvironment.

Identification of hub biomarkers and immune cell infiltration characteristics of polymyositis by bioinformatics analysis.

Background: Polymyositis (PM) is an acquirable muscle disease with proximal muscle involvement of the extremities as the main manifestation; it is a category of idiopathic inflammatory myopathy. This study aimed to identify the key biomarkers of PM, while elucidating PM-associated immune cell infiltration and immune-related pathways. Methods: The gene microarray data related to PM were downloaded from the Gene Expression Omnibus database. The analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks were performed on differentially expressed genes (DEGs). The hub genes of PM were identified using weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) algorithm, and the diagnostic accuracy of hub markers for PM was assessed using the receiver operating characteristic curve. In addition, the level of infiltration of 28 immune cells in PM and their interrelationship with hub genes were analyzed using single-sample GSEA. Results: A total of 420 DEGs were identified. The biological functions and signaling pathways closely associated with PM were inflammatory and immune processes. A series of four expression modules were obtained by WGCNA analysis, with the turquoise module having the highest correlation with PM; 196 crossover genes were obtained by combining DEGs. Subsequently, six hub genes were finally identified as the potential biomarkers of PM using LASSO algorithm and validation set verification analysis. In the immune cell infiltration analysis, the infiltration of T lymphocytes and subpopulations, dendritic cells, macrophages, and natural killer cells was more significant in the PM. Conclusion: We identified the hub genes closely related to PM using WGCNA combined with LASSO algorithm, which helped clarify the molecular mechanism of PM development and might have great significance for finding new immunotherapeutic targets, and disease prevention and treatment.

Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment.

The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

STAT3ß disrupted mitochondrial electron transport chain enhances chemosensitivity by inducing pyroptosis in esophageal squamous cell carcinoma.

The clinical efficacy of cisplatin in the treatment of esophageal squamous cell carcinoma (ESCC) is undesirable. Signal transducer and activator of transcription 3ß (STAT3ß), a splice variant of STAT3, restrains STAT3α activity and enhances chemosensitivity in ESCC. However, the underlying molecular mechanisms remain poorly understood. Here, we found that high expression of STAT3ß contributes to cisplatin sensitivity and enhances Gasdermin E (GSDME) dependent pyroptosis in ESCC cells after exposure to cisplatin. Mechanistically, STAT3ß was located into the mitochondria and its high expression disrupts the activity of the electron transport chain, resulting in an increase of ROS in cisplatin treatment cells. While high levels of ROS caused activation of caspase-3 and GSDME, and induced cell pyroptosis. STAT3ß blocked the phosphorylation of STAT3α S727 in mitochondria by interacting with ERK1/2 following cisplatin treatment, disrupting electron transport chain and inducing activation of GSDME. Clinically, high expression of both STAT3ß and GSDME was strongly associated with better overall survival and disease-free survival of ESCC patients. Overall, our study reveals that STAT3ß sensitizes ESCC cells to cisplatin by disrupting mitochondrial electron transport chain and enhancing pyroptosis, which demonstrates the prognostic significance of STAT3ß in ESCC therapy.

Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting.

Esophageal cancer (EC) is a type of aggressive cancer without clinically relevant molecular subtypes, hindering the development of effective strategies for treatment. To define molecular subtypes of EC, we perform mass spectrometry-based proteomic and phosphoproteomics profiling of EC tumors and adjacent non-tumor tissues, revealing a catalog of proteins and phosphosites that are dysregulated in ECs. The EC cohort is stratified into two molecular subtypes-S1 and S2-based on proteomic analysis, with the S2 subtype characterized by the upregulation of spliceosomal and ribosomal proteins, and being more aggressive. Moreover, we identify a subtype signature composed of ELOA and SCAF4, and construct a subtype diagnostic and prognostic model. Potential drugs are predicted for treating patients of S2 subtype, and three candidate drugs are validated to inhibit EC. Taken together, our proteomic analysis define molecular subtypes of EC, thus providing a potential therapeutic outlook for improving disease outcomes in patients with EC.

Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China.

Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and ≥6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.

[Application of residual crown of premolar restored with two shapes of fiber post systems].

PURPOSE: To compare the effects of premolars restored with 2 different types of fiber post systems, so as to provide experience for restoration of residual crown of premolars. METHODS: Fifty-three residual crowns of premolar restored with fiber post systems were collected, and randomly divided into 2 groups: parallel fiber post group and double taper fiber post group. Repairing effect and operation difficulty were compared. The data was analyzed with SPSS 13.0 software package. RESULTS: There was no significant difference in success rate between the 2 groups, four complications occurred in parallel fiber post group and one in double taper fiber post group. CONCLUSIONS: The success rate between parallel fiber post groups and double taper fiber post group was not different, but the complication in double taper fiber post group is lower than parallel fiber post group.

Fluorescence-guided resection of high-grade gliomas: a systematic review and meta-analysis.

OBJECTIVE: The present systematic review and meta-analysis was to analyze of the advantages of intraoperative fluorescence-guided resection of high-grade gliomas. METHODS: Systematic computerized searches of the PubMed and Web of Knowledge were performed. The outcomes included diagnostic value for identification of tumor tissue, gross total resection, and prognosis. The summary receiver operating characteristic curves (SROC), the pooled sensitivities, the pooled specificities, the pooled odd ratio (OR) and the pooled hazard ratio (HR) were estimated by meta-analysis. RESULTS: Twelve studies were included. The pooled sensitivity and the pooled specificity for identification of tumor tissue was 0.84 (95% CI: 0.81-0.87), and 0.91 (95% CI: 0.87-0.94), respectively. And the overall weighted AUC of the SROC curve was 0.9520 ± 0.0116. The summary OR of the gross total resection rate in patients with fluorescein-guided resection compared with patients with no fluorescein was 4.372 (95% CI 2.937-6.508). Fluorescein-guided resection was associated with a reduced risk of progression-free survival compared with no fluorescein, with HR 0.73 (95% CI 0.57-0.94, P = 0.01). The pooled HR of overall survival was 1.000 (95% CI 0.960-1.040) between two groups. No significant publication bias was found. CONCLUSION: Fluorescence-guided resection of high-grade gliomas is effective for diagnosing tumor margins, increasing gross total resection, and reducing the risk of progression-free survival. But this conclusion should be confirmed by large sample randomized controlled clinical trials.

Corrosion behavior of pure titanium in the presence of Actinomyces naeslundii.

It is well known that some microorganisms affect the corrosion of dental metal. Oral bacteria such as Actinomyces naeslundii may alter the corrosion behavior and stability of titanium. In this study, the corrosion behavior of titanium was studied in a nutrient-rich medium both in the presence and the absence of A. naeslundii using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and electrochemical impedance spectroscopy (EIS). A. naeslundii was able to colonize the surface of titanium and then form a dense biofilm. The SEM images revealed the occurrence of micropitting corrosion on the metal surface after removal of the biofilm. The electrochemical corrosion results from EIS showed a significant decrease in the corrosion resistant (R(p)) value after immersing the metal in A. naeslundii culture for 3 days. Correspondingly, XPS revealed a reduction in the relative levels of titanium and oxygen and an obvious reduction of dominant titanium dioxide (TiO2) in the surface oxides after immersion of the metal in A. naeslundii culture. These results suggest that the metabolites produced by A. naeslundii can weaken the integrity and stability of the protective TiO2 in the surface oxides, which in turn decreases the corrosion resistance of titanium, resulting in increased corrosion of titanium immersed in A. naeslundii solution as a function of time.

Hemi-semi laminectomy approach for the microsurgical treatment of spinal schwannomas.

OBJECTIVE: To evaluate the safety and efficiency of hemi-semi laminectomy approach for the microsurgical treatment of spinal schwannomas. METHODS: A total of 22 patients underwent hemi-semi laminectomy for the microsurgical removal of spinal schwannomas during a period of 2009 and 2011 in Affiliated Hospital of Nantong University. We retrospectively analyzed the clinical outcomes of these patients. RESULTS: Of them, 5 cases were diagnosed with cervical schwannomas, 9 with thoracic schwannomas, and 8 with lumbar schwannomas. All the tumors including two dumbbell schwannomas were totally removed without major complications. Postoperatively, all patients were followed up from 6 to 36 months. The symptoms and signs were obviously improved, and no tumor recurrence or spinal deformity occurred. CONCLUSION: Hemi-semi laminectomy is a safe and effective method for resection of spinal schwannomas.

[A new method of fabricating photoelastic model by rapid prototyping].

PURPOSE: To explore a novel method of fabricating the photoelastic model using rapid prototyping technique. METHODS: A mandible model was made by rapid prototyping with computerized three-dimensional reconstruction, then the photoelastic model with teeth was fabricated by traditional impression duplicating and mould casting. RESULTS: The photoelastic model of mandible with teeth, which was fabricated indirectly by rapid prototyping, was very similar to the prototype in geometry and physical parameters. The model was of high optical sensibility and met the experimental requirements. CONCLUSION: Photoelastic model of mandible with teeth indirectly fabricated by rapid prototyping meets the photoelastic experimental requirements well.

Bacterial diversity of subgingival plaque in 6 healthy Chinese individuals.

The subgingival microbial ecology is complex, and little is known regarding its bacteria species composition in healthy Chinese individuals. This study aimed to identify the subgingival microbiota from 6 healthy Chinese subjects. Subgingival samples from 6 volunteers were collected, the 16S rRNA gene was amplified using broad-range bacterial primers, and clone libraries were constructed. For the initial 2,439 sequences analyzed, 383 species-level operational taxonomic units (SLOTUs) belonging to seven phyla were identified, estimated as 51% [95% confidence interval (CI) 44-55] of the SLOTUs in this ecosystem. Most (85%) of the bacterial sequences, falling into 228 types of species, corresponded to known and cultivated species. However, 146 (6%) sequences, comprising 104 phylotypes, had <97% similarity to prior database sequences. Ten bacterial genera were conserved among all 6 individuals, comprising 2,000 (82%) of the 2,439 clones analyzed. Ten species were noted in all of the 6 subjects, comprising 1,435 (58.8%) of the 2,439 clones. Streptococcus infantis was the species most frequently cloned. Furthermore, certain species which may participate in the pathogenesis of periodontal disease were present in the 6 subjects. Although the initial subgingival plaque community of each subject was unique in terms of diversity and composition, 10 common key species were found in the 6 Chinese individuals. These ten species of bacteria in the human subgingival plaque in the 6 healthy individuals may be key species which, to some extent, affect periodontal health. Destruction of these key species in subgingival bacteria may break the microbiota balance and may easily lead to over-breeding conditions resulting in pathogenic oral disease.

[Three-dimensional finite element analysis of the influence of implant location on the stress distribution for implant-supported fixed partial dentures].

PURPOSE: To evaluate the influence of implant location on the stress distribution for implant-supported fixed partial dentures by 3-D finite element analysis. METHODS: Four 3-D finite element models with different implant location were constructed. Four different loading conditions(vertical distributed,oblique distributed,vertical concentrated,oblique concentrated) were applied to investigate the stress distribution by finite element analysis software ABAQUS 6.5-1. RESULTS: Under the distributed loading, the maximum von Mises stress in all of the four models was located on the cortical bone around the neck of implant.The von Mises stress of the the cortical bone and the implant under oblique distributed loading increased significantly,and was 2.9-5.6 times bigger than that under vertical distributed loading. Under the concentrated loading, the maximum von Mises stress in all of the four models was located on the crestal region around the neck of the implant adjacent to the pontic.The stress concentration was the highest in the distal cantilever. CONCLUSIONS: It is unreasonable for the design of 456X with distal cantilever. Within the limitation of this study, the design of 45X7 reveals better stress distribution.

[The effects of different welding wires on the mechanical properties of laser welding joints].

PURPOSE: To evaluate the mechanical properties and microstructure of laser-welded joints with different welding wires for clinical use of welding wire. METHODS: The standard tensile test and three-point bending test rods were made from Co-Cr and Ni-Cr alloy, and were laser-welded with different welding wire (commercially welding wire and casting wire). Then the tensile rods were tested for the ultimate tensile strength (UTS), and the bending rods for the ultimate bending strength (UBS). The results was analyzed by one-way ANOVA. The tensile fracture surface were examined by scanning electron microscopy (SEM). Metallurgical analysis were also performed on polished longitudinal sectioned samples. RESULTS: For Co-Cr alloy, the UTS of casting wire group and commercially welding wire group was respectively (606.40+/-82.53)MPa and (693.61+/-47.68)MPa; the UBS was respectively (997.95+/-88.89)MPa and (1160.76+/-91.59)MPa. ANOVA showed a significant difference of UTS and UBS between the two groups at the 0.05 level (P<0.05). For Ni-Cr alloy, the UTS of casting wire group and commercially welding wire group was respectively (558.14+/-46.75)MPa and (582.32+/-35.43)MPa; the UBS was respectively (1084.75+/-46.02)MPa and (1078.29+/-36.25)MPa. There was no significant difference between the two groups (P>0.05). SEM and metallurgical examination showed the welded zone exhibiting more cracks in the casting wire group than in the commercially welding wire group. CONCLUSION: It would be advisable to work with commercially welding wire for the joints that need better strength.

[The mechanic retention of the casting post with keeper in magnetic retentor overdenture].

PURPOSE: To reduce the cost of the fabrication of the magnetic retentor,and meet the clinical requirements, nonprecious alloy such as Co-Cr alloy was used to fabricate the magnetic retentor in overdenture , instead of the precious alloy. METHODS: A mandibular canine was chosen for root canal preparation in vitro. Thirty two resin posts were made in the same root canal with self-curing resin. The 32 resin posts were randomly divided into 4 groups. Among them,2 groups were fabricated with soft Co-Cr alloy, gold alloy(55.6%Au) respectively in vitro. Another 2 groups were fabricated with Co-Cr alloy, and the surface of the root casting post with keeper were treated with gold deposit and gold coating technique. After that, test of dislodgment force was done and one-way ANOVA was performed with SAS 6.2 software package. RESULTS: The dislodgment force of the root casting posts with keeper which were fabricated with the Co-Cr, Ni-Cr, and gold alloy had significant difference(P<0.01). While after surface treatment by gold deposit and gold coating technique on root casting posts with keeper that were fabricated with Co-Cr and Ni-Cr alloy, there was no significant difference in dislodgment force, compared with that of gold alloy. CONCLUSIONS: After surface treatment of the root casting posts with keeper which were fabricated with the Co-Cr and Ni-Cr alloy, the same clinical retentive effect can be obtained as the one that was fabricated with gold alloy.

[Clinical observation of treating nonrestorable teeth with orthodontics, periodontal therapy and prosthodontics].

PURPOSE: To evaluate the clinical results of treating nonrestorable teeth with conjunctive efforts of orthodontic-prosthodontic disciplines and periodontal therapy. METHODS: 10 cases, 8 anterior teeth, 2 premolar were selected, with a large vertical root fracture lingually or labially extending 2 to 3 mm below the gingival margin. The teeth were erupted coronally by orthodontic forces, and stabilized by the appliances for 8 weeks to 6 months, then periodontal surgery was performed, at last the final restoration was completed. RESULTS: After a series of treatments, an acceptable restoration was fabricated which fit the periodontal,restorative and esthetic requirements. Radiographs showed suitable C/R (crown and root) ratio of the final restoration. CONCLUSION: Forced eruption may be a useful approach in treating isolated nonrestorable teeth.

[Effect of irradiation power on the mechanical properties of laser-welded titanium joints.].

PURPOSE: To make an clinical implication for the use of laser welding pure titanium,this study investigate the effect of irradiation power on the mechanical properties of laser-welded joints. METHODS: The pure titanium tensile test and three-point bending test rods were laser-welded with different irradiation power. Then the tensile rods were tested for the ultimate tensile strength (UTS), and the bending rods for the ultimate bending strength (UBS). The tensile fracture surface was examined by scanning electron microscopy (SEM). Metallurgical analysis was also performed on polished longitudinal sectioned samples. RESULTS: A small portion of the central area in group 1.4 kW was not joined. ANOVA showed no significant difference of OTS and VBS between group 1.6 kW and group 1.8 kW at the 0.05 level. SEM examination and metallurgical analysis showed that there were defects such as pores and cracks in the welding zone; and as the irradiation power increased, there were more pores and cracks. CONCLUSION: The increase in laser irradiation power cannot increase melting depth significantly.

[An experimental study on laser-welded dissimilar alloys in dentistry.].

PURPOSE: This study evaluated the mechanical properties and microstructure of the joints of laser-welded dissimilar alloys usually used in clinical nowadays. METHODS: The dissimilar alloys for Co-Cr alloy,Ni-Cr alloy and pure titanium were laser-welded. The joints were tested for the ultimate tensile strength (UTS) and the ultimate bending strength (UBS). The tensile fracture surfaces were examined by scanning electron microscopy (SEM). Metallurgical analysis was also performed on polished longitudinal sectioned samples. RESULTS: Laser-welded dissimilar alloys between Co-Cr and Ni-Cr alloy can yield satisfactory mechanical properties, and there was no significant difference of UTS and UBS between Co-Cr welding wire group and Ni-Cr welding wire group (P>0.05). The laser-welded joints for dissimilar metal of pure titanium and Co-Cr,pure titanium and Ni-Cr, showed more brittle characteristics and severe defects (pores and cracks). CONCLUSIONS: With Co-Cr or Ni-Cr welding wire, the laser-welded dissimilar alloys of Co-Cr alloy and Ni-Cr alloy can yield satisfactory joints. But pure titanium and Co-Cr alloy, pure titanium and Ni-Cr alloy cannot be directly melted together.