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BackgroundEsophageal cancer is currently a worldwide health problem. Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer, and its treatment methods and therapeutic effects are relatively limited, so it also requires the unremitting efforts of basic and clinical researchers to overcome difficulties. Bibliometric analysis can help sort out global research trends and hotspots, but no bibliometric analysis of ESCC has been reported. Therefore, we performed this study to analyze the global trends and potential hotspots of ESCC to indicate future research directions.MethodsThe articles related to ESCC research were collected from the WoS Core Collection SCI-EXPANDED database from 2012 to 2022. The article information was analyzed by BiblioShiny and VOSviewer. Results were presented as bar and network visualization to describe the current trend of ESCC research. This was a retrospective study evaluating data that is publicly available online and at libraries and institutional review board approval, as such, was not demanded.ResultsThe global publication trend illustrated a strong growth in the ESCC research field (annual growth rate of 11.4%) and the citation trend increased from an average of 2.98 citations per article per year in 2012 to an average of 3.84 citations per article per year in 2019. With the corresponding author’s country, China contributed the largest number (5,063 articles). The scholars from China and USA had the most collaboration (427 times). China had the largest number of institutions conducting ESCC research. Oncotarget, Oncology Letters, and Annals of Surgical Oncology published the most articles, while Cancer Research, International Journal of Cancer, and Journal of Clinical Oncology had the most local citations. Furthermore, the clinical research hotspots involved in the treatment of ESCC and the basic research hotspots involved in tumor malignant phenotype have received the most attention in recent years.ConclusionOur study demonstrated that the research of ESCC has developed rapidly in recent years, and the academic institutions in China have played a decisive role in this field. The global research purpose is to find effective therapies against ESCC, so some emerging hotspots related to ESCC treatment, such as endoscopic therapy, chemoradiotherapy, immunotherapy, tumor microenvironment, and the epithelial-mesenchymal transition will receive more attention and develop rapidly in the future.

BackgroundClostridium difficile (C. difficile) is a main cause of antibiotic-associated diarrhoea in humans. Several studies have been performed to reveal the prevalence rate of C. difficile in cats and dogs. However, little is known about the epidemiology of C. difficile in healthy pets in China. This study aimed to assess the burden of C. difficile shedding by healthy dogs and cats in China. Furthermore, the genetic diversity and antimicrobial susceptibility patterns of the recovered isolates were determined.MethodsA total of 175 faecal samples were collected from 146 healthy dogs and 29 cats. C. difficile strains were isolated and identified from the feces of these pets. The characterized C. difficile strains were typed by multilocus sequence typing (MLST), and the MICs of the isolates were determined against ampicillin, clindamycin, tetracycline, moxifloxacin, chloramphenicol, cefoxitin, metronidazole and vancomycin by the agar dilution method.ResultsOverall, 3 faecal samples (1.7%) were C. difficile culture positive. One sample (0.7%) from a dog was C. difficile culture positive, while two cats (7.0%) yielded positive cultures. The prevalence rate differed significantly between cats and dogs. These isolates were typed into 3 MLST genotypes and were susceptible to chloramphenicol, tetracycline, metronidazole and moxifloxacin and resistant to ampicillin, clindamycin and cefoxitin. Notably, one strain, D141–1, which was resistant to three kinds of antibiotics and carried toxin genes, was recovered in the faeces of a healthy dog.ConclusionOur results suggest that common pets may be a source of pathogenic C. difficile, indicating that household transmission of C. difficile from pets to humans can not be excluded.

Homeobox A7 (HOXA7) plays essential roles in multiple malignancies and was reported to be overexpressed in esophageal squamous cell carcinoma (ESCC). However, its functions in the ESCC tumor microenvironment remain to be explored. In this study, we showed that HOXA7 was overexpressed in ESCC among HOXA family members and correlated with tumor-associated macrophage (TAM) infiltration both in The Cancer Genome Atlas database and ESCC clinical samples. Moreover, transactivation of C-C motif chemokine ligand 2 (CCL2) by HOXA7 was identified (real-time quantitative PCR [RT-qPCR], western blot analysis, ELISA, and ChIP-qPCR), which was detected to drive chemotaxis and M2 polarization of macrophages both in vitro (Transwell assay) and in vivo (xenograft tumors models). In addition, CCL2 triggers macrophage expression of epidermal growth factor (EGF) (RT-qPCR and ELISA), which promotes tumor proliferation and metastasis by activating its receptor EGFR. In addition, EGF-induced ESCC cell proliferation and migration can be abrogated by HOXA7 knockdown (CCK-8 proliferation assay, EdU fluorescence, and Transwell assay). These results indicate a novel mechanistic role of HOXA7 in the cross-talk between ESCC and TAMs, which could be an underlying therapeutic target for ESCC. K E Y W O R D S C-C motif chemokine ligand 2 (CCL2), epidermal growth factor receptor (EGFR), esophageal squamous cell carcinoma (ESCC), homeobox A7 (HOXA7), tumor immunology, tumorassociated macrophage (TAM)

Background Cisplatin (DDP)-based chemotherapy is commonly adopted as the first-line treatment for patients with oesophageal squamous cell carcinoma (OSCC), but the high rate of drug resistance limits its clinical application and the underlying mechanisms at play remain unclear. The aims of this study were to elucidate the role of abnormal signal transmission and metabolism in the chemoresistance of OSCC under hypoxia and to identify targeted drugs that enhance the sensitivity of DDP chemotherapy. Methods Upregulated genes in OSCC were determined by RNA sequencing (RNA-seq), the Cancer Genome Atlas (TCGA) database, immunohistochemistry (IHC), real-time quantitative PCR (RT-qPCR), and western blotting (WB). The clinicopathological significance of insulin-like growth factor-I receptor (IGF1R), argininosuccinate synthetase 1 (ASS1), and pyrroline-5-carboxylate reductase 1 (PYCR1) in OSCC was analysed using tissue micriarray (TMA). Metabolic abnormalities were determined by untargeted metabolomics analysis. The DDP-resistance role of IGF1R, ASS1, and PYCR1 in OSCC was investigated in vitro and in vivo. Results Generally, tumour cells exist in a hypoxic microenvironment. By genomic profiling, we determined that IGF1R, as a receptor tyrosine kinase (RTK), was upregulated in OSCC under low-oxygen conditions. Clinically, enhanced IGF1R expression was associated with higher tumour stages and a poorer prognosis in OSCC patients, and its inhibitor, linsitinib, showed synergistic effects with DDP therapy in vivo and in vitro. Since oxygen-deprivation frequently lead to metabolic reprogramming, we further learned via metabolomics analysis that abnormal IGF1R pathways promoted the expression of metabolic enzymes ASS1 and PYCR1 by the transcriptional activity of c-MYC. In detail, enhanced expression of ASS1 promotes arginine metabolism for biological anabolism, whereas PYCR1 activates proline metabolism for redox balance, which maintains the proliferation ability of OSCC cells during DDP treatment under hypoxic conditions. Conclusion Enhanced expression of ASS1 and PYCR1 via IGF1R pathways rewired arginine and proline metabolism, promoting DDP resistance in OSCC under hypoxia. Linsitinib targeting IGF1R signaling may lead to promising combination therapy options for OSCC patients with DDP resistance.