Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study - ERAP2, MET, CXCL9, and AGT - are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.

UNASSIGNED: Small Bowel Adenocarcinoma (SBA) is rare, occult and life-threatening malignancy in digestive system. Given low incidence and nonspecific symptoms, SBA is frequently detected in later stages. Double contrast enhanced ultrasound (DCEUS) is an innovative imaging technique applied to visualize the gastrointestinal tract, merging intravenous contrast-enhanced ultrasound with oral contrast-enhanced ultrasound. In this case, DCEUS was utilized and successfully detected an SBA of the jejunum.
UNASSIGNED: A Chinese woman, aged 64, sought consultation in the gastroenterology department at our hospital, reporting symptoms of abdominal pain. Three months before entering the hospital, she underwent gastroscopy and colonoscopy which suggested chronic gastritis, and she was treated with oral drugs. However, her symptoms were not relieved, and even worsened. To further investigate, DCEUS was performed. The oral contrast agent dilated the luminal space of the upper gastrointestinal tract, resolving the hindrance caused by gas in the gastrointestinal tract and creating an acoustic window for scanning. Through this acoustic window, oral agent contrast-enhanced ultrasound (OA-CEUS) revealed a localized thickening of jejunal intestinal wall measuring 4x3 cm. Following intravenous injection of ultrasound contrast agent, the jejunal lesion exhibited faster enhancement and heterogeneous hyper-enhancement. Finally, the patient underwent jejunal tumor resection. Pathological examination revealed a jejunal adenocarcinoma.
UNASSIGNED: The timely diagnosis of SBA can be challenging. DCEUS may have the potential to contribute to diagnosis and detailed evaluation of SBA, particularly in cases involving jejunum. Further researches are needed to fully explore the benefits of DCEUS in the standard diagnostic approach for small bowel diseases.

Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. In vitro assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.

BACKGROUND: Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac cancer (MECC) is commonly observed in this region in clinical practice. However, the genomic characteristics of MECC remains unclear.
METHODS: In this study, a total of 2123 clinical samples of EC and GCA were analyzed to determine the frequency of multifocal tumors, as well as their occurrence sites and pathological types. Cox proportional hazards regression was used to model the relationship between age, sex, and tumor state concerning survival in our analysis of the cohort of 541 patients with available follow-up data. We performed whole-genome sequencing on 20 tumor foci and 10 normal samples from 10 MECC patients to infer clonal structure on 6 MECC patients to explore genome characteristics.
RESULTS: The MECC rate of EC and GCA was 5.65% (121 of 2123). Age and sex were potential factors that may influence the risk of MECC (p < 0.001). Furthermore, MECC patients showed worse survival compared with single tumor patients. We found that 12 foci from 6 patients were multicentric origin model (MC), which exhibited significant heterogeneity of variations in paired foci and had an increased number of germline mutations in immune genes compared to metastatic model. In MC cases, different lesions in the same patient were driven by distinct mutation and copy number variation (CNV) events. Although TP53 and other driver mutation genes have a high frequency in the samples, their mutation sites show significant heterogeneity in paired tumor specimens. On the other hand, CNV genes exhibited higher concordance in paired samples, especially in the amplification of oncogenes and the deletion of tumor suppressor genes.
CONCLUSIONS: The extent of inter-tumor heterogeneity suggests both monoclonal and polyclonal origins of MECC, which could provide insight into the genome diversity of MECC and guide clinical implementation.

瘘管相关性肛门腺癌是一种罕见的肛门肿瘤，本文报道1例。该患者为37岁男性，肛瘘伴反复肛旁结块、肿痛溃脓20余年，磁共振成像检查示左侧高位肛周脓肿伴复杂性括约肌间瘘。镜下观察：纤维及炎性肉芽组织中见大量细胞外黏液，黏液被纤维间隔分成大小不一的黏液湖，部分纤维间隔表面衬覆梁索状异型腺上皮，局部乳头状增生，细胞多呈柱状，核圆形或卵圆形位于基底部，散在少量杯状细胞，局部细胞异型明显，极性紊乱，核仁清晰，小灶区域黏液湖内可见簇状或印戒样细胞，局灶区域伴出血及含铁血黄素沉积。免疫组织化学：异型上皮细胞细胞角蛋白（CK）7、CK20、MUC2、CDX2、SATB2、Villin、MSH2、MSH6、PMS2、MLH1阳性，MUC5AC部分阳性，突触素局灶区域阳性，MUC6、GCDFP15、嗜铬粒素A阴性。分子检测：KRAS基因第2号外显子第12位密码子突变，NRAS、BRAF V600E及PIK3CA基因未见突变。本文回顾其临床病理特征并复习相关文献，旨在提高对该病的认识，避免漏诊、误诊。.

阑尾杯状细胞腺癌少见，本文报道1例以卵巢肿瘤为首发症状的转移性阑尾杯状细胞腺癌。患者女，67岁。腹痛2个月，CT示盆腔巨大囊实性肿物，考虑附件来源。术中送检左卵巢肿物，镜下观察大片坏死物中见印戒样/杯状细胞呈片状、筛状、腺管样或单个细胞排列。冷冻病理考虑转移性腺癌，建议临床检查消化道。术中探查发现阑尾肿物。遂行全子宫、双附件+右半结肠切除术。镜下观察少许阑尾肿瘤组织学形态与卵巢肿物一致，其他区域肿瘤细胞似神经内分泌细胞呈巢团、缎带状排列。卵巢和阑尾肿瘤均表达SATB2、CDX2，阑尾肿瘤局灶表达突触素。患者术后接受化疗。随访10个月，未见复发。.

目的： 探讨非典型宫颈管腺细胞（atypical endocervical cells，AEC）的临床病理学特征。 方法： 收集首都医科大学附属北京妇产医院2021年3月至2023年12月宫颈液基细胞学判读为AEC病例的人乳头瘤病毒（humanpapilloma virus，HPV）、组织学等资料并分析。 结果： AEC共123例，检出率为0.09%（123/131 966），包括98例非典型宫颈管腺细胞-非特异（AEC，nototherwise specified，AEC-NOS）和25例非典型宫颈管腺细胞-倾向于肿瘤（AEC，favor neoplastic，AEC-FN）。AEC-NOS及AEC-FN病例HPV阳性率分别为35.6%、65.2%。AEC-NOS病例中73例有组织学随访结果，13例为高级别上皮病变，包括2例子宫内膜非典型增生、7例宫颈HPV相关性腺癌及原位腺癌、4例宫颈高级别鳞状上皮内病变（HSIL）及鳞状细胞癌。AEC-FN病例中20例有组织学结果，16例组织学为高级别上皮病变，包括2例子宫内膜腺癌、8例宫颈HPV相关性原位腺癌及腺癌、1例宫颈胃型腺癌、5例宫颈HSIL及鳞状细胞癌；2例活检病理为良性的AEC-FN病例，复阅细胞涂片后，细胞学仍高度提示存在宫颈高级别腺上皮病变。 结论： AEC提示宫颈癌及癌前病变风险性增高，尤其是宫颈腺癌及原位腺癌；HPV阴性的AEC病例出现宫颈癌及癌前病变的风险性明显较HPV阳性者低；对于AEC-FN病例，无论是否感染HPV、无论初次活检结果如何，都要引起高度重视。.

Objective To verify the anti-tumor effect of the mesenchymal-epithelial transition single-chain antibody (Met scFv) on subcutaneously transplanted tumors in nude mice. Methods A tumor model was established in nude mice by subcutaneous injection of A549 lung adenocarcinoma cells. Once the tumors were formed, IRDye680 LT N-hydroxysuccinimide (NHS) ester-labeled Met scFv was administered intraperitoneally. Real-time monitoring was conducted using a small animal imager to observe the dynamic distribution of the antibody in tumor-bearing mice. The affinity between c-Met and the antibody in tumor cells was detected. Tumor volume changes were observed and the tumor growth curve were plotted following regular tail vein injections of Met scFv. Immunohistochemical staining was employed to determine whether Met scFv could effectively bind to the c-Met antigen in tumor tissues. Results The distribution of Met scFv in nude mice showed that it was primarily located in the peritoneal cavity within the first 3 hours. After approximately 48 hours, fluorescent signals began to accumulate in the tumor tissue. Immunohistochemical staining of the tumors revealed high expression of c-Met in the tumor tissues; regular tail vein injections of Met scFv significantly slowed down the growth of tumors in mice. Conclusion Met scFv specifically recognizes tumor cells in vivo and exhibites significant anti-tumor activity.

BACKGROUND: Colorectal cancer is the third most common malignancy worldwide and is one of the leading causes of cancer-related mortality. Ubiquitin-specific peptidase 18 (USP18) protein has been reported to exert different tumor-related effects in distinct tumor types. Here, we initially investigated the expression and signaling pathways of USP18 in colon adenocarcinoma (COAD).
METHODS: A quantitative real-time PCR was conducted to evaluate the mRNA level of USP18 in cultured cells. Immunohistochemical staining was used to explore the protein expression of USP18 in clinical COAD samples. Specific knockdown was achieved by transient transfection of small interfering RNAs into SW480 and HT29 cells using Lipo3000. Cell conting kit-8 assay, transwell assay and matrigel-transwell assays were conducted to evaluate proliferation, migration and invasion capacities, respectively. Western blotting was performed to analyze downstream signaling pathways. A chi-squared test and univariate and multivariate analyses were used to evaluate the clinical data. Xenografts from mice model were assessed to validate the in vitro findings.
RESULTS: Higher USP18 level was identified in COAD tissues and was positively correlated with advanced tumor stage. High USP18 protein expression indicated poorer prognosis of COAD patients. Silencing USP18 suppressed COAD cell proliferation and invasion via destabilizing extracellular signal-regulated kinase (ERK) protein and suppressing ERK downstream pathways. Simultaneously silencing interferon-stimulated gene 15 (ISG15) with USP18 can partially rescue the tumor cell viability, indicating its involvement in USP18 signaling. The oncogenic effects of USP18 were also confirmed in mice models.
CONCLUSIONS: USP18 plays oncogenic effects in colon adenocarcinoma via ISG15-ERK pathways. High USP18 expression indicates poor clinical outcomes for colon adenocarcinoma patients.

OBJECTIVE: This study aimed to explore the potential causal relationship between dietary habits and Gastroesophageal Reflux Disease (GERD).
METHODS: Using the inverse-variance weighted method, a two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between 22 dietary habits and GERD. The stability and reliability of the results were assessed using leave-one-out analysis, heterogeneity tests, and tests for horizontal pleiotropy based on the effect measure odds ratio (OR) and 95% confidence interval (CI).
RESULTS: The results of the MR analysis indicated a positive association between alcohol drinking (OR=1.472; 95% CI, 1.331 to 1.629; p<1.0×10-3) and salt added to food (OR=1.270; 95% CI, 1.117 to 1.443; p<1.0×10-3) with the risk of GERD. Conversely, bread intake (OR=0.613; 95% CI, 0.477 to 0.790; p<1.0×10-3), cereal intake (OR=0.613; 95% CI, 0.391 to 0.677; p<1.0×10-3), cheese intake (OR=0.709; 95% CI, 0.593 to 0.846; p<1.0×10-3), dried fruit intake (OR=0.535; 95% CI, 0.404 to 0.709; p<1.0×10-3), fresh fruit intake (OR=0.415; 95% CI, 0.278 to 0.619; p<1.0×10-3), and oily fish intake (OR=0.746; 95% CI, 0.633 to 0.879; p<1.0×10-3) were negatively associated with the risk of GERD. Sensitivity analysis showed no evidence of reverse causation, pleiotropy, or heterogeneity.
CONCLUSIONS: Alcohol and salt added to food raised GERD risk, while bread intake, cereal intake, cheese intake, intake of certain dried fruits and certain fresh fruits, and oily fish lowered it. Our study affirms the potential causal link between these diets and GERD, offering insights into targeted prevention strategies.