Esophageal adenocarcinoma (EAC) and gastric cancer (GC) remain major causes of cancer-related mortality worldwide, largely because of late-stage diagnosis. Barrett’s esophagus (BE) is the established precursor setting for EAC, whereas gastric intestinal metaplasia is an important precursor lesion in the intestinal-type gastric carcinogenesis pathway. Aberrant DNA methylation arises early in both pathways and may offer greater sensitivity and specificity than histology or serology alone, while also illuminating the biology of neoplastic progression. This review evaluates the evidence and translational potential of DNA methylation biomarkers in upper gastrointestinal adenocarcinoma.

PubMed, Web of Science, and EMBASE were searched for studies published before May 2026 addressing DNA methylation biomarkers in BE, EAC, gastric intestinal metaplasia, and GC. Tissue-based, minimally invasive, and circulating biomarkers were reviewed, with emphasis on diagnostic performance, progression risk, biological significance, and clinical translation.

Methylation alterations accumulate during progression from precancerous lesions to invasive cancer and distinguish disease states in tissue and minimally invasive specimens. Methylation-based assays show promising diagnostic performance in BE and EAC, including nonendoscopic cytology-based approaches and risk-stratification assays, and circulating methylated DNA shows potential for noninvasive detection of EAC and GC. However, heterogeneity in populations, specimens, assay platforms, and study designs, together with limited prospective validation, remains a barrier to implementation.

The field is moving rapidly from discovery toward practice: Cytosponge-TFF3 with biomarker panels has been evaluated in real-world UK surveillance pathways, the EsoCheck/EsoGuard methylation assay is clinically available, and Esopredict is the first epigenetic prognostic assay clinically validated to risk-stratify BE, while multicancer early detection assays undergo prospective evaluation. Multicenter studies of clinical utility and cost-effectiveness remain the decisive step before routine adoption.

The IMbrave050 trial suggested that adjuvant immune checkpoint inhibitor therapy may benefit patients with hepatocellular carcinoma exceeding the “up-to-7” criterion. This study aimed to compare survival outcomes and safety between such patients receiving adjuvant programmed cell death protein 1 inhibitors and those undergoing active surveillance after curative resection.

Data were prospectively collected from patients at 13 medical centers in China between 2019 and 2024. The study was designed according to a target trial emulation framework, and propensity score matching was used to reduce confounding. The primary endpoint was recurrence-free survival; secondary endpoints included overall survival and incidence of treatment-related adverse events.

Median follow-up was 32.7 months (interquartile range, 20.9–47.5). Propensity score matching yielded 200 patients per group. Median recurrence-free survival was longer in the adjuvant group (28.0 months; 95% confidence interval [CI], 21.7–34.3) than in the surveillance group (14.4 months; 95% CI, 10.7–18.1; hazard ratio, 0.58; 95% CI, 0.45–0.74). Median overall survival was not reached in the adjuvant group and was 45.0 months (95% CI, 37.8–52.1) in the surveillance group (hazard ratio, 0.63; 95% CI, 0.45–0.89). The most frequent grade 3–4 treatment-related adverse events were hand–foot skin reaction (7.2%), elevated alanine aminotransferase (5.8%), and elevated aspartate aminotransferase (5.3%).

Adjuvant programmed cell death protein 1 inhibitors, with or without molecularly targeted agents, were associated with longer recurrence-free survival and acceptable safety in patients with hepatocellular carcinoma exceeding the “up-to-7” criterion.

CXC chemokine receptor 2 (CXCR2) expression has been observed in normal neuroendocrine cells, but its role in neuroendocrine neoplasms is less well established. We aimed to evaluate CXCR2 expression with somatostatin receptor type 2 (SSTR2) expression in pancreatic neuroendocrine tumors (PanNETs) and small intestinal neuroendocrine tumors (SI-NETs).

This was a cross-sectional study. Pathology archives were searched for PanNETs with ≥2 resected liver metastases and SI-NETs with resected liver metastases, mesenteric tumor deposits (MTDs), and/or peritoneal metastases. Immunohistochemistry for CXCR2 was performed on de-identified tissue microarrays containing PanNETs and SI-NETs. SSTR2 and CXCR2 immunohistochemistry was also performed on tumor blocks from primary and metastatic PanNETs and SI-NETs. Based on H-scores, expression was scored as negative (<50), weak (50–100), moderate (>100–200), or strong (>200). Marker expression was descriptively reported among primary tumors, liver metastases, MTDs, and peritoneal metastases.

Among 12 primary PanNETs and 38 liver metastases, mean CXCR2 H-scores were 269.6 ± 36.7 and 254.6 ± 75.5, respectively, and mean SSTR2 H-scores were 261.5 ± 61.9 and 259.3 ± 70.9, respectively. All 84 SI-NET lesions showed moderate/strong CXCR2 expression, whereas 12 showed negative/weak SSTR2 expression. CXCR2 H-scores were 284.0 ± 26.5 in primary tumors, 272.5 ± 28.7 in MTDs, 269.6 ± 42.8 in liver metastases, and 265.0 ± 51.5 in peritoneal metastases. SSTR2 expression appears to be lower in MTDs than in primary tumors (182.2 ± 76.5 vs 235.9 ± 55.9).

CXCR2 is moderately/strongly expressed in most sampled PanNETs and all sampled SI-NETs. In SI-NETs, moderate/strong CXCR2 expression is less heterogeneous than SSTR2 expression.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent worldwide and is frequently encountered in patients undergoing liver transplantation and hepatic surgery. Although hepatic steatosis was once considered a relatively benign condition, accumulating evidence indicates that MASLD is associated with reduced tolerance to ischemic stress and increased susceptibility to ischemia–reperfusion injury, which may contribute to graft dysfunction and postoperative liver injury. In this mini review, we used the concept of hepatic resilience, referring to the ability of the liver to maintain homeostasis during stress and recover after injury. We discussed how MASLD may reduce hepatic resilience through mechanisms involving lipotoxicity, mitochondrial dysfunction, oxidative stress, inflammatory activation, regulated cell death, and impaired regeneration. MASLD represents a heterogeneous disease spectrum, and susceptibility to ischemia–reperfusion injury may differ according to disease stage and phenotype, particularly in the presence of progressive inflammation and fibrosis. We further summarized strategies aimed at improving hepatic resilience, including metabolic optimization, mitochondrial protection, modulation of reperfusion-associated inflammation, and enhancement of tissue repair. However, current evidence remains limited by the paucity of human studies and validated approaches for assessing hepatic resilience. Further investigation of these mechanisms may help develop individualized strategies to protect the liver in patients with MASLD during hepatic surgery and transplantation.

Fuzheng Huayu, a patent herbal product, has shown promise in liver fibrosis and cirrhosis. The effect of Fuzheng Huayu on portal hypertension due to cirrhosis and the consequent complications needs further investigation. In this study, we aimed to evaluate the association of adjunctive Fuzheng Huayu plus entecavir with liver-related events and variceal regression in patients with compensated HBV-related cirrhosis.

A post hoc analysis was conducted using data from two randomized controlled trials implemented at eight clinical centers in China (ClinicalTrials.gov numbers: NCT02945982; NCT02945956). Patients with compensated hepatitis B virus-related cirrhosis were enrolled from October 2017 to March 2021. The primary endpoint was a composite of liver events and the individual components, including variceal bleeding, ascites, overt hepatic encephalopathy, and hepatocellular carcinoma.

A total of 218 participants (Fuzheng Huayu group: 110 and control group: 108; mean age, 51.5 years; 66.5% male; median observational follow-up time, 23.1 months) were included in the primary analysis. The occurrence of total liver events was less frequent in the Fuzheng Huayu group than in the control group (hazard ratio = 0.408 [0.187–0.892], P = 0.020). Among the individual components of liver events, the incidence of ascites was significantly lower in the Fuzheng Huayu group than in the control group (1.8% vs. 9.3%, P = 0.016). In addition, the rate of variceal regression was significantly higher in the Fuzheng Huayu group (27.3% vs. 10.2%, P < 0.001). Finally, there were no significant differences in the occurrence of adverse events between the two groups.

In this post hoc analysis of two randomized controlled trials, adjunctive Fuzheng Huayu plus entecavir was associated with fewer liver-related events, particularly ascites, and a higher rate of variceal regression than entecavir alone in patients with compensated hepatitis B virus-related cirrhosis. These findings warrant confirmation in adequately powered prospective studies.

Since their first inception, neuroendocrine neoplasms of the breast have undergone many iterations of classification and definition. Taken together with their extremely low incidence, the ever-evolving landscape has made diagnosis, treatment, and research exceedingly challenging.

Our patient is a 45-year-old female who had a breast mass with clinical workup favoring a breast primary. A diagnosis of small cell carcinoma was established after an extensive clinical and pathologic workup. The mass did not respond to traditional neoadjuvant platinum-based chemotherapy, and she underwent a total mastectomy. Shortly thereafter, imaging revealed widely metastatic disease involving the brain, chest, abdomen, and pelvis. She received whole-brain radiation and, given the previous lack of response to chemotherapy, was recommended to try off-label tarlatamab. To date, with a short-term follow-up of 5 months, after whole-brain radiotherapy administered concurrently with the first cycle of tarlatamab, subsequent imaging showed near-complete radiographic resolution of extracranial metastatic disease, while the brain lesions also showed radiographic resolution on follow-up MRI.

We report the novel and preliminary use of tarlatamab in a patient with small cell neuroendocrine carcinoma of the breast, with short-term follow-up. We also discuss the most critical challenges associated with this rare pathologic diagnosis and the important elements to consider to ensure that metastatic disease is excluded.

Colorectal cancer is a major cause of cancer morbidity and mortality worldwide, including in China. Screening can facilitate earlier detection and reduce disease burden, while primary healthcare institutions are central to population outreach, risk assessment, referral, and follow-up. However, resource constraints, limited public awareness, low screening adherence, and fragmented coordination continue to hinder implementation in community and rural settings. This mini review summarizes the epidemiological and health-economic rationale for colorectal cancer screening in primary healthcare and discusses organizational models, risk-stratified screening and referral, workforce training, quality control, data management, and information sharing. Available evidence supports coordinated pathways that link noninvasive initial screening to timely colonoscopy and follow-up, supported by clear governance, trained personnel, and traceable data systems. The ongoing Yazhou District program is included briefly as a descriptive example of how these components may be organized in practice. Future research should evaluate uptake, positivity, colonoscopy completion, lesion detection, adverse events, costs, and longer-term outcomes in diverse primary-care settings.

Traumatic brain injury (TBI) induces neuroimmune activation and metabolic reprogramming in microglia, but the transcriptional regulators underlying these responses remain unclear. This study aimed to integrate single-cell and bulk transcriptomic datasets to identify microglia-associated regulatory genes and characterize their potential roles in post-TBI neuroinflammatory and immunometabolic dysregulation.

We integrated single-cell RNA sequencing data (GSE101901) with a bulk training dataset (GSE58485) and an independent bulk validation dataset (GSE242025) from murine TBI models. hdWGCNA, differential expression, pseudotime, CIBERSORT, and in silico transcription factor binding-site analyses were performed to identify and characterize candidate genes. Key-gene expression was additionally validated by RT-qPCR in male C57BL/6 mice assigned to Sham and TBI groups (n = 5 per group). The Drug Gene Interaction Database was used for exploratory drug-gene prediction.

Single-cell profiling suggested descriptive shifts in the proportions of microglia, astrocytes, and neurons after TBI. hdWGCNA identified 90 microglia-associated genes, 43 of which overlapped with nominally differentially expressed genes; 89 genes met the Benjamini–Hochberg-adjusted P < 0.05 threshold in the bulk analysis. Cross-dataset validation identified increased Ccl4 and Lgals3 expression and decreased Egr1 expression. Motif scanning identified four predicted EGR1 motif occurrences in the Ccl4 promoter and six occurrences at three unique locations in the Lgals3 promoter. RT-qPCR in TBI and Sham mice (n = 5 per group) supported the same directional expression changes in Ccl4, Lgals3, and Egr1.

A candidate Ccl4/Lgals3/Egr1 expression pattern characterized by Ccl4 and Lgals3 upregulation and Egr1 downregulation was associated with post-TBI neuroinflammatory and immunometabolic changes. Further mechanistic validation is required.