Kai Deng

Background: Remnant gastric cancer (RGC) may develop over markedly different intervals after gastrectomy. We investigated the time-dependent clinicopathological patterns of RGC after Billroth II reconstruction and their implications for endoscopic surveillance. Methods: We retrospectively reviewed patients diagnosed with RGC at West China Hospital between October 2012 and October 2022. Patients were classified by the indication for initial gastrectomy (malignant or benign disease) and the interval to RGC detection (≤3 years, >3 to ≤10 years, and >10 years). Results: Sixty-one patients were included; 39 (63.9%) had tumors at the anastomotic site. Histology was classifiable in 48 patients, of whom 45 had undifferentiated carcinoma (93.8%; 73.8% of the total cohort). The interval to RGC detection was shorter in the carcinoma group than in the benign-disease group (4.8 ± 5.7 vs. 31.6 ± 12.9 years, p < 0.001). Eighteen of 36 patients (50.0%) in the carcinoma group were diagnosed within 3 years, whereas 23 of 25 patients (92.0%) in the benign-disease group were diagnosed after 10 years. All 18 RGCs diagnosed ≤3 years after the initial gastrectomy occurred in patients whose initial indication was gastric carcinoma. In exploratory unadjusted pairwise comparisons among patients with known distant-metastasis status, distant metastasis was more frequent in the ≤3-year group than in the >10-year group (11/17 [64.7%] vs. 6/25 [24.0%], p = 0.012), whereas surgery for RGC was less frequent (5.6% vs. 53.8%, p = 0.001). Conclusions: RGC after Billroth II reconstruction showed distinct temporal patterns. Associations with metastatic burden and surgical treatment were exploratory, and the effects of postoperative interval and initial indication could not be reliably separated. These hypothesis-generating findings require prospective validation before specific surveillance intervals can be recommended.

Objective: To compare the circumferential proportion of mucosal defects, defect length, and the length-to-residual mucosal proportion (LRP) index for predicting esophageal stricture after endoscopic submucosal dissection (ESD) in patients with mucosal defects ≥6 cm, and to explore LRP in defects >10 cm. Methods: This retrospective study included 378 patients undergoing esophageal ESD from February 2014 to June 2020, grouped by stricture status. LRP was defined as defect length divided by residual mucosal proportion, with residual mucosal proportion set at a lower bound of 0.05 for statistical calculation. Receiver operating characteristic analysis compared the three indicators, including subgroup analysis for defects >10 cm. Results: Postoperative stricture occurred in 82 patients (21.7%). Circumferential proportion, defect length, and LRP were higher in the stricture group than in the non-stricture group (all p < 0.001). In the overall cohort, circumferential proportion and LRP showed comparable discrimination (AUC 0.877 vs. 0.876; p = 0.825), both outperforming defect length alone (AUC 0.694; both p < 0.001). In defects >10 cm, LRP showed the highest numerical AUC (0.913), followed by circumferential proportion (0.886) and defect length (0.668). Multivariable analysis confirmed that LRP was independently associated with stricture (per 10-unit increase: OR = 1.225; 95% CI, 1.150–1.304; p < 0.001). Conclusions: LRP was comparable to circumferential proportion and may serve as an exploratory complementary metric in long-segment defects, warranting external validation.

The heterogeneity of HIV-1 reservoirs in latency depth poses a major barrier to cure, yet the underlying mechanisms remain unclear. Here, we established a monoclonal T cell system modeling two latency phenotypes: spontaneously reactivated and deep latent proviruses. Using high-resolution chromatin conformation capture targeting the proviral 5’long terminal repeat, along with assays for chromatin accessibility, histone modifications, and three-dimensional genome architecture, we systematically investigated determinants of latency heterogeneity. Deep latent proviruses preferentially integrated into heterochromatic regions, whereas reactivated proviruses resided near promoters and super-enhancers with elevated local active marks. Spatial contacts between provirus and active chromatin elements, as well as nuclear compartment identity, did not differ between phenotypes. Instead, local linear genomic features, not long-range three-dimensional interactions, emerged as dominant determinants of latency depth. Our study provides a framework for understanding HIV-1 latency heterogeneity, redefines its mechanistic basis, and highlights the need to target distinct latency depths for cure.

As the primary receptor for HIV-1 entry, human CD4 is widely recognized as the hallmark of HIV-1 target cells. However, viral negative factor (Nef) and viral protein U (Vpu) down-regulate surface CD4 on infected cells, raising an intriguing question: If an infected CD4 ⁺ T cell survives and establishes latency, can CD4 expression recover? By tracking the fate of HIV-1–infected CD4 ⁺ T cells, we unexpectedly found that a subset of these cells directly convert to CD8 ⁺ T cells. T cell receptor (TCR) sequencing and single-cell RNA sequencing data revealed that these induced CD8 ⁺ T cells primarily originated from regulatory CD4 ⁺ T cells, which retained a regulatory-like phenotype postconversion. Mechanistically, HIV-1 viral protein R (Vpr) specifically induced this conversion by up-regulating transforming growth factor–β1 (TGF-β1), which, in turn, activates a TGF-β–dependent signaling pathway essential for CD8 lineage reprogramming. Critically, ex vivo analyses confirmed that CD8 ⁺ T cells from both untreated and antiretroviral therapy (ART)–suppressed people living with HIV-1 (PLWH) harbor transcriptionally active viral RNA or intact proviral DNA. Furthermore, we identified that human leukocyte antigen (HLA) class II–restricted CD8 ⁺ T cells, which were present in PLWH but absent in healthy controls, share TCR clonotypes with their antigen-specific CD4 ⁺ T cell counterparts, providing direct evidence for HIV-1–driven CD4-to-CD8 conversion in vivo. Collectively, these findings uncover a viral mechanism of host-cell reprogramming, demonstrate that CD8 ⁺ T cells constitute a previously overlooked component of the HIV-1 reservoir, and broaden our understanding of latent reservoir heterogeneity, an essential consideration for future cure strategies.

Background: Esophageal cancer (EC) lacks robust biomarkers to guide prognosis and therapy. Histone chaperone–related genes (HCRGs) shape chromatin states, but their roles in EC remain unclear. We integrated histone chaperone–based transcriptomic stratification with two-sample Mendelian randomization (MR) to identify genes with genetic evidence consistent with EC susceptibility and clinical relevance. Methods: RNA-seq and clinical data from TCGA-ESCA (184 tumors with available RNA-seq data and 13 normal samples) and an external cohort (GSE53624; 119 tumors, 119 normals) were analyzed. Prognosis-associated HCRGs informed unsupervised clustering. Differentially expressed genes common to cluster and tumor-versus-normal contrasts entered a two-sample MR framework using eQTL instruments and an EC GWAS (998 cases, 475,308 controls; European ancestry). Sensitivity analyses and the Steiger directionality test were then performed, followed by expression analysis to identify hub genes. We assessed survival associations, performed functional enrichment and immune deconvolution (CIBERSORT), modeled drug sensitivity (GDSC-based prediction), built a clinicogenomic nomogram, and validated expression by RT-qPCR in paired tissues. Results: HCRG-based clustering separated patients with distinct overall survival. MR implicated 26 genes in EC risk; among these, ADORA2B and SAPCD2 were consistently overexpressed in tumors (external validation and RT-qPCR) yet higher tumor expression predicted longer survival. Both genes were linked to cell-cycle and spliceosome programs; ADORA2B showed additional immuno-metabolic enrichment, whereas SAPCD2 mapped to metabolic/proteostasis pathways. High-expression groups exhibited reduced regulatory T-cell proportions and broader immune shifts. Predicted drug response suggested greater sensitivity to vinorelbine/etoposide but reduced sensitivity to paclitaxel in ADORA2B/SAPCD2-high tumors. A prognostic nomogram combining gene expression with stage and nodal status achieved 1–3-year AUCs of 0.67–0.75. Conclusions: Integrating HCRG-guided stratification with MR nominates ADORA2B and SAPCD2 as MR-supported biomarkers that are overexpressed in EC yet mark favorable prognosis, a pattern consistent with a less immunosuppressive microenvironment and distinct chemosensitivity. These genes warrant histology-stratified validation and mechanistic studies and may aid risk stratification and therapeutic decision-making.

Background Early detection of gastric cancer is vital for improving patient outcomes. While endoscopy with biopsy remains the gold standard for diagnosis, its invasiveness hinders its use in population screening. Computed tomography (CT), though widely available, has limited sensitivity for early gastric cancer (EGC). This exploratory study aimed to identify characteristic imaging indicators of EGC on multi-spectral CT (MSCT). Methods This retrospective study analyzed MSCT data from 141 patients (144 lesions) to identify and analyze imaging characteristics of EGC. Receiver operating characteristic analysis was employed to evaluate the discrimination performance of various parameters, and a least absolute shrinkage and selection operator (LASSO) regression model was constructed for discrimination. Subsequently, data from lesions and adjacent normal gastric mucosa in 51 EGC patients were used for external validation of the model’s discrimination efficacy. Results MSCT imaging revealed that the mean CT and effective atomic number (Effective-Z) values of EGC lesions were significantly higher than those of adjacent normal mucosa in both arterial and venous phases. Although multiple parameters showed significant differences, the discrimination efficacy of any single indicator was limited. The multivariate discrimination model constructed with LASSO regression demonstrated excellent performance, achieving area under the curve (AUC) values exceeding 0.90 in the training set, internal validation set, and external independent validation. Conclusion MSCT shows significant advantages in the imaging evaluation of EGC. The identification model constructed by integrating multiple imaging parameters may effectively improve the discrimination rate of EGC, providing a new reference for clinical practice. Graphical abstract

Background: Endoscopic resection (ER) is the main treatment for T1 superficial esophageal cancer (SEC). Additional surgical resection (ASR) is recommended to improve the prognosis of patients with non-curative resection who are at high risk of recurrence and metastasis. However, the survival benefit of ASR compared to non-ASR remains unclear. We conducted a systematic review and meta-analysis to quantify the survival benefits of ASR versus non-ASR, providing robust data for clinical decision-making. Method: We searched PubMed, Cochrane, Embase, and Web of Science databases for studies published before 24 February 2025. The primary outcome was overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS). Two independent reviewers screened and extracted the data and resolved disagreements by consensus. Risk of bias was assessed with Newcastle–Ottawa Scale. Results: The review identified 15 retrospective studies involving 1348 patients. Analysis showed that patients with ASR had significant survival advantages over non-ASR patients in OS, RFS, and DSS. Hazard ratios (HRs) with 95% confidence intervals (CIs) were as follows: OS (HR = 3.06; 95% CI: 2.11–4.43), RFS (HR = 1.68; 95% CI: 1.16–2.41), and DSS (HR = 4.11; 95% CI: 1.64–10.28). Survival curves indicated that at 3, 5, and 10 years, the OS rates were 95.9% versus 88.0%, 91.4% versus 78.2%, and 86.7% versus 56.9% for the ASR and non-ASR groups, respectively. Similarly, the RFS rates were 93.4% versus 82.9%, 83.6% versus 73.8%, and 74.5% versus 57.5%. For DSS, the rates were 98.4% versus 94.5%, 97.8% versus 91.1%, and 97.8% versus 87.9%. Log-rank tests confirmed significance for all comparisons except 10-year DSS. Conclusions: For patients with T1 SEC who had non-curative ER, ASR therapy provides advantages over non-ASR therapy. However, within 5 years, the DSS difference between the ASR and non-ASR groups is likely to be minimal, with a range of approximately 4–6%.