Colorectal diseases pose a serious threat to human health, and conventional endoscopy has limitations in lesion characterization. This consensus aims to clarify the indications, operational specifications, image interpretation criteria, and quality control requirements for probe-based confocal laser endomicroscopy (pCLE) in lower gastrointestinal diseases, particularly colorectal cancer, precancerous lesions and polyps, and inflammatory bowel disease (IBD). A systematic literature search covered PubMed, Embase, the Cochrane Library, CNKI, and Wanfang Database through August 2026. Evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts participated in two rounds of discussion and online voting, with agreement ≥80% required for consensus. Eight recommendations were finalized: five strong and three weak. Strong recommendations address colorectal lesion differentiation, targeted biopsy, mucosal barrier assessment, ulcerative colitis mucosal healing and relapse prediction, and IBD-associated colorectal neoplasia surveillance. Weak recommendations address distal resection margin assessment during radical surgery for low rectal cancer, irritable bowel syndrome research, and adjunctive IBD diagnosis and differentiation. Evidence for endoscopic resection margin assessment remains insufficient, and pCLE is not recommended for routine diagnosis of irritable bowel syndrome. pCLE provides adjunctive microscopic information for colorectal lesion characterization, targeted biopsy, and IBD assessment and surveillance; in IBD diagnosis, it does not replace conventional endoscopic and histopathological evaluation. This consensus provides evidence-based guidance for standardized clinical application.

N-acetyltransferase 10 (NAT10), a major RNA acetyltransferase mediating N4-acetylcytidine modification, has been implicated in cancer progression. We examined its cancer-type-specific associations with clinical outcomes, genomic features, and tumor immune characteristics.

We analyzed public TCGA and GTEx datasets using UCSC Xena and complementary resources, including GEPIA2, HPA, cBioPortal, TIMER2.0, STRING, LinkedOmics, and CancerSEA. Analyses included NAT10 expression, pathological stage, survival, genomic alterations, immune-cell infiltration, stemness, and molecular pathways. Exploratory immune-checkpoint-blockade (ICB) survival analyses used Kaplan–Meier Plotter cohorts receiving anti-PD-1 (n = 411), anti-PD-L1 (n = 459), or anti-CTLA-4 (n = 112).

NAT10 expression was elevated in multiple cancer types and was associated with adverse survival in selected malignancies. Higher NAT10 expression correlated positively with estimated myeloid-derived suppressor cell and cancer-associated fibroblast infiltration and negatively with several T-cell and natural killer-cell populations. NAT10-associated genes were enriched in RNA-processing pathways. In exploratory ICB cohorts, higher NAT10 expression was nominally associated with longer overall survival following anti-PD-1 therapy (hazard ratio (HR) = 0.68, 95% confidence interval (CI): 0.52–0.90) and anti-PD-L1 therapy (HR = 0.72, 95% CI: 0.56–0.92), but not anti-CTLA-4 therapy (HR = 0.66, 95% CI: 0.39–1.11).

NAT10 shows cancer-type-dependent prognostic, molecular, and immune associations. Its associations with survival after ICB are exploratory and require independent clinical and mechanistic validation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a rapidly increasing global health concern, driven by metabolic stress, chronic inflammation, and progressive fibrotic remodeling. Myeloid-derived suppressor cells (MDSCs) have emerged as pivotal yet context-dependent modulators of MAFLD pathogenesis. This review summarizes the biological characteristics of MDSCs, their immunosuppressive mechanisms, and their multifaceted roles in MAFLD progression, including hepatic steatosis, chronic inflammation, and fibrogenesis. Quantitative synthesis reveals that murine models demonstrate MDSC expansion (∼3-fold with a high-fat diet, P < 0.05) and suppression of MDSC-associated proinflammatory mediators (e.g., MitoTEMPO reduced hepatic S100A8 mRNA by 5.9-fold, P < 0.001). In one human cohort (n = 98), hepatic CD33+/HLA-DR− MDSC density correlated with inflammation grade (Spearman r = 0.610, P < 0.001) and fibrosis stage (r = 0.687, P < 0.001), though this cross-sectional dataset lacked MAFLD-specific stratification and longitudinal validation. We further discuss emerging MDSC-targeted strategies and explicitly acknowledge current translational gaps. Collectively, this review provides a mechanistic and critically appraised framework positioning MDSCs as both promising therapeutic targets and potential biomarkers for MAFLD.

On the surface there does not appear to be a connection between chickenpox and migraine but, on closer examination, both conditions are associated with neuroinflammation and, because almost every human throughout history was infected with the varicella-zoster virus, it is possible that it could have triggered certain medical disorders in our ancestors. We propose a hypothesis that the acute chickenpox infection may have contributed to the appropriate environment to prime the brains of early humans for migraine. Several inflammatory mediators and immune cells involved in migraine also participate in the immune response to primary varicella infection. This, together with the fact that the virus establishes chronic latency in the trigeminal ganglia, may have contributed to a sensitized trigeminovascular system that could produce migraine if the correct susceptibility genes and exposures were present. These postinfectious neuroinflammatory reactions would also have the capability of producing a hyperexcitable cortex, hypothalamic generator and cortical spreading depression, which are the key components of migraine pathophysiology. Other supporting observations include the coexistence of varicella-zoster virus and migraine in early humans, the fact that chickenpox occurs prior to the age of migraine onset in most individuals, and the recent recognition that the proportion of US migraine patients with moderate-to-severe disability rose from 22.0% to 42.4% following implementation of the varicella vaccination program. We propose that chickenpox may have acted as an evolutionary trigger for migraine.

Pegylated interferon alpha (PegIFNα) has been associated with altered lipid metabolism, but long-term lipid trajectories in chronic hepatitis B remain poorly characterized. We evaluated lipid profiles and virological parameters during 144 weeks of PegIFNα-based therapy.

This single-center retrospective cohort study included 129 patients with chronic hepatitis B who completed 144 weeks of PegIFNα monotherapy, PegIFNα plus tenofovir alafenamide, or PegIFNα plus entecavir. Serum lipids, hepatitis B surface antigen (HBsAg), hepatitis B e antigen, and hepatitis B virus DNA were assessed at baseline and weeks 24, 48, 72, 96, and 144. Within-patient changes were analyzed with paired tests. Associations between early lipid changes and on-treatment HBsAg seroclearance at week 144 were examined with logistic regression.

From baseline to week 144, mean high-density lipoprotein cholesterol (HDL-C) increased by 0.10 ± 0.25 mmol/L (95% confidence interval, 0.06 to 0.15; P < 0.001) and mean total cholesterol decreased by 0.15 ± 0.41 mmol/L (95% confidence interval, −0.22 to −0.08; P < 0.001). Changes in triglycerides, low-density lipoprotein cholesterol, and the triglyceride-to-HDL-C ratio were not significant. HDL-C declined early and later recovered above baseline. At week 144, 37 patients (28.7%) achieved on-treatment HBsAg seroclearance (≤ 0.05 IU/mL). Of the 34 patients with HBsAg seroclearance at week 96, 13 had detectable HBsAg again at week 144. Early lipid changes were not associated with this endpoint.

HDL-C shows an early decline followed by recovery above baseline, whereas total cholesterol decreases modestly, with no significant net changes in triglycerides, low-density lipoprotein cholesterol, or the triglyceride-to-HDL-C ratio. Early lipid changes are not significantly associated with on-treatment HBsAg seroclearance. The durability of HBsAg loss requires post-treatment follow-up.

We compared logistic regression, random forest, and extreme gradient boosting (XGBoost) for classifying current colorectal cancer screening status among U.S. adults aged 45–75 years.

We analyzed 2024 Behavioral Risk Factor Surveillance System data for 227,647 adults aged 45–75 years with determinable screening status. Data were split into stratified training and held-out test sets before imputation. Missing predictors were handled with 20 multiply imputed datasets; imputation and preprocessing were fitted in training data and applied to held-out data. Model performance was assessed using five-fold cross-validation and the held-out test set.

In the test set, areas under the receiver operating characteristic curve were 0.771 for logistic regression, 0.778 for random forest, and 0.781 for XGBoost; corresponding areas under the precision-recall curve were 0.884, 0.888, and 0.890. Brier scores were 0.152, 0.153, and 0.149, respectively. At model-specific Youden thresholds, sensitivity ranged from 75.5% to 78.6% and specificity from 62.5% to 66.3%.

XGBoost has the highest discrimination and lowest Brier score, but differences among models are small. The models classify current screening status in this analytic cohort; external validation is needed before use in screening outreach.

CRKL is a non-catalytic Src homology 2 (SH2)/Src homology 3 (SH3)-domain adaptor protein implicated as an oncogenic driver across a wide range of human malignancies, yet existing literature is fragmented across tumor-type-specific studies of uneven evidentiary strength; evidence for CRKL is often conflated with studies of its paralog Crk, and directly conflicting functional findings in at least one cancer type remain unreconciled. This review synthesizes CRKL’s structure and signaling mechanism across ten cancer types: breast, hepatocellular, non-small-cell lung, pancreatic, ovarian, gastric, laryngeal squamous cell, and colorectal carcinoma, cutaneous melanoma, and chronic myeloid leukemia (CML), framed against the Insulin Receptor Substrate (IRS) family as a conceptual precedent for adaptor-protein oncogenesis. In several solid tumors reviewed, CRKL overexpression or amplification shows a recurring signaling framework involving SH2-mediated docking onto activated oncoproteins coupled through its SH3 domains to C3G, SOS1, and DOCK180, driving RAS/RAP1-ERK signaling, proliferation, and MMP2/MMP9-dependent invasion, with overexpression generally associated with advanced stage and reduced survival. Hepatocellular carcinoma is a documented exception, where human-tissue and murine cell-line studies report opposing functional directions for CRKL. Evidentiary strength varies substantially across cancers: CML has the strongest translational evidence, with phosphorylated CRKL used as a pharmacodynamic biomarker of BCR-ABL kinase inhibition in clinical-trial and research settings, distinct from routine BCR::ABL1 monitoring; most solid tumors are supported by preclinical amplification, expression, and knockdown data; and immune-related associations with CRKL have been reported in melanoma, while a direct immune-evasion mechanism has been demonstrated in hepatocellular carcinoma; these relationships remain largely unexamined elsewhere. This review identifies concrete research gaps, including the unresolved CRKL-Crk relationship and the largely unpursued opportunity to target CRKL’s SH2/SH3 interfaces therapeutically. Overall, CRKL emerges as a recurrently implicated oncogenic adaptor with strong mechanistic and translational support in selected settings, most notably CML, and a rational candidate for future drug discovery, rather than an already-established pan-cancer therapeutic target.

Ascites is the most frequent complication of cirrhosis, signaling the transition from compensated to decompensated liver disease. While traditionally linked to portal hypertension, arterial vasodilation, and renal sodium retention, previous research has broadened our understanding of its pathophysiology. The hepatic and splanchnic lymphatic systems are increasingly recognized as potential contributors to decompensation in cirrhosis. The elevated sinusoidal pressure in cirrhosis markedly increases lymph production, which is initially compensated by expanded lymphatics and lymphangiogenesis. However, progressive cirrhosis impairs lymphatic function by inducing abnormal lymphangiogenesis, vessel dilation, and poor contractility, which collectively reduce drainage. When lymph overproduction exceeds the maximum drainage capacity of the lymphatic system, the fluid leaks through the subcapsular lymphatics, leading to leakage of protein-rich lymph through the liver surface into the peritoneal cavity—a phenomenon often referred to as a “weeping liver.” The osmotic gradient of this protein-rich fluid, combined with hydrostatic pressures and lymphatic failure, may draw additional fluid from the splanchnic circulation and contribute to ascites development and progression. Simultaneously, dysfunction of the gut-splanchnic lymphatic axis may promote intestinal edema, bacterial translocation, and systemic inflammation, thereby reinforcing portal hypertension and contributing to downstream manifestations such as intestinal lymphangiectasia and refractory ascites. Yet, despite its pathophysiological relevance, the contribution of lymphatic failure to the complications of cirrhosis remains widely underappreciated. Recognizing this critical axis may help identify novel therapeutic targets in patients with cirrhosis. This review provides a detailed overview of lymphatic failure as a contributor to altered fluid dynamics and secondary complications in cirrhosis, offering a contextual evaluation of its therapeutic implications.