Colorectal cancer (CRC) is one of the most common malignancies worldwide and a leading cause of cancer-related mortality. The gut microbiome has attracted growing attention because of its involvement in CRC initiation and progression, early detection, prognostic evaluation, and therapeutic response. However, CRC microbiome studies continue to face inconsistent findings and limited reproducibility, partly because of differences in specimen type. Directly comparing microbial signals from fecal, mucosal, and intratumoral samples may therefore bias mechanistic interpretation and mislead clinical translation. From a spatial-niche perspective, this review summarizes the distinct characteristics, formation mechanisms, interrelationships, and clinical implications of fecal, mucosal, and intratumoral microbiota during CRC progression. We further propose a "seed bank-colonizers-specialized populations" model to conceptualize the continuous but non-equivalent hierarchy among these niches. By providing a clearer spatially stratified framework, this review aims to help move CRC microbiome research beyond descriptive associations toward precision-oriented applications supported by mechanistic interpretability, reproducible evidence, and clinical translatability.

Thyroid cancer (TC) and colorectal cancer are common malignancies of the endocrine and gastrointestinal systems, respectively, and continue to impose a substantial global disease burden. The tumor immune microenvironment (TIME) plays a central role in tumor initiation, progression, and therapeutic response; however, the cellular composition and intercellular communication networks within the TIME exhibit marked heterogeneity between these two malignancies. Recent advances in single-cell sequencing and spatial transcriptomics have revealed complex and dynamic alterations in immune cell subsets, stromal cell functions, cytokine networks, and metabolic programs within the TIME. In particular, bidirectional communication between tumor cells and immune cells has emerged as a critical determinant of immune evasion and therapeutic resistance. Nevertheless, most existing studies have focused on individual tumor types, and systematic comparisons of the shared and distinct features of the TIME in thyroid cancer and colorectal cancer remain limited. Moreover, combination therapeutic strategies targeting the TIME are still under active investigation. This review systematically compares the immune microenvironments of thyroid cancer (TC) and colorectal cancer (CRC), highlighting the development of more precise and effective immunotherapeutic strategies for thyroid cancer and colorectal cancer.

Colorectal cancer (CRC) remains a major cause of cancer mortality, with up to 26% of adenomas missed on conventional colonoscopy. Artificial intelligence (AI)-based computer-aided detection (CADe) systems may reduce these miss rates. We aimed to validate the iIDEAS-C CADe module in a prospective cohort, with co-primary endpoints of adenomas per colonoscopy (APC) and lesion-level miss rate.

In this prospective, nonrandomized, single-center study (NCT05784935), consecutive adults (18-75 years) undergoing screening, surveillance, or diagnostic colonoscopy were enrolled between February and May 2023. Each colon segment was inspected twice: an initial blinded withdrawal without CADe, followed by a second inspection with iIDEAS-C. Missed lesions were those identified by CADe during the second inspection and confirmed endoscopically. Secondary outcomes included PDR, ADR, PPC, lesion characteristics, and procedural times.Two hundred patients (mean age 44.1 ± 12.7 years; 64% male) were included. Eighty-two polyps were detected across 42 patients (PDR = 21%). Endoscopists detected 61/82 polyps (74.4%), yielding a per-polyp miss rate of 25.6%. The iIDEAS-C module detected all 82 lesions, achieving 0% per-polyp and per-adenoma miss rate. Missed lesions were mostly diminutive and proximal. PPC increased from 0.305 to 0.410 (p < 0.0001), PDR from 17.5% to 21.0% (p = 0.016), and APC from 0.115 to 0.140 (p = 0.029). No adverse events occurred.

The iIDEAS-C module demonstrated a 0% lesion-level miss rate and significantly improved key detection metrics, especially for small proximal lesions. Larger multicenter studies are warranted to confirm these findings and assess long-term outcomes. ClinicalTrials.gov: NCT05784935. Trial Registration: ClinicalTrials.gov identifier: NCT05784935.

Chronic pancreatitis (CP) creates an inflammatory pancreatic microenvironment and is an established risk factor for pancreatic cancer (PC). However, immune-inflammatory links between CP and PC remain unclear. Isorhamnetin (ISO), a natural flavonoid with anti-inflammatory and antitumor activities, may influence pancreatic inflammatory signaling. This study investigated ISO-associated molecular networks shared by CP and PC, examined the relationships between prioritized targets and transcriptome-estimated immune-cell infiltration, and evaluated the effects of ISO in pancreatic cancer cells.

CP- and PC-associated targets were collected from disease databases, and ISO targets were obtained from drug-target prediction platforms. Disease- and ISO-related targets were analyzed using protein-protein interaction networks, functional enrichment, and hub-gene screening. The expression, prognostic relevance, diagnostic performance, and immune infiltration associations of hub genes were evaluated using TCGA-PAAD, GTEx, Kaplan-Meier Plotter, ROC analysis, and CIBERSORTx. Molecular docking and 100 ns molecular dynamics simulations assessed ISO-target binding stability. Two-sample Mendelian randomization (MR) explored potential causal associations between genetically proxied circulating levels of the six hub proteins and CP or PC risk. The effects of ISO on proliferation, wound closure, apoptosis, and target protein expression were examined in PANC-1 and BXPC-3 cells.

372 overlapping CP- and PC-associated targets and 48 ISO-related targets were identified. EGFR, AKT1, MMP9, BCL2, TNF, and IL6 were screened as hub genes. Functional enrichment indicated targets were involved in inflammatory responses, cytokine-related signaling, apoptosis regulation, epithelial proliferation, pancreatic cancer-related pathways, and PI3K-Akt signaling. Hub-gene expression was correlated with CIBERSORTx-estimated immune-cell fractions, including activated natural killer cells and several T-cell subsets. Molecular docking and molecular dynamics simulations provided preliminary support for ISO-target interactions and complex stability. Across the 12 prespecified protein-outcome combinations, MMP9-CP was the only nominal IVW association. In vitro, ISO reduced the viability and wound closure of PANC-1 and BXPC-3 cells, promoted apoptosis, and decreased EGFR, AKT1, BCL2, and TNF-α protein expression in a concentration-dependent manner.

ISO may influence CP- and PC-associated molecular networks through multitarget regulation involving EGFR, AKT1, MMP9, BCL2, TNF, and IL6. These findings provide hypothesis-generating computational, genetic, and cellular evidence supporting investigation of ISO in pancreatic inflammation-associated tumor biology. However, immune regulatory effects, MMP9/IL6 protein modulation, and EGFR/AKT pathway activation require further experimental validation.

Clear cell renal cell carcinoma (ccRCC) is a major subtype of renal cell carcinoma and characterized by metabolic reprogramming, especially glycolysis. Neurexophilin 4 (NXPH4) is associated with malignancy of several cancers. However, its function in ccRCC remains unclear. In the current study, several online bioinformatics databases confirmed that NXPH4 was highly expressed in ccRCC tissues and was correlated with poor prognosis in patients with ccRCC. Notably, inhibition of NXPH4 suppressed cell viability, invasion and migration of ccRCC cells, and promoted cell apoptosis; while its overexpression produced the opposite effects. Further online database revealed a positive correlation between NXPH4 expression and glycolysis-related genes LDHA and HK2 in ccRCC tissues. Suppression of NXPH4 obviously decreased protein expression of LDHA and HK2 in ccRCC cells. Importantly, knockdown of NXPH4 attenuated glycolysis by inhibiting glucose uptake, lactate, ATP levels, extracellular acidification rate (ECAR) and increasing oxygen consumption rate (OCR); however, NXPH4 up-regulation promoted glycolysis. Intriguingly, the pro-tumor effects of NXPH4 were reversed by the glycolysis antagonist 2-DG. Additionally, NXPH4 elevation activated the PI3K/AKT pathway, while blocking this pathway significantly offset NXPH4-driven glycolysis, viability, invasion and migration. Collectively, NXPH4 may contribute to cancer cell growth and metastatic potential in ccRCC by activating the PI3K/AKT-evoked glycolysis, supporting it as a promising therapeutic target for ccRCC.

The recruitment of immune cells to the tumor microenvironment (TME) is an important component of immune regulation and tumor progression. Studying the spatial and temporal relationships between immune and tumor cells in vivo can provide insight into interactions within the TME. However, visualizing and quantifying these interactions in intact organisms remains challenging using conventional imaging and histological approaches. Zebrafish provide a valuable model for cancer research owing to their genetic tractability, rapid development, and optical transparency during early developmental stages, enabling visualization of fluorescently labeled cells in vivo. Here, we present a protocol to generate, identify, image, and quantify immune and tumor cells that are differentially labeled with fluorescent markers in a zebrafish model of neuroblastoma. The protocol includes breeding and screening of compound transgenic zebrafish, live imaging of larvae, preparation and imaging of adult tumor-bearing fish, and quantification of immune cells surrounding and within tumor regions. Using transgenic reporter lines, CD4⁺ immune cells and MYCN-driven neuroblastoma cells can be visualized and analyzed at different developmental stages. The workflow enables assessment of immune cell localization relative to tumors in both larval and adult fish and can be used to compare immune cell abundance across disease stages. This protocol provides a reproducible approach for imaging and quantifying immune cells within the TME in vivo using zebrafish and may facilitate studies of immune-tumor interactions in other cancer models.

A considerable proportion of patients experience post-acute sequelae of COVID-19 (PASC). Increasing evidence suggests sex-related differences, yet systematic longitudinal analyses remain limited. This study aimed to examine sex-specific differences in symptoms, psychological burden, work productivity and physical activity over ten months following acute COVID-19.

In this prospective, dynamically enrolled cohort study, patients with ongoing symptoms after confirmed SARS-CoV-2 infection were followed over a 10-month observation period. Patients conducted at the post-COVID outpatient clinic of the department of respiratory medicine and infectious diseases at Hannover Medical School, Germany. The assessment included patient-reported outcome measures, pulmonary function tests, six-minute walk tests, and capillary blood gas analysis. All outcome comparisons between sexes were adjusted for age, BMI, COVID-19 severity, and comorbidities using generalised linear mixed-effects models, with sex-by-time interaction terms tested to assess whether differences changed over follow-up, and p-values corrected for multiple testing across all outcome comparisons using the Holm method. A sensitivity analysis was performed in the subgroup of patients with complete follow-up at all four visits.

Five hundred ninety patients attended to our clinic and a total of 433 patients were eligible and consecutively enrolled. Males were older (56 years vs. 52 years, p = 0.002), had more cardiovascular comorbidities (16% vs. 5%, p < 0.001), and experienced more severe COVID-19 (28% vs. 8%, p < 0.001). After adjustment for age, BMI, COVID-19 severity, and comorbidities, and Holm correction for multiple testing across all 27 outcome comparisons, females showed higher fatigue (Fatigue Assessment Scale, adjusted β = 3.3, Holm-adjusted p = 0.006), higher anxiety (GAD-2, β = 0.5, p = 0.021), lower quality of life (EQ-5D-3L, β = -0.6, p = 0.004), and greater work productivity impairment, both as a continuous score (WPAI-VAS, β = 1.3, p = 0.031) and as a binary indicator of clinically relevant impairment (OR = 3.0, p = 0.020). Females also had higher percent-predicted (pp) total lung capacity (p < 0.0001) and lower pCO₂ (p < 0.0001), whereas males had higher pp diffusion capacity (p = 0.001). Headache (p < 0.001) and chest tightness (p = 0.011) were reported more frequently by females. None of these differences varied significantly over the 10-month follow-up (all sex-by-time interaction p ≥ 0.41), indicating no evidence that these differences changed over time. No significant sex differences remained after adjustment for depression (PHQ-2), lung function parameters, sex/height-adjusted exercise capacity, post-exercise dyspnoea or oxygen saturation, or most acute-COVID-19 symptoms other than headache and chest tightness. Regression models separately for each sex revealed fever (OR = 2.48, 95% CI: 1.11-5.57, p = 0.027) and diarrhoea (OR 2.33, 95%CI: 1.05-5.16, p = 0.038) during acute COVID-19 were associated with higher odds of work productivity impairment (WPAI-VAS ≥ 2) in males. In females, higher BMI (OR = 2.06, 95% CI: 1.13-3.76, p = 0.018) and dyspnoea during acute COVID-19 (OR = 4.38, 95% CI: 1.55-12.40, p = 0.005) were associated with increased odds. Formal interaction analyses showed a significant interaction only for dyspnoea after Holm correction.

After accounting for baseline imbalance in age, BMI, COVID-19 severity, and comorbidities, and after correcting for multiple testing, sex-specific differences persisted for fatigue, anxiety, quality of life, and work productivity impairment, as well as selected lung function parameters. These differences did not change significantly across the 10-month observation period and did not show a significant sex-by-time interaction. The findings support the need for individualised, sex-specific follow-up focused on fatigue, psychological burden, and work productivity in patients with PASC.

Objective: To compare demographic characteristics and healthcare-seeking behaviors of patients with chronic obstructive pulmonary disease (COPD) identified through community-based pulmonary function test (PFT) screening and symptom-prompted diagnosis via a regional health information platform in Songjiang district, Shanghai. Methods: A total of 2 038 COPD patients aged ≥40 years were included from a suburban population-based cohort and a regional healthcare information platform, including 216 screening diagnosed patients and 1 822 symptom-prompted diagnosed patients (the patients diagnosed in outpatients). Demographic characteristics and outpatient visits, hospitalizations, and respiratory-related visits during follow-up were compared. Associations between case-finding pathways and healthcare-seeking behaviors were analyzed by using a hurdle negative binomial regression model. Results: Compared with the screening-diagnosed group, the symptom-prompted diagnosed patients had higher proportion of women, lower prevalence of smoking and alcohol consumption, higher prevalence of respiratory comorbidities, and higher severity grade by Global Initiative for Chronic Obstructive Lung Disease. Compared with the screening diagnosed group, the symptom-prompted diagnosed group had higher risk for outpatient visits, respiratory illness-related outpatient visits, hospitalizations, and respiratory illness-related hospitalizations, with ORs of 17.28 (95%CI: 1.46-204.32), 13.30 (95%CI: 8.28-21.36), 2.26 (95%CI: 1.66-3.08), and 4.07 (95%CI: 2.10-8.31), respectively. In addition, the outpatient visit density, respiratory illness-related outpatient visit density, and hospitalization density were higher in the symptom-prompted diagnosed group than in screening diagnosed group, with RRs of 2.00 (95%CI: 1.80-2.22), 2.84 (95%CI: 2.35-3.43), and 1.52 (95%CI: 1.14-2.02) , respectively. Conclusions: Healthcare-seeking behaviors differed significantly by COPD case- finding pathway. The symptom-prompted diagnosed patients showed higher healthcare-seeking intensity, whereas community-based PFT screening was more likely to identify early-stage patients with lower healthcare dependence, supporting pathway-specific stratified management of COPD.

Objective: To analyzes the current status of delayed medical consultation and influencing factors in pulmonary tuberculosis (TB) patients aged ≥65 years in Henan Province from 2020 to 2024, and provide scientific evidence for the improvement of the prevention and control of pulmonary TB in the elderly. Methods: The information were collected from the Tuberculosis Information Management Subsystem of Chinese Information System for Disease Control and Prevention. Study participants were pulmonary TB patients aged ≥65 years who were registered and managed in Henan from January 1, 2020, to December 31, 2024. A retrospective epidemiological survey was conducted to collect information of elderly pulmonary TB patients with delayed medical consultation to understand the distribution and temporal variation trends of those with delayed medical consultation, and χ² test and multivariate logistic regression model were used to identify the influencing factors of delayed medical consultation. Results: A total of 50 031 elderly pulmonary TB patients were included, in whom 26 783 had delayed medical consultation, with an overall delayed consultation rate of 53.53%. The median time (Q₁, Q₃) of delayed consultation was 16.0 (4.0, 37.0) days. The delayed consultation rate remained stable at 50.49%-50.94% from 2020 to 2022, then increased rapidly to 55.97% in 2023 and 58.41% in 2024, showing an accelerating upward trend (trend χ²=193.65, P<0.001). In terms of regional distribution, the delayed consultation rate was lowest in Zhumadian (32.00%) and highest in Luohe (77.27%), the difference was significant (χ²=2 428.79, P<0.001). Multivariate logistic regression analysis revealed that the risk factors for delayed medical consultation included jobless/unemployment (aOR=1.24, 95%CI: 1.14-1.36), direct hospital visit (aOR=3.86, 95%CI: 3.07-4.85), referral (aOR=3.45, 95%CI:2.75-4.34), follow-up (aOR=4.31, 95%CI: 3.42-5.42), no complication (aOR=2.15, 95%CI:1.97-2.35), recurrence (aOR=1.30, 95%CI: 1.22-1.39), return visit (aOR=1.84, 95%CI:1.01-3.33), and lack of etiological results (aOR=1.99, 95%CI: 1.29-3.06). Conversely, protective factors were being man (aOR=0.93, 95%CI: 0.89-0.97), population at low risk (aOR=0.59, 95%CI: 0.53-0.65), and non-floating population (aOR=0.89, 95%CI: 0.82-0.96). Conclusions: The rate of delayed medical consultation in elderly pulmonary TB patients in Henan remained stable from 2020 to 2022, then increased rapidly in 2023 and 2024, with an unbalanced regional distribution. More attention should be paid to the early detection of elderly pulmonary TB, especially in women, farmers, floating population, cases identified by passive screening (direct hospital visit, referral and follow-up), those have recurrent illness or lack etiological test results. It is suggested to effectively conduct digital chest radiography screening for the elderly population in combination with basic public health services and strengthen the full-course management and regular follow-up of recurrent patients.

Reports worldwide on suspected child maltreatment (CM) during and after the COVID-19 pandemic have been inconsistent. As no study has yet systematically examined whether structural disruptions to child protection systems have left measurable and lasting traces in referral patterns beyond the acute crisis phase, this study investigated the pandemic's impact on suspected CM referrals to the Forensic Examination Center for Children and Adolescents (FOKUS) in Vienna, Austria, and whether enduring shifts in CM presentation and referral dynamics have occurred.

Retrospective study using patient administrative data of suspected CM cases referred to FOKUS between 16 March 2019 and 15 March 2023, covering the periods before, during and after the pandemic.

A total of 401 patients were referred to FOKUS during the study period. During the COVID-19 period, suspected physical abuse cases declined by 55.3% (p=0.029), while sexual abuse cases remained stable. Post-pandemic reports of suspected physical abuse returned to pre-pandemic levels, whereas suspected sexual abuse cases increased (p=0.013). Suspected sexual abuse cases showed a progressive increase in median age over time (p=0.025). Psychological support was more frequently required during the pandemic (63.5% vs 43.8% pre-pandemic, p=0.019), with elevated need continuing into the post-pandemic period (59.8%, p=0.018).

The ongoing rise in suspected sexual abuse cases accompanied by different age victim profiles and increased need of psychological support following the pandemic indicates that a return to pre-pandemic norms is unlikely and the notion of 'back to normal' seems an oversimplification.