Search Results (1,071)

Background/Objectives: Organ shortage is a major barrier to transplantation, leading to the emergence of marginal donor organs and extended criteria donor grafts and, alongside these, machine perfusion as a platform for reconditioning grafts to meet transplantation standards. Despite functioning as a reconditioning platform in its own right, machine perfusion also allows for the delivery of therapeutic agents directly to grafts prior to transplant. Cell-based and cell-derived therapies have been increasingly explored for delivery during this window, although evidence is fragmented across individual organ systems, and whether ex vivo benefit is confirmed post-transplant remains unclear. This systematic review aimed to synthesise the evidence from both perfusion-phase findings and post-transplant findings across solid organ machine perfusion, evaluating the concordance between the two. Methods: This review was prospectively registered on PROSPERO and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Included studies delivered cell-based or cell-derived therapies during ex vivo machine perfusion of a solid organ. The SYRCLE tool was used across all studies to assess risk of bias, and given substantial heterogeneity in cell type, protocol, and organ models, findings were synthesised narratively, with a sensitivity analysis restricted to the subset of studies incorporating a transplantation phase. Results: Thirty-one studies met inclusion criteria, spanning kidney (n = 10), liver (n = 11), lung (n = 9), and heart (n = 1). Mechanisms converged largely on immunomodulatory and metabolic pathways, most consistently reported across organs, alongside a less consistent but notable cross-organ parallel in regenerative progenitor activation between liver and kidney. Benefit was reported more consistently at the molecular and histological levels rather than the physiological level. Eight of the studies proceeded to transplantation, of which half showed a beneficial post-transplant result, and half showed mixed results. Conclusions: Cell-based and cell-derived therapies are best understood as adjuncts to the existing reconditioning capacity of machine perfusion. Molecular and mechanistic benefit was consistently reported; however, confirmation beyond the perfusion phase remained incomplete across organ systems. Mechanisms supported by direct interventional evidence represent priority candidates for further preclinical validation and independent replication. Full article

Early extubation after pediatric liver transplantation (PLTx) is increasingly incorporated into enhanced-recovery pathways, yet definitions, selection criteria, and outcome reporting remain inconsistent. This narrative review synthesizes evidence identified through PubMed/MEDLINE (January 2000 through August 2026), citation screening, and supplementary screening of recent reports. Immediate extubation denotes tracheal extubation in the operating room, whereas early extubation has been defined through 24 postoperative hours; delayed extubation and prolonged mechanical ventilation are similarly heterogeneous. The available evidence informs a dynamic framework in which preoperative characteristics define baseline vulnerability, the intraoperative course reflects whether that vulnerability has been overcome or amplified, and the early postoperative course validates the decision. Young age, low body weight, growth failure, or higher disease-severity scores may increase risk but should not function as absolute exclusions; conversely, low scores may underestimate disease-specific risk in metabolic disorders. Direct readiness indicators include effective ventilation, neurological and quantitative neuromuscular recovery, normothermia, stable hemodynamics without escalating vasoactive support, controlled bleeding, satisfactory abdominal closure, and improving acid–base status and lactate clearance. Early extubation is associated with shorter intensive-care and hospital stays in selected cohorts, but causality remains uncertain because evidence is predominantly retrospective and single-center. Standardized definitions and prospective multicenter validation are required. Full article

Ecological and resource-related challenges increasingly require reconsideration of private-law categories. This article examines Article 9 of the Chinese Civil Code, the so-called Green Principle, as a heuristic tool for identifying the dogmatic effects of direct normative embedding of ecological values in civil-law reasoning. The analysis is based on a qualitative study of Supreme People’s Court Typical Cases from 2021–2026, supported by selected ordinary court judgments and Chinese legal scholarship. The article identifies three partly overlapping mechanisms: ecological integration of public and private law, ecological correction of obligations and remedies, and ecological gap-filling in new infrastructural conflicts. These mechanisms show how public-law standards may enter civil adjudication; how resource-related considerations may affect performance, termination and remedies; and how courts may formulate coordination rules where private law has not yet stabilised relevant rules. The article concludes that Article 9 of the CCC should not be treated as a model for direct transplantation, but as a diagnostic device. Its comparative value lies in mapping specific issues that ecological private law must address while preserving legal certainty, dogmatic coherence and its autonomous character. Full article

Background: Luminex-based single antigen bead assays are widely used for HLA antibody assessment in transplantation, but their semi-quantitative fluorescence outputs may be affected by technical, signal-dependent, and bead-specific factors. This single-center study evaluated inter-operator variability under routine laboratory conditions. Methods: Twenty serum samples were tested for each assay format: Class I SAB, Class II SAB, and screening. For each assay type, the same serum set was independently tested by four trained operators using the same Luminex FlexMap 3D instrument and xPONENT software version 4.3. Sera were EDTA treated, and exported trimmed mean fluorescence intensity values were analyzed at the sample–bead level. Variability was assessed using log-transformed inter-operator spread, threshold-based discordance, variance decomposition, direct item-level operator deviations, and bead-level variability profiling. Results: Overall variability was limited, with median item-level log-range values of 0.185, 0.172, and 0.181 in Class I, Class II, and screening assays, respectively. The analytical item accounted for most total variance. However, global discordance of 1.84–5.57% increased markedly near fixed thresholds, reaching 58.7–88.9% in Class I, 26.6–96.2% in Class II, and 57.1–90.9% in screening assays. Variability was signal dependent and unevenly distributed across beads. Conclusions: Luminex-based HLA antibody assays were globally reproducible but showed localized, signal- and bead-dependent vulnerability, particularly in threshold-sensitive regions. Full article

Colorectal cancer (CRC) arises within a complex microbial ecosystem that may influence carcinogenesis, tumor immunity, and therapeutic response. This is particularly relevant in metastatic disease, where most tumors are microsatellite-stable/mismatch repair-proficient (MSS/pMMR) and derive little meaningful benefit from immune checkpoint inhibitor (ICI) monotherapy. Specific pathobionts, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, have been implicated in genotoxic, inflammatory, and checkpoint-related mechanisms that may contribute to tumor progression and immune evasion, whereas selected commensals and microbiota-derived metabolites may support antitumor immunity in a context-dependent manner. This review integrates translational evidence linking microbial taxa and functions, metabolites, neutrophil biology, bacterial extracellular vesicles, and T-cell dysfunction with CRC progression and immunotherapy response. This review critically examines emerging microbiome-directed strategies, including fecal microbiota transplantation, next-generation probiotics, defined bacterial consortia, dietary and perioperative interventions, postbiotics, and bacteriophage-based approaches, as potential means of modifying immune resistance in MSS/pMMR CRC. Although early clinical signals from microbiota-modulating combinations are encouraging, the available evidence remains limited by small cohorts, heterogeneous interventions, and the absence of randomized CRC-specific studies. Microbiome-based biomarkers and therapeutics therefore remain investigational, and standardized sampling, prospective validation, and carefully designed trials will be required before microbiome modulation enters routine CRC care. Full article

Cognitive frailty combines physical frailty with cognitive impairment without dementia, identifying older adults vulnerable to adverse outcomes. Candidate microbiome-related pathways in cognitive frailty include dysfunction of the intestinal epithelial and blood–brain barriers, altered microbial metabolites, systemic and vascular inflammation, anabolic resistance, and neuroinflammation. However, direct evidence is scarce, and most findings derive from physical frailty, sarcopenia, mild cognitive impairment, or Alzheimer’s disease, inviting overinterpretation. This review integrates a multi-database evidence map with a domain-based synthesis of phenotypes, mechanisms, biomarkers, confounding, interventions, and clinical translation. Conducted up to 31 July 2026, the search identified one eligible primary human study directly examining the gut microbiome in cognitive frailty. Its small sample, age and educational imbalances, 16S-based resolution, and lack of external validation preclude clinical biomarker claims despite apparent discrimination. Larger metagenomic frailty studies report lower microbial diversity, gene richness, and butyrate-production capacity, with partial cross-population replication. Dietary, prebiotic, and probiotic trials demonstrate microbiome target engagement and report selected physical or cognitive benefits, but these outcomes are inconsistent, rarely assessed together, and not established as microbiome-mediated; fecal microbiota transplantation remains experimental. The microbiome should be considered a potential component of multidomain risk models rather than a stand-alone biomarker. Translation requires standardized phenotyping, longitudinal multi-omics, causal diagrams, external validation, and trials with concurrent physical and cognitive endpoints. Full article

Pleural and thoracic air-leak complications after hematopoietic cell transplantation (HCT) are clinically important but underrepresented in broad post-transplant pulmonary reviews. Direct evidence is concentrated in adult allogeneic HCT. In a cohort of 618 adults, clinically significant pleural effusion had a 1-year cumulative incidence of 9.9% (95% confidence interval, 7.7–12.5%). A separate computed tomography-based cohort of 178 first allogeneic HCT recipients reported a day-100 cumulative incidence of 41.0%; these estimates are not directly comparable because the populations, ascertainment methods, endpoints, and follow-up differed. In 50 HCT recipients undergoing thoracentesis, a specific diagnosis was established in 26%, with 5 pneumothoraces and 0 hemothoraces. Thoracic air-leak syndrome is uncommon but carries poor outcomes in reported adult and pediatric series. This focused narrative review distinguishes direct HCT evidence from data extrapolated from hematologic malignancy, general pleural practice, critical care, interventional radiology, and cellular therapy. We organize evaluation by urgency, transplant phase, and radiographic pattern; define chronic graft-versus-host disease serositis as a diagnosis of exclusion; summarize chylothorax and pleural infection management; and provide procedure-specific safety considerations for thoracentesis, small-bore drainage, indwelling pleural catheters, intrapleural enzyme therapy, and pleural biopsy. No prospective HCT-specific trials validate these procedural pathways. Clinicians should therefore use ultrasound or image guidance; apply procedure-specific rather than uniform hemostatic thresholds; and integrate infection risk, platelet trajectory, anticoagulant exposure, oxygenation, operator setting, and expected benefit. The two clinical frameworks presented are proposed and non-validated. Full article

Background/Objectives: Most patients with colorectal liver metastases (CRLM) present with disease beyond upfront technical resectability. Advances in systemic therapy, surgical technique, and liver-directed therapies have expanded the proportion of patients who can achieve curative-intent treatment, yet substantial heterogeneity in practice persists. This review provides a structured synthesis of current management strategies for borderline resectable, initially unresectable, and never resectable CRLM. Methods: A structured literature search of PubMed/MEDLINE, Embase, Scopus and the Cochrane Library was performed to identify studies published between 2000 and 2026 using the eligibility criteria described in Part 1 of this review. Findings were synthesized narratively across systemic, surgical, and liver-directed treatment strategies. Results: Future liver remnant augmentation through regenerative procedures offers higher rates of conversion to resection in borderline cases. Conversion chemotherapy enables secondary resection in 12–35% of initially unresectable patients, with regimen selection guided by RAS/BRAF status, primary tumor sidedness, and performance status; however, most pivotal trials were designed for the broader metastatic colorectal cancer population, with conversion to resection rarely serving as the primary endpoint. For never resectable liver-only disease, liver transplantation demonstrates survival advantage in highly selected patients and iterative local therapy remains an area of active investigation. Across all settings, achieving complete local treatment remains the strongest determinant of long-term survival. Conclusions: Management of complex CRLM requires individualized, multidisciplinary decision-making with repeated reassessment of resectability throughout treatment. The evidence is constrained by heterogeneous resectability definitions, reliance on trials not designed for CRLM-specific endpoints, and limited data on several emerging strategies. Standardized eligibility frameworks and CRLM-specific trial designs are needed to advance the field. Full article

Focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome and progression to end-stage kidney disease (ESKD). It remains one of the most consequential glomerular diseases in kidney transplantation because of its risk of recurrence in the allograft. Rather than a single disease, FSGS is a histopathological pattern of podocyte injury arising from primary, genetic, and secondary causes. Recurrent FSGS (rFSGS) is predominantly a feature of primary disease, affecting approximately 30–60% of recipients, often within the first weeks after transplantation, and is associated with approximately a fivefold increase in graft loss and markedly reduced five-year graft survival. The circulating-factor hypothesis remains the most accepted pathogenic model, supported by rapid post-transplant recurrence, response to plasma exchange, and resolution following re-transplantation of affected allografts into unaffected recipients. Candidate mediators—including suPAR, anti-nephrin antibodies, and cardiotrophin-like cytokine factor-1—have been proposed, but none have been validated as a reliable biomarker. Pre-transplant stratification requires identification of the native phenotype, exclusion of secondary causes, and genetic testing in selected cases. Management is largely empirical: plasma exchange combined with rituximab is the mainstay of disease-directed therapy, supplemented by maximal RAAS inhibition, immunosuppression, and supportive care. Emerging therapies—daratumumab, sparsentan, and SGLT2 inhibitors—offer promise but require further study. Prognosis depends on the therapeutic response, with complete remission restoring graft survival to near-baseline levels. Re-transplantation remains feasible but demands individualised counselling and consideration of pre- or peri-operative prophylaxis in the highest-risk recipients. Full article

Since the first successful kidney transplant in 1954, transplant medicine has advanced significantly, achieving favorable one-year outcomes. However, despite excellent short-term outcomes, long-term renal allograft survival remains sub-optimal, with acute rejection continuing to be a major contributor to death-censored allograft loss. Current approaches for post-transplant surveillance and rejection monitoring rely on either nonspecific markers that often detect injury late in their course or invasive procedures associated with procedural risks and complications. To address these limitations, numerous non-invasive biomarkers have been introduced into solid organ transplantation research with the goal of improving allograft surveillance, facilitating earlier detection of rejection and complementing existing diagnostic approaches. Although several biomarkers have demonstrated clinical promise, none currently possess sufficient accuracy to replace kidney allograft biopsy. Biomarkers under investigation include blood-, tissue- and urine-based specimens. Their development and validation as independent markers have been limited by smaller sample size, heterogenous targets, variable performance characteristics and suboptimal sensitivity and specificity. In response, the field has increasingly shifted toward multimodal approaches that combine biomarkers and incorporate artificial intelligence to improve diagnostic accuracy and outcomes prediction. This review summarizes current biomarkers, discusses their limitations and explores future directions for biomarker development and clinical implementation. Full article

The yanglou buildings of Quanzhou are composite architectural heritage shaped by overseas Chinese and local traditions whose front facades provide an observable interface for comparing local and foreign cultural combinations. As existing studies emphasize plan typology and lack quantitative facade comparison, this study takes 40 yanglou buildings built by overseas Chinese between the late Qing dynasty and the 1960s in urban Quanzhou, Jinjiang, Shishi, and Nan’an and constructs a workflow of data survey, acculturation quantification, stage identification, and discriminative contribution analysis. The results show marked heterogeneity: the veranda presents strong object culture expressions, the wall elements are dominated by subject culture, and the hierarchy in the composition is unstable. FCM results show that the facades approximate continuous transitions rather than a single linear sequence. PLSR results show that the subject and object culture proportions in the veranda and wall elements and the object and renewal culture proportions in their compositions contribute more discriminatively to stage identification. This study shows that Quanzhou yanglou buildings are not direct transplantations of Western styles but composite heritage grounded in subject culture, absorbing object culture features and generating only limited renewal culture, providing a quantitative framework for stage identification, value interpretation, and differentiated conservation. Full article

Crohn’s disease (CD) is a chronic inflammatory disorder characterized by complex interactions among genetic susceptibility, environmental factors, dysregulated immune responses, and alterations of the intestinal microbiota. Although corticosteroids, immunomodulators, biologics, and advanced small-molecule therapies remain central to disease management, a substantial proportion of patients experience primary non-response, loss of response, or treatment-related adverse effects. This has stimulated interest in complementary therapeutic strategies targeting host–microbe interactions and intestinal microbial homeostasis. This review critically examines emerging microbiome-directed approaches for CD, with particular emphasis on pathobionts such as adherent-invasive Escherichia coli (AIEC). We discuss the available evidence for antibiotics, antimicrobial peptides (AMP), gut bacteriophages, fecal microbiota transplantation (FMT), and selected nutraceutical and dietary interventions. While some approaches show promising biological or clinical signals, the strength of evidence varies considerably, ranging from in vitro and animal studies to randomized clinical trials and meta-analyses. Antibiotic therapies targeting intestinal pathogens have shown heterogeneous results, suggesting the need for pathogen-guided and intracellularly active antimicrobial strategies. Novel approaches, including AIEC-specific phages and AMP-based interventions, represent promising microbiome-sparing alternatives capable of selectively modulating disease-associated microorganisms. Furthermore, FMT and nutraceuticals may contribute to restoring microbial balance and strengthening intestinal homeostasis, although their efficacy requires further validation in controlled clinical trials. Overall, these strategies support a transition toward precision medicine approaches integrating microbial profiling, host immune characterization, and targeted antimicrobial interventions to improve therapeutic outcomes in CD. Full article

Background: Hemolytic jaundice, characterized by excessive bilirubin production and hepatic dysfunction, currently lacks effective therapeutic strategies targeting its underlying mechanisms. Methods: This study evaluated the therapeutic potential of the aqueous extract of Inonotus obliquus (IO) in ameliorating hemolytic jaundice through modulation of the gut–liver axis. A murine model of hemolytic jaundice was induced by phenylhydrazine (PHZ) administration, and IO was orally administered as the intervention. Antibiotic depletion and FMT verified gut microbiota dependence. Liver injury, serum bilirubin, gut microbiome, and metabolites were assessed. Results: IO treatment significantly alleviated PHZ-induced hemolytic jaundice in mice. Notably, antibiotic-mediated depletion of the gut microbiota abolished the hepatoprotective effects of IO, whereas fecal microbiota transplantation (FMT) from IO-treated donors conferred marked amelioration of hyperbilirubinemia in recipient mice. Integrative multi-omics analysis identified Limosilactobacillus reuteri and Lactobacillus johnsonii as the predominant microbial species altered by IO. Furthermore, IO upregulated the expression of farnesoid X receptor (FXR) and pregnane X receptor (PXR) in both hepatic and intestinal tissues and also increased the expression of bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2). These alterations were correlated with an increased excretion of bile acids and bilirubin into the intestinal lumen, thereby mitigating hepatic injury. This process may be associated with the modulation of gut microbiota. Conclusions: These findings collectively provide evidence of a significant correlation between IO treatment and the mitigation of hemolytic jaundice, achieved by modulating the enterohepatic circulation of bile acids and bilirubin through the regulation of gut microbiota. Our results highlight the potential of IO as a microbiota-directed nutritional strategy for the management of jaundice. Full article

While the mesonephros persists in the adult mouse ovary and contributes to folliculogenesis, its inductive role in oogonial stem cell (OSC) differentiation remains uncertain. In this study, we investigated whether mesonephros-derived cells direct OSCs toward follicle-like structures in vitro. OSCs were co-cultured with mesonephros cells, and morphological assessments and factor expression analyses were conducted at multiple time points. On day 14 of co-culture, 10× Genomics single-cell and bulk RNA sequencing were performed to profile transcriptomic changes, while renal capsule transplantation was conducted to evaluate the functional potential of co-cultured clusters in recipient mice. Transcriptomic analyses revealed a robust expression of mesonephros-specific genes and a significant enrichment of PI3K/AKT pathway-associated genes in co-cultured cells. Notably, transplanted clusters exhibited signs of estrogen secretion with maintained graft integrity. Collectively, these findings demonstrate that the mesonephros promotes OSC differentiation into follicle-like structures, with the PI3K/AKT pathway identified as a candidate mediator of this process. Our study provides novel insights into the developmental regulation of ovarian folliculogenesis and offers a valuable experimental model for future investigations. Full article

Background: COVID-19-associated acute kidney injury (AKI) is common in severe disease, but its long-term kidney implications are heterogeneous and incompletely defined. Objective: To synthesize recovery phenotypes and longitudinal outcomes, reconcile conflicting evidence on whether COVID-associated AKI differs from other-cause AKI, and set out implications for surveillance and management. Methods: The evidence base was assembled through a targeted PubMed/MEDLINE search for COVID-19 and kidney dysfunction (January 2020 to August 2026), hand-searching of reference lists, and direct retrieval of pivotal longitudinal cohorts and clinical practice guidelines. Longitudinal cohorts and comparative studies were prioritized. Findings: AKI severity, duration, kidney replacement therapy, lower baseline estimated glomerular filtration rate (eGFR), and incomplete early recovery consistently identify patients at greatest risk. Longitudinal studies disagree on whether COVID-AKI confers more risk than AKI from other illnesses: early cohorts reported steeper eGFR loss, whereas a later 9624-patient cohort found lower adjusted major adverse kidney events. This divergence reflects differences in kidney reference point, outcome construction, ascertainment, and handling of competing death rather than genuine contradiction. Population studies show long-term kidney failure is concentrated after hospitalization and severe disease. Candidate biomarkers remain investigational. Conclusions: Post-COVID kidney risk is severity- and phenotype-dependent rather than universal. Follow-up is most defensible after hospitalized AKI, incomplete recovery, advanced chronic kidney disease (CKD), dialysis, or transplantation and applies existing post-AKI guidance rather than a COVID-specific schedule. Survivors who meet Kidney Disease: Improving Global Outcomes (KDIGO) criteria for CKD at three months, namely a GFR below 60 mL/min/1.73 m² or a persistent marker of kidney damage, become eligible for guideline-directed therapy, though no trial has enrolled on recent AKI. Prospective studies should test whether structured follow-up improves outcomes. Full article