A common feature of severe COVID-19 and two common metabolic comorbidities, type 2 diabetes mellitus (T2DM) and obesity, is a persistent inflammatory response. Heat shock proteins (HSPs) are key regulators of cell proteostasis under stressful conditions, including inflammation, oxidative stress, hyperglycemia, and hyperlipidemia. The aim of the present study was to investigate associations between polymorphic variants in genes encoding HSPs and T2DM or obesity among patients with severe or critical COVID-19.

A total of 195 patients with severe or critical COVID-19 were included, of whom 39 had T2DM and 101 had obesity. T2DM and obesity were analyzed as separate, non-mutually-exclusive outcomes. Genotyping was performed using a TaqMan probe-based real-time polymerase chain reaction assay to detect single nucleotide polymorphisms (SNPs). Bioinformatics resources, including GTExPortal, eQTLGen, atSNP, and Gene Ontology, were used for functional annotation. Associations between HSP genetic variants and T2DM or obesity were analyzed. This study was conducted as a case-control analysis within a severe COVID-19 cohort and is reported in accordance with the STROBE guidelines.

Among patients with severe or critical COVID-19, SNP rs1043618 HSPA1A (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.01–3.27, Pperm = 0.04), rs910652 HSPA12B (OR = 2.23, 95% CI = 1.18–4.21, Pperm = 0.01), and rs4926222 DNAJB1 (OR = 2.15, 95% CI = 1.08–4.27, Pperm = 0.03) were associated with higher odds of T2DM, whereas rs13161158 HSPA4 (OR = 0.11, 95% CI = 0.01–0.91, Pperm = 0.0075) and rs7189628 DNAJA2 (OR = 0.08, 95% CI = 0.01–0.65, Pperm = 0.001) were associated with lower odds of T2DM. In addition, SNP rs753856 HSPA6 (effect allele G) was associated with higher odds of obesity (OR = 2.11, 95% CI = 1.07–4.19, Pperm = 0.03).

Selected HSP SNPs are associated with T2DM or obesity among patients with severe or critical COVID-19. Functional annotation suggests plausible biological mechanisms, including cell proteostasis, inflammatory pathways, glucose metabolism, and adipogenic differentiation; however, independent and functional validation is required.

Extensive burn injuries are associated with a profound systemic response, the severity of which increases with the extent of tissue damage. Beyond local destruction, extensive burns induce a sustained immune-inflammatory disturbance that alters immune regulation and contributes to secondary organ failure and infectious complications. These mechanisms are major determinants of adverse outcomes in critically ill patients with burns. In this context, therapeutic strategies targeting immune dysregulation have gained increasing attention. Immunomodulatory approaches aim to limit excessive inflammatory signaling while maintaining effective host defense. Among extracorporeal blood purification techniques, hemoadsorption has emerged as a potential adjunctive therapy designed to reduce circulating inflammatory mediators, particularly cytokines, and to attenuate systemic inflammatory burden. Rather than providing another general overview of extracorporeal blood purification, this review focuses specifically on the cellular and mechanistic basis of burn-induced immune dysregulation and offers a stratified, critical appraisal of the experimental and clinical evidence for hemoadsorption in burns, together with current safety considerations and unresolved questions that should guide future research. Experimental studies and early clinical observations suggest that hemoadsorption may contribute to hemodynamic stabilization and modulation of inflammation in critically ill patients, including those with severe burns. However, clinical evidence in this specific population remains scarce, and its impact on patient-centered outcomes has not yet been established. Although available data suggest that this technique is generally well tolerated, the non-selective removal of circulating molecules underscores the need for careful patient selection and close monitoring. Future investigations should focus on defining the appropriate indications, optimal timing, and treatment duration of hemoadsorption for burn care. Comparative studies with other immunomodulatory strategies are required to clarify its role within the therapeutic armamentarium for burn-induced immune dysfunction.

Interactions among tumors, nerves, and immune cells influence cancer progression, but the mechanisms coordinating these compartments remain incompletely understood. Bioelectric signaling has been proposed as an additional coordinating layer, yet direct in vivo evidence for a tumor–nerve–immune electrical axis remains limited. In non-tumor models, RUSH3D-HR enables mesoscale in vivo imaging of dynamic cellular behaviors, including neutrophil swarming and migrasome dynamics, and has revealed reduced splenic neutrophil swarming following electroacupuncture at Zusanli (ST36). These observations provide dynamic cellular readouts and demonstrate an intervention-associated response; however, the platform does not directly measure membrane voltage, ionic currents, or electric fields, and these findings establish neither electrical coupling nor a specific neural circuit. In this mini review, we examine the proposed axis as a focused, falsifiable complement to broader cancer neuroscience. We distinguish direct observations from mechanistic hypotheses, consider established biochemical explanations involving neurotransmitters and inflammatory mediators, and discuss how context-dependent neural effects, supporting glial cells, opioids, and cancer-induced nerve injury may modify tumor–nerve–immune interactions. We then outline a staged experimental roadmap in tumor models, integrating RUSH3D-HR with voltage and ion reporters, extracellular electrophysiological recordings, and compartment-specific perturbations. This framework prioritizes temporal relationships, identification of candidate signal sources and responding compartments, and causal tests that discriminate electrical contributions from biochemical and systemic effects. Establishing reproducible links between electrical measurements, cellular behavior, and tumor outcomes will be essential for evaluating the axis. Until such evidence is obtained, the tumor–nerve–immune electrical axis should be regarded as a hypothesis-generating experimental program rather than a validated physiological circuit.

Despite the 2012 Berlin definition standardizing acute respiratory distress syndrome (ARDS) diagnosis, pharmacological therapies have consistently failed in phase 3 trials, partly reflecting the syndrome’s profound biological heterogeneity. We synthesize evidence on ARDS subphenotyping to evaluate prospects for precision medicine. This narrative review was informed by targeted searches of PubMed/MEDLINE, Embase, and Web of Science from database inception through February 2026, supplemented by an updated PubMed/MEDLINE search through September 2026. Representative clinical trials, multicenter cohorts, mechanistic studies, and methodological reports were selected to support a critical synthesis of ARDS subphenotyping, its therapeutic implications, and barriers to clinical translation. Hyperinflammatory and hypoinflammatory subphenotypes—originally identified using plasma biomarkers (IL-6, IL-8, and soluble tumor necrosis factor receptor 1) in the ARMA and ALVEOLI cohorts—demonstrate reproducible differences in mortality, with worse outcomes in the hyperinflammatory subphenotype, and have shown potential treatment-effect heterogeneity in secondary analyses. Approximately 30%–35% of patients exhibit the hyperinflammatory profile, characterized by greater vasopressor requirements and organ failure. Radiological phenotypes (focal versus non-focal) on computed tomography imaging have been associated with differences in lung recruitability and physiological responses to ventilatory interventions, although the LIVE trial did not demonstrate an overall survival benefit from morphology-guided ventilation. Recent multi-omics studies (transcriptomic, proteomic, and metabolomic) reveal distinct endotypes involving dysregulated innate immunity, endothelial activation, and aberrant coagulation. Machine learning algorithms, particularly unsupervised clustering and deep learning-based computed tomography radiomics, have been investigated for more rapid phenotyping, but reported performance varies by task, cohort, and validation design. However, prospective, phenotype-guided randomized trials remain limited. Subphenotype stratification offers a mechanistically grounded framework for re-evaluating therapies that were ineffective in unselected populations and for investigating phenotype-informed ventilatory strategies. Clinical implementation requires standardized, bedside-compatible biomarker panels and definitive trials demonstrating that phenotype-specific interventions improve patient-centered outcomes.

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.

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.

Human serum albumin (HSA) is a multifunctional carrier protein that helps maintain vascular barrier integrity and intravascular fluid homeostasis and has long been used in the management of critically ill patients, including those with acute brain injury. HSA is thought to exert neuroprotective effects through four complementary mechanisms: oncotic/volume expansion and hemodilution, antioxidant and anti-inflammatory effects, HSA-nitric oxide-mediated antithrombotic activity, and glycocalyx stabilization, although the precise pathways remain incompletely understood. Despite its biological rationale, the clinical efficacy of HSA in severe neurological disorders remains inconclusive, and few guidelines provide specific recommendations for its use in neurological care. This uncertainty stems primarily from the complex etiology and heterogeneous pathophysiology of neurological disorders, as well as inconsistent findings across existing studies. This narrative review aims to summarize the current evidence on HSA use in traumatic brain injury, acute ischemic stroke, and aneurysmal subarachnoid hemorrhage, identify existing knowledge gaps, and provide insights for future research and clinical practice. We screened records from PubMed, Embase, the Cochrane Library, CNKI, and Yiigle, as well as ClinicalTrials.gov, ChiCTR, and ChinaDrugTrials. A total of 29 human and animal studies were included. Collectively, available evidence supports a biological rationale for HSA therapy in neurocritical care, yet its clinical benefit remains incompletely established and substantial challenges persist. Prospective randomized controlled trials are warranted to clarify the efficacy and safety of HSA and determine whether preliminary encouraging findings can inform standardized guidelines and expert consensus recommendations, particularly regarding optimal concentration, timing, and patient selection.