Severe burns cause unique pathophysiological alterations especially on the immune system. A murine scald model was optimized as a basis for the understanding of immunological reactions in response to heat induced injury. The understanding of the roles of neutrophil extracellular traps (NETs) and DNases will support the development of new surgical or pharmacological strategies for the therapy of severe burns.

We studied C57BL/6 mice (n=30) and employed four scalding protocols with varying exposure times to hot water. An additional scald group with a shorter observational time was generated to reduce mortality and study the very early phase of pathophysiology. At 24h or 72h, blood was drawn and tissue (wound, liver, lung, spleen) was analyzed for the presence of NETs, oxidative stress, apoptosis, bacterial translocation, and extracellular matrix re-organization. In addition, we analyzed the transcriptome from lung and liver tissues.

Exposure to hot water for 7s led to significant systemic and local effects and caused considerable late mortality. Therefore, we used an observation time of 24h in this groups. To study later phases of burns (72h) an exposure time of 6s is optimal. Both conditions led to significant disorganization of collagen, increased oxidative stress, NET formation (by immunodetection of H3cit, NE, MPO), apoptosis (cC3) and alterations of the levels of DNase1 and DNase1L3. Transcriptome analysis revealed remarkable alterations in genes involved in acute phase signaling, cell cohesion, extracellular matrix organization, and immune response.

We identified two scald models that allow the analysis of early (24h) or late (72h) severe burn effects, thereby generating reproducible and standardized scald injuries. The study elucidated the important involvement of neutrophil activity and the role of NETs in burns. Extensive transcriptome analysis characterized the acute phase and tissue remodeling pathways involved in the process of healing and may serve as crucial basis for future in-depth studies.

Data on severe and extensive burns in China are limited, as is data on the prevalence of a range of related gastrointestinal (GI) disorders [such as stress ulcers, delayed defecation, opioid-related bowel immotility, and abdominal compartment syndrome (ACS)]. We present a multicentre analysis of coincident GI dysfunction and its effect on burn-related mortality.

This retrospective analysis was conducted on patients with severe [≥ 20% total burn surface area (TBSA)] and extensive (> 50% TBSA or > 25% full-thickness TBSA) burns admitted to three university teaching institutions in China between January 1, 2011 and December 31, 2020. Both 30- and 90-day mortality were assessed by collating demographic data, burn causes, admission TBSA, % full-thickness TBSA, Baux score, Abbreviated Burn Severity Index (ABSI) score, and Sequential Organ Failure Assessment (SOFA) score, shock at admission and the presence of an inhalation injury. GI dysfunction included abdominal distension, nausea/vomiting, diarrhoea/constipation, GI ulcer/haemorrhage, paralytic ileus, feeding intolerance and ACS. Surgeries, length of intensive care unit (ICU) stay, pain control [in morphine milligram equivalents (MME)] and overall length of hospital stay (LOHS) were recorded.

We analyzed 328 patients [75.6% male, mean age: (41.6 ± 13.6) years] with a median TBSA of 62.0% (41.0-80.0%); 256 (78.0%) patients presented with extensive burns. The 90-day mortality was 23.2% (76/328), with 64 (84.2%) of these deaths occurring within 30 d and 25 (32.9%) occurring within 7 d. GI dysfunction was experienced by 45.4% of patients and had a significant effect on 90-day mortality [odds ratio (OR) = 14.070, 95% confidence interval (CI) 5.886-38.290, P < 0.001]. Multivariate analysis showed that GI dysfunction was associated with admission SOFA score and % full-thickness TBSA. Overall, 88.2% (67/76) of deceased patients had GI dysfunction [hazard ratio (HR) for death of GI dysfunction = 5.951], with a survival advantage for functional disorders (diarrhoea, constipation, or nausea/vomiting) over GI ulcer/haemorrhage (P < 0.001).

Patients with severe burns have an unfavourable prognosis, as nearly one-fifth died within 90 d. Half of our patients had comorbidities related to GI dysfunction, among which GI ulcers and haemorrhages were independently correlated with 90-day mortality. More attention should be given to severe burn patients with GI dysfunction.

Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown to promote carcinogenesis. An example is the enhanced risk for several types of cancer in patients with CF, especially cancers of the GI tract. CFTR also acts as a tumor suppressor in diverse sporadic epithelial cancers in many tissues, primarily due to the silencing of CFTR expression via multiple mechanisms, but especially due to epigenetic regulation. This review provides an update on the latest research linking CFTR-deficiency to GI cancers, in both CF patients and in sporadic GI cancers, with a particular focus on cancer of the intestinal tract. It will discuss changes in the tissue landscape linked to CFTR-deficiency that may promote cancer development such as breakdowns in physical barriers, microbial dysbiosis and inflammation. It will also discuss molecular pathways and mechanisms that act upstream to modulate CFTR expression, such as by epigenetic silencing, as well as molecular pathways that act downstream of CFTR-deficiency, such as the dysregulation of the Wnt/β-catenin and NF-κB signaling pathways. Finally, it will discuss the emerging CFTR modulator drugs that have shown promising results in improving CFTR function in CF patients. The potential impact of these modulator drugs on the treatment and prevention of GI cancers can provide a new example of personalized cancer medicine.

Burn injury is an intractable problem in the field of surgery where screening relevant target genes and exploring pathological mechanisms through bioinformatic methods has become a necessity. Herein, we integrated three burn injury mRNA microarray datasets from the Gene Expression Omnibus database to analyze the hub differentially expressed genes (DEGs) between burn injury patient samples and healthy human samples; we conducted multiple functional enrichment analyses and constructed the protein-protein interaction (PPI) network. Finally, we evaluated the immune infiltration in the burn injury microenvironment. A total of 84 intersection DEGs (32 upregulated and 52 downregulated) were screened in burn injury patients via integrated analyses. Upregulated genes were primarily enriched in regulation of T cell activation, regulation of response to DNA damage stimulus, positive regulation of innate immune response, positive regulation of defense response. We also identified 10 hub genes from the PPI network (CCNB2, MYO10, TTK, POLQ, VASP, TIMP1, CDK16, MMP1, ZYX, and PKMYT1). Next, we found that 22 immune cells were substantially changed during the burn injury by CIBERSORT. In addition, we verified that VASP and POLQ are two novel diagnostic markers in burn processes with high diagnostic efficacy via immunohistochemistry. In summary, we identified several key genes involved in burn injury and provided a favorable basis for elucidating the molecular mechanisms of burn injury through comprehensive bioinformatic analysis.