Epigenetic modifications in the development of bronchopulmonary dysplasia: a review.

While perinatal medicine advancements have bolstered survival outcomes for premature infants, bronchopulmonary dysplasia (BPD) continues to threaten their long-term health. Gene-environment interactions, mediated by epigenetic modifications such as DNA methylation, histone modification, and non-coding RNA regulation, take center stage in BPD pathogenesis. Recent discoveries link methylation variations across biological pathways with BPD. Also, the potential reversibility of histone modifications fuels new treatment avenues. The review also highlights the promise of utilizing mesenchymal stem cells and their exosomes as BPD therapies, given their ability to modulate non-coding RNA, opening novel research and intervention possibilities. IMPACT: The complexity and universality of epigenetic modifications in the occurrence and development of bronchopulmonary dysplasia were thoroughly discussed. Both molecular and cellular mechanisms contribute to the diverse nature of epigenetic changes, suggesting the need for deeper biochemical techniques to explore these molecular alterations. The utilization of innovative cell-specific drug delivery methods like exosomes and extracellular vesicles holds promise in achieving precise epigenetic regulation.

Polylysine-modified near-infrared-emitting carbon dots assemblies: Amplification of tumor accumulation for enhanced tumor photothermal therapy.

A key challenge to enhance the therapeutic outcome of photothermal therapy (PTT) is to improve the efficiency of passive targeted accumulation of photothermal agents at tumor sites. Carbon dots (CDs) are an ideal choice for application as photothermal agents because of their advantages such as adjustable fluorescence, high photothermal conversion efficiency, and excellent biocompatibility. Here, we synthesized polylysine-modified near-infrared (NIR)-emitting CDs assemblies (plys-CDs) through post-solvothermal reaction of NIR-emitting CDs with polylysine. The encapsulated structure of plys-CDs was confirmed by determining morphological, chemical, and luminescent properties. The particle size of CDs increased to approximately 40 ± 8 nm after polylysine modification and was within the size range appropriate for achieving superior enhanced permeability and retention effect. Plys-CDs maintained a high photothermal conversion efficiency of 54.9 %, coupled with increased tumor site accumulation, leading to a high efficacy in tumor PTT. Thus, plys-CDs have a great potential for application in photothermal ablation therapy of tumors.

Mitochondrial DNA Leakage and cGas/STING Pathway in Microglia: Crosstalk Between Neuroinflammation and Neurodegeneration.

Neurodegenerative diseases, characterized by abnormal deposition of misfolded proteins, often present with progressive loss of neurons. Chronic neuroinflammation is a striking hallmark of neurodegeneration. Microglia, as the primary immune cells in the brain, is the main type of cells that participate in the formation of inflammatory microenvironment. Cytoplasmic free mitochondrial DNA (mtDNA), a common component of damage-associated molecular patterns (DAMPs), can activate the cGas/stimulator of interferon genes (STING) signalling, which subsequently produces type I interferon and proinflammatory cytokines. There are various sources of free mtDNA in microglial cytoplasm, but mitochondrial oxidative stress accumulation plays the vital role. The upregulation of cGas/STING pathway in microglia contributes to the abnormal and persistent microglial activation, accompanied by excessive secretion of neurotoxic inflammatory mediators such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which exacerbates the damage of neurons and promotes the development of neurodegeneration. Currently, novel therapeutic approaches need to be found to delay the progression of neurodegenerative disorders, and regulation of the cGas/STING signaling in microglia may be a potential target.

Clinical features and surgical treatments of scoliosis in neurofibromatosis type 1: a systemic review and meta-analysis.

BACKGROUND: Neurofibromatosis type 1 (NF 1) is an autosomal-dominant tumor predisposition genetic disease affecting approximately 1 in 3000 live births. The condition could present various manifestations ranging from skin abnormalities to neurological tumors. The musculoskeletal system could also be frequently affected, and scoliosis is the most common orthopedic manifestation. Characterized by the early-onset and rapid progression tendency, NF 1-related dystrophic scoliosis presented discrepancies from idiopathic scoliosis in terms of natural history, clinical features, and management outcomes and thus required special attention. In the current study, the authors conducted a systemic review to outline the body of evidence of the natural history, clinical characteristics, surgical outcomes, and surgical complications of NF 1-induced scoliosis, aiming to provide an elucidative insight into this condition. METHOD: Systemic review and meta-analysis were conducted according to the latest Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) guidelines. The search was performed in Medline, Embase, and Web of Science Core Collection up to December 27, 2022, using related keywords. Clinical features such as frequencies, segmental involvement, and hereditary information were summarized and described qualitatively. Meta-analysis was conducted using R software and the 'meta' package to yield an overall outcome of efficacy and safety of surgical management, precisely, spinal fusion procedure and growing rods procedure. Corrective rate of Cobb angle, sagittal kyphosis angle, and T1-S1 length post-operative and at the last follow-up was used to evaluate the efficacy, and the occurrence of surgery-related complications was used to evaluate the safety. RESULT: A total of 37 articles involving 1023 patients were included. Approximately 26.6% of the NF 1 patients would present with scoliosis. Patients tend to develop scoliosis at an earlier age. The thoracic part turned out to be the most affected segment. No obvious correlation between scoliosis and genotype or hereditary type was observed. Both spinal fusion and growing rod surgery have shown acceptable treatment outcomes, with spinal fusion demonstrating better performance in terms of effectiveness and safety. The growing rods technique seemed to allow a better lengthening of the spine. The mainstay post-operative complications were implant-related complications but could be managed with limited revision surgery. Severe neurological deficits were rarely reported. CONCLUSION: Scoliosis, especially the subtype characterized by dystrophic bony changes, is a significant orthopedic manifestation of NF1. It has an early onset, a tendency to persistently and rapidly progress, and is challenging to deal with. The current review outlines the available evidence from the perspective of natural history, clinical features, and the treatment efficacy and safety of the mainstay surgical options. Patients with NF1 scoliosis will benefit from a better understanding of the disease and evidence based treatment strategies.

Machine learning-based exosome profiling of multi-receptor SERS sensors for differentiating adenocarcinoma in situ from early-stage invasive adenocarcinoma.

Exosomes, extracellular vesicles released by cells, hold potential as diagnostic markers for the early detection of lung cancer. Despite their clinical promise, current technologies lack rapid and effective means to discriminate between exosomes derived from adenocarcinoma in situ (AIS) and early-stage invasive adenocarcinoma (IAC). This challenge arises from the intrinsic structural heterogeneity of exosomes, necessitating the development of advanced methodologies for precise differentiation. Here, we demonstrate a novel approach for plasma exosome detection utilizing multi-receptor surface-enhanced Raman spectroscopy (SERS) technology to differentiate between AIS and early-stage IAC. To accomplish this, we synthesized a stable and uniform two-dimensional SERS substrate (BC/Au NPs film) by fabricating gold nanoparticles onto bacterial cellulose. We then enhanced its capabilities by introducing multi-receptor SERS functionality via modifying the substrate with both low-specificity and physicochemical-selective molecules. Furthermore, by strategically combining all capturer-exosome SERS spectra, comprehensive "combined-SERS spectra" are reconstructed to enhance spectral variations of the exosome. Combining these features with partial least squares regression-discriminant analysis (PLS-DA) modeling significantly improved discriminatory accuracy, achieving 90% sensitivity and 95% specificity in distinguishing AIS from early-stage IAC. Our developed SERS sensor provides an effective method for early detection of lung cancer, thereby paving a new way for innovative advancements in diagnosing lung cancer.

TNF and IFNγ-induced cell death requires IRF1 and ELAVL1 to promote CASP8 expression.

TNFα and IFNγ (TNF/IFNγ) synergistically induce caspase-8 activation and cancer cell death. However, the mechanism of IFNγ in promoting TNF-initiated caspase-8 activation in cancer cells is poorly understood. Here, we found that in addition to CASP8, CYLD is transcriptionally upregulated by IFNγ-induced transcription factor IRF1. IRF1-mediated CASP8 and CYLD upregulation additively mediates TNF/IFNγ-induced cancer cell death. Clinically, the expression levels of TNF, IFNγ, CYLD, and CASP8 in melanoma tumors are increased in patients responsive to immune checkpoint blockade (ICB) therapy after anti-PD-1 treatment. Accordingly, our genetic screen revealed that ELAVL1 (HuR) is required for TNF/IFNγ-induced caspase-8 activation. Mechanistically, ELAVL1 binds CASP8 mRNA and extends its stability to sustain caspase-8 expression both in IFNγ-stimulated and in basal conditions. Consequently, ELAVL1 determines death receptors-initiated caspase-8-dependent cell death triggered from stimuli including TNF and TRAIL by regulating basal/stimulated caspase-8 levels. As caspase-8 is a master regulator in cell death and inflammation, these results provide valuable clues for tumor immunotherapy and inflammatory diseases.

2'-Hydroxychalcone Induces Autophagy and Apoptosis in Breast Cancer Cells via the Inhibition of the NF-κB Signaling Pathway: In Vitro and In Vivo Studies.

2'-Hydroxychalcone is a hydroxyl derivative of chalcones, which are biosynthetic precursors of flavonoids and rich in the human diet. The anticancer activity of 2'-hydroxychalcone has been reported in several cancers but remains to be investigated in breast cancer. In the current study, 2'-hydroxychalcone showed significant cytotoxicity against breast cancer cell lines MCF-7 and CMT-1211. It could inhibit breast cancer cell proliferation, migration, and invasion in vitro and suppress tumor growth and metastasis in vivo. Mechanistic investigation revealed that the NF-κB pathway was significantly inhibited by 2'-hydroxychalcone treatment accompanied by an excessive intracellular accumulation of reactive oxygen species, induction of endoplasmic reticulum stress, and activation of JNK/MAPK. In addition, 2'-hydroxychalcone elevated the autophagic levels in breast cancer cells equipped with increasing numbers of autophagy vesicles and complete autophagic flux. Finally, autophagy-dependent apoptosis was observed in 2'-hydroxychalcone-induced cell death. In conclusion, 2'-hydroxychalcone enhances the autophagic levels and induces apoptosis in breast cancer cells, which could be contributed to the inhibition of the pro-survival NF-κB signaling, indicating a promising potential for 2'-hydroxychalcone in future anticancer drug development.

Upregulation of IDO gene expression reduces the immunogenicity of epidermal cells and strengthens the immune protection of epidermal cells during transplantation treatment of wounds.

BACKGROUND: Epidermal cell transplantation is a feasible treatment option for large wounds; however, sources of autologous epidermal cells are often limited. Allogeneic epidermal cells can be cultured conveniently; however, related immune rejection needs to be addressed. Herein, we hypothesized that the immunogenicity of epidermal cells with high indoleamine 2,3-dioxygenase (IDO) expression may be reduced by gene transfection. METHODS/RESULTS: To test this hypothesis, we obtained stable transfectants by transfecting epidermal stem cells with a lentiviral vector encoding the IDO gene and screening them for puromycin resistance (a marker for successful transfection). The phenotype tested using cell counting kit -8 and Transwell assays confirmed that IDO-transfected epidermal cells maintained their characteristics. Co-culture of IDO-transfected epidermal cells with allogeneic CD4+ T cells in vitro showed that the upregulation of IDO expression in epidermal cells inhibited the proliferation of CD4+ T cells (P < 0.001, P < 0.001, and P < 0.001, respectively) and promoted their apoptosis (P = 0.00028, P = 0.0006, and P = 0.00247, respectively) and transformation into functional regulatory T cells (Tregs) (P = 0.0051, P = 0.0132, and P = 0.0248, respectively) compared with Con, NC, and 1-MT groups. The increased proportion of Tregs may be related to the overexpression of IDO, which promoted the expression of transforming growth factor beta (TGF-ß) (P = 0.0001, P = 0.0013, and, P = 0.0009) and interleukin (IL) 10 (IL-10) (P = 0.0062, P = 0.0058, and P = 0.0119) while inhibited the expression of IL-2 (P = 0.0012, P = 0.0126, and P = 0.0066). We further verified these effects in vivo as transplanted IDO-transfected epidermal stem cells were effective in treating wounds in mice. On days 5 and 7, wounds treated with IDO cells healed faster than those in the other groups (day 5: P = 0.012 and P = 0.0136; day 7: P = 0.0242 and P = 0.0187, respectively), whereas this effect was significantly inhibited by 1-methyltryptophan (1-MT) (day 5: P = 0.0303; day 7: P = 0.0105). Immunofluorescence staining detected IDO and CD4+ Foxp3+ Tregs in the transplanted wounds, which may promote Foxp3+ Tregs in the wound tissue (day 5: P < 0.0001, P < 0.0001, and P < 0.0001; day 7: P < 0.0001, P < 0.0001, and P < 0.0001), respectively) and decrease CD4+ T cells (day 5: P < 0.0001, P < 0.0001, and P < 0.0001; day 7: P < 0.0001, P < 0.0001, and P < 0.0001). CONCLUSION: Our results suggest that the upregulation of IDO expression in epidermal stem cells can reduce their immunogenicity by promoting Tregs, thus inducing the immune protection of epidermal stem cells.

Higher Expression of Human Endogenous Retrovirus-K was Observed in Peripheral B Lymphocytes of Leukemia and Lymphoma Patients.

Hematological malignant tumors (HMTs) are serious diseases that threaten human health and life with high mortality. Therefore, it is necessary to develop novel strategies for diagnosis and treatment. Human endogenous retroviruses (HERVs) have recently attracted increasing attention as potential targets for cancer diagnosis and therapy. In this study, we explored the association between HERV-K expression levels and HMTs development. Clinical data and peripheral blood samples were collected from 236 leukemia, 384 lymphoma patients, and 69 healthy controls. Quantitative polymerase chain reaction was used to detect the expression of HERV-K gag, pol, and env genes in peripheral blood mononuclear cells or different cell subpopulations. Differently expressed HERV-K genes were further tested by using deep sequencing method, and further analyzed with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. B cell- and T cell-related cytokines in patients were also detected by enzyme-linked immunosorbent assay (ELISA). The results showed that the expression levels of the HERV-K gag, pol, and env genes in patients were significantly higher than in healthy controls. There was a correlation between the expression level of HERV-K and the clinicopathological parameters of leukemia patients. HERV-K expression was increased in the B lymphocytes of leukemia and lymphoma patients, but not in the T cells or neutrophils. The GO and KEGG analyses showed that abnormal expression of the HERV-K locus in patients affected immune regulation. The analysis of cytokines proved that the B cell-related cytokines, including interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon-gamma, were significantly decreased in patients, while the T cell-related cytokines, including IL-3, IL-12, and TNF-ß, were not significantly changed. In conclusion, HERV-K genes might participate in the occurrence and development of leukemia and lymphoma, and might be biomarkers for the detection or evaluation of leukemia and lymphoma.

The epidemiology of alcohol burns at a major burn centre in North China.

This study was designed to explore the epidemiological characteristics and potential preventive strategies of alcohol burns. In this five-year, retrospective study, 163 patients with alcohol burns (admitted from 1 January 2015 to 31 May 2020 were included. There was a male-to-female ratio of 1.1:1, a mean age of 34.1±16.8 years, and a mean burn size of 13.3±13.7% total body surface area (TBSA). The number of patients with alcohol burns was similar year by year during the five-year period. Just over half of patients (n=84, 51.5%) sustained a third-degree burn injury, which was significantly associated with a longer hospital stay and the need for surgery. The most prevalent aetiology was cupping (n=49, 29.5%), followed by cooking hotpot (n=37, 22.7%). Of the patients, seven (4.29%) sustained injuries during experiments at school and one patient sustained injury when using alcohol spray for disinfection against COVID-19. The incidence of facial burn injury (n=105, 64.4%) was significantly higher than previously reported data (33.2%). The result of the study showed that cupping and hotpot were the main causes of alcohol burns in Beijing, which should be taken into consideration for prevention. It is necessary to strengthen safety management of classes at school where experiments are undertaken and to educate the general public on the proper means of disinfecting against COVID-19.

Ultra-sensitive detection of tumor necrosis factor alpha based on silver-coated gold core shell and magnetically separated recognition of SERS aptamer sensors.

A highly sensitive tumor necrosis factor α (TNF-α) detection method based on a surface-enhanced Raman scattering (SERS) magnetic patch sensor is reported. Magnetic beads (MNPs) and core shells were used as the capture matrix and signaling probe, respectively. For this purpose, antibodies were immobilized on the surface of magnetic beads, and then Au@4-MBN@Ag core-shell structures coupled with aptamers and TNF-α antigen were added sequentially to form a sandwich immune complex. Quantitative analysis was performed by monitoring changes in the characteristic SERS signal intensity of the Raman reporter molecule 4-MBN. The results showed that the limit of detection (LOD) of the proposed method was 4.37 × 10-15 mg·mL-1 with good linearity (R2 = 0.9918) over the concentration range 10-12 to 10-5 mg·mL-1. Excellent assay accuracy was also demonstrated, with recoveries in the range 102% to 114%. Since all reactions occur in solution and are separated by magnetic adsorption of magnetic beads, this SERS-based immunoassay technique solves the kinetic problems of limited diffusion and difficult separation on solid substrates. The method is therefore expected to be a good clinical tool for the diagnosis of the inflammatory biomarker THF-α and in vivo inflammation screening.

Metaphyseal Metal Sleeves for Reconstruction of Severe Knee Bone Defects: Excellent Survival Rate at a Mean Follow-Up of 6.4 Years.

OBJECTIVE: Management of bone loss in complex primary and revision total knee arthroplasty is key to the surgeries. Metaphyseal metal sleeves have been increasingly used recently to reconstruct severe knee metaphyseal bone defects. This study aimed to investigate the outcomes of the metaphyseal sleeve reconstructing Anderson Orthopedic Research Institute (AORI) type II and type III bone defects of knee joint. METHODS: From 2014 to 2019, a total of 44 knees were enrolled in this clinical retrospective study after the screening, including seven cases of primary TKA and 37 cases of revision TKA. The types of bone defects involved in this study were AORI types II and III, and did not involve AORI type I bone defects. Patients' knee function preoperatively and postoperatively as well as quality of life were recorded and analyzed. Analysis included the American Knee Society Score (KSS), hospital for special surgery knee score (HSS), the Western Ontario and McMaster Universities (WOMAC) index, the Short Form 12 (SF-12) health survey, visual analogue scale score, and radiographic assessment with a mean follow-up of 6.4 years. Paired t-tests were used to determine the significance of changes in clinical scores and knee mobility. RESULTS: A mean follow-up of 77.2 (±17.6, standard deviation [SD]) months was performed, and none of the patients underwent knee revision for infection or aseptic loosening. At the last follow-up, the KSS knee score changed statistically from 37.1 (±19.7) preoperatively to 86.5 (±13.6, SD, p < 0.001) postoperatively and the KSS function score from 32.7 (±24.0) preoperatively to 78.3 (±15.6, SD, p < 0.001) postoperatively. The knee mobility improved from a mean of preoperative 72.61° (±33.42°, SD) to 108.52° (±24.15°, SD, p < 0.001). Postoperative radiographs showed that the host bone was tightly integrated with the metaphyseal metal sleeve, and there was no obvious translucent line formation around the sleeve. Of the patients, 86.4% had a postoperative satisfaction score ≥8 (10-point scale). CONCLUSION: At the mean follow-up of 6.4 years, the survival rate of the metaphyseal sleeves was 100%. Metaphyseal sleeves combined with cementless stems is an excellent and viable option for reconstruction of AORI type II and type III bone defects of the knee.

MicroRNA biomarkers and their use in evaluating the prognosis of lung cancer.

OBJECTIVE: We aim to use the microRNA (miRNA, micro-ribonucleic acid) data of lung cancer tissues to establish a miRNA biomarker database for lung cancer that can be used for marker screening and analysis of lung cancer prognosis. METHODS: We obtained lung cancer-related data from The Cancer Genome Atlas (TCGA) and analyzed the miRNA expression profiles of lung cancer tissues and normal tissues using bioinformatics techniques to develop a new composite miRNA-based model for the prognostic assessment of lung cancer. The predictive power of this model was verified and evaluated based on grouping of data. We also performed RT-qPCR using lung cancer tissues from patients diagnosed with lung cancer. RESULTS: There was a significant difference between the miRNA expression profiles of lung cancer tissues and normal tissues adjacent to the cancerous lesions. The prognostic survival of patients with lung cancer was closely related to onset age and staging (p = 0.012) but was not related to gender (p = 0.39) and race (p = 0.51). Using three methods of survival model construction, we identified three miRNA composites, namely hsa-mir-21, hsa-mir-141, and has-mir-490, as markers for the prognosis of lung cancer. As confirmed by RT-qPCR, the expressions of hsa-miR-21-5p and hsa-miR-141-5p were upregulated, whereas hsa-miR-490-3p expression was downregulated in lung cancer lesion tissues. CONCLUSION: The three miRNA composites identified, namely hsa-mir-21, hsa-mir-141, and hsa-mir-490, have the potential to serve as novel prognostic biomarkers and therapeutic targets for lung cancer.

Deliberately Staged Combined Endovascular Embolization and Subsequent Microsurgery Resection for the Treatment of Cerebral Arteriovenous Malformations.

OBJECTIVE: Complex cerebral arteriovenous malformations (AVMs) require a combined therapy of endovascular embolization and microsurgical resection to eliminate the lesion and maximize neurological protection, while a deliberate time interval might contribute to optimal clinical outcomes. The present study aimed to explore the feasibility of this paradigm. METHODS: All patients who underwent deliberately planned presurgery embolization and microsurgery resection between 2015 and 2023 were reviewed, with baseline data, postoperative complications, and follow-up outcomes recorded. The modified Rankin scale (mRS) was used to evaluate clinical outcomes, with mRS 0-2 defined as good. RESULTS: A total of 30 patients were included in the study (15 were ruptured AVMs). The median Spetzler-Martin grade of baseline AVMs was 3 (interquartile range: 2-3). The median interval between the last embolization and microsurgery was 5 days (interquartile range: 2.25-7). The complete removal rate was 100%, and the overall permanent complication rate was 16.67%. At the last follow-up, 26 patients achieved mRS 0-2, while 28 had improved or unaltered mRS. The last follow-up mRS significantly improved from baseline and discharge (P = 0.0006 and P = 0.006). The last follow-up mRS decreased by 0.65 for each additional day of time interval before the 4.4-day inflection point (ß = -0.65, P = 0.02) in the AVM ruptured cohort. CONCLUSIONS: The deliberately staged combined procedure of embolization and microsurgery might be a safe and efficacious strategy for Spetzler-Martin grade 2-5 AVMs, 4-5 days might be an appropriate staged time interval for ruptured AVMs, although further studies are needed to substantiate these findings.

A study on the preoperative risk factors for primary healing failure in the reconstruction of deep sternal wound infection with platelet-rich plasma and negative pressure trauma therapy.

Deep sternal wound infection (DSWI) is a relatively complex wound in wound reconstruction surgery. Because plastic surgeons deal with DSWI patients late. The primary healing (healing by first intention) after reconstruction of DSWI is restricted by many preoperative risk factors. The purpose of this study is to explore and analyse the risk factors of primary healing failure in patients with DSWI treated with platelet-rich plasma (PRP) and negative pressure trauma therapy (NPWT). 115 DSWI patients treated with the PRP and NPWT (PRP + NPWT) modality were retrospectively (2013-2021) analysed. They were divided into two groups according to primary healing results after the first PRP + NPWT treatment. Univariate and multivariate analyses were used to compare the data of the two groups to find out the risk factors and their optimal cut-off values were identified by ROC analysis. The primary healing results, debridement history, wound size, sinus, osteomyelitis, renal function, bacterial culture, albumin (ALB), platelet (PLT) between the two groups were significantly different (P < 0.05). Binary logistic regression showed that osteomyelitis, sinus, ALB and PLT were the risk factors affecting primary healing outcomes (P < 0.05). ROC analysis showed that AUC for ALB in the non-primary healing group was 0.743 (95% CI: 0.650-0.836, P < 0.05) and its optimal cutoff value of 31 g/L was associated with primary healing failure with a sensitivity of 96.9% and specificity of 45.1%. AUC for PLT in the non-primary healing group was 0.670 (95% CI: 0.571 ~ 0.770, P < 0.05) its optimal cutoff value of 293 × 109 /L was associated with primary healing failure with a sensitivity of 72.5% and specificity of 56.3%. In the cases included in this study, the success rate of primary healing of DSWI treated with PRP + NPWT was not affected by the most common preoperative risk factors for wound non-union. It is indirectly confirmed that PRP + NPWT is an ideal treatment. However, it should be noted that it will still be adversely affected by sinus osteomyelitis, ALB and PLT. The patients need to be carefully evaluated and corrected before reconstruction.

Transcriptome analysis of hepatic injury caused by delayed resuscitation following severe burns in rats.

BACKGROUND: Delayed resuscitation (DR) can induce hepatic reperfusion injury after severe burns. The underlying molecular mechanisms of DR-induced hepatic injury remain unidentified. This study sought to predict candidate genes and molecular pathways in a DR-induced hepatic injury preclinical model. METHODS: Rats were randomized into three groups: the sham injury (Sham) group; the DR group, which had third-degree burns covering 30% of the body surface area and DR; and the early resuscitation (ER) group, in which ER was administered. The liver tissue was harvested for the purpose of evaluating hepatic injury and performing transcriptome sequencing. Differentially expressed genes (DEGs) for DR versus Sham and ER versus DR were analyzed respectively. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Ingenuity Pathway Analysis were used. The DEGs and critical module genes were intersected to obtain critical genes. Immune infiltration and competing endogenous RNA networks were also analyzed. Validation was conducted using quantitative real-time polymerase chain reaction. RESULTS: Hepatic injury was evident in DR rats. There were 2,430 DEGs between DR and Sham and 261 DEGs between ER and DR. Differentially expressed genes were mostly enriched in metabolic process for DR versus Sham, and immune and inflammatory processes for ER versus DR. Four critical genes (Tff3, C1galt1, Cd48, and MGC105649) were obtained by screening. Five immune cells were significantly different between DR and Sham, and seven immune cells were significantly different between ER and DR in immunoassays. Three critical genes, 75 miRNAs, 7 lncRNAs, and 197 edges constituted the mRNA-miRNA-lncRNA linkages, which included C1galt1-rno-miR-330-5p-Pvt1, among others. CONCLUSION: This is the first attempt to perform a high-throughput analysis of gene expression profiles in DR-induced hepatic injury. It shows that immunity and inflammation-related RNAs and pathways play an important role in the progression of hepatic injury. It also provides insight into some important RNAs and regulatory targets related to disease.

Identification of differentially expressed HERV-K(HML-2) loci in colorectal cancer.

Colorectal cancer is one of the malignant tumors with the highest mortality rate in the world. Survival rates vary significantly among patients at various stages of the disease. A biomarker capable of early diagnosis is required to facilitate the early detection and treatment of colorectal cancer. Human endogenous retroviruses (HERVs) are abnormally expressed in various diseases, including cancer, and have been involved in cancer development. Real-time quantitative PCR was used to detect the transcript levels of HERV-K(HML-2) gag, pol, and env in colorectal cancer to systematically investigate the connection between HERV-K(HML-2) and colorectal cancer. The results showed that HERV-K(HML-2) transcript expression was significantly higher than healthy controls and was consistent at the population and cell levels. We also used next-generation sequencing to identify and characterize HERV-K(HML-2) loci that were differentially expressed between colorectal cancer patients and healthy individuals. The analysis revealed that these loci were concentrated in immune response signaling pathways, implying that HERV-K impacts the tumor-associated immune response. Our results indicated that HERV-K might serve as a screening tumor marker and a target for tumor immunotherapy in colorectal cancer.

A Potential Resuscitation Route on Battlefield: Immediate Intraperitoneal Fluid Administration Post-burn Shows Satisfactory Fluid Absorption and Anti-shock Effects.

INTRODUCTION: Timely fluid resuscitation remains the key to the early treatment of severe burns. Intraperitoneal (IP) fluid administration is a simple, rapid resuscitation strategy via a puncture in the abdominal wall. This study aimed to evaluate the fluid absorption and anti-shock effects of IP delivery in the early stage after severe burns. MATERIALS AND METHODS: A 30% total body surface area full-thickness burn model was established using male C57BL/6 mice. A total of 126 mice were randomly assigned into six groups (n = 21): the sham injury group (SHAM), the burn group without fluid resuscitation (NR), and the four IP resuscitation groups (IP-A/B/C/D, each being intraperitoneally administered with 60, 80, 100, and 120 mL/kg of sodium lactate Ringer's solution post-injury). Three-hour post-burn, six mice in each group were randomly selected and sacrificed for blood and tissue sampling to detect the IP fluid absorption rate and evaluate organ damage because of low perfusion. The remaining 15 mice in each group were observed for the vital signs within 48-h post-injury, and their survival rate was calculated. RESULTS: The 48-h survival rate increased in the IP-A (40.0%), IP-B (66.7%), IP-C (60.0%), and IP-D (13.3%) groups, compared with the NR group (0%). The mean arterial pressure, body temperature, and heart rate of mice were significantly stabilized in the IP groups. For the first 3-h post-injury, the absorption rates of groups IP-A (74.3% ± 9.5%) and IP-B (73.3% ± 6.9%) were significantly higher than those of groups IP-C (59.7% ± 7.1%) and IP-D (48.7% ± 5.7%). The levels of arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, lactate, and hematocrit were better maintained in the IP groups. Intraperitoneal resuscitation remarkably reduced the injury scores in burn-induced histopathology of the liver, kidneys, lungs, and intestines, accompanied by decreased alanine transaminase, creatinine, interleukin-1, and tumor necrosis factor-α in plasma, and augmented superoxide dismutase 2 and inhibited malondialdehyde in tissues. Group IP-B has the best performance for these indices. CONCLUSIONS: Intraperitoneal administration of isotonic saline post-burn can be adequately and rapidly absorbed, thereby boosting circulation and perfusion, precluding shock, alleviating organ damage caused by ischemia and hypoxia, and significantly increasing the survival rate. This technique, with a potential to be a supplement to existing resuscitation methods on the battlefield, is worth further investigation.

Correlation of the gut microbiome and immune-related adverse events in gastrointestinal cancer patients treated with immune checkpoint inhibitors.

Introduction: The wide application of immune checkpoint inhibitors has significantly improved the survival expectation of cancer patients. While immunotherapy brings benefits to patients, it also results in a series of immune-related adverse events (irAEs). Increasing evidence suggests that the gut microbiome is critical for immunotherapy response and the development of irAEs. Methods: In this prospective study, we recruited 95 patients with advanced/unresectable gastrointestinal cancers treated with immunotherapy and report a comprehensive analysis of the association of the gut microbiome with irAEs. Metagenome sequencing was used to analyze the differences in bacterial composition and metabolic pathways of baseline fecal samples. Results: In summary, we identified bacterial species and metabolic pathways that might be associated with the occurrence of irAEs in gastric, esophageal, and colon cancers. Ruminococcus callidus and Bacteroides xylanisolvens were enriched in patients without severe irAEs. Several microbial metabolic pathways involved in the urea cycle, including citrulline and arginine biosynthesis, were associated with irAEs. We also found that irAEs in different cancer types and toxicity in specific organs and the endocrine system were associated with different gut microbiota profiles. These findings provide the basis for future mechanistic exploration.