Development and validation of a nomogram for pneumonia risk in burn patients with inhalation injury: a multicenter retrospective cohort study.

BACKGROUND: Burn patients with inhalation injury are at higher risk of developing pneumonia, and yet there is no reliable tool for the assessment of the risk for such patients at admission. This study aims to establish a predictive model for pneumonia risk for burn patients with inhalation injury based on clinical findings and laboratory tests. METHOD: This retrospective study enrolled 546 burn patients with inhalation injury. They were grouped into a training cohort and a validation cohort. The least absolute shrinkage and selection operator (LASSO) regression analysis and binary logistic regression analysis were utilized to identify risk factors for pneumonia. Based on the factors, a nomogram for predicting pneumonia in burn patients with inhalation injury was constructed. Areas under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in both the training and validation cohorts. RESULTS: The training cohort included 432 patients, and the validation cohort included 114 patients, with a total of 225 (41.2%) patients experiencing pneumonia. Inhalation injury, tracheal intubation/tracheostomy, low serum albumin, and high blood glucose were independent risk factors for pneumonia in burn patients with inhalation injury and they were further used to build the nomogram. The AUC of the nomogram in the training and validation cohorts were 0.938 (95% CI: 0.917-0.960) and 0.966 (95% CI: 0.931-1), respectively. The calibration curve for probability of pneumonia showed optimal agreement between the prediction by nomogram and the actual observation, and the DCA indicated that the constructed nomogram conferred high clinical net benefit. CONCLUSION: This nomogram can accurately predict the risk of developing pneumonia for burn patients with inhalation injury, and help professionals to identify high-risk patients at an early stage as well as to make informed clinical decisions.

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.

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.

Paracoccus albicereus sp. nov., isolated from the shallow-sea hydrothermal system off Kueishantao Island.

Strain designated TK19116T was isolated from the shallow-sea hydrothermal systems off Kueishantao Island in Taiwan, China. The bacterium was Gram-stain-negative, aerobic, oxidase-positive and catalase-positive. Cells of the strain TK19116T were short-rod-shaped and non-motile. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that strain TK19116T belonged to the genus Paracoccus, with the highest sequence similarity to Paracoccus alkanivorans 4-2T (97.1 %). The average nucleotide identity values between the strain TK19116T with Paracoccus alkanivorans 4-2T, Paracoccus zhejiangensis J6T, Paracoccus siganidrum M26T and Paracoccus tegillarcae BM15T were 75.3, 76.7, 76.7 and 75.8%, respectively. The digital DNA-DNA hybridization value between the strain TK19116T with Paracoccus alkanivorans 4-2T, Paracoccus zhejiangensis J6T, Paracoccus siganidrum M26T and Paracoccus tegillarcae BM15T were 19.7, 20.3, 20.5 and 20.0%, respectively. The main respiratory quinone of strain TK19116T was ubiquinone 10. The polar lipids include aminolipid, phosphatidylcholine, diphosphatidylglycerol, glycolipid, phosphatidylglycerol and phospholipid. The principal fatty acid of strain TK19116T was summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c). The G+C content of the chromosomal DNA was 64.2 %. The combination of the results of the phylogenetic, phenotypic and chemotaxonomic analysis, strain TK19116T represents a novel species of the genus Paracoccus, for which the name Paracoccus albicereus sp. nov. is proposed. The type strain is TK19116T (= MCCC 1K08025T=JCM 35527T).

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.

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.

Review on risk factors, classification, and treatment of sternal wound infection.

Sternal wound infection (SWI) is the most common complication of the median sternal incision. The treatment time is long, and the reconstruction is difficult, which causes challenges for surgeons. Plastic surgeons were often involved too late in such clinical scenarios when previous empirical treatments failed and the wound damage was relatively serious. Accurate diagnosis and risk factors against sternal wound infection need to be in focus. Classification of different types of sternotomy complications post-cardiac surgery is important for specific categorization and management. Not familiar with this kind of special and complex wound, objectively increasing the difficulty of wound reconstruction. The purpose of this comprehensive review is to review the literature, introduce various SWI risk factors related to wound nonunion, various classification characteristics, advantages and disadvantages of various wound reconstruction strategies, to help clinicians understand the pathophysiological characteristics of the disease and choose a better treatment method.

An innovated elastic compression hemostasis technique for extremity excision in patients with extensive burns: A prospective clinical randomized controlled trial.

OBJECTIVE: To introduce an innovative elastic compression hemostasis technique for extremity excision in extensively burnt patients and investigate its effectiveness. METHODS: Ten patients were included and divided into 2 groups: the control group (4 patients, 12 extremities) receiving the conventional hemostasis technique and the experimental group (6 patients, 14 extremities) receiving the innovative technique. General data of the patients were collected, excision size measured, hemostasis time recorded, average blood loss per 1% total body surface area of the excised wound calculated, incidence of subcutaneous hematoma and take rate determined. RESULTS: The 2 groups had no statistical difference in the baseline data. Average blood loss per 1% total body surface area of the excised wound in the upper and the lower extremities was (62.1 ± 11.5) mL and (35.6 ± 11.0) mL in the experimental group, significantly less than (94.3 ± 6.9) mL and (82.3 ± 6.2) mL in the control group; a reduction of 34.1% and 56.8% respectively. Hemostasis time in the upper and the lower extremities were (5.0 ± 0.7) min/1% total body surface area and (2.6 ± 0.3) min/1% total body surface area, respectively, in the experimental group, significantly less than (7.4 ± 0.6) min/1% total body surface area and (4.0 ± 0.9) min/1% total body surface area in the control group; a reduction of 31.8% and 34.9% respectively. The incidences of subcutaneous hematoma were 7.1% and 8.3%, and the take rate (85.9 ± 6.0)% and (86.5 ± 4.8)% in the experimental and the control group, respectively, with no statistically significant differences. CONCLUSION: The innovative elastic compression hemostasis technique is a reliable new method that significantly reduces blood loss during extremity excision in patients with extensive burns and is worth wider understanding and application.

WITHDRAWN: Transdifferentiation of Human Neonatal Foreskin Fibroblasts into Keratinocyte-like Cells via Regulating the AKT/P53/WNT/LEF1 Axis

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the journal Current Stem Cell Research & Therapy.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham editorial policy on article withdrawal can be found at https://benthamscience.com/pages/editorial-policies-main BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

The Epidermal Barrier Structure and Function of Re-Harvested Skin from Non-Scalp Donor Sites.

AIM: The aim of this study was to explore the epidermal barrier structure and function of re-harvested skin from non-scalp donor sites. METHODS: Six patients with large-area deep burns who met the inclusion and exclusion criteria were subjected to split-thickness skin excision three times on the same healthy non-scalp donor sites, with an interval of 14 days. The donor skin thus harvested was labeled as primary skin (S1), secondary skin (S2), and tertiary skin (S3). The transepidermal water loss (TEWL) and stratum corneum water content (SCH) of donor skin were detected before each surgery, and the donor skin was harvested during the surgery. The donor skin was stained with hematoxylin and eosin (HE) and involucrin, loricrin, filaggrin, small molecule proline-rich protein 3 (SPRR3), ZO-3, JAM-A, and JAM-C, or observed by transmission electron microscopy. RESULTS: The epidermal barrier function of the re-harvested skin from the non-scalp donor sites became impaired. The histopathological structure of the re-harvested skin from non-scalp donor sites became abnormal. The barrier of the epidermal stratum corneum of the re-harvested skin from non-scalp donor sites was damaged. The epidermal tight junction barrier in the re-harvested skin from non-scalp donor sites was damaged. CONCLUSIONS: As the number of harvesting increases, the epidermal barrier function of the skin decreased, and the damage to the barrier structure increased. Hence, it is vitally important to restore the epidermal barrier function for re-harvesting in non-scalp donor sites.

Effects and Mechanisms of Peritoneal Resuscitation on Acute Kidney Injury After Severe Burns in Rats.

INTRODUCTION: Acute kidney injury (AKI) is a common complication in severe burn patients with poor prognosis and high mortality. Reduced kidney perfusion induced by the decreased effective circulating blood volume after severe burn is a common cause of AKI. Routine intravenous resuscitation (IR) is difficult or delayed in extreme conditions such as war and disaster sites. Peritoneal resuscitation (PR) is a simple, rapid resuscitation strategy via a puncture in the abdominal wall. This study investigated whether PR is a validated resuscitation strategy for AKI after severe burns in rats and explored its mechanisms. MATERIALS AND METHODS: Eighty Sprague-Dawley rats were randomized into four groups: (1) sham group; (2) IR group, which was characterized by the full thickness burn of 50% of the total body surface area received IR immediately post-injury; (3) early PR group, in which rats with the same burn model received PR immediately post-injury; and (4) delayed resuscitation (DR) group, in which rats with the same burn model received no resuscitation within 3-hour post-injury. PR and DR groups animals received IR after 3-hour post-injury. The survival rate, mean arterial pressure, renal histopathology, renal function, indicators of renal injury, and renal hypoxia-inducible factor-1α and NADPH oxidase 4 (NOX4) proteins of rats were measured at 3 h, 12 h, and 24 h post-injury. RESULTS: Compared with rats in the DR group, rats in the PR group had a significantly improved survival rate (100% vs. 58.3% at 24 h, P = 0.0087), an increased mean arterial pressure (92.6 ± 6.6 vs. 65.3 ± 10.7, 85.1 ± 5.7 vs. 61.1 ± 6.9, 90.1 ± 8.7 vs. 74.9 ± 7.4 mmHg, at 3 h, 12 h, and 24 h, P < 0.01), a reduced renal water content rate (51.6% ± 5.0% vs. 70.1% ± 6.8%, 57.6% ± 7.7% vs. 69.5% ± 8.7%, at 12 h and 24 h, P < 0.01), attenuated histopathological damage, reduced serum creatinine expression (36.36 ± 4.27 vs. 49.98 ± 2.42, 52.29 ± 4.31 vs. 71.32 ± 5.2, 45.25 ± 2.55 vs. 81.15 ± 6.44 µmol/L, at 3 h, 12 h, and 24 h, P < 0.01) and BUN expression (7.62 ± 0.30 vs. 10.80 ± 0.58, 8.61 ± 0.32 vs. 28.58 ± 1.99, 8.09 ± 0.99 vs. 20.95 ± 1.02 mmol/L, at 3 h, 12 h, and 24 h, P < 0.01), increased kidney injury markers neutrophil gelatinase-associated lipocalin expression (95.09 ± 7.02 vs. 101.75 ± 6.23, 146.77 ± 11.54 vs. 190.03 ± 9.87, 112.79 ± 15.8 vs. 194.43 ± 11.47 ng/mL, at 3 h, 12 h, and 24 h, P < 0.01) and cystatin C expression (0.185 ± 0.006 vs. 0.197 ± 0.006, 0.345 ± 0.036 vs. 0.382 ± 0.013, 0.297 ± 0.012 vs. 0.371 ± 0.028 ng/mL, at 3 h, 12 h, and 24 h, P < 0.01), and reduced renal hypoxia-inducible factor-1α and NADPH oxidase 4 protein expression (P < 0.01). There was no significant difference between rats in the PR group and the IR group in the above indicators. CONCLUSIONS: Early PR could protect severe burn injury rats from AKI. It may be an alternative resuscitation strategy in severe burn injury when IR cannot be achieved.

A novel skin grafting modality: prefabricated large sheet of postage-stamp autografts and allografts to repair extensive burn wounds; a prospective matched-control study.

BACKGROUND: The excessively long operative time has been the greatest barrier to the success of transplanting postage-stamp auto- and allografts directly and piece-by-piece onto extensive burn wounds. To solve this challenge, the authors present a novel grafting modality, that is, the prefabricated-large-sheet grafting that moves the labor-intensive and time-consuming process of grafts-positioning before grafting and thereby markedly shortens the operative time. METHODS: Twenty-one operations using the novel modality were performed on 11 patients with extensive deep burns. The grafting time using the novel modality was recorded and compared with that of the conventional piece-by-piece grafting. Eventually, the take rates of the two modalities were compared. RESULTS: All patients were healed and discharged. The average grafting time per unit area (100 cm2) of prefabricated-large-sheet grafting and piece-by-piece grafting were (0.41±0.09) min and (7.46±1.07) min, respectively, and the difference is statistically significant(P<0.001). The average take rate of the prefabricated sheets was (85.43±6.14)% and that of the piece-by-piece transplanted grafts was (87.29±5.23)% and there is no significant difference(P>0.05). CONCLUSIONS: The prefabricated-large-sheet grafting significantly reduces the intraoperative grafting time while ensures uniformity of the skin grafts and secures good outcomes, thereby making the intermingled transplantation of postage-stamp auto- and allografts, which has been an excellent modality per se but limited to repair small residual wounds, now feasible to repair extensive deep burn wounds. It is worth wider understanding and application in the treatment of extensive deep burns.

Transcriptome reveals the dysfunction of pancreatic islets after wound healing in severely burned mice.

BACKGROUND: Severely burned patients have a higher risk of diabetes mellitus after healing, but its mechanism remains unclear. Therefore, the purpose of the study was to explore the influence of burns on pancreatic islets of mice after wound healing. METHODS: Forty-two male C57BL/6 mice were randomized into a sham group and a burn group and subjected to sham treatment or a third-degree burn model of 30% total body surface area. Fasting blood glucose was detected weekly for 8 weeks after severe burns. Glucose-stimulated insulin secretion was measured 8 weeks post severe burns. Islets of the two groups were isolated and mRNA libraries were sequenced by the Illumina sequencing platform. The expressions of differentially expressed genes (DEGs) related to the cell cycle and the amounts of mitochondrial DNA were detected by quantitative real-time polymerase chain reaction after gene ontology, gene set enrichment analysis, and protein-protein network analysis. Hematoxylin-eosin staining of pancreatic tail tissue and adenosine triphosphate (ATP) assay of islets were performed. RESULTS: The levels of fasting blood glucose were significantly higher within 8 weeks post severe burns. Glucose-stimulated insulin secretion was impaired at the eighth week post severe burns. Totally 128 DEGs were selected. Gene ontology and gene set enrichment analysis indicated that the pathways related to the cell cycle, protein processing, and oxidative phosphorylation were downregulated. The expressions of DEGs related to the cell cycle showed a consistent trend with mRNA sequencing data, and most of them were downregulated post severe burns. The cell mass of the burn group was less than that of the sham group. Also, the concentration of ATP and the amount of mitochondrial DNA were lower in the burn group. CONCLUSION: In the model of severe-burned mice, disorders in glucose metabolism persist for 8 weeks after burns, which may be related to low islet cell proliferation, downregulation of protein processing, and less ATP production.

Elevated Serum Procalcitonin to Predict Severity and Prognosis of Extensive Burns.

PURPOSE: To analyze the factors affecting the elevation of serum procalcitonin (PCT) in patients with extensive burns, and explore its potential value in evaluating the severity and prognosis. METHODS: Clinical data of 139 patients with extensive burns admitted to our burn center from January 2014 to December 2019 were retrospectively analyzed. Spearman's Rank correlation coefficient was used to analyze the factors influencing the elevated PCT levels. The predictive power of PCT for death was evaluated by receiver operating characteristic (ROC) and multiple logistic regression analysis. RESULTS: 72 cases exhibited elevated serum PCT concentrations during the shock phase, but none of them had obvious signs of infection. PCT level in the shock phase was positively correlated with burn area, depth, degree of inhalation injury, delay in fluid resuscitation, APACHE II, and SOFA scores. The peak values of PCT during shock and infection phases were significantly higher in the non-survivors than in the survivors. The areas under the ROC curve for predicting death were 0.788 and 0.926, respectively, and 5.4 ng/mL (OR = 5.33) and 8.5 ng/mL (OR = 14.49) were the high-risk thresholds for death prediction. CONCLUSIONS: Serum PCT level in the shock phase is a potential indicator for evaluating the severity of burns, while the PCT level during the infection period can be used as an early warning indicator for severe systemic infection. High levels of PCT peaks during the shock and infection periods indicate an increased risk of poor prognosis, and targeted treatment is required accordingly.

Mitochondria play a key role in oxidative stress-induced pancreatic islet dysfunction after severe burns.

BACKGROUND: Severe burns are often complicated with hyperglycemia in part caused by pancreatic islet dysfunction. Previous studies have revealed that in diabetes mellitus, the pancreatic islet dysfunction is partly attributed to oxidative stress. However, the role and mechanism of oxidative stress in hyperglycemia after severe burns remain unclear. Therefore, the purpose of this study was to explore the level and mechanism of oxidative stress in pancreatic islets after severe burns and the antioxidant effect of sodium pyruvate. METHODS: A 30% total body surface area full-thickness burn model was established using male C57BL/6 mice. Fasting blood glucose and glucose-stimulated insulin secretion (GSIS) 24 hours post severe burns were detected. The levels of reactive oxygen species (ROS) and mitochondrial ROS of islets were detected. The activities of complexes in the mitochondrial respiratory chain of islets were measured. The main antioxidant defense system, glutaredoxin system, and thioredoxin system-related indexes were detected, and the expression of manganese superoxide dismutase (Mn-SOD) was measured. In addition, the antioxidant activity of sodium pyruvate was evaluated post severe burns. RESULTS: After severe burns, fasting blood glucose levels increased, while GSIS levels decreased, with significantly elevated ROS levels of pancreatic islets. The activity of complex III decreased and the level of mitochondrial ROS increased significantly post severe burns. For the detoxification of ROS, the expressions of thioredoxin 2, thioredoxin reductase 2, and Mn-SOD located in mitochondria decreased. Sodium pyruvate reduced the level of mitochondrial ROS in islet cells and improved the GSIS of islets after severe burns. CONCLUSION: The high level of mitochondrial ROS of islets is caused by reducing the activity of complex III in mitochondrial respiratory chain, inhibiting mitochondrial thioredoxin system, and downregulating Mn-SOD post severe burns. Sodium pyruvate plays an antioxidant role post severe burns in mice islets and improves the islet function.

CAVIN2 is frequently silenced by CpG methylation and sensitizes lung cancer cells to paclitaxel and 5-FU.

Aim: To explore the biological functions and clinical significance of CAVIN2 in lung cancer. Materials & methods: Methylation-specific PCR was used to measure promoter methylation of CAVIN2. The function of CAVIN2 was tested by Cell Counting Kit-8, colony formation, Transwell, flow cytometric analysis, acridine orange/ethidium bromide, chemosensitivity assay and xenograft assay. Results: CAVIN2 is significantly downregulated by promoter methylation in lung cancer. CAVIN2 overexpression inhibits lung cancer cell migration and invasion. Furthermore, ectopic expression of CAVIN2 inhibits cell proliferation in vivo and in vitro by inducing G2/M cell cycle arrest, which sensitizes the chemosensitivity of lung cancer cells to paclitaxel and 5-fluorouracil, but not cisplatin. Conclusion: CAVIN2 is a tumor suppressor in non-small-cell lung cancer and can sensitize lung cancer cells to paclitaxel and 5-fluorouracil.

Role and mechanism of PI3K/AKT/FoxO1/PDX-1 signaling pathway in functional changes of pancreatic islets in rats after severe burns.

AIMS: Studies on diabetes mellitus have shown that the phosphoinositide 3-kinase (PI3K)/serine threonine kinase (AKT)/forkhead box protein O1 (FoxO1) signaling pathway can regulate insulin secretion by modulating the expression of pancreatic and duodenal homeobox-1 (PDX-1). Therefore, it was hypothesized that the pathway also played an important role in functional abnormalities of pancreatic islets after severe burns. This study aimed to explore the role and mechanism of the PI3K/AKT/FoxO1/PDX-1 signaling pathway in functional changes of pancreatic islets in rats post severe burns. MAIN METHODS: Rats were grouped, subjected to full thickness burn injuries involving 50% total body surface area (TBSA), and injected intraperitoneally with BPV (HOpic) (0.6 mg/kg) or DMSO (0.55 mg/kg) once a day for three days. Glucose metabolism related indexes were measured by the glucometer, transmission electron microscopy (TEM) and enzyme-linked immunosorbent assay (ELISA). PI3K/AKT/FoxO1/PDX-1 signaling pathway related indexes were detected through immunofluorescence, western blot and RT-qPCR analyses. KEY FINDINGS: Dysglycemia and impaired insulin secretion occurred in rats, the activity of the PI3K/AKT/FoxO1/PDX-1 signaling pathway in the islets fell, and PDX-1 was translocated from the nucleus to the cytoplasm post severe burns. When BPV (HOpic) was used, glucose metabolism and insulin secretion were improved, the activity of the PI3K/AKT/FoxO1/PDX-1 signaling pathway in the islets was up-regulated, and PDX-1 was redistributed from the cytoplasm to the nucleus. SIGNIFICANCE: The activity of the PI3K/AKT/FoxO1/PDX-1 signaling pathway declined following severe burns. When its activity was up-regulated, insulin secretion could be improved, thus ameliorating hyperglycemia.

TTK regulates proliferation and apoptosis of gastric cancer cells through the Akt-mTOR pathway.

TTK (also known as Mps1) is the core component of the spindle assembly checkpoint, which ensures proper distribution of chromosomes to daughter cells to maintain genome integrity and to balance growth and division. However, the function of TTK in tumorigenesis has not been extensively studied, especially in relation to the development of gastric cancer. In this study, survival and tumor recurrence data related to TTK expression level in gastric cancer patients were collected and analyzed. We observed that TTK expression was negatively correlated with survival and tumor recurrence in vivo. TTK was also upregulated in gastric cancer cells and was observed to be essential for the proliferation and survival of gastric cancer cells. Knockdown of TTK inhibited proliferation and increased apoptosis. Furthermore, we report that TTK regulates the proliferation and apoptosis of tumor cells through the Akt-mTOR pathway. Knockdown of TTK inhibited activation of Akt-mTOR signaling. In summary, our data indicate that TTK is involved in the regulation of gastric cancer proliferation and apoptosis.

Molecular mechanism mediating enteric bacterial translocation after severe burn: the role of cystic fibrosis transmembrane conductance regulator.

BACKGROUND: Gut ischemia and hypoxia post severe burn leads to breakdown of intestinal epithelial barrier and enteric bacterial translocation (EBT), resulting in serious complications, such as systemic inflammatory response syndrome, sepsis and multiple organ failure. Cystic fibrosis transmembrane conductance regulator (CFTR) is known to be downregulated by hypoxia and modulate junctional complexes, which are crucial structures maintaining the intestinal barrier. This study aimed to investigate whether CFTR plays a role in both regulating the intestinal barrier and mediating EBT post severe burn, as well as the signaling pathways involved in these processes. METHODS: An in vitro Caco-2 cell model subjected to hypoxic injury and an in vivo mouse model with a 30% total body surface area full-thickness dermal burn were established. DF 508 mice (mice with F508del CFTR gene mutation) were used as an in vivo model to further demonstrate the role of CFTR in maintaining normal intestinal barrier function. QRT-PCR, western blot, ELISA, TER assay and immunofluorescence staining were used to detect the expression and localization of CFTR and tight junction proteins, as well as the function of tight junctions. RESULTS: Our data indicated that, in Caco-2 cells, the hypoxia condition significantly reduced CFTR expression; activated extracellular signal-regulated kinase and nuclear factor-κB signaling; elevated secretion of inflammatory factors (tumor necrosis factor-α, interleukin-1ß and interleukin-8); downregulated zonula occludens-1, occludin and E-cadherin expression; decreased transepithelial electrical resistance values; and led to a cellular mislocation of ZO-1. More importantly, knockdown of CFTR caused similar alterations. The upregulation of inflammatory factors and downregulation of tight junction proteins (ZO-1 and occludin) induced by knockdown of CFTR could be reversed by specific extracellular signal-regulated kinase or nuclear factor-κB inhibition. In support of the in vitro data, exuberant secretion of pro-inflammatory mediators and EBT was observed in the intestine of severely burnt mice in vivo. EBT occurred in DF508 mice (mice with the F508del CFTR gene mutation), accompanied by augmented tumor necrosis factor-α, interleukin-1ß and interleukin-8 levels in the ileum compared to wildtype mice. In addition, vitamin D3 was shown to protect the intestinal epithelial barrier from hypoxic injury. CONCLUSIONS: Collectively, the present study illustrated that CFTR and downstream signaling were critical in modulating the intestinal epithelial junction and EBT post severe burn.

Use of a modified endotracheal tube for self-expandable metallic Y-shaped airway stent deployment without rigid bronchoscope or fluoroscopic guidance.

BACKGROUND: Self-expandable metallic Y-shaped airway stents (SEMYS) are commonly used in the management of airway stenosis and fistulae caused by thoracic neoplasms. METHODS: A new technique using a slightly modified regular endotracheal tube has been developed for the deployment of SEMYS with flexible bronchoscopy alone. The technique and devices are described. RESULTS: To date, successful deployment of SEMYS with this method has been carried out successfully in 17 out of 20 patients without major complications while the other 3 required conversion to rigid bronchoscopy because of limited pharyngeal cavity space, massive hemorrhage and severe cicatrization of the airway, respectively. CONCLUSIONS: This simplified deployment technique with the modified endotracheal tube enables safe, simple and fast insertion of SEMYS in a regular bronchoscopy suite, which may benefit the vast less privileged institutions where SEMYS are necessary but rigid bronchoscopy and fluoroscopy are not available. The skill of the bronchoscopist, cautious selection of patients and effective coordination of the operating team are crucial for the procedure.