Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: A multicenter double-blind randomized controlled trial.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8+ T cells than the placebo group at 3 (2.300,P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8+ T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).

Comparison of oncologic outcomes between pancreaticoduodenectomy and total pancreatectomy for pancreatic adenocarcinoma.

BACKGROUND: Pancreatoduodenectomy (PD) and total pancreatectomy (TP) are two surgical methods to treat patients with pancreatic head adenocarcinoma (PHAC). However, the oncologic outcomes of TP for PHAC remain controversial. In this study, we compared early mortality and long-term survival patients undergoing TP and those with PD. METHODS: All patients diagnosed with non-metastatic PHAC who underwent PD or TP from 1988 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to balance the inter-group covariates. Cancer-specific survival (CSS) was the primary endpoint. RESULTS: A total of 4748 patients (743 TP and 4005 PD) were included in the study. Some 740 patients who underwent TP were matched with 1479 who had PD. After PSM, there was no difference between TP and PD groups regarding 30-day mortality (3.5% vs. 2.7%, p = 0.290) and 90-day mortality (9.9% vs. 8%, p = 0.135). More importantly, TP showed comparable survival in comparison to PD, prior or after excluding patients who died within 30 and 90 days. Besides, multivariate analysis revealed that tumor size, tumor stage, N stage, chemotherapy, and radiation were significant prognostic factors. CONCLUSION: PD and TP have similar early mortality and long-term survival for patients with PHAC. In selected patients, TP can be used when oncologically appropriate.

Minimally invasive management of concomitant gallstones and common bile duct stones: an updated network meta-analysis of randomized controlled trials.

BACKGROUND: To update a 2018 meta-analysis on the comparative efficacy and safety of four surgical techniques in patients with concomitant gallstones and common bile duct (CBD) stones. METHODS: Randomized controlled trials (RCTs) comparing laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct exploration (LCBDE), LC plus preoperative endoscopic retrograde cholangiopancreatography (PreERCP), LC plus intraoperative ERCP (IntraERCP), and LC plus postoperative ERCP (PostERCP) were included. Primary and secondary outcomes were compared using odds ratio, weighted mean difference, and 95% confidence intervals. RESULTS: Twenty-five RCTs involved 3145 patients were included. Of these, 1188 (37.8%) underwent LC + PreERCP, 1183 (37.6%) LC + LCBDE, 689 (21.9%) LC + IntraERCP, and 85 (2.7%) LC + PostERCP. This analysis demonstrated that LC plus IntraERCP was the most likely approach to achieve technical success and reduce morbidity. No significant differences were observed between the four treatments concerning major morbidity, mortality, and operative time. LC plus LCBDE was effective for increasing biliary leak and conversion as well as decreasing postoperative hemorrhage and total costs. Additionally, LC plus PreERCP was associated with higher postoperative pancreatitis, while LC plus IntraERCP was associated with a shorter length of hospital stay. There was significant heterogeneity in operative time, hospital stay, and total costs (τ2 > 1). CONCLUSIONS: This analysis provides evidence that LC plus IntraERCP appears to be the optimal strategy for patients with concomitant gallstones and CBD stones owing to its advantage in technical success and morbidity. LC plus LCBDE is associated with higher biliary leak and lower postoperative hemorrhage, whereas LC plus PreERCP is associated with higher postoperative pancreatitis.

Nutritional practice in critically ill COVID-19 patients: A multicenter ambidirectional cohort study in Wuhan and Jingzhou.

BACKGROUND AND OBJECTIVES: The novel coronavirus disease (COVID-19) epidemic is spreading all over the world. With the number of cases increasing rapidly, the epidemiological data on the nutritional practice is scarce. In this study, we aim to describe the clinical characteristics and nutritional practice in a cohort of critically ill COVID-19 patients. METHODS AND STUDY DESIGN: This is a multicenter, ambidirectional cohort study conducted at 11 hospitals in Hubei Province, China. All eligible critical COVID-19 patients in the study hospital intensive care units at 00:00, March 6th, 2020, were included. Data collection was performed via written case report forms. RESULTS: A total of 44 patients were identified and enrolled, of whom eight died during the 28-day outcome follow- up period. The median interval between hospital admission and the study day was 24 (interquartile range, 13- 26) days and 52.2% (23 of 44) of patients were on invasive mechanical ventilation. The median nutrition risk in critically ill (mNUTRIC) score was 3 (interquartile range, 2-5) on the study day. During the enrolment day, 68.2% (30 of 44) of patients received enteral nutrition (EN), while 6.8% (3 of 44) received parenteral nutrition (PN) alone. Nausea and aspiration were uncommon, with a prevalence of 11.4% (5 of 44) and 6.8% (3 of 44), respectively. As for energy delivery, 69.7% (23 of 33) of patients receiving EN and/or PN were achieving their prescribed targets. CONCLUSIONS: The study showed that EN was frequently applied in critical COVID-19 patients. Energy delivery may be suboptimal in this study requiring more attention.

Efficacy and Safety of Intralesional Triamcinolone Versus Combination of Triamcinolone with 5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis.

BACKGROUND: Although keloids and hypertrophic scars are common benign hyperproliferative growths of dermal fibroblasts, the clinical problems including physical and psychological problems are significant and impairing, with few proven treatments. Intralesional triamcinolone acetonide (TAC) and combination of TAC with 5-fluorouracil (5-FU) are widely used to treat keloids and hypertrophic scars, but their efficacy and safety remain controversial. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and CNKI for relevant trials. RESULTS: The mean scar height and the erythema score in the TAC + 5-FU group were lower than those in the TAC group after treatment (P < 0.05). The effectiveness based on observer assessment after treatment in the TAC + 5-FU group was superior than that in the TAC group (P < 0.05); further, the subgroup analysis showed the TAC + 5-FU group was also superior than the TAC group in the treatment of hypertrophic scars (P = 0.01), and there were no significant differences in the treatment of keloid (P = 0.12). The effectiveness based on patient self-assessment after treatment in the TAC + 5-FU group was also superior than the TAC group (P < 0.05). The overall complication rate in the TAC + 5-FU group was lower than the TAC group (P < 0.05). CONCLUSIONS: Combination of TAC with 5-FU is more effective and safer than TAC alone therapy in the treatment of keloids and hypertrophic scars. Data on keloids alone or hypertrophic scars alone are, however, limited. A better understanding of effective after intralesional combination of TAC with 5-FU in the treatment of keloids alone or hypertrophic scars alone is imperative. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Safety and Efficacy of Intralesional Verapamil Versus Intralesional Triamcinolone Acetonide for Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis.

BACKGROUND: Keloids and hypertrophic scars often result after skin trauma. Currently, intralesional triamcinolone acetonide (TAC) is the criterion standard in nonsurgical management of keloids and hypertrophic scars. Intralesional verapamil may be an effective alternative modality, but it has been insufficiently studied. Accordingly, the study authors conducted a systematic review and meta-analysis of randomized controlled trials to compare the efficacy and safety of the two drugs. METHODS: The study authors systematically searched the MEDLINE, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases for relevant trials published in any language through September 2018. RESULTS: According to the four studies included in this review, TAC improved scar pliability and vascularity more than verapamil after 3 weeks (P < .05). For scar height and scar pigmentation, no statistical difference was observed between the treatments (P > .05). The difference in effects on symptoms was not statistically significant (P = .89). For pain and telangiectasia, no statistical difference was observed (P > .05). Verapamil resulted in fewer cases of skin atrophy (P < .05). CONCLUSIONS: It appears that TAC is more effective than verapamil for improving scar pliability and vascularity in keloids and hypertrophic scars after 3 weeks of treatment. However, verapamil has fewer adverse drug reactions than TAC, which allows for a longer treatment period and the possibility that it might be effective for patients who cannot receive TAC.

Sinus Wounds Management.

With aging populations and the increased incidence of cerebrovascular disease, diabetes, and other diseases, more and more patients suffer from pressure injuries. Pressure injuries are often difficult to heal because of the presence of sinus tracts, which make it difficult to clean and change dressings. Sinus wounds are common in patients with pressure injuries, but also occur after abdominal wall incision and in patients who have experienced a physical trauma that created a wound. It is difficult for clinicians to observe, evaluate, and repair sinus wounds because of the small surface defect and large and deep basement of each wound. This article reviews existing assessment methods and treatments for sinus wounds and proposes a new evaluation method and treatment (three-dimensional reconstruction and endoscopic techniques) to further improve treatment and provide better quality of care for patients with this type of wound.

Identification of cuproptosis-related gene clusters and immune cell infiltration in major burns based on machine learning models and experimental validation.

Introduction: Burns are a global public health problem. Major burns can stimulate the body to enter a stress state, thereby increasing the risk of infection and adversely affecting the patient's prognosis. Recently, it has been discovered that cuproptosis, a form of cell death, is associated with various diseases. Our research aims to explore the molecular clusters associated with cuproptosis in major burns and construct predictive models. Methods: We analyzed the expression and immune infiltration characteristics of cuproptosis-related factors in major burn based on the GSE37069 dataset. Using 553 samples from major burn patients, we explored the molecular clusters based on cuproptosis-related genes and their associated immune cell infiltrates. The WGCNA was utilized to identify cluster-specific genes. Subsequently, the performance of different machine learning models was compared to select the optimal model. The effectiveness of the predictive model was validated using Nomogram, calibration curves, decision curves, and an external dataset. Finally, five core genes related to cuproptosis and major burn have been was validated using RT-qPCR. Results: In both major burn and normal samples, we determined the cuproptosis-related genes associated with major burns through WGCNA analysis. Through immune infiltrate profiling analysis, we found significant immune differences between different clusters. When K=2, the clustering number is the most stable. GSVA analysis shows that specific genes in cluster 2 are closely associated with various functions. After identifying the cross-core genes, machine learning models indicate that generalized linear models have better accuracy. Ultimately, a generalized linear model for five highly correlated genes was constructed, and validation with an external dataset showed an AUC of 0.982. The accuracy of the model was further verified through calibration curves, decision curves, and modal graphs. Further analysis of clinical relevance revealed that these correlated genes were closely related to time of injury. Conclusion: This study has revealed the intricate relationship between cuproptosis and major burns. Research has identified 15 cuproptosis-related genes that are associated with major burn. Through a machine learning model, five core genes related to cuproptosis and major burn have been selected and validated.

Microarray analysis of tRNA-derived small RNA (tsRNA) in LPS-challenged macrophages treated with metformin.

Metformin, a widely used anti-diabetic drug, has demonstrated its efficacy in addressing various inflammatory conditions. tRNA-derived small RNA (tsRNA), a novel type of small non-coding RNA, exhibits diverse regulatory functions and holds promise as both a diagnostic biomarker and a therapeutic target for various diseases. The purpose of this study is to investigate whether the abundance of tsRNAs changed in LPS versus LPS + metformin-treated cells, utilizing microarray technology. Firstly, we established an in vitro lipopolysaccharide (LPS)-induced inflammation model using RAW264.7 macrophages and assessed the protective effects of metformin against inflammatory damage. Subsequently, we extracted total RNA from both LPS-treated and metformin + LPS-treated cell samples for microarray analysis to identify differentially abundant tsRNAs (DA-tsRNAs). Furthermore, we conducted bioinformatics analysis to predict target genes for validated DA-tsRNAs and explore the biological functions and signaling pathways associated with DA-tsRNAs. Notably, metformin was found to inhibit the inflammatory response in RAW264.7 macrophages. The microarray results revealed a total of 247 DA-tsRNAs, with 58 upregulated and 189 downregulated tsRNAs in the Met + LPS group compared to the LPS group. The tsRNA-mRNA network was visualized, shedding light on potential interactions. The results of bioinformatics analysis suggested that these potential targets of specific tsRNAs were mainly related to inflammation and immunity. Our study provides compelling evidence that metformin exerts anti-inflammatory effects and modulates the abundance of tsRNAs in LPS-treated RAW264.7 macrophages. These findings establish a valuable foundation for using tsRNAs as potential biomarkers for metformin in the treatment of inflammatory conditions.

Long noncoding RNA XIST promotes cell proliferation and migration in diabetic foot ulcers through the miR-126-3p/EGFR axis.

BACKGROUND: The prevalence of diabetic foot ulcers (DFUs) has caused serious harm to human health. To date, a highly effective treatment is lacking. Long noncoding RNA X-inactive specific transcript (lncRNA XIST) has been the subject of mounting research studies, all of which have found that it serves as a protective factor against certain diseases; however, its function in DFUs is not entirely understood. This study was performed to determine the importance of the lncRNA XIST in the pathogenesis and biological function of DFUs. METHODS: Diabetic ulcer skin from rats was analysed using haematoxylin-eosin (HE), Masson's trichrome, and immunohistochemistry (IHC) staining. The differences in the expression of genes and proteins were examined with real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Next, the interaction was verified with a dual luciferase gene reporter assay. In addition, CCK-8, Transwell, and wound healing assays were used to assess the proliferation and migration of HaCaT cells. RESULTS: The lncRNA XIST and epidermal growth factor receptor (EGFR) were downregulated, while microRNA-126-3p (miR-126-3p) was increased in diabetic ulcer rat skin tissues and high glucose-induced HaCaT cells. In addition, we found that the lncRNA XIST binds to miR-126-3p and that EGFR is directly targeted by miR­126­3p. Silencing XIST contributed to upregulated miR-126-3p expression, thus lowering EGFR levels and inhibiting the proliferative and migratory abilities of high glucose-treated HaCaT cells; however, the miR-126-3p inhibitor and overexpression of EGFR reversed this effect. CONCLUSION: Decreased lncRNA XIST expression inhibits the proliferative and migratory abilities of high glucose-induced HaCaT cells by modulating the miR-126-3p/EGFR axis, causing delayed wound healing.

Association of energy delivery with short-term survival in mechanically ventilated critically ill adult patients: a secondary analysis of the NEED trial.

BACKGROUND AND AIMS: The optimal energy delivery for mechanically ventilated patients is controversial, particularly during the first week of ICU admission. This study aimed to investigate the association between different caloric adequacy and 28-day mortality in a cohort of critically ill adults on mechanical ventilation. METHODS: This is a secondary analysis of a multicenter, cluster-randomized controlled trial. Eligible patients were divided into four quartiles (Q1-Q4) according to caloric adequacy calculated by the actual average daily energy delivery during the first seven days of ICU stay divided by energy requirement as a percentage. Cox proportional hazards models were used to examine the impact of different quartiles of caloric adequacy on 28-day mortality in the whole cohort and subgroups with different nutritional risk status at enrollment. RESULTS: A total of 1587 patients were included in this study, with an overall 28-day mortality of 15.8%. The average caloric adequacy was 26.3 ± 11.9% (Q1), 52.5 ± 5.5% (Q2), 71.7 ± 6.4% (Q3), 107.0 ± 22.2% (Q4), respectively (p < 0.001 among quartiles). Compared with Q1, Q3 was associated with lower mortality in the unadjusted model (hazard ratio [HR] = 0.536; 95% confidence interval [CI], 0.375-0.767; P = 0.001) and adjusted model (adjusted HR = 0.508; 95% CI, 0.339-0.761; P = 0.001). This association remained valid in the subgroup of high nutritional risk patients (unadjusted HR = 0.387; 95% CI, 0.238-0.627; P < 0.001 and adjusted HR = 0.369; 95% CI, 0.216-0.630; P < 0.001, respectively), but not in those with low risk. CONCLUSIONS: Energy delivery near the 70% energy requirements in the first week of ICU stay was associated with reduced 28-day mortality among mechanically ventilated critically ill patients, especially in patients with high nutrition risk at admission.

Prolonged vs intermittent intravenous infusion of ß-lactam antibiotics for patients with sepsis: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis.

BACKGROUND: The prolonged ß-lactam antibiotics infusion has been an attractive strategy in severe infections, because it provides a more stable free drug concentration and a longer duration of free drug concentration above the minimum inhibitory concentration (MIC). We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of prolonged vs intermittent intravenous infusion of ß-lactam antibiotics for patients with sepsis. METHODS: This study was prospectively registered on PROSPERO database (CRD42023447692). We searched EMBASE, PubMed, and Cochrane Library to identify eligible studies (up to July 6, 2023). Any study meeting the inclusion and exclusion criteria would be included. The primary outcome was all-cause mortality within 30 days. Two authors independently screened studies and extracted data. When the I2 values < 50%, we used fixed-effect mode. Otherwise, the random effects model was used. TSA was also performed to search for the possibility of false-positive (type I error) or false-negative (type II error) results. RESULTS: A total of 4355 studies were identified in our search, and nine studies with 1762 patients were finally included. The pooled results showed that, compared with intermittent intravenous infusion, prolonged intravenous infusion of beta-lactam antibiotics resulted in a significant reduction in all-cause mortality within 30 days in patients with sepsis (RR 0.82; 95%CI 0.70-0.96; P = 0.01; TSA-adjusted CI 0.62-1.07). However, the certainty of the evidence was rated as low, and the TSA results suggested that more studies were needed to further confirm our conclusion. In addition, it is associated with lower hospital mortality, ICU mortality, and higher clinical cure. No significant reduction in 90-day mortality or the emergence of resistance bacteria was detected between the two groups. CONCLUSIONS: Prolonged intravenous infusion of beta-lactam antibiotics in patients with sepsis was associated with short-term survival benefits and higher clinical cure. However, the TSA results suggested that more studies are needed to reach a definitive conclusion. In terms of long-term survival benefits, we could not show an improvement.

Upregulation of circ_0080968 in diabetic foot ulcer inhibits wound healing via repressing the migration and promoting proliferation of keratinocytes.

BACKGROUND: Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus whose pathogenesis remains unclear. Circular RNA (circRNA) refers to a group of covalently closed non-coding RNAs that are reported to be dysregulated in patients with DFU. However, the mechanism whereby dysregulation in circRNAs contributes to DFU remains unclear. In this study, we investigated the role of dysregulated circRNAs in DFU. MATERIALS AND METHODS: A gene expression dataset was downloaded from the Gene Expression Omnibus portal and analyzed by the limma package of R. The levels of 24 upregulated circRNAs were detected in two independent cohorts by RT-qPCR. Interactions between miRNAs and circRNAs were predicted through bioinformatics and confirmed using a dual luciferase assay. The circularity and subcellular localization of circRNA-080968 was examined by northern blotting after digestion with RNase-R and in situ hybridization. Cell migration and proliferation were examined using Transwell and MTT assays. The apoptotic cells were detected by flow cytometry. RESULTS: The level of circRNA-080968 was upregulated in DFU tissues compared to that of non-DFU samples and normal human wounds. CircRNA-080968 was mainly localized in the cytoplasm and its overexpression inhibited the migration and promoted the proliferation of keratinocytes. MiR-326 and miR-766-3p were identified to interact with and be negatively correlated with circRNA-080968 levels. Increased glucose upregulated circRNA-080968, and its overexpression accelerated the degradation of both miR-326 and miR-766-3p. Reduced levels of miR-326 and miR-766-3p upregulated the expression of several genes controlling cell adhesion and proliferation which are related to the pathogenesis of DFU. CONCLUSIONS: The upregulation of circRNA-080968 in DFU induced the degradation of miR-326 and miR-766-3p, which further repressed the migration and increased the proliferation of keratinocytes.

Prognostic and risk factor analysis of cancer patients after unplanned ICU admission: a real-world multicenter study.

To investigate the occurrence and 90-day mortality of cancer patients following unplanned admission to the intensive care unit (ICU), as well as to develop a risk prediction model for their 90-day prognosis. We prospectively analyzed data from cancer patients who were admitted to the ICU without prior planning within the past 7 days, specifically between May 12, 2021, and July 12, 2021. The patients were grouped based on their 90-day survival status, and the aim was to identify the risk factors influencing their survival status. A total of 1488 cases were included in the study, with an average age of 63.2 ± 12.4 years. The most common reason for ICU admission was sepsis (n = 940, 63.2%). During their ICU stay, 29.7% of patients required vasoactive drug support (n = 442), 39.8% needed invasive mechanical ventilation support (n = 592), and 82 patients (5.5%) received renal replacement therapy. We conducted a multivariate COX proportional hazards model analysis, which revealed that BMI and a history of hypertension were protective factors. On the other hand, antitumor treatment within the 3 months prior to admission, transfer from the emergency department, general ward, or external hospital, high APACHE score, diagnosis of shock and respiratory failure, receiving invasive ventilation, and experiencing acute kidney injury (AKI) were identified as risk factors for poor prognosis within 90 days after ICU admission. The average length of stay in the ICU was 4 days, while the hospital stay duration was 18 days. A total of 415 patients died within 90 days after ICU admission, resulting in a mortality rate of 27.9%. We selected 8 indicators to construct the predictive model, which demonstrated good discrimination and calibration. The prognosis of cancer patients who are unplanned transferred to the ICU is generally poor. Assessing the risk factors and developing a risk prediction model for these patients can play a significant role in evaluating their prognosis.

Difficulty in central venous catheter placement due to congenital partial anomalous pulmonary venous return: A case report.

Congenital partial anomalous pulmonary venous return (PAPVR) is rare and present in 0.04%-0.7% of the population. This may pose a significant problem for clinicians performing internal jugular venous catheter placement. This report depicts an abnormal internal jugular venous catheter placement due to a PAPVR to help physicians recognize and deal with variant pulmonary veins.

The expression profile of lung long non-coding RNAs and mRNAs in a mouse model of smoke inhalation injury.

To study the potential expression of lung long non-coding RNAs (lncRNAs) and mRNAs during smoke inhalation injury (SII), using a SII mouse model that we created in our previous work. Microarray was used to investigate the lncRNAs and mRNAs profiles. A bioinformatics analysis was performed. Changes in the top 10 down-regulated and 10 up-regulated lncRNAs were validated using Quantitative Reverse Transcription-PCR (RT-qPCR). The acute lung injury (ALI) mouse model was successfully induced by smoke inhalation, as confirmed by the aberrantly modified cell numbers of red blood cells and neutrophils counts, increased levels of TNF-α, IL-1ß, Bax, caspase-7, caspase-3, and decreased Bcl-2 content in lung tissues. When compared to the control mice, 577 lncRNAs and 517 mRNAs were found to be aberrantly expressed in the SII mice. According to the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the altered mRNAs were enriched in acute-phase response, oxidoreductase activity, oxidation-reduction process, glutathione metabolism, the wnt signaling pathway, and ferroptosis. A lncRNA-related competitive endogenous RNA (ceRNA) network, including 383 lncRNAs, 318 MicroRNAs (miRNAs), and 421 mRNAs specific to SII, was established. The changes in NONMMUT026843.2, NONMMUT065071.2, ENSMUST00000235858.1, NONMMUT131395.1, NONMMUT122516.1, NONMMUT057916.2, and NONMMUT013388.2 in the lung matched the microarray results. Our findings help to provide a more comprehensive understanding of the pathogenesis of SII as well as new insights into potential therapeutic targets.

Metformin Improves Burn Wound Healing by Modulating Microenvironmental Fibroblasts and Macrophages.

Metformin, a biguanide, exerts different functions through various signaling pathways. In order to investigate the function and mechanism of metformin in burn wounds, we established burn rat models, subcutaneously injected metformin to treat the wounds, and observed the morphologies and the expression of collagen I, collagen III, fibronectin, and pro-inflammatory markers. In vitro experiments were performed to investigate the effects of metformin on the proliferation, migration, and collagen I synthesis of the mouse embryonic fibroblast (NIH 3T3) cell line and on the proliferation, apoptosis, and immune response of the mouse mononuclear macrophage (RAW 264.7) cell line. Finally, we studied the regulatory effects of metformin on a co-culture of RAW 264.7/NIH 3T3 cells. We found that 100 mM of metformin reduced dermal thickness, collagen I deposition, and mRNA expression of IL1ß and CCL2 in rat burn wounds. In vitro experiments revealed that metformin inhibited the proliferation of NIH 3T3 and RAW 264.7 cells. Metformin attenuated NIH 3T3 cell migration via the AMPK/mTOR pathway and attenuated collagen I synthesis through the TGFß1/Smad3 pathway. Metformin inhibited the apoptosis of RAW 264.7 cells induced by 10 µg/mL LPS. Metformin downregulated the mRNA expression of IL1ß and CCL2 in RAW 264.7 cells under 1 µg/mL LPS induction by inhibiting NF-κB p65 phosphorylation. In a RAW 264.7/NIH 3T3 co-culture, metformin attenuated collagen I synthesis in NIH 3T3 cells by inhibiting RAW 264.7 paracrine secretion of TGF-ß1. This provides new evidence related to the development of metformin for potentially improving burn wound healing.

Association between caloric adequacy and short-term clinical outcomes in critically ill patients using a weight-based equation: Secondary analysis of a cluster-randomized controlled trial.

Background: There is controversy over the optimal energy delivery in intensive care units (ICUs). In this study, we aimed to evaluate the association between different caloric adequacy assessed by a weight-based equation and short-term clinical outcomes in a cohort of critically ill patients. Methods: This is a secondary analysis of a cluster-randomized controlled trial (N = 2,772). The energy requirement was estimated as 25 kcal/kg of body weight. The study subjects were divided into three groups according to their caloric adequacy as calculated by the mean energy delivered from days 3 to 7 of enrollment divided by the estimated energy requirements: (1) received < 70% of energy requirement (hypocaloric), (2) received 70-100% of energy requirement (normocaloric), and (3) received > 100% of energy requirement (hypercaloric). Cox proportional hazards models were used to analyze the association between caloric adequacy and 28-day mortality and time to discharge alive from the ICU. Results: A total of 1,694 patients were included. Compared with normocaloric feeding, hypocaloric feeding significantly increased the risk of 28-day mortality (hazard ratio [HR] = 1.590, 95% confidence interval [CI]: 1.162-2.176, p = 0.004), while hypercaloric feeding did not. After controlling for potential confounders, the association remained valid (adjusted HR = 1.596, 95% CI: 1.150-2.215, p = 0.005). The caloric adequacy was not associated with time to discharge alive from the ICU in the unadjusted and the adjusted models. Conclusion: Energy delivery below 70% of the estimated energy requirement during days 3-7 of critical illness is associated with 28-day mortality. Clinical trial registration: [https://www.isrctn.com/ISRCTN12233792], identifier [ISRCTN12233792].

rhKGF-2 Attenuates Smoke Inhalation Lung Injury of Rats via Activating PI3K/Akt/Nrf2 and Repressing FoxO1-NLRP3 Inflammasome.

Smoke inhalation injury is an acute pathological change caused by thermal stimulation or toxic substance absorption through respiratory epithelial cells. This study aims to probe the protective effect and mechanism of recombinant human keratinocyte growth factor 2 (rhKGF-2) against smoke inhalation-induced lung injury (SILI) in rats. The SILI was induced in rats using a smoke exposure model, which were then treated with rhKGF-2. The rat blood was collected for blood-gas analysis, and the levels of inflammatory factors and oxidative stress markers in the plasma were measured. The rat lung tissues were collected. The pathological changes and cell apoptosis were determined by hematoxylin-eosin (HE) staining and TdT-mediated dUTP nick end labeling (TUNEL) assay, and the PI3K/Akt/Nrf2/HO-1/NQO1, and FoxO1-NLRP3 inflammasome expression were verified by western blot (WB). Both of the human alveolar epithelial cell (HPAEpiC) and primary rat alveolar epithelial cell were exposed to lipopolysaccharide (LPS) for making in-vitro alveolar epithelial cell injury model. After treatment with rhKGF-2, GSK2126458 (PI3K inhibitor) and AS1842856 (FoxO1 inhibitor), the cell viability, apoptosis, inflammation, oxidative stress, reactive oxygen species (ROS), PI3K/Akt/Nrf2, HO-1/NQO1, and FoxO1-NLRP3 in HPAEpiC and primary rat alveolar epithelial cell were examined. The data suggested that rhKGF-2 reduced LPS-induced HPAEpiC cell and primary rat alveolar epithelial cell apoptosis and the expression of inflammatory factors and oxidative stress factors. Moreover, rhKGF-2 improved the blood gas and alleviated SILI-induced lung histopathological injury in vivo via repressing inflammation, NLRP3 inflammasome activation and oxidative stress. Mechanistically, rhKGF-2 activated PI3K/Akt pathway, enhanced Nrf2/HO-1/NQO1 expression, and attenuated FoxO1-NLRP3 inflammasome both in vitro and in vivo. However, pharmaceutical inhibition of PI3K/Akt pathway attenuated rhKGF-2-mediated protective effects against SILI, while suppressing FoxO1 promoted rhKGF-2-mediated protective effects. Taken together, this study demonstrated that rhKGF-2 mitigated SILI by regulating the PI3K/Akt/Nrf2 pathway and the FoxO1-NLRP3 axis, which provides new reference in treating SILI.

Negative-pressure wound therapy in skin grafts: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Although skin grafts are widely used in reconstruction of large skin defect and complex wounds, many factors lead to suboptimal graft take. Negative-pressure wound therapy (NPWT) reportedly increases the graft take rates when added to skin grafting, but a summary analysis of the data of randomized controlled trials has yet to be performed. We conducted this systematic review and meta-analysis of randomized controlled trials to compare the effectiveness and safety of NPWT and non-NPWT for patients with skin grafts. METHODS: We searched PubMed, Embase, Cochrane Library, and CNKI for relevant trials based on predetermined eligibility criteria from database establishment to February 2020. Two reviewers screened citations and extracted data independently. The quality of the included studies was evaluated according to the Cochrane Handbook, whereas statistical heterogeneity was assessed using chi-square tests and I2 statistics. Review Manager 5.3 was used for statistical analysis. RESULTS: Ten randomized controlled trials with 488 patients who underwent NPWT or non-NPWT were included. Compared with non-NPWT, NPWT yielded an improved the percentage of graft take, a reduction in days from grafting to discharge, with lower relative risk of re-operation, and no increased relative risk of adverse event. Further, the subgroup analysis showed an improved the percentage of graft take in negative pressure of 80 mmHg, and no improved the percentage of graft take in negative pressure of 125 mmHg. CONCLUSION: NPWT is more effective than non-NPWT for the integration of skin grafts, and the negative pressure of 80 mmHg can be recommended. Data on adverse events and negative pressure are, however, limited. A better understanding of complications after NPWT and the ideal negative pressure for the integration of skin grafts is imperative.