Placenta-derived mesenchymal stem cells promote diabetic wound healing via exosomal protein interaction networks.

There is a lack of effective treatment options for diabetic refractory wounds, which presents a critical clinical issue that needs to be addressed urgently. Our research has demonstrated that human placenta-derived mesenchymal stem cells (plaMSCs) facilitate the migration and proliferation of HaCat cells, thereby enhancing diabetic wound healing primarily via the exosomes derived from plaMSCs (plaMSCs-Ex). Using label-free proteomics, plaMSCs and their exosomes were analysed for proteome taxonomic content in order to explore the underlying effective components mechanism of plaMSCs-Ex in diabetic wound healing. Differentially expressed proteins enriched in plaMSCs-Ex were identified and underwent bioinformatics analysis including GO annotation, KEGG pathway enrichment, gene set enrichment analysis (GSEA) and protein-protein interaction analysis (PPI). Results showed that the proteins enriched in plaMSCs-Ex are significantly involved in extracellular matrix organisation, epithelium morphogenesis, cell growth, adhesion, proliferation and angiogenesis. PPI analysis filtered 2 wound healing-related clusters characterised by hub proteins such as POSTN, FN1, SPARC, TIMP1, SERPINE1, LRP1 and multiple collagens. In brief, the exosomal proteins derived from plaMSCs reveal diverse functions of regeneration and tissue remodelling based on proteomics analysis and potentially play a role in diabetic wound healing.

Status quo and factors of depression and anxiety in patients with non-muscle invasive bladder cancer after plasma electrocision.

BACKGROUND: Bladder cancer is a type of cancer with a high incidence in men. Plasma electrosurgery (PES) is often used in the treatment of bladder cancer. Postoperative complications often cause depression and anxiety in patients after surgery. AIM: To investigate the current state of depression and anxiety after PES in patients with non-muscle-invasive bladder cancer and analyze the factors affecting them. METHODS: A retrospective study was conducted to compare the baseline data of patients by collecting their medical history and grouping them according to their mental status into negative and normal groups. Logistic regression analysis was used to explore the risk factors affecting the occurrence of anxiety and depression after surgery in patients with bladder cancer. RESULTS: Comparative analyses of baseline differences showed that the patients in the negative and normal groups differed in terms of their first surgery, economic status, educational level, and marital status. A logistic regression analysis showed that it affected the occurrence of anxiety in patients with bladder cancer, and the results showed that whether the risk factors were whether or not it was the first surgery, monthly income between 3000 and 3000-6000, secondary or junior high school education level, single, divorced, and widowed statuses. CONCLUSION: The risk factors affecting the onset of anxiety and depression in bladder cancer patients after PES are the number of surgeries, economic status, level of education, and marital status. This study provides a reference for the clinical treatment and prognosis of bladder cancer patients in the future.

Association between admission pan-immune-inflammation value and short-term mortality in septic patients: a retrospective cohort study.

Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan-Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan-Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P < 0.001]. The relationship between log2-PIV and 28-day mortality was non-linear with a predicted inflection point at 8. To the right of the inflection point, high log2-PIV was associated with an increased 28-day mortality risk [HR (95% CI) 1.13 (1.09, 1.18), P < 0.001]. However, to the left of this point, this association was non-significant [HR (95% CI) 1.01 (0.94, 1.08), P = 0.791]. Similar results were found for 90-day mortality. Our study showed a non-linear relationship between PIV and 28-day and 90-day mortality risk in septic patients.

Identification of lignans as selective cyclooxygenase-2 inhibitors from the extract of Acanthopanacis cortex.

Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans (1-4) and 12 known lignans (5-16) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1-16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1-16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2, 6-8 and 13-16 demonstrate better COX-2 inhibitory effects with IC50 values from 0.75 to 8.17 µΜ. These findings provide useful information for the search for natural selective COX-2 inhibitors.

Association of Delirium with Long-Term Mortality in Critically Ill Patients with COPD Who Survived to Discharge: A Retrospective Cohort Study.

BACKGROUND: Critically ill patients with chronic obstructive pulmonary disease (COPD) face significant mortality after hospital discharge. Delirium is common in patients with COPD, but its impact on long-term mortality in critically ill COPD patients who survive to discharge remains uncertain. METHODS: Critically ill patients with COPD who survived to discharge were selected from the Medical Information Mart for Intensive Care IV database. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. The primary outcome was 365- and 180-day mortality after discharge. The secondary outcomes included 90- and 30-day mortality following discharge, length of intensive care unit (ICU) and hospital stays, and nursing care needs after hospital discharge. RESULTS: Of the 2621 survivors of critically ill COPD patients, 982 had suffered delirium during their ICU stay and 709 died within 365 days after hospital discharge. Delirium was significantly associated with 365-day mortality after hospital discharge (adjusted hazard ratio [HR] 1.22; 95% confidence interval [CI] 1.02-1.47). The results were consistent for 180-, 90-, and 30-day post-discharge mortality (adjusted HR [95% CI]: 1.35 [1.09-1.66], 1.48 [1.16-1.89], and 1.68 [1.21-2.32], respectively). Additionally, patients with delirium had longer ICU and hospital stay (adjusted ß 2.75; 95% CI 2.35-3.16 and 4.25; 95% CI 3.51-4.98, respectively) and increased nursing care needs after hospital discharge (adjusted odds ratio, 1.56; 95% CI 1.13-2.14). CONCLUSION: ICU delirium was an independent risk factor for both long-term and short-term mortality in critically ill patients with COPD who survived to discharge.

Machine learning to predict lymph node metastasis in T1 esophageal squamous cell carcinoma：a multicenter study.

BACKGROUND: Existing models do poorly when it comes to quantifying the risk of Lymph node metastases (LNM). This study aimed to develop a machine learning model for LNM in patients with T1 esophageal squamous cell carcinoma (ESCC). METHODS AND RESULTS: The study is multicenter, and population based. Elastic net regression (ELR), random forest (RF), extreme gradient boosting (XGB), and a combined (ensemble) model of these was generated. The contribution to the model of each factor was calculated. The models all exhibited potent discriminating power. The Elastic net regression performed best with externally validated AUC of 0.803, whereas the NCCN guidelines identified patients with LNM with an AUC of 0.576 and logistic model with an AUC of 0. 670. The most important features were lymphatic and vascular invasion and depth of tumor invasion. CONCLUSIONS: Models created utilizing machine learning approaches had excellent performance estimating the likelihood of LNM in T1 ESCC.

CTR > 0.7 predicts the subgroup of lung adenocarcinomas ≤ 2 cm at risk of poor outcome treated by sublobar resection compared to lobar resection.

BACKGROUND: A standard surgical procedure for patients with small early-stage lung adenocarcinomas remains unknown. Hence, we aim in this study to assess the clinical utility of the consolidation-to-tumor ratio (CTR) when treating patients with small (2 cm) early stage lung cancers. METHODS: A retrospective cohort of 298 sublobar resection and 266 lobar resection recipients for early stage lung adenocarcinoma ≤ 2 cm was assembled from the First Affiliated Hospital of Chongqing Medical University between 2016 and 2019. To compare survival rates among the different groups, Kaplan-Meier curves were calculated, and the log-rank test was used. A multivariate Cox proportional hazard model was constructed utilizing variables that were significant in univariate analysis of survival. RESULTS: In the study, 564 patients were included, with 298 patients (52.8%) undergoing sublobar resection and 266 patients (47.2%) undergoing lobar resection. Regarding survival results, there was no significant difference in the 5-year overall survival (OS, P = 0.674) and 5-year recurrence-free survival (RFS, P = 0.253) between the two groups. Cox regression analyses showed that CTR ≥ 0.75(P < 0.001), age > 56 years (P = 0.007), and sublobar resection(P = 0.001) could predict worse survival. After examining survival results based on CTR categorization, we segmented the individuals into three categories: CTR<0.7, 0.7 ≤ CTR<1, and CTR = 1.The lobar resection groups had more favorable clinical outcomes than the sublobar resection groups in both the 0.7 ≤ CTR < 1(RFS: P < 0.001, OS: P = 0.001) and CTR = 1(RFS: P = 0.001, OS: P = 0.125). However, for patients with 0 ≤ CTR < 0.7, no difference in either RFS or OS was found between the lobar resection and sublobar resection groups, all of which had no positive events. Patients with a CTR between 0.7 and 1 who underwent lobar resection had similar 5-year RFS and OS rates compared to those with a CTR between 0 and 0.7 who underwent sublobar resection (100% vs. 100%). Nevertheless, a CTR of 1 following lobar resection resulted in notably reduced RFS and OS when compared to a CTR between 0.7 and 1 following lobar resection (P = 0.005 and P = 0.016, respectively). CONCLUSION: Lobar resection is associated with better long-term survival outcomes than sublobar resection for small lung adenocarcinomas ≤ 2 cm and CTR ≥ 0.7.

Radiation-based immunogenic vaccine combined with a macrophage "checkpoint inhibitor" for boosting innate and adaptive immunity against metastatic colon cancers.

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a "checkpoint" to facilitate immune silence in the tumor microenvironment. Therefore, we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250, a macrophage MerTK "checkpoint inhibitor," for treating peritoneal carcinomatosis in colon cancer. By incorporating UNC2250 into the treatment regimen, immunosuppressive efferocytosis of macrophages, which relies on MerTK-directed recognition of phosphatidylserine on vaccines, was effectively blocked. Consequently, the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages, thereby simultaneously eliciting robust adaptive and innate immunity. This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.

UHPLC-PDA-Q-TOF-MS-α-amylase-FLD activity detection system and molecular docking.

INTRODUCTION: Traditional and some scientific literature document the antidiabetic effects of the Ziziphi Spinosae Semen (ZSS). However, the bioactive compounds of ZSS responsible for the antidiabetic effects are not well known. OBJECTIVES: This study aimed to investigate the material basis of the antidiabetic effects of ZSS by inhibiting α-amylase. METHODOLOGY: An online analysis platform was established and optimized using an ultra-performance liquid chromatography-photo-diode array-quadrupole-time-of-flight-mass spectrometry-α-amylase-fluorescence detector (UHPLC-PDA-Q-TOF-MS-α-amylase-FLD) system to screen α-amylase inhibitors in ZSS rapidly. The inhibitory effect of these compounds was confirmed by molecular docking screening. and the molecular interactions between α-amylase and active compounds were evaluated, which strongly supported the experimental results. RESULTS: Seventy-eight compounds were identified in the ZSS extract, eleven of which were screened to have significant α-amylase binding activity. CONCLUSION: This study demonstrated the feasibility of using an established platform to screen for effective components in ZSS, providing a practical method for the rapid screening of potential antidiabetic active ingredients in traditional Chinese medicine.

Diterpenoids from Acanthopanacis Cortex and their anti-inflammatory activity studies.

Acanthopanacis Cortex (A.-C) with a long history of more than1000 years, has been used to treat rheumatism effectively. Nineteen diterpenoids have been isolated from A.-C, including six new compounds (1-6). Among them, compounds 7, 9-11, 13, and 17 were discovered from A.-C for the first time. The structures of 1-6 were determined by analyzing their NMR data and comparing their experimental and calculated electronic circular dichroism spectra. Moreover, the single-crystal X-ray diffraction data of 1, 2, 8, and 14 were provided. The anti-inflammatory activity of 1-5 and 7-18 on neutrophil elastase, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) has been studied in vitro, and the results showed that 15 had almost no inhibitory effects on COX-1 at 200 µM but a significant activity against COX-2 with an IC50 of 0.73 ± 0.006 µΜ. It indicated that compound 15 can provide valuable information for the design of selective COX-2 inhibitors.

Knockdown of Ubiquitin-Conjugating Enzyme E2 T Abolishes the Progression of Head and Neck Squamous Cell Carcinoma by Inhibiting NF-Κb Signaling and inducing Ferroptosis.

BACKGROUND: Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role in the carcinogenesis of Head And Neck Squamous Cell Carcinoma (HNSC) is limited. METHODS: UBE2T expression in HNSC patient samples and the correlation between its expression and patients' survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T lentivirus. The xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis. RESULTS: The increased expression of UBE2T was noted in tumor tissues of patients with HNSC, correlating with a significantly reduced overall survival time in this patient cohort. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-ΚB signaling and induced ferroptosis in HNSC. CONCLUSION: Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target.

Age affects vascular morphology and predictiveness of anatomical landmarks for aortic zones in trauma patients: implications for resuscitative endovascular balloon occlusion of the aorta.

PURPOSE: Understanding the vascular morphology is fundamental for resuscitative endovascular balloon occlusion of the aorta. This study aimed to evaluate the effect of aging on length and diameter of aorta and iliac arteries in trauma patients, and to investigate the predictiveness of anatomical landmarks for aortic zones. METHODS: A total of 235 patients in a regional trauma center registry from September 1, 2018, to January 3, 2024, participated in the study. Reconstruction of computed tomography was applied to the torso area. The marginal diameter and length of aorta and iliac arteries were measured. Anatomical landmark distances and aortic marginal lengths were compared. RESULTS: The length and diameter of aorta and iliac arteries increased with age, and a tortuous and enlarged morphology was observed in older patients. There was a good regression between age and diameter of the aorta. Neither the jugular notch, the xiphisternal joint, nor the umbilicus could reliably represent specific margins of aortic zones. The distance between the mid-sternum and femoral artery (427 ± 25 to 442 ± 25 mm for right, and 425 ± 28 to 440 ± 26 mm for left) was predictive for zone 1 in all groups. The distance between the lower one-third junction of the xiphisternum to the umbilicus and femoral artery (232 ± 19 to 240 ± 17 mm for right, and 229 ± 20 to 237 ± 19 mm for left) was predictive for zone 3 aorta. CONCLUSION: Aging increases the length and diameter of aorta and iliac arteries, with a tortuous and enlarged morphology in geriatric populations. The mid-sternum and the lower one-third junction of the xiphisternum to the umbilicus were predictive landmarks for zone 1 and zone 3, respectively.

Assessment of the Significance and Clinical Implications of Stress Hormones in Acute Pressure Injuries Among Trauma Patients.

Objective: This study examines the dynamic changes of stress hormones, including insulin (INS), fasting blood glucose (FBG), glucagon (Glu), and cortisol (Cort), in trauma patients. By monitoring these changes and observing acute pressure injury (API) occurrences on the skin, the research analyzes the influence of stress hormones on API development in trauma patients. Methods: A prospective analysis involved 218 trauma patients admitted to a grade III-A general hospital in Wenzhou from April 2021 to June 2023. Among them, 44 cases developed API (API group), and 174 cases did not (control group). Levels of INS, Cort, Glu, and FBG were measured in both groups. Additionally, Abbreviated Injury Scale-Injury Severity Score (AIS-ISS) surveys and API severity assessments were conducted. Correlations between stress hormone levels and AIS-ISS were discussed. The predictive effects of AIS-ISS and stress hormones on API occurrence in trauma patients were analyzed using receiver operating characteristic (ROC) curves. The relationship between stress hormone levels and API severity was also observed. Results: Study's outcomes indicated distinct relationships between stress hormone levels and API occurrence in trauma patients. Specifically, INS demonstrated a negative correlation with AIS-ISS, highlighting its potential as a significant factor. Glu, Cort, and FBG revealed positive associations, emphasizing their roles in influencing API development (P < .05). The diagnostic efficacy of stress hormones in predicting API occurrence, as represented by the Area Under Curve (AUC) = 0.8100. Notably, within the API group, INS levels demonstrated a decline with worsening API. Conversely, Glu, Cort, and FBG exhibited increases in tandem with the aggravation of API symptoms (P < .05). Conclusions: This research suggests that assessing stress hormone levels in clinical settings can effectively predict API occurrence. Early testing could aid in the development of preventive or intervention measures, reducing the incidence and harm of API in trauma patients.

Comparison of diffusion ranges at different local anesthetic volumes during superior laryngeal nerve block.

OBJECTIVES: Ultrasound-guided superior laryngeal nerve (SLN) block is a practical and painless approach to avoid the hemodynamic stress response during endotracheal intubation and relieve sore throat after laryngeal surgery. The main purpose of this study was to establish an optimal dosage of local anesthetic when performing SLN block to help anesthetists balance analgesia and side effects. METHODS: Twenty fresh larynx specimens were obtained immediately after resection and then injected with 2-, 3-, 4-, or 5- mL of a lidocaine-blue dye mixture at bilateral SLN puncture sites. Superficial areas of deposited blue dye were measured. Dye leakage and surrounding dyed tissue were recorded. Another 40 patients were included in the ultrasound investigation. Distances between the internal branch of the SLN (iSLN) and adjacent structures were calculated. RESULTS: The dye spread area was greater with the administration of larger doses, especially to the visceral space. A 2- or 3-mL injection of local anesthetic was sufficient to infiltrate the SLN gap. A higher incidence of dye leaking out of the thyrohyoid membrane and anterior epiglottis space was observed; furthermore, there was substantially more dyed hyoid/thyroid cartilage with 4 and 5 mL of injected dye mixture than 2 mL. There was no significant difference between the specimen and ultrasound measurements of for length of iSLN-adjacent structures. CONCLUSIONS: In the Chinese population, 2- or 3- mL of local anesthetic is a safe dose during SLN block. A larger volume could overflow from the cavity to cause complications. The thyrohyoid membrane combined with the superior laryngeal artery is a reliable target for positioning the iSLN during ultrasound-guided regional anesthesia.

Mitochondrial-Targeted Metal-Phenolic Nanoparticles to Attenuate Intervertebral Disc Degeneration: Alleviating Oxidative Stress and Mitochondrial Dysfunction.

As intervertebral disc degeneration (IVDD) proceeds, the dysfunctional mitochondria disrupt the viability of nucleus pulposus cells, initiating the degradation of the extracellular matrix. To date, there is a lack of effective therapies targeting the mitochondria of nucleus pulposus cells. Here, we synthesized polygallic acid-manganese (PGA-Mn) nanoparticles via self-assembly polymerization of gallic acid in an aqueous medium and introduced a mitochondrial targeting peptide (TP04) onto the nanoparticles using a Schiff base linkage, resulting in PGA-Mn-TP04 nanoparticles. With a size smaller than 50 nm, PGA-Mn-TP04 possesses pH-buffering capacity, avoiding lysosomal confinement and selectively accumulating within mitochondria through electrostatic interactions. The rapid electron exchange between manganese ions and gallic acid enhances the redox capability of PGA-Mn-TP04, effectively reducing mitochondrial damage caused by mitochondrial reactive oxygen species. Moreover, PGA-Mn-TP04 restores mitochondrial function by facilitating the fusion of mitochondria and minimizing their fission, thereby sustaining the vitality of nucleus pulposus cells. In the rat IVDD model, PGA-Mn-TP04 maintained intervertebral disc height and nucleus pulposus tissue hydration. It offers a nonoperative treatment approach for IVDD and other skeletal muscle diseases resulting from mitochondrial dysfunction, presenting an alternative to traditional surgical interventions.

Association between oxidative balance score and frailty in chronic obstructive pulmonary disease.

Background: Oxidative stress is associated with frailty and adverse outcomes in chronic obstructive pulmonary disease (COPD). The oxidative balance score (OBS) assesses oxidative stress from diet and lifestyle, with higher OBS indicating more antioxidants than oxidants. A cross-sectional study was conducted to investigate the potential association between OBS and frailty in US adults with COPD. Methods: A total of 1201 COPD subjects from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were assessed for frailty using the Frailty Index. OBS, consisting of 20 dietary and lifestyle factors, was the exposure variable. Weighted multiple logistic regression, subgroup analysis, and restricted cubic spline curves were used to assess the association between OBS and frailty. Results: Compared with the lowest OBS reference group (Q1), the adjusted odds ratios (ORs) for the highest quartile group (Q4) for OBS, dietary OBS, and lifestyle OBS were 0.41 (95% CI: 0.19-0.92), 0.37 (95% CI: 0.20-0.71), and 0.41 (95% CI: 0.24-0.71), respectively. All trend p-values were less than 0.05. Subgroup and RCS analyses revealed a negative linear association between OBS and frailty, with a significant reduction in frailty risk observed in women compared to men. Conclusions: OBS was negatively associated with frailty in COPD. The higher the OBS, the lower the risk of frailty, especially in women. Identifying at-risk populations with OBS and through antioxidant diet and lifestyle are potential ways to reduce the prevalence of frailty.

Social anxiety and loneliness among older adults: a moderated mediation model.

BACKGROUND: Few studies have clarified the mechanisms linking social anxiety and loneliness in older populations. The study aimed to explore how social network mediate the relationship between social anxiety and loneliness in older adults, with perceived social support playing a moderating role. METHODS: A total of 454 older patients completed the Social Avoidance and Distress Scale, Lubben Social Network Scale-6, Chinese version of the Short Loneliness Scale and Perceived Social Support Scale. Bootstrap and simple slope methods were used to test the moderated mediation model. RESULTS: Social anxiety had a significant positive predictive effect on loneliness and social network partially mediated this relationship. The relationship between social anxiety and social network, as well as the relationship between social network and loneliness, was moderated by perceived social support. Specifically, perceived social support buffered the effects of social anxiety on social network, but the buffering effect diminished with increasing levels of social anxiety. On the social network and loneliness pathway, the social network of older persons with higher perceived social support has a stronger prediction of loneliness. CONCLUSIONS: The study found that social anxiety can contribute to loneliness by narrowing older adults' social network. High perceived social support can buffer this process, but do not overstate its protective effects. Thus, interventions to reduce social anxiety and improve social network and social support may help prevent and alleviate loneliness in older adults.

Epidemiology and Clinical Characteristics of Pediatric Sepsis in PICUs in Southwest China: A Prospective Multicenter Study.

OBJECTIVES: To describe the epidemiological characteristics of pediatric sepsis in Southwest China PICUs. DESIGN: A prospective, multicenter, and observational study. SETTING: Twelve PICUs in Southwest China. PATIENTS: The patients admitted to the PICU from April 1, 2022, to March 31, 2023. The age ranged from 28 days to 18 years. All patients met the criteria of severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 31 PICUs invited to participate, 12 PICUs (capacity of 292 beds) enrolled patients in the study. During the study period, 11,238 children were admitted to the participating PICUs, 367 (3.3%) of whom met the diagnosis of severe sepsis or septic shock. The most prevalent sites of infection were the respiratory system (55%) and the digestive system (15%). The primary treatments administered to these patients included antibiotics (100%), albumin (61.3%), invasive mechanical ventilation (58.7%), glucocorticoids (55.6%), blood products (51%), gammaglobulin (51%), and vasoactive medications (46.6%). Sepsis-related mortality in the PICU was 11.2% (41/367). Nearly half of the sepsis deaths occurred within the first 3 days of PICU admission (22/41, 53.7%). The mortality rate of septic shock (32/167, 19.2%) was significantly higher than that of severe sepsis (9/200, 4.5%; p < 0.001). The outcomes of a multivariate logistic regression analysis suggested that a higher pediatric Sequential Organ Failure Assessment score, and the use of invasive mechanical ventilation and vasoactive medications were independently associated with PICU mortality in children with sepsis. CONCLUSIONS: This report updates the epidemiological data of pediatric sepsis in PICUs in Southwest China. Sepsis is still a life-threatening disease in children.

Ubiquitylation of RUNX3 by RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, but the early diagnosis rate is low. The RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in several cancers but its mechanism of action in LUAD is unclear. In this study, the biological activity of MEX3C was assessed in LUAD. MEX3C and RUNX3 mRNA levels in the tissues of LUAD patients were determined using reverse transcription­quantitative PCR. The involvement of MEX3C in the growth and metastasis of LUAD cells was measured by EdU assay, CCK-8, colony formation, Transwell assay, TUNEL, and flow cytometry. Expression of apoptosis and epithelial-mesenchymal transition related proteins were determined using western blotting analysis. LUAD cells transfected with si-MEX3C were administered to mice subcutaneously to monitor tumor progression and metastasis. We found that MEX3C is strongly upregulated in LUAD tissue sections, and involved in proliferation and migration. A549 and H1299 cells had significantly higher levels of MEX3C expression compared to control HBE cells. Knockdown of MEX3C dramatically decreased cell proliferation, migration, and invasion, and accelerated apoptosis. Mechanistically, we demonstrate MEX3C induces ubiquitylation and degradation of tumor suppressor RUNX3. Moreover, RUNX3 transcriptionally represses Suv39H1, as revealed by RNA pull-down and chromatin immunoprecipitation assays. The in vivo mice model demonstrated that knockdown of MEX3C reduced LUAD growth and metastasis significantly. Collectively, we reveal a novel MEX3C-RUNX3-Suv39H1 signaling axis driving LUAD pathogenesis. Targeting MEX3C may represent a promising therapeutic strategy against LUAD.