SOD2 promotes the immunosuppressive function of mesenchymal stem cells at the expense of adipocyte differentiation.

The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue-derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, were decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondrial mass but promoted glycolysis in an SOD2-dependent manner. MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance the immunosuppressive activity of MSCs in the inflammatory microenvironment.

Development and validation of a nomogram for predicting overall survival in patients with stage III-N2 lung adenocarcinoma based on the SEER database.

Background: There is variability in the prognosis of stage III-N2 lung adenocarcinoma (LUAD) patients. The current tumor-node-metastasis (TNM) staging is not sufficient to precisely estimate the prognosis of stage III-N2 LUAD patients. The Surveillance, Epidemiology, and End Results (SEER) database collected first-hand information from a large number of LUAD patients. Based on the SEER database, this study aimed to determine the prognostic factors that affect overall survival (OS) in stage III-N2 LUAD patients and then establish a nomogram for predicting OS in this type of cancer to identify the high-risk population that may require more frequent surveillance or intensive care. Methods: Data for 1,844 stage III-N2 primary LUAD patients who were registered between 2010 and 2015 were obtained from the SEER database. These patients were randomly assigned to either training (n=1,290) or validation (n=554) cohorts at a 7:3 ratio. The univariate and multivariate Cox regression (UCR and MCR) analyses were performed to find the relevant independent prognostic factors. To predict the OS based on these prognostic factors, a nomogram was then developed. The performance of the nomogram was examined based on the calibration curves, and receiver operating characteristic (ROC) curves. The ability of nomogram to stratify patient risk was validated by Kaplan-Meier survival analysis. Results: Age, gender, tumor location, T-stage and treatment modality (chemotherapy, radiation therapy, surgery and scope of lymph node dissection) of stage III-N2 LUAD patients were significantly associated with prognosis. The area under the curve (AUC) values of OS predicted by the nomogram constructed with these factors at 12-, 36- and 60-month were 0.784, 0.762 and 0.763 in the training cohort, whereas 0.707, 0.685 and 0.705 in the validation cohort, respectively. Additionally, calibration curves demonstrated concordance between predicted and observed outcomes. Nomogram risk stratification provides a meaningful distinction between patients with various survival risks. Conclusions: A survival prediction model that may be useful for risk stratification and decision-making is developed and validated for stage III-N2 LUAD patients. A high-risk patient predicted by the prediction model may require more frequent surveillance or intensive care.

Iron metabolism-related indicators as predictors of the incidence of acute kidney injury after cardiac surgery: a meta-analysis.

BACKGROUND: Some studies have found that ferroptosis plays an important role in the incidence of acute kidney injury (AKI) after cardiac surgery. However, whether iron metabolism-related indicators can be used as predictors of the incidence of AKI after cardiac surgery remains unclear. OBJECTIVES: We aimed to systematically evaluate whether iron metabolism-related indicators can be used as predictors of the incidence of AKI after cardiac surgery via meta-analysis.Search methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched from January 1971 to February 2023 to identify prospective observational and retrospective observational studies examining iron metabolism-related indicators and the incidence of AKI after cardiac surgery among adults.Data Extraction and Synthesis: The following data were extracted by two independent authors (ZLM and YXY): date of publication, first author, country, age, sex, number of included patients, iron metabolism-related indicators, outcomes of patients, patient types, study types, sample, and specimen sampling time. The level of agreement between authors was determined using Cohen's κ value. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of studies. Statistical heterogeneity across the studies was measured by the I2 statistic. The standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect size measures. Meta-analysis was performed using Stata 15. RESULTS: After applying the inclusion and exclusion criteria, 9 articles on iron metabolism-related indicators and the incidence of AKI after cardiac surgery were included in this study. Meta-analysis revealed that after cardiac surgery, baseline serum ferritin (µg/L) (I2 = 43%, fixed effects model, SMD = -0.3, 95% CI:-0.54 to -0.07, p = 0.010), preoperative and 6-hour postoperative fractional excretion (FE) of hepcidin (%) (I2 = 0.0%, fixed effects model, SMD = -0.41, 95% CI: -0.79 to -0.02, p = 0.038; I2 = 27.0%, fixed effects model, SMD = -0.49, 95% CI: -0.88 to -0.11, p = 0.012), 24-hour postoperative urinary hepcidin (µg/L) (I2 = 0.0%, fixed effects model, SMD = -0.60, 95% CI: -0.82 to -0.37, p < 0.001) and urine hepcidin/urine creatinine ratio (µg/mmoL) (I2 = 0.0%, fixed effects model, SMD = -0.65, 95% CI: -0.86 to -0.43, p < 0.001) were significantly lower in patients who developed to AKI than in those who did not. CONCLUSION: After cardiac surgery, patients with lower baseline serum ferritin levels (µg/L), lower preoperative and 6-hour postoperative FE of hepcidin (%), lower 24-hour postoperative hepcidin/urine creatinine ratios (µg/mmol) and lower 24-hour postoperative urinary hepcidin levels (µg/L) are more likely to develop AKI. Therefore, these parameters have the potential to be predictors for AKI after cardiac surgery in the future. In addition, there is a need for relevant clinical research of larger scale and with multiple centers to further test these parameters and prove our conclusion.Trial Registration: PROSPERO identifier: CRD42022369380.

Analysis of the anxiety level and influencing factors during the coronavirus disease 2019 epidemic among the parents of students in China.

Background: Due to the outbreak of Coronavirus Disease 2019, there has been a significant impact on the mental health of parents. However, no detailed study on the mental health status of parents has been conducted to date. Methods: This study was a cross-sectional used a whole-group random sampling method to conduct an online questionnaire survey with 102,883 parents in Guangdong Province, China, April 25, 2020 and May 14, 2020. Anxiety was assessed by using the Generalized Anxiety Disorder tool (GAD-7). Potential factors of anxiety were estimated using univariate analysis and multivariate logistic regression analysis by SPSS 22.0 statistical software. Results: Among the total 94,705 parents who have completed the questionnaire survey (92.05% response rate). The incidence of anxiety was 23.77%. Parents' anxiety symptoms are more likely to be caused by female family roles, higher levels of education, unemployed or jobless employment status, children not being an only child, and children having negative attitudes toward online courses. Conclusions: Our research shows that most parents experienced mild anxiety during the Coronavirus Disease 2019 epidemic. Our findings provide strong evidence for investigating and focusing on the mental health of this population during the COVID-19 epidemic. Therefore, governments and healthcare departments at all levels should actively provide psychological counseling services to relieve their anxiety symptoms.

Association between obesity indicators and cardiometabolic disease in Chinese adults.

BACKGROUND: Obesity is an established risk factor for cardiometabolic disease. Different measurements of obesity with cardiometabolic disease have been compared in recent studies in Western countries. However, obesity-related criteria for the Chinese population differ from the standard World Health Organization guidelines, and similar research in Chinese adults is limited. MEASURES: Data were obtained from a comprehensive intervention project involving a community population with cardiovascular and cerebrovascular risk factors in Shenzhen in 2015. A total of 4,000 participants (1,605 men and 2,395 women) with a mean age of 56.01±9.78 years were included in this study. Categorical data are reported as percentages, and continuous data are reported as mean ± standard deviation. Logistic regression analyses were conducted to examine the associations of body mass index (BMI), waist circumference (WC), and neck circumference (NC) with hypertension, diabetes, and dyslipidemia among Chinese adults. RESULTS: The participants had a mean BMI of 24.25±3.33 kg/m2, mean NC of 33.59±4.16 cm, and mean WC of 82.44±9.84 cm (men: 85.46±9.10 cm, women: 80.40±9.81 cm). Blood pressure, plasma glucose, and lipid levels in the BMI, WC, and NC groups were statistically significant (p < 0.05). BMI, WC, and NC were positively correlated with systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, and triglyceride and negatively correlated with low-density lipoprotein cholesterol (p < 0.05), while the risk of hypertension, diabetes, and dyslipidemia increased with an increase in BMI, WC, and NC (p < 0.05). One SD of BMI, WC, and NC resulted in an increase of 41%, 22%, and 31% risk of hypertension; 45%, 34%, and 47% risk of diabetes; and 37%, 32%, and 23% risk of dyslipidemia, respectively. CONCLUSIONS: Compared to BMI and NC, WC was more strongly associated with cardiometabolic diseases in Chinese adults.

Vigilance associates with the low-dimensional structure of fMRI data.

The human brain exhibits rich dynamics that reflect ongoing functional states. Patterns in fMRI data, detected in a data-driven manner, have uncovered recurring configurations that relate to individual and group differences in behavioral, cognitive, and clinical traits. However, resolving the neural and physiological processes that underlie such measurements is challenging, particularly without external measurements of brain state. A growing body of work points to underlying changes in vigilance as one driver of time-windowed fMRI connectivity states, calculated on the order of tens of seconds. Here we examine the degree to which the low-dimensional spatial structure of instantaneous fMRI activity is associated with vigilance levels, by testing whether vigilance-state detection can be carried out in an unsupervised manner based on individual BOLD time frames. To investigate this question, we first reduce the spatial dimensionality of fMRI data, and apply Gaussian Mixture Modeling to cluster the resulting low-dimensional data without any a priori vigilance information. Our analysis includes long-duration task and resting-state scans that are conducive to shifts in vigilance. We observe a close alignment between low-dimensional fMRI states (data-driven clusters) and measurements of vigilance derived from concurrent electroencephalography (EEG) and behavior. Whole-brain coactivation analysis revealed cortical anti-correlation patterns that resided primarily during higher behavioral- and EEG-defined levels of vigilance, while cortical activity was more often spatially uniform in states corresponding to lower vigilance. Overall, these findings indicate that vigilance states may be detected in the low-dimensional structure of fMRI data, even within individual time frames.

Visit-to-visit variability of blood pressure and risk of macrovascular and microvascular complications in patients with type 2 diabetes: A Chinese primary-care cohort study.

BACKGROUND: We evaluated the effects of visit-to-visit variability of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on macrovascular and microvascular complications among patients with type 2 diabetes. METHODS: A total of 11 043 patients with type 2 diabetes from primary healthcare institutions between January 2010 and June 2020 were included. The visit-to-visit blood pressure variability was calculated using three metrics: SD, coefficient of variation (CV), and average real variability (ARV), obtained over a 12-month measurement period. The associations of visit-to-visit blood pressure variability with macrovascular and microvascular complications were evaluated using multivariate-adjusted Cox proportional hazards models, and hazard ratio (HR) with 95% confidence interval (CI) were reported. RESULTS: There were 330 macrovascular events and 542 microvascular events. Compared to those for participants with the lowest quartile of SD of SBP and DBP, increased risks were observed in patients with the highest quartile of SD of SBP and DBP for macrovascular complications (SD-SBP: HR = 1.78, 95% CI: 1.24-2.57; SD-DBP: HR = 2.20, 95% CI: 1.50-3.25) and microvascular complications (SD-SBP: HR = 1.85, 95% CI: 1.39-2.46; SD-DBP: HR = 1.82, 95% CI: 1.36-2.44). CV and ARV of SBP and DBP also had statistically significant associations with macrovascular and microvascular complications. The optimal variability of blood pressure target was SD of SBP <6.45 mm Hg and SD of DBP <4.81 mm Hg. CONCLUSIONS: Visit-to-visit blood pressure variability may be a potential predictor for macrovascular and microvascular complications in patients with type 2 diabetes.

Serum total bilirubin and new-onset hypertension in perimenopausal women: a cross-sectional study.

OBJECTIVE: Previous studies have shown negative associations between total bilirubin (TBIL) and hypertension. However, the association of TBIL with new-onset hypertension in perimenopausal women is unknown. METHODS: A total of 196 perimenopausal women were included in this cross-sectional study of which 85 had new-onset hypertension. All participants underwent 24-hour ambulatory blood pressure monitoring and a clinical assessment including anthropometrics. Sociodemographic, lifestyle, and menopausal symptoms (modified Kupperman Index [mKI]) were measured by questionnaire. A fasting blood sample was taken to measure a wide range of biomarkers and hormone levels. Restricted cubic spline regression was used to investigate potential nonlinearity. Multivariable logistic and robust linear regression analyses adjusting for minimal sufficient adjustment sets based on directed acyclic graphs were performed to test the association of TBIL with hypertension/blood pressure. We examined mKI-stratified analyses and a TBIL-mKI interaction term to explore potential effect modification by number of menopausal symptoms. RESULTS: Hypertensive women had significantly lower TBIL levels than did normotensive women (11.15 vs 12.55 µmol/L, P = 0.046). Univariate restricted cubic spline regression showed nonsignificant nonlinearity ( P value for nonlinearity, 0.339). Multivariable regression analyses adjusted for minimal sufficient adjustment sets revealed that higher TBIL level was associated with lower odds of hypertension (odds ratio, 0.91 per µmol/L TBIL; 95% confidence interval [CI], 0.84-0.98; P = 0.019). Total bilirubin showed a significant inverse association with average 24-hour diastolic blood pressure ( ß = -0.36 mm Hg per µmol/L TBIL; 95% CI, -0.62 to -0.10; P = 0.008) but not with 24-hour systolic blood pressure ( ß = -0.37 mm Hg per µmol/L TBIL; 95% CI, -0.79 to 0.06; P = 0.090). Stratified analyses suggested stronger inverse associations of TBIL with hypertension and 24-hour blood pressure in women with fewer menopausal symptoms (mKI ≤10), although the TBIL-mKI interaction was not significant. CONCLUSIONS: In perimenopause, TBIL was inversely associated with diastolic blood pressure and new-onset hypertension, diagnosed using 24-hour ambulatory blood pressure monitoring.

Isoprenylcysteine carboxyl methyltransferase promotes the progression of tongue squamous cell carcinoma via the K-Ras and RhoA signaling pathways.

OBJECTIVE: This research investigated the biological role of isoprenylcysteine carboxyl methyltransferase (ICMT) in tongue squamous cell carcinoma (TSCC) progression meanwhile to explore the conceivable mechanism. METHODS: The mRNA and protein expression were measured using real-time PCR and Western blot. Cell proliferation, apoptosis, cycle distribution, migration and invasion were evaluated by CCK-8 assay, flow cytometry, wound-healing assay and transwell assay. The anti-tumor activity of ICMT silencing was observed in nude mice. RESULTS: Our results indicated that silencing of ICMT-mediated methylation effectively inhibited TSCC cells proliferation in vitro and reduced tumor growth in vivo. Moreover, ICMT knockdown also induced cell apoptosis and cell cycle arrest of both CAL-27 and SCC-4 cells. In addition, CAL-27 and SCC-4 cells migration and invasion were weakened by ICMT siRNA. Mechanistically, ICMT deficiency significantly decreased the K-Ras and RhoA membrane targeting localization, leading to the suppression of K-Ras- and RhoA-mediated downstream signaling in CAL-27 and SCC-4 cells. CONCLUSIONS: Altogether, our findings identified a crucial role played by ICMT in the progression of TSCC and the potential mechanisms by which exerted its effects, indicating that targeting ICMT may represent a promising therapeutic strategy for TSCC.

Interindividual Signatures of fMRI Temporal Fluctuations.

The complexity and variability of human brain activity, such as quantified from Functional Magnetic Resonance Imaging (fMRI) time series, have been widely studied as potential markers of healthy and pathological states. However, the extent to which fMRI temporal features exhibit stable markers of inter-individual differences in brain function across healthy young adults is currently an open question. In this study, we draw upon two widely used time-series measures-a nonlinear complexity measure (sample entropy; SampEn) and a spectral measure of low-frequency content (fALFF)-to capture dynamic properties of resting-state fMRI in a large sample of young adults from the Human Connectome Project. We observe that these two measures are closely related, and that both generate reproducible patterns across brain regions over four different fMRI runs, with intra-class correlations of up to 0.8. Moreover, we find that both metrics can uniquely differentiate subjects with high identification rates (ca. 89%). Canonical correlation analysis revealed a significant relationship between multivariate brain temporal features and behavioral measures. Overall, these findings suggest that regional profiles of fMRI temporal characteristics may provide stable markers of individual differences, and motivate future studies to further probe relationships between fMRI time series metrics and behavior.

Long Intergenic Non-Coding RNAs in the Mammary Parenchyma and Fat Pad of Pre-Weaning Heifer Calves: Identification and Functional Analysis.

Enhanced plane of nutrition at pre-weaning stage can promote the development of mammary gland especially heifer calves. Although several genes are involved in this process, long intergenic non-coding RNAs (lincRNAs) are regarded as key regulators in the regulated network and are still largely unknown. We identified and characterized 534 putative lincRNAs based on the published RNA-seq data, including heifer calves in two groups: fed enhanced milk replacer (EH, 1.13 kg/day, including 28% crude protein, 25% fat) group and fed restricted milk replacer (R, 0.45 kg/day, including 20% crude protein, 20% fat) group. Sub-samples from the mammary parenchyma (PAR) and mammary fat pad (MFP) were harvested from heifer calves. According to the information of these lincRNAs' quantitative trait loci (QTLs), the neighboring and co-expression genes were used to predict their function. By comparing EH vs R, 79 lincRNAs (61 upregulated, 18 downregulated) and 86 lincRNAs (54 upregulated, 32 downregulated) were differentially expressed in MFP and PAR, respectively. In MFP, some differentially expressed lincRNAs (DELs) are involved in lipid metabolism pathways, while, in PAR, among of DELs are involved in cell proliferation pathways. Taken together, this study explored the potential regulatory mechanism of lincRNAs in the mammary gland development of calves under different planes of nutrition.

Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis.

BACKGROUND: Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. METHODS: The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. RESULTS: hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). CONCLUSION: Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.

Interrupted Time-Series Analysis to Evaluate the Impact of a National Antimicrobial Stewardship Campaign on Antibiotic Prescribing: A Typical Practice in China's Primary Care.

BACKGROUND: After implementing the 2011 national antimicrobial stewardship campaign, few studies focused on evaluating its effect in China's primary care facilities. METHODS: We randomly selected 11 community health centers in Shenzhen, China, and collected all outpatient prescriptions of these centers from 2010 to 2015. To evaluate the impact of local interventions on antibiotic prescribing, we used a segmented regression model of interrupted time series to analyze 7 outcomes (ie, percentage of prescriptions with antibiotics, and percentages of prescriptions with broad-spectrum antibiotics, with parenteral antibiotics, and with 2 or more antibiotics in all prescriptions or antibiotic-containing prescriptions). RESULTS: Overall, 1 482 223 outpatient prescriptions were obtained. The intervention was associated with a significant immediate change (-5.2%, P = .04) and change in slope (-3.1% per month, P < .01) for the percentage of prescriptions with antibiotics, and its relative cumulative effect at the end of the study was -74.0% (95% confidence interval, -79.0 to -69.1). After the intervention, the percentage of prescriptions with broad-spectrum and with parenteral antibiotics decreased dramatically by 36.7% and 77.3%, respectively, but their percentages in antibiotic-containing prescriptions decreased insignificantly. Percentage of prescriptions with two or more antibiotics in all prescriptions or antibiotic-containing prescriptions only showed immediate changes, but significant changes in slope were not observed. CONCLUSIONS: A typical practice in Shenzhen, China, showed that strict enforcement of the antimicrobial stewardship campaign could effectively reduce antibiotic prescribing in primary care with a stable long-term effect. However, prescribing of broad-spectrum and parenteral antibiotics was still prevalent. More targeted interventions are required to promote appropriate antibiotic use.

Spermidine endows macrophages anti-inflammatory properties by inducing mitochondrial superoxide-dependent AMPK activation, Hif-1α upregulation and autophagy.

Distinct metabolic programs, either energy-consuming anabolism or energy-generating catabolism, were required for different biological functions. Macrophages can adopt different immune phenotypes in response to various cues and exhibit anti- or pro-inflammatory properties relying on catabolic pathways associated with oxidative phosphorylation (OXPHOS) or glycolysis. Spermidine, a natural polyamine, has been reported to regulate inflammation through inducing anti-inflammatory (M2) macrophages. However, the underlying mechanisms remain elusive. We show here that the M2-polarization induced by spermidine is mediated by mitochondrial reactive oxygen species (mtROS). The levels of mitochondrial superoxide and H2O2 were markedly elevated by spermidine. Mechanistically, mtROS were found to activate AMP-activated protein kinase (AMPK), which in turn enhanced mitochondrial function. Furthermore, hypoxia-inducible factor-1α (Hif-1α) was upregulated by the AMPK activation and mtROS and was required for the expression of anti-inflammatory genes and induction of autophagy. Consistent with previous report that autophagy is required for the M2 polarization, we found that the M2 polarization induced by spermidine was also mediated by increased autophagy. The macrophages treated with spermidine in vitro were found to ameliorate Dextran Sulfate Sodium (DSS)-induced inflammatory bowel disease (IBD) in mice. Thus, spermidine can elicit an anti-inflammatory program driven by mtROS-dependent AMPK activation, Hif-1α stabilization and autophagy induction in macrophages. Our studies revealed a critical role of mtROS in shaping macrophages into M2-like phenotype and provided novel information for management of inflammatory disease by spermidine.

Ubiquitin-specific peptidase 17 promotes cisplatin resistance via PI3K/AKT activation in non-small cell lung cancer.

The suppression of ubiquitin-specific peptidase 17 (USP17) has previously been found to result in reduced tumorigenesis and invasion of non-small cell lung cancer (NSCLC) cells. However, the functions and underlying mechanisms of USP17 in NSCLC progression remain unclear. In the present study, cisplatin treatment was found to upregulate USP17 expression in a dose-dependent manner. Furthermore, USP17-overexpressing (USP17-OE) NSCLC A549 and H1299 cells were generated for mechanistic studies. The results from the Cell Counting Kit-8 assay revealed increased cell proliferation in USP17-OE cells compared with that of control cells. Moreover, the viability of USP17-OE cells was significantly higher than that of the control cells, when treated with cisplatin. The results of the biochemical studies demonstrated enhanced PI3K and AKT phosphorylation in USP17-OE NSCLC cells, whereas USP17-knockdown decreased these levels of phosphorylation. By contrast, an AKT inhibitor abolished the USP17-mediated enhancement of proliferation. Moreover, suppression of USP17 or the combination of the AKT inhibitor and cisplatin significantly reduced cell viability. Overall, the results of the present study suggest that PI3K/AKT activation is the underlying mechanism of USP17-mediated cisplatin resistance in NSCLC.

Surgical fixation of rib fractures decreases intensive care length of stay in flail chest patients.

BACKGROUND: Nonoperative treatment is currently the standard therapy for rib fractures. However, there is a trend towards surgical fixation from conservative management over the last decade. While surgical fixation of rib fractures has shown promising results, its impact on the clinical results remains unclear based on the current literature. As such, the present study aims to compare the short-term outcomes of multiple rib fracture patients treated by surgical fixation with traditional conservative management. METHODS: Data for patients with multiple (three or more) rib fractures admitted to our department between January 2012 and January 2019 were retrospectively collected and analyzed. Propensity score matched patients were compared between those treated with surgical rib fixation and those of nonoperatively treated. Primary outcomes were hospital length of stay for multiple rib fracture patients, and intensive care unit (ICU) length of stay for flail chest patients. Secondary outcomes included in hospital mortality, ICU usage rate, duration of ventilator support, ventilator usage rate, and pneumonia. RESULTS: The study included 1,201 patients with mean age of 50.1±12.7 years, of whom 954 (79.4%) were male. The average number of rib fractures was 6.3±2.4, with a mean injury severity score of 20.5±7.3. Among them, 563 (46.9%) patients had surgical rib fixation and 638 (53.1%) patients received nonoperative treatment. There were 191 patients with a flail chest, 133 (69.6%) had operative rib fixation and 58 (30.4%) were nonoperatively treated. After propensity score match, the hospital length of stay was not significantly differed between surgery and conservative management in multiple rib fracture patients (10.7±3.4 vs. 10.2±3.8 days, P=0.067), nor were the secondary outcomes, in terms of in hospital mortality (0.9% vs. 1.1%, P=0.704), ICU usage rate (12.3% vs. 12.9%, P=0.820), duration of ventilator support (100.1±13.9 vs. 99.8±20.7 hours, P=0.822), ventilator usage rate (12.0% vs. 12.9%, P=0.732), and pneumonia (24.3% vs. 24.9%, P=0.861). For patients with a flail chest, shorter ICU length of stay was found to be associated with surgical rib fixation comparing with nonoperative treatment (5.5±1.9 vs. 6.7±2.1 days, P=0.011). No secondary outcomes such as in hospital mortality (4.4% vs. 4.4%, P=1.000), ICU usage rate (20.0% vs. 22.2%, P=0.796), duration of ventilator support (113.1±20.4 vs. 131.2±19.5 hours, P=0.535), ventilator usage rate (20.0% vs. 20.0%, P=1.000), pneumonia (28.9% vs. 31.1%, P=0.818) were significant different between the operative and nonoperative groups. CONCLUSIONS: Surgical rib fixation results in a shorter ICU length of stay in patients with a flail chest, and a comparable outcome for patients with multiple rib fractures when compared with nonoperative treatment.

Skeletal muscle stem cells confer maturing macrophages anti-inflammatory properties through insulin-like growth factor-2.

Cytokines produced by immune cells have been demonstrated to act on muscle stem cells (MuSCs) and direct their fate and behavior during muscle repair and regeneration. Nevertheless, it is unclear whether and how MuSCs can also in turn modulate the properties of immune cells. Here, we showed that in vitro expanded MuSCs exhibited a potent anti-inflammatory effect when infused into mice suffering from inflammatory bowel disease (IBD). Supernatant conditioned by MuSCs similarly ameliorated IBD. This beneficial effect of MuSCs was not observed when macrophages were depleted. The MuSC supernatant was found to greatly attenuate the expression of inflammatory cytokines but increase the expression of programmed death-ligand 1 in macrophages treated with lipopolysaccharide and interferon gamma. Further analysis revealed that MuSCs produce a large amount of insulin-like growth factor-2 (IGF-2) that instructs maturing macrophages to undergo oxidative phosphorylation and thus acquire anti-inflammatory properties. Interestingly, the IGF-2 production by MuSCs is much higher than by mesenchymal stem cells. Knockdown or neutralization of IGF-2 abrogated the anti-inflammatory effects of MuSCs and their therapeutic efficacy on IBD. Our study demonstrated that MuSCs possess a strong anti-inflammatory property and the bidirectional interactions between immune cells and MuSCs have important implications in muscle-related physiological and pathological conditions.

Association between neck circumference and cardiometabolic disease in Chinese adults: a community-based cross-sectional study.

OBJECTIVES: Several studies have indicated that neck circumference (NC) was associated with cardiometabolic disease in some Western countries. However, there are limited data regarding this association among Chinese adults. DESIGN: A community-based cross-sectional study. SETTING: A multistage-stratified random cluster survey was conducted in Xixiang Street, Bao'an District of Shenzhen in southeast China. PARTICIPANTS: This study included 4000 participants (1605 men and 2395 women) with a mean age of 56.0±9.8 years. MAIN OUTCOME MEASURES: Categorical data were reported as percentage and continuous data were reported as mean±SD. Receiver operating characteristic analysis and logistic regression analysis were used to evaluate the association of NC with cardiometabolic disease. RESULTS: The mean NC values were 35.50±4.23 cm for men and 32.32±3.59 cm for women. After adjusting for body mass index and waist circumference, NC was significantly associated with the risk of hypertension (OR: 1.42 in women), decreased high-density lipoprotein (HDL) levels (OR: 1.27 in men; OR: 1.12 in women), high triglyceride (TG) levels (OR: 1.54 in women) and diabetes (OR: 1.41 in men; OR: 1.37 in women). Among men, the optimal NC cut-off values were 38.10 cm for identifying hypertension, 32.32 cm for decreased HDL levels, 36.6 cm for high TG levels and 36.6 cm for diabetes. Among women, the optimal NC cut-off values were 32.35 cm for identifying hypertension, 33.40 cm for decreased HDL levels, 32.90 cm for high TG levels and 33.40 cm for diabetes. CONCLUSIONS: NC was significantly associated with cardiometabolic disease in Chinese population. Although further studies are needed to confirm the optimal cut-off values, evaluating NC may be useful for predicting cardiometabolic disease risk during clinical assessments.

Fabrication and Properties of Superhydrophobic Waterborne Polyurethane Composites with Micro-Rough Surface Structure Using Electrostatic Spraying.

Waterborne polyurethane (WPU) coatings hold advantages of good toughness, low cost and environmental protection. However, the low water contact angle (WCA), poor wear and corrosion resistance make them unsuitable for application in the superhydrophobic coatings such as antipollution flashover coatings for transmission lines, self-cleaning coatings for outdoor equipment and waterproof textiles. A series of superhydrophobic WPU composites (SHWPUCs) with micro-rough surface structure was prepared by electrostatic spraying nano-SiO2 particles on WPU composites with low surface energy. It showed that as the hydrophobic system content rose the WCAs of the composites first increased and then remained stationary; however, the adhesion and corrosion resistance first increased and then decreased. An appropriate addition of the hydrophobic system content would lead to a dense coating structure, but an excessive addition could increase the interfaces in the coating and then reduce the coating performance. When the mass ratio of the WPU dispersion, polytetrafluoroethylene (PTFE) particles and modified polydimethylsiloxane was 8:0.3:0.4, 10 g/m2 nano-SiO2 particles were sprayed on the uncured coating surface to construct the SHWPUC with a WCA of 156°. Compared with pure WPU coating, its adhesion and corrosion resistance increased by 12.5% and one order of magnitude, respectively; its wear rate decreased by 88.8%.

Thoracic trauma: a descriptive review of 4168 consecutive cases in East China.

Thoracic trauma in China was scarcely reported. This study aimed to summarize the clinical profiles and to analyze the management approaches of patients with traumatic thoracic injury.Data for consecutive patients with thoracic trauma from January 2003 to January 2018 were retrospectively collected and analyzed. Patients' profiles and clinical outcomes were compared between those patients treated with a dedicated thoracic trauma team and those without.The study included 4168 patients with mean age of 49.0 years, of whom 82.1% were male. Traffic accident accounted for 42.7% of the injuries. Most of the patients (66.8%) had rib fractures. Associated injuries were present in 48.3% of the patients; of them 86.0% were extremity fractures. Majority of the patients were managed without surgical procedures other than tube thoracostomy (33.2%). ICU service was needed in 12.0% of the patients. Patients treated with thoracic trauma team were older (53.59 ±â€Š16.8 year vs 45.1 ±â€Š18.0 year, P < .001), less male (78.3% vs 85.2%, P < .001), with higher injury severity scores (17.5 ±â€Š10.1 vs 13.7 ±â€Š8.2, P < .001), required more ventilator support (48.3% vs 25.3%, P < .001) and underwent more tube thoracostomy and other surgeries (43.8% vs 24.2%, and 34.4% vs 14.1%, respectively, all P < .001), yet with a shorter hospital stay (11.7 ±â€Š9.0 days vs 12.7 ±â€Š8.8 days, P < .001), and numerically lower ICU usage and mortality when compared to those without.Thoracic trauma in China usually affects mid-age males. Traffic accident is the top one etiology. The most common type of thoracic injuries is rib fracture. Associated injuries occur frequently. Nonoperative treatment and tube thoracostomy are effective for majority of the patients. A multidisciplinary approach with a dedicated thoracic trauma team could improve the treatment for these patients.