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Background: Childhood trauma is a common and potent risk factor for developing major depressive disorder in adulthood, associated with earlier onset, more chronic or recurrent symptoms, and greater probability of having comorbidities. Some studies indicate that evidence-based pharmacotherapies and psychotherapies for adult depression might be less efficacious in patients with a history of childhood trauma than patients without childhood trauma, but findings are inconsistent. Therefore, we examined whether individuals with major depressive disorder, including chronic forms of depression, and a reported history of childhood trauma, had more severe depressive symptoms before treatment, had more unfavourable treatment outcomes following active treatments, and were less likely to benefit from active treatments relative to a control condition, compared with individuals with depression without childhood trauma. Methods: We did a comprehensive meta-analysis (PROSPERO CRD42020220139). Study selection combined the search of bibliographical databases (PubMed, PsycINFO, and Embase) from Nov 21, 2013, to March 16, 2020, and full-text randomised clinical trials (RCTs) identified from several sources (1966 up to 2016–19) to identify articles in English. RCTs and open trials comparing the efficacy or effectiveness of evidence-based pharmacotherapy, psychotherapy, or combination intervention for adult patients with depressive disorders and the presence or absence of childhood trauma were included. Two independent researchers extracted study characteristics. Group data for effect-size calculations were requested from study authors. The primary outcome was depression severity change from baseline to the end of the acute treatment phase, expressed as standardised effect size (Hedges' g). Meta-analyses were done using random-effects models. Findings: From 10 505 publications, 54 trials met the inclusion criteria, of which 29 (20 RCTs and nine open trials) contributed data of a maximum of 6830 participants (age range 18–85 years, male and female individuals and specific ethnicity data unavailable). More than half (4268 [62%] of 6830) of patients with major depressive disorder reported a history of childhood trauma. Despite having more severe depression at baseline (g=0·202, 95% CI 0·145 to 0·258, I2=0%), patients with childhood trauma benefitted from active treatment similarly to patients without childhood trauma history (treatment effect difference between groups g=0·016, –0·094 to 0·125, I2=44·3%), with no significant difference in active treatment effects (vs control condition) between individuals with and without childhood trauma (childhood trauma g=0·605, 0·294 to 0·916, I2=58·0%; no childhood trauma g=0·178, –0·195 to 0·552, I2=67·5%; between-group difference p=0·051), and similar dropout rates (risk ratio 1·063, 0·945 to 1·195, I2=0%). Findings did not significantly differ by childhood trauma type, study design, depression diagnosis, assessment method of childhood trauma, study quality, year, or treatment type or length, but differed by country (North American studies showed larger treatment effects for patients with childhood trauma; false discovery rate corrected p=0·0080). Most studies had a moderate to high risk of bias (21 [72%] of 29), but the sensitivity analysis in low-bias studies yielded similar findings to when all studies were included. Interpretation: Contrary to previous studies, we found evidence that the symptoms of patients with major depressive disorder and childhood trauma significantly improve after pharmacological and psychotherapeutic treatments, notwithstanding their higher severity of depressive symptoms. Evidence-based psychotherapy and pharmacotherapy should be offered to patients with major depressive disorder regardless of childhood trauma status. Funding: None.

PLK1 and Smad4 are two important factors in prostate cancer initiation and progression. They have been reported to play the opposite role in Pten-deleted mice, one is an oncogene, the other is a tumor suppressor. Moreover, they could reversely regulate the PI3K/AKT/mTOR pathway and the activation of MYC. However, the connections between PLK1 and Smad4 have never been studied. Here, we showed that PLK1 could interact with Smad4 and promote the ubiquitination and degradation of Smad4 in PCa cells. PLK1 and PELO could bind to different domains of Smad4 and formed a protein complex. PELO facilitated the degradation of Smad4 through cooperating with PLK1, thereby resulting in proliferation and metastasis of prostate cancer cell. Changes in protein levels of Smad4 led to the alteration of biological function that caused by PLK1 in prostate cancer cells. Further studies showed that PELO upregulation was positively associated with high grade PCa and knockdown of PELO expression significantly decreased PCa cell proliferation and metastasis in vitro and vivo. PELO knockdown in PCa cells could enhance the tumor suppressive role of PLK1 inhibitor. In addition, blocking the interaction between PELO and Smad4 by using specific peptide could effectively inhibit PCa cell metastasis ability in vitro and vivo. Overall, these findings identified a novel regulatory relationship among PLK1, Smad4 and PELO, and provided a potential therapeutic strategy for advanced PCa therapy by co-targeting PLK1 and PELO.

Anxiety disorders are debilitating psychiatric diseases that affect ∼16% of the world's population. Although it has been proposed that the central nucleus of the amygdala (CeA) plays a role in anxiety, the molecular and circuit mechanisms through which CeA neurons modulate anxiety-related behaviors are largely uncharacterized. Soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of polyunsaturated fatty acids (PUFAs), and has been shown to play a role in psychiatric disorders. Here, we reported that sEH was enriched in neurons in the CeA and regulated anxiety-related behaviors in adult male mice. Deletion of sEH in CeA neurons but not astrocytes induced anxiety-like behaviors. Mechanistic studies indicated that sEH was required for maintaining the the excitability of sEH positive neurons (sEHCeAneurons) in the CeA. Using chemogenetic manipulations, we found that sEHCeAneurons bidirectionally regulated anxiety-related behaviors. Notably, we identified that sEHCeAneurons directly projected to the bed nucleus of the stria terminalis (BNST; sEHCeA–BNST). Optogenetic activation and inhibition of the sEHCeA–BNSTpathway produced anxiolytic and anxiogenic effects, respectively. In summary, our studies reveal a set of molecular and circuit mechanisms of sEHCeAneurons underlying anxiety.SIGNIFICANCE STATEMENTSoluble epoxide hydrolase (sEH), a key enzyme that catalyzes the degradation of EETs, is shown to play a key role in mood disorders. It is well known that sEH is mostly localized in astrocytes in the prefrontal cortex and regulates depressive-like behaviors. Notably, sEH is also expressed in central nucleus of the amygdala (CeA) neurons. While the CeA has been studied for its role in the regulation of anxiety, the molecular and circuit mechanism is quite complex. In the present study, we explored a previously unknown cellular and circuitry mechanism that guides sEHCeAneurons response to anxiety. Our findings reveal a critical role of sEH in the CeA, sEHCeAneurons and CeA-bed nucleus of the stria terminalis (BNST) pathway in regulation of anxiety-related behaviors.

Objective To systematically describe the short stature of patients with Diamond-Blackfan anemia and to explore factors affecting the height development of patients with Diamond-Blackfan anemia. Study design This cross-sectional study was conducted at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and the height, weight, and clinical data of 129 patients with Diamond-Blackfan anemia were collected from June 2020 to September 2020. Results The median height-age-z score (HAZ) of children affected by Diamond-Blackfan anemia was −1.54 (−6.36-1.96). Short stature was found in 37.98% of the patients. Specific Diamond-Blackfan anemia growth curves were developed for weight, height, and body mass index, separately for male and female patients. Multivariable logistic regression models showed that female sex (aOR 4.92; 95% CI 1.29-18.71; P = .0195), underweight (aOR 10.41, 95% CI 1.41-76.98, P = .0217), cardiovascular malformations (aOR 216.65; 95% CI 3.29-14279.79; P = .0118), and RPL11(aOR 29.14; 95% CI 1.18-719.10; P = .0392) or RPS26 (aOR 53.49; 95% CI 1.40-2044.30; P = .0323) mutations were independent risk factors for short stature. In the subgroup of patients who were steroid-dependent, patients with a duration of steroid therapy over 2 years (OR 2.95; 95% CI 1.00-8.66; P = .0494) or maintenance dose of prednisone >0.1 mg/kg per day (OR 3.30; 95% CI 1.02-10.72; P = .0470) had a higher incidence of short stature. Conclusions Patients with Diamond-Blackfan anemia had a high prevalence of short stature. The risk of short stature increased with age and was associated with sex, underweight, congenital malformations, and RPL11 or RPS26 mutations. The duration of steroid therapy and maintenance dose of steroid was significantly associated with the incidence of short stature in steroid-dependent patients with Diamond-Blackfan anemia.

ObjectivesOverweight and obesity are harmful to human health. However, the latest trends of Chinese childhood overweight and obesity prevalence are not available. The aim of this study was to examine the trends from 2000 to 2019 among students in China.MethodsWe analyzed data of 66,072 students in the Chinese National Survey on Students' Constitution and Health from 2000 to 2019. Overweight and obesity were defined based on the standard formulated by the International Obesity Task Force (IOTF standard), the World Health Organization (WHO standard), and the Working Group on Obesity in China (WGOC standard), respectively. The χ2-test was used to test the trends of overweight and obesity prevalence and logistic regression was conducted to evaluate the prevalence odds ratios of boys vs. girls and urban vs. rural areas.ResultsThe prevalence of obesity/overweight and obesity combined was 6.03/23.58% (IOTF standard), 10.56/25.88% (WGOC standard) and 10.75/29.69% (WHO standard) in 2019. From 2000 to 2019, according to the WGOC standard, the prevalence increased from 2.51 to 10.56% for obesity and increased from 9.81 to 25.88% for overweight and obesity combined (P for trend < 0.001). Obesity/overweight and obesity were greater problems in boys than girls and urban than rural areas, but urban-rural differences decreased over time.ConclusionOverweight and obesity prevalence increased significantly in children and adolescents in China from 2000 to 2019. The prevalence of overweight and obesity in rural areas may contribute to a large percentage of children with overweight and obesity.

OBJECTIVE: To investigate the distribution of body mass index (BMI) and risk factors for obesity in children with Diamond-Blackfan Anemia (DBA). METHODS: The children with DBA who attended National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 2003 to December 2020 were enrolled as subjects. The related clinical data and treatment regimens were recorded. The height and weight data measured within 1 week before or after follow-up time points were collected to calculate BMI. The risk factors for obesity were determined by multivariate regression analysis in children with DBA. RESULTS: A total of 129 children with DBA were enrolled, among whom there were 80 boys (62.0%) and 49 girls (38.0%), with a median age of 49 months (range 3-189 months). The prevalence rate of obesity was 14.7% (19/129). The multivariate logistic regression analysis showed that the absence of ribosomal protein gene mutation was closely associated with obesity in children with DBA (adjusted OR=3.63, 95%CI: 1.16-11.38, adjusted P=0.027). In children with glucocorticoid-dependent DBA, obesity was not associated with age of initiation of glucocorticoid therapy, duration of glucocorticoid therapy, and maintenance dose of glucocorticoids (P>0.05). CONCLUSIONS: There is a high prevalence rate of obesity in children with DBA, and the absence of ribosomal protein gene mutation is closely associated with obesity in children with DBA.

Summary Anti-neurofascin-155 (NF155) antibodies have been observed in two cases with neuromyelitis optica spectrum disorders (NMOSD). This study investigated the prevalence of anti-NF155 antibodies in patients with NMOSD and the clinical features of anti-NF155 antibody-positive patients. Sera from 129 patients with NMOSD were screened with anti-NF155 antibodies by cell-based assay (CBA) and re-examined using immunostaining of teased mouse sciatic nerve fibres. Fifty-six patients with multiple sclerosis (MS) and 50 healthy controls (HC) were also enrolled for detecting anti-NF155 antibodies. A total of 12.40% (16 of 129) of patients with NMOSD were positive for anti-NF155 antibodies confirmed by both CBA and immunostaining. Immunoglobulin (Ig) G1 was the predominant subclass. However, none of 56 MS patients or 50 HC were positive for anti-NF155 antibodies. Anti-NF155 antibody-positive NMOSD patients had a higher proportion of co-existing with autoimmune diseases (p

Acute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACS) and it is associated with higher short-term and long-term morbidity and mortality. Therefore, it is of paramount importance to identify those ACS patients at risk for the development of AKI. The objective of this study was to evaluate two different plasma biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) in early detecting the development of AKI in ACS patients.172 ACS patients admitted to the Coronary Care Unit in Yantai Yuhuangding Hospital were prospectively enrolled. Their blood samples were obtained on admission and subjected to enzyme-linked immunosorbent assay to determine the levels of novel biomarkers. The clinical data and biomarkers were recorded and analyzed.In this study, 23 (13.4%) patients had a diagnosis of AKI. Statistical analysis demonstrated that in ACS patients with AKI, the following two biomarkers were significantly higher than these without AKI: plasma calprotectin (5942.26 ± 1955.88 ng/mL vs. 3210.29 ± 1833.60 ng/mL, p 0.001) and plasma NGAL (164.91 ± 43.63 ng/mL vs. 122.48 ± 27.33 ng/mL, p 0.001). Plasma calprotectin and NGAL could discriminate the development of AKI respectively with an area under the ROC curve (AUC) of 0.864 and 0.850. A combination of the two plasma biomarkers calprotectin and NGAL could early discriminate AKI in ACS patients with an AUC of 0.898.This study demonstrated a promising panel of plasma calprotectin and NGAL as early diagnostic biomarkers for AKI in ACS patients.

Although the smoking rate of HIV, HBV or HCV infected people is much higher than that of the general population, smoking cessation interventions have long been ineffective. Therefore, further understanding of the underlying social reasons behind the poor behavior of this population is needed. We aimed to examine the estimates of prevalence, time-trend, and association of smoking among people living with HIV, HBV, or HCV. This cohort was composed of 32,115 individuals from the National Health and Nutrition Examination Survey (NHANES 1999–2018). All adults aged 21–59 who self-reported smoking status and had been tested for HIV, HBV, and HCV were included in this analysis. The time trend analysis of smoking and quitting rates in different years of survey follow-up and different infected populations. Multivariable logistic regression analysis was used to identify the risk factors related to smoking behavior of HIV|HBV|HCV infected people. Overall, the smoking rates of the people infected HIV|HBV|HCV were 1.35–1.93 times higher from 1999 to 2018. Compared to smokers without HIV&HBV&HCV, smokers living with HIV|HBV|HCV were more likely to be older (aged 30–39, 9.92, 6.07 to 16.21; aged 40–49, OR = 3.51, CI = 2.49 to 4.94), more males (1.99, 1.54 to 2.55), lower education level (1.78, 1.39 to 2.29), lower economic level (2.05, 1.59 to 2.65), unemployed (1.63, 1.21 to 2.20), suffering depression (1.35, 1.05 to 1.72), and drug users (7.65, 5.04 to 11.59). Taken together, studies have shown that complex psychosocial characteristics and behavioral factors, including individual economic status, mental diseases (such as depression) and illegal drug use (such as marijuana and heroin) hinder their efforts to quit smoking. Therefore, it is very important to take targeted smoking cessation interventions to meet the unique situation and needs of this special group.

Increasing evidence has suggested a critical role for endothelial‐to‐mesenchymal transition (EndoMT) in a variety of pathological conditions. MicroRNA‐200c‐3p (miR‐200c‐3p) has been implicated in epithelial‐to‐mesenchymal transition. However, the functional role of miR‐200c‐3p in EndoMT and neointimal hyperplasia in artery bypass grafts remains largely unknown. Here we demonstrated a critical role for miR‐200c‐3p in EndoMT. Proteomics and luciferase activity assays revealed that fermitin family member 2 (FERM2) is the functional target of miR‐200c‐3p during EndoMT. FERMT2 gene inactivation recapitulates the effect of miR‐200c‐3p overexpression on EndoMT, and the inhibitory effect of miR‐200c‐3p inhibition on EndoMT was reversed by FERMT2 knockdown. Further mechanistic studies revealed that FERM2 suppresses smooth muscle gene expression by preventing serum response factor nuclear translocation and preventing endothelial mRNA decay by interacting with Y‐box binding protein 1. In a model of aortic grafting using endothelial lineage tracing, we observed that miR‐200c‐3p expression was dramatically up‐regulated, and that EndoMT contributed to neointimal hyperplasia in grafted arteries. MiR‐200c‐3p inhibition in grafted arteries significantly up‐regulated FERM2 gene expression, thereby preventing EndoMT and reducing neointimal formation. Importantly, we found a high level of EndoMT in human femoral arteries with atherosclerotic lesions, and that miR‐200c‐3p expression was significantly increased, while FERMT2 expression levels were dramatically decreased in diseased human arteries. Collectively, we have documented an unexpected role for miR‐200c‐3p in EndoMT and neointimal hyperplasia in grafted arteries. Our findings offer a novel therapeutic opportunity for treating vascular diseases by specifically targeting the miR‐200c‐3p/FERM2 regulatory axis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Introduction: The delipid extracorporeal lipoprotein filter from plasma (DELP) has been approved for the treatment of acute ischemic stroke (AIS) by the China Food and Drug Administration, but its effectiveness and mechanism are not yet fully determined. The purpose of this study was to evaluate the effect of DELP treatment on AIS patients after intravenous thrombolysis. Methods: A retrospective study was performed on AIS patients with no improvement within 24 h after intravenous thrombolysis who were subsequently treated with or without DELP. Primary outcome was the proportion with a modified Rankin scale (mRS) of 0–1 at 90 days. Secondary outcomes were changes in National Institute of Health Stroke Scale (NIHSS) score from 24 h to 14 days after thrombolysis, and the rate of improvement in stroke-associated pneumonia (SAP). The main safety outcomes were the rates of symptomatic intracranial hemorrhage and mortality. To investigate its mechanisms, serum biomarkers were measured before and after DELP. Results: A total of 252 patients were recruited, 63 in the DELP group and 189 matched patients in the NO DELP group. Compared with the NO DELP group, the DELP group showed an increase in the proportion of mRS 0–1 at 90 days (p = 0.042). More decrease in NIHSS from 24 h to 14 days (p = 0.024), a higher rate of improvement in SAP (p = 0.022), and lower mortality (p = 0.040) were shown in DELP group. Furthermore, DELP decreased levels of interleukin (IL)-1β, E-selectin, malondialdehyde, matrix metalloprotein 9, total cholesterol, low-density lipoprotein, and fibrinogen, and increased superoxide dismutase (p< 0.05). Conclusions: DELP following intravenous thrombolysis should be safe, and is associated with neurological function improvement, possibly through multiple neuroprotective mechanisms. Prospective trials are needed.

Many factors contribute to the health risks encountered by astronauts on missions outside Earth's atmosphere. Spaceflight-induced potential adverse neurovascular damage and late neurodegeneration are a chief concern. The goal of the present study was to characterize the effects of spaceflight on oxidative damage in the mouse brain and its impact on blood-brain barrier (BBB) integrity. Ten-week-old male C57BL/6 mice were launched to the International Space Station (ISS) for 35 days as part of Space-X 12 mission. Ground control (GC) mice were maintained on Earth in flight hardware cages. Within 38 ± 4 hours after returning from the ISS, mice were euthanized and brain tissues were collected for analysis. Quantitative assessment of brain tissue demonstrated that spaceflight caused an up to 2.2-fold increase in apoptosis in the hippocampus compared to the control group. Immunohistochemical analysis of the mouse brain revealed an increased expression of aquaporin4 (AQP4) in the flight hippocampus compared to the controls. There was also a significant increase in the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) and a decrease in the expression of the BBB-related tight junction protein, Zonula occludens-1 (ZO-1). These results indicate a disturbance of BBB integrity. Quantitative proteomic analysis showed significant alterations in pathways responsible for neurovascular integrity, mitochondrial function, neuronal structure, protein/organelle transport, and metabolism in the brain after spaceflight. Changes in pathways associated with adhesion and molecular remodeling were also documented. These data indicate that long-term spaceflight may have pathological and functional consequences associated with neurovascular damage and late neurodegeneration.

Objective To explore the value of CT texture analysis (CTTA) for determining coronavirus disease 2019 (COVID-19) severity. Methods The clinical and CT data of 81 patients with COVID-19 were retrospectively analyzed. The texture features were extracted using LK2.1. The two-sample t test or Mann–Whitney U test was used to find the significant features. Minimum redundancy and maximum relevance (MRMR) method was performed to find the features with maximum correlation and minimum redundancy. These features were then used to construct a radiomics texture model to discriminate the severe patients using multivariate logistic regression method. Besides, a clinical model was also built. ROC analyses were conducted to evaluate the performance of two models. The correlations of clinical features and textural features were analyzed using the Spearman correlation analysis. Results Of the total cases included, 60 were common and 21 were severe. (1) For textural features, 20 radiomics features selected by MRMR showed good performance in discriminating the two groups (AUC > 70%). (2) For clinical features, chi-square tests or Mann–Whitney U tests identified 16 clinical features as significant, and 12 were discriminative (p 70%. (3) Prediction models for textural features and clinical features were established, and both showed high predictive accuracy. The AUC values of textural features and clinical features were 0.93 (0.86–1.00) and 0.95 (0.95–0.99), respectively. (4) The Spearman correlation analysis showed that most textural and clinical features had above-moderate correlations with disease severity (> 0.4). Conclusion Texture analysis can provide reliable and objective information for differential diagnosis of COVID-19. Key Points • CT texture analysis can well differentiate common and severe COVID-19 patients. • Some textural features showed above-moderate correlations with clinical factors. • CT texture analysis can provide useful information to judge the severity of COVID-19. Electronic supplementary material The online version of this article (10.1007/s00330-020-07012-3) contains supplementary material, which is available to authorized users.

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment and contribute to tumor cell proliferation and metastasis. Microfibrillar-associated protein 5 (MFAP5), a component of elastic microfibers and an oncogenic protein in several types of tumors, is secreted by CAFs. However, the role of MFAP5 in the bladder cancer remains unclear. Here, we report that MFAP5 is upregulated in bladder cancer and is associated with poor patient survival. Downregulation of MFAP5 in CAFs led to an impairment in proliferation and invasion of bladder cancer cells. Luciferase reporter assays and electrophoretic mobility shift assays (EMSA) showed QKI directly downregulates MFAP5 in CAFs. In addition, CAFs-derived MFAP5 led to an activation of the NOTCH2/HEY1 signaling pathway through direct interaction with the NOTCH2 receptor, thereby stimulating the N2ICD release. RNA-sequencing revealed that MFAP5-mediated PI3K-AKT signaling activated the DLL4/NOTCH2 pathway axis in bladder cancer. Moreover, downregulation of NOTCH2 by short hairpin RNA or the inactivating anti-body NRR2Mab was able to reverse the adverse effects of MFAP5 stimulation in vitro and in vivo. Together, these results demonstrate CAFs-derived MFAP5 promotes the bladder cancer proliferation and metastasis and provides new insight for targeting CAFs as novel diagnostic and therapeutic strategy.

Background Hemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner. Results In this study, we constructed a hemostatic sponge OBNC-DFO by fermentation of Komagataeibacterxylinus combined with TEMPO oxidation to obtain oxidized bacterial nanocellulose (OBNC). Then angiogenetic drug desferrioxamine (DFO) was grafted through an amide bond, and it promoted clot formation and activated coagulation reaction by rapid blood absorption due to the high total pore area (approximately 42.429 m2/g measured by BET). The further release of DFO stimulated the secretion of HIF-1α and the reconstruction of blood flow, thus achieving rapid hemostasis and vascularization in damaged tissue. This new hemostatic sponge can absorb water at a rate of approximate 1.70 g/s, rapidly enhancing clot formation in the early stage of hemostasis. In vitro and in vivo coagulation experiments (in rat tail amputation model and liver trauma model) demonstrated superior pro-coagulation effects of OBNC and OBNC-DFO to clinically used collagen hemostatic sponges (COL). They promoted aggregation and activation of red blood cells and platelets with shorter whole blood clotting time, more robust activation of endogenous coagulation pathways and less blood loss. In vitro cellular assays showed that OBNC-DFO prevailed over OBNC by promoting the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the release of DFO enhanced the secretion of HIF-1α, further strengthening vascularization in damaged skin. In the rat skin injury model, 28 days after being treated with OBNC-DFO, skin appendages (e.g., hair follicles) became more intact, indicating the achievement of structural and functional regeneration of the skin. Conclusion This hemostatic and vascularization-promoting oxidized bacterial nanocellulose hemostatic sponge, which rapidly activates coagulation pathways and enables skin regeneration, is a highly promising hemostatic and pro-regenerative repair biomaterial. Graphical Abstract

Background The implementation of national antiretroviral therapy (ART) and expanded ART policies results in that more and more HIV-infected patients receive ART in Kunming, Yunnan province, China. At the same time, however, the number of patients, who drop-out from ART, are also increasing. In this study, we explored the factors that may account for drop-out. Methods Four hundred and thirty-nine HIV-infected patients, who received or used to receive ART, were recruited in this study. Their age is among 18 and 75. All patients were divided into two group: ART group (187 patients) and drop-out group (252 patients). Appropriate bio-statistics analysis, including univariate analysis and Multivariate analysis, were used to identify factors associated with drop-out. Results Data from all patients were analyzed. Univariate analysis suggested that the factors associated with drop-out may include age, residential area, educational level, occupation, monthly income, the access to minimum living allowance, HIV transmission route, and living status. On the other hand, factors including area, monthly income, the access to minimum living allowance, and referral methods of follow-up institutions account for drop-out in multivariate analysis. Conclusions This study identified a number of factors associated with drop out from ART. Based on our findings,appropriate interventions should be introduced decrease drop-out.

To investigate the characteristics of platelet antibody in patients with hematological diseases, so as to research the effect of immunized platelet transfusion refractoriness (PTR) on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recepients with malignant hematological diseases patients.The clinical data of platelet antibody positive patients tested by Capture-P in the First Affiliated Hospital of Soochow University from July 1, 2014 to July 1, 2019 were retrospectively analyzed, including sex, age, disease, platelet transfusion assessments, CD34In 5 years, 913 (7.28%) hematologic patients with platelet antibody positive were identified, the detection rate of females (513 cases) were higher than males (400 cases). Among the 913 patients, the antibody positive rates of 520 patients with malignant hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome) showed significantly statistical different (10.27%, 8.01%, and 7.20%) (P0.01), and the positive rate of the acute myeloid leukemia of those patients was higher than myelodysplastic syndrome patients(α0.0125). There were 35 cases diagnosed as immunized PTR before allo-HSCT, the platelet increments, 14 h correct count increment, progression-free survival rate and overall survival rate of those patients were significantly lower than those in negative transfusion effective patients (P0.01), while the percentage of ABO matching was significantly higher (α0.0125).The positive rate of platelet antibody identification is high in females and acute myeloid leukemia patients, and immunized PTR caused by antibody is a risk factor for poor prognosis of allo-HSCT in malignant hematological disease patients.免疫性血小板输注无效对恶性血液病异基因造血干细胞移植患者的影响.探讨血小板抗体在血液病患者中产生的特点，研究免疫性血小板输注无效对恶性血液病异基因造血干细胞移植（allo-HSCT）患者临床预后的影响.回顾性分析2014年7月1日－2019年7月1日苏州大学附属第一医院利用Capture-P方法鉴定血小板抗体阳性患者的性别、年龄、疾病、血小板输注、CD345年内，共有913例血小板抗体鉴定阳性血液病患者（7.28%），女性（513例）多于男性（400例），其中520例恶性血液病（急性髓细胞白血病、急性淋巴细胞白血病和骨髓增生异常综合征）患者抗体阳性率（10.27%、8.01%和7.20%）明显不同（P0.01），急性髓系白血病患者的抗体阳性率高于骨髓增生异常综合征的（α0.0125）。移植前共有35例免疫性血小板输注无效患者，其血小板增加数、14 h校正血小板增高指数、无进展生存率和总生存率明显低于阴性输注有效组（P0.01），而ABO全相合比例明显高于阴性输注有效组（α0.0125）.女性和急性髓系白血病患者血小板抗体鉴定阳性率高，由抗体引起的免疫性血小板输注无效是引起恶性血液病患者allo-HSCT预后不良的风险因素.

The sterile inflammation (SI) of the urinary tract is a common problem requiring serious consideration after prostatectomy. This study mainly focuses on the role of the reactive oxygen species-NLR family, pyrin domain-containing 3 (ROS-NLRP3) signaling pathway in SI after thulium laser resection of the prostate (TmLRP). Urinary cytokines were determined in patients who received TmLRP, and heat shock protein 70 (HSP70) was detected in the resected tissues. The involvement of ROS signaling in HSP70-induced inflammation was explored in THP-1 cells with or without N-acetyl- l-cysteine (NAC) pretreatment. The function of NLRP3 and Caspase-1 was determined by Western blot analysis, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction. These phenomena and mechanisms were verified by the beagle models that received TmLRP. Clinical urine samples after TmLRP showed high expression of inflammatory factors and peaked 3-5 days after surgery. The high expression of HSP70 in the resected tissues was observed. After HSP70 stimulation, the expression of ROS, NLRP3, Caspase-1, and interleukin-18 (IL-18) increased significantly and could be reduced by ROS inhibitor NAC. The expression of IL-1β and IL-18 could be inhibited by NLRP3 or Caspase-1 inhibitors. In beagle models that received TmLRP, HSP70, NLRP3, Caspase-1, IL-1β, and IL-18 were highly expressed in the wound tissue or urine, and could also be reduced by NAC pretreatment. Activation of the ROS-NLRP3 signaling pathway induces SI in the wound after prostatectomy. Inhibition of this pathway may be effective for clinical prevention and treatment of SI and related complications after prostatectomy.

Background Previous studies have revealed that current secondhand smoke exposure showed highly suggestive evidence for increased risk of simultaneous sleep problems in children. Data on the associations between early-life exposure to SHS with subsequent sleep problems in children were scarce. We aimed to evaluate the associations of early-life SHS exposure with sleep problems in children. Methods In this cross-sectional study, children were recruited from elementary and middle schools in Liaoning Province, China between April 2012 and January 2013. We assessed early-life SHS exposure (pregnancy and the first 2 years of life) via questionnaires. Sleep problems and different types of sleep-related symptoms were measured based on the validated tool of the Sleep Disturbance Scale for Children (SDSC). Generalized linear mixed models were applied to estimate the associations of early-life SHS exposure with sleep problems. Results We included a total of 45,562 children (22,657 [49.7%] males; mean [SD] age, 11.0 [2.6] years) and 6167 of them (13.5%) were exposed to early-life SHS during both pregnancy and the first 2 years of life. Compared with unexposed counterparts, children exposed to early-life SHS had higher total T-scores of SDSC (β = 4.32; 95%CI: 4.06, 4.58) and higher odds of increased sleep problems (OR = 2.14; 95%CI: 1.89, 2.42). When considering different sleep-related symptoms, the associations between early-life SHS exposure and symptom of sleep-wake transition disorders (i.e., bruxism) were the strongest in all analyses. Conclusions Early-life SHS exposure was associated with higher odds of global sleep problems and different sleep-related symptoms in children aged 6–18 years. Our findings highlight the importance to strengthen efforts to support the critical importance of maintaining a smoke-free environment especially in early life.

Studies on the obesogenic effect of air pollution on children have been mixed and sparse. Moreover, due to insufficient air monitoring, few studies have investigated the role of more tiny but unregulated particles (ambient particles with a diameter of 0.1 μm or less, ultrafine particles).We sought to explore the associations between long-term exposure to ambient ultrafine particles (UFPs) and childhood obesity in Chinese children.In this cross-sectional study, we randomly recruited 47,990 children, aged 6-18 years, from seven cities in Northeastern China between 2012 and 2013. Child age- and sex-specific z-scores for body mass index (BMI Z-score) and weight status were generated using the World Health Organization growth reference. Four-year average concentrations of UFPs and airborne particulates of diameter ≤ 1 μm (PMWe found that UFPs exposure was associated with greater childhood BMI Z-score and a higher likelihood of obesity. Compared with the lowest quartile, higher quartiles of UFPs were associated with greater odds for obesity prevalence in children (i.e., the adjusted OR was 1.25; 95 % CI, 1.12-1.39; 1.43; 95 % CI, 1.27-1.61; and 1.41; 95 % CI, 1.25-1.58 for the second, third, and fourth quartile, respectively). Similar associations were observed for PMLong-term UFPs exposure was associated with a greater likelihood of childhood obesity, and stronger associations on BMI Z-score were observed in boys and children living close to roadways. This study indicates that more attention should be paid to the health effects of UFPs, and routinely monitoring of UFPs should be considered.

Background Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives. Objectives To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes. Methods We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification. Results After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models. Conclusions Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs.

Acute nephrotoxicity is a common adverse reaction of tacrolimus therapy; however, its risk factors in pediatric nephrotic syndrome (NS) remain to be evaluated. The objective of this study was to investigate the risk factors and characteristics of tacrolimus-induced acute nephrotoxicity in children with NS. Past records of children with NS admitted to our hospital from 2014 to 2018 were reviewed. The incidence and characteristics of nephrotoxicity were analyzed. Multivariate logistic regression analysis was used to identify the risk factors of nephrotoxicity. A clinically applicable risk score was developed and validated. Tacrolimus-induced nephrotoxicity occurred in 25 of 129 patients, 13 patients were grade 1, and the renal function was recovered in 22 patients. Multivariate regression analysis showed that the maximum trough concentrations (C12h) of tacrolimus (OR, 1.48; 95% CI, 1.16 to 1.88; P < 0.001), huaiqihuang granules (OR, 0.095; 95% CI, 0.014 to 0.66; P = 0.017), and diarrhea (OR, 22.00; 95% CI, 1.58 to 306.92; P = 0.022) were independently associated with tacrolimus-induced nephrotoxicity. The maximum C12h were significantly higher in patients with nephrotoxicity (median 9.0 ng/ml) and the cut-off value for acute nephrotoxicity was 6.5 ng/ml. The area under the receiver operating characteristic curve was 0.821 for the proposed model based on the observations used to create the model and 0.817 obtained from k-fold cross-validation. High trough concentration of tacrolimus and diarrhea can potentiate the risk of tacrolimus-induced acute nephrotoxicity in children with NS, while huaiqihuang granules can protect this condition.

Hypoxia‐inducible factor 1α (HIF‐1α) plays a critical role in the apoptotic process during cardiac ischaemia/reperfusion (I/R) injury. This study aimed to investigate whether post‐treatment with dexmedetomidine (DEX) could protect against I/R‐induced cardiac apoptosis in vivo and in vitro via regulating HIF‐1α signalling pathway. Rat myocardial I/R was induced by occluding the left anterior descending artery for 30 minutes followed by 6‐hours reperfusion, and cardiomyocyte hypoxia/reoxygenation (H/R) was induced by oxygen‐glucose deprivation for 6 hours followed by 3‐hours reoxygenation. Dexmedetomidine administration at the beginning of reperfusion or reoxygenation attenuated I/R‐induced myocardial injury or H/R‐induced cell death, alleviated mitochondrial dysfunction, reduced the number of apoptotic cardiomyocytes, inhibited the activation of HIF‐1α and modulated the expressions of apoptosis‐related proteins including BCL‐2, BAX, BNIP3, cleaved caspase‐3 and cleaved PARP. Conversely, the HIF‐1α prolyl hydroxylase‐2 inhibitor IOX2 partly blocked DEX‐mediated cardioprotection both in vivo and in vitro. Mechanistically, DEX down‐regulated HIF‐1α expression at the post‐transcriptional level and inhibited the transcriptional activation of the target gene BNIP3. Post‐treatment with DEX protects against cardiac I/R injury in vivo and H/R injury in vitro. These effects are, at least in part, mediated via the inhibition of cell apoptosis by targeting HIF‐1α signalling.

Extended spaceflight has been shown to adversely affect astronaut visual acuity. The purpose of this study was to determine whether spaceflight alters gene expression profiles and induces oxidative damage in the retina. Ten week old adult C57BL/6 male mice were flown aboard the ISS for 35 days and returned to Earth alive. Ground control mice were maintained on Earth under identical environmental conditions. Within 38 (+/−4) hours after splashdown, mice ocular tissues were collected for analysis. RNA sequencing detected 600 differentially expressed genes (DEGs) in murine spaceflight retinas, which were enriched for genes related to visual perception, the phototransduction pathway, and numerous retina and photoreceptor phenotype categories. Twelve DEGs were associated with retinitis pigmentosa, characterized by dystrophy of the photoreceptor layer rods and cones. Differentially expressed transcription factors indicated changes in chromatin structure, offering clues to the observed phenotypic changes. Immunofluorescence assays showed degradation of cone photoreceptors and increased retinal oxidative stress. Total retinal, retinal pigment epithelium, and choroid layer thickness were significantly lower after spaceflight. These results indicate that retinal performance may decrease over extended periods of spaceflight and cause visual impairment.

The health risks associated with spaceflight-induced ocular structural and functional damage has become a recent concern for NASA. The goal of the present study was to characterize the effects of spaceflight and reentry to 1 g on the structure and integrity of the retina and blood-retinal barrier (BRB) in the eye. To investigate possible mechanisms, changes in protein expression profiles were examined in mouse ocular tissue after spaceflight. Ten week old male C57BL/6 mice were launched to the International Space Station (ISS) on Space-X 12 at the Kennedy Space Center (KSC) on August, 2017. After a 35-day mission, mice were returned to Earth alive. Within 38 +/− 4 hours of splashdown, mice were euthanized and ocular tissues were collected for analysis. Ground control (GC) and vivarium control mice were maintained on Earth in flight hardware or normal vivarium cages respectively. Repeated intraocular pressure (IOP) measurements were performed before the flight launch and re-measured before the mice were euthanized after splashdown. IOP was significantly lower in post-flight measurements compared to that of pre-flight (14.4–19.3 mmHg vs 16.3–20.3 mmHg) (p

Background Perfluoroalkyl substances (PFASs) are synthetic chemicals widely used in industry and for commercial products. Their immunomodulatory effects are a growing health concern in children. Hand, Foot and Mouth Disease (HFMD) is a common childhood viral infection, and increased incidence of which has parallel the rise in PFAS exposure in the Asia-Pacific region. Objective We conducted the first study to assess whether prenatal exposure to PFAS was associated with a reduction in HFMD virus antibodies in infants. Methods We enrolled 201 mother-infant pairs from the Guangzhou Birth Cohort Study from July to October 2013. High performance liquid chromatography-mass spectrometry was employed to determine concentrations of specific PFAS isomers in cord blood. Neutralizing antibodies titers were measured against two HFMD viruses, enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), in cord blood serum and blood serum at three months of age. Results Higher umbilical cord blood PFAS concentrations were associated with lower EV71 and CA16 antibody concentrations. A doubling in the composite sum of cord blood PFASs in three month old infants was associated with significant increase in the risk of HFMD antibody concentration below clinical protection level (≥1:8 titers) for CA16 (odds ratio, OR: 2.74 [95% confidence interval (CI): 1.33, 5.61] and for EV71 (OR = 4.55, 95% CI: 1.45, 4.28). This association was higher in boys at three months of age for CA16. Conclusions Our findings suggest that cord blood PFAS exposure is associated with lower HFMD antibody in infancy. Given the widespread nature of PFAS exposures and the high global incidence of HFMD globally, these findings have substantial public health implications and therefore, these associations need to be replicated in a larger study to more definitively address the risk.

Aims: This study investigated the effect of olprinone on ischemia-reperfusion (I/R) induced cardiac injury, and the underlying mechanism. Main methods: Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by 24 h reperfusion. After the start of reperfusion, rats were respectively treated with olprinone in three different dosages (0.2, 0.6, 2 mg/kg, intraperitoneal injection, i.p./12 h). Twenty-four hours later, a mean arterial pressure (MAP) heart function analysis system was used to monitor hemodynamic parameters; TTC staining method was used to detect the myocardial infarct size; 24-hour mortality of rats was recorded; western blot was used to detect the protein expressions of Caspase-3, Bax, Bcl-2, Beclin-1 and LC3-II/LC3-I. Results: Cardiac function in I/R group was lower than that in sham group (dp/dt max: 1348.29 ± 266.01 vs. 3333.73 ± 1258.03, -dp/dt max: 1163.23 ± 588.18 vs. 3198.93 ± 1416.00, P

Diabetic nephropathy (DN) is one of the leading causes of death in diabetes mellitus (DM). Early warning and therapy has significant clinical value for DN. This research sought to find biomarkers to predict the occurrence and development of DN and the intervention of Ginkgo biloba leaves extract (GBE) by quantifying fatty acids, amino acids, and nucleosides and nucleobases in rat plasma. Samples were respectively collected at the weekend of 5-10 weeks after diabetic rats induced by streptozotocin were defined. Plasma fasting blood-glucose, kidney index, blood urea nitrogen, creatinine, urine albumin excretion and ultrastructural morphology of kidney were measured or observed. Fatty acids, amino acids and nucleosides and nucleobases in rat plasma were analyzed by gas chromatography or liquid phase chromatography and mass spectrometry, respectively. From the biochemical index and morphological change of kidney, the rats from the 5th to 7th week were in the stage of DM while from the begin of 8th week the rats were suggested in the early stage of DN. The results of quantitative metabolomics showed that 16 differential metabolites were related to the progression of DN, and oleic acid, glutamate and guanosine might be the potential biomarkers of kidney injury. 14 differential metabolites were related to GBE against the progression of DN, while oleic acid and glutamate might be the potential biomarkers of GBE against kidney injury. Those findings potentially promote the understanding of the pathogenic progression of DN and reveal the therapeutic mechanism of GBE against DN.

We conducted a cross-sectional study to investigate the associations between recent home renovation exposure and lung function in children. We randomly recruited 7326 school children residing in 24 districts from seven cities in northeastern China. We collected information about home renovations from parents using a questionnaire and lung function measurements from children using spirometer recordings gathered by trained professionals and expressed as the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), maximal mid-expiratory flow (MMEF), and peak expiratory flow (PEF). We identified higher odds of diminished lung function among these with home renovation in the previous 2 years compared to those without home renovation in the previous 2 years, for FVC (odds ratios [ORs] = 1.84 [95%CI: 1.58, 2.15]; FEV1: ORs = 2.82 [95%CI: 2.36, 3.36]; PEF: ORs = 1.51 [95%CI: 1.24, 1.83]; and MMEF: ORs = 1.90 [95%CI: 1.60, 2.24]). The associations were stronger among children exposed to new polyvinyl chloride (PVC) flooring compared to children exposed to other surface materials. Our results were consistent throughout the analysis of each type of renovation materials. In conclusion, recent home renovation exposure was associated with poor lung function among children. Strategies to protect home owners and their families from respiratory hazards during and after renovation are required.

Previous investigations on the associations of polyfluoroalkyl substances (PFASs) with overweight/obesity are mixed. Moreover, little information has been reported about the association between isomers of PFASs with body mass index (BMI), waist circumference (WC) or overweight. To address this shortcoming in the literature, we conducted a study involving 1612 Chinese adults (1204 men and 408 women), ages 22–96 years old, from Shenyang, China, to analyze serum isomers of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other PFASs. Height, weight and WC were measured by a standardized protocol of WHO. Results indicated that increased serum concentrations of all (both branched and linear) isomers of PFASs were associated with a higher prevalence of overweight, and these associations were more pronounced in women. The adjusted odds ratios (ORs) from logistic regression analyses among women were 1.45 (95% confidence interval [CI]: 1.06, 1.99) for linear PFOS isomers, 1.33 (95% CI: 1.00, 1.77) for branched PFOS isomers, 1.39 (95% CI: 1.06, 1.81) for 3 + 4 + 5m PFOS, 1.54 (95% CI: 1.08, 2.21) for linear PFOA isomers, and 1.62 (95% CI: 1.05, 2.51) for branched PFOA isomers, respectively. Associations with increased WC were yielded a similar pattern. Linear regression models also showed positive associations between PFASs and BMI or WC. In conclusion, this study suggests that PFASs and their isomers are positively associated with overweight or increased WC, and the associations are stronger in women. Furthermore, PFOA and its isomers displayed the most robust obesogenic associations. Keywords: Perfluoroalkyl substances (PFASs), PFASs isomers, Overweight, Anthropometry, Obesity, Isomers of C8 Health Project

This study aims to evaluate the early predictive value for postoperative sepsis and 30-day mortality in liver transplant patients using sequential organ failure assessment (SOFA). A total of 96 liver transplant patients were enrolled into this study from February 2015 to June 2018. The general information, biochemical findings, and postoperative 30-day mortality of these patients were statistically analyzed. The SOFA scores, C-reactive protein (CRP), and procalcitonin (PCT) at postoperative day (POD) 3, 5, and 7 were significantly higher in the sepsis group than in the non-sepsis group, and the differences were statistically significant. Receiver operating characteristic (ROC) curve showed that SOFA scores at POD 1, 3, 5, and 7 had higher sensitivity and specificity in predicting the incidence of sepsis within 30 days. The difference in 30-day survival rate between patients with SOFA scores of > 5 and patients with SOFA scores of ≤ 5 at POD 1–7 was statistically significant (P

Background Aberrant expression of B7 homologue 3 (B7 H3) has been observed in various malignancies. Our previous study demonstrated that knocking down of B7 H3 inhibited cell proliferation, invasion and enhanced the therapeutic efficacy of chemotherapy in mantle cell lymphoma (MCL). However, the mechanism regulating of B7 H3 expression remains unknown. Here, we present a new regulatory microRNA of B7 H3, miR-506, that directly targets B7 H3 and may play an inhibitory role in MCL progression. Methods The expression of miR-506 and B7 H3 was investigated by real-time quantitative PCR (RT-qPCR). B7 H3 was confirmed to be a novel direct target gene of miR-506 by a dual-luciferase assay and western blot analysis. MiR-506 overexpression in the Maver and Z138 MCL cell lines was established using lentiviral transduction. Cell counting kit-8, flow cytometry and Transwell assays were used to detect changes in cell proliferation, cycle distribution, migration and invasion, respectively. Results The RT-qPCR results showed that miR-506 was expressed at a low level, while B7 H3 was overexpressed in MCL patients and cell lines. By using a bioinformatics analysis combined with a dual-luciferase assay, we determined that miR-506 could target the 3‘-untranslated region (3′-UTR) of B7 H3 mRNA. Moreover, miR-506 had a negative regulatory effect on B7 H3 expression according to the western blotting and RT-qPCR results. In terms of function, increased expression of miR-506 led to reduced MCL cell proliferation, invasion and migration, caused cell cycle arrested at G0/G1 phase, similar to the effects of B7 H3 knockdown. Furthermore, we measured the expression of invasion-related proteins by western blotting and found that miR-506 could reduce MMP-2 and MMP-9 expression in MCL cells. Rescue experiments suggested that the restoration of B7 H3 expression in MCL cells reversed the inhibition of proliferation and invasion induced by miRNA-506 overexpression. Conclusions Our findings suggest that miR-506 functions as a tumor suppressor miRNA and plays a significant role in inhibiting human MCL cell proliferation and metastasis by suppressing B7 H3 expression.

Previous studies have indicated that outdoor light at night (LAN) is associated with a higher prevalence of overweight or obesity in adults. However, the association of LAN levels with overweight or obesity in children is still unknown. This study utilized data from the Seven Northeastern Cities study, which included 47,990 school-aged children and adolescents (ages 6-18 years). Outdoor LAN levels were measured using satellite imaging data. Weight and height were used to calculate age-sex-specific body mass index (BMI) Z-scores based on the World Health Organization (WHO) growth standards. Overweight status and obesity were defined using the Chinese standard. Information regarding socioeconomic status, sleep-related characteristics, and obesogenic factors were obtained using a questionnaire. A generalized linear mixed model examined the associations of outdoor LAN levels (in quartiles) with the outcomes of interest. Compared to children in the lowest quartile of outdoor LAN levels, children exposed to higher outdoor LAN levels had larger BMI Z-scores and higher odds of being overweight (including obesity) or obese, with the largest estimates in the third quartile [BMI Z-score: β = 0.26, 95% CI: 0.18-0.33; overweight (including obesity): OR = 1.40, 95% CI: 1.25-1.56; obesity: OR = 1.46, 95% CI: 1.29-1.65]. There was a significant sex difference (P

ImportanceDelayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown.ObjectiveTo investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant.Design, setting, and participantsThis single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population.InterventionsPatients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine.Main outcomes and measuresThe primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30.ResultsOf the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit.Conclusions and relevanceThis randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants.Trial registrationChinese Clinical Trial Registry Identifier: ChiCTR1900025493.

The Medial Habenular (MHb) and the Lateral Habenular nuclei are 2 main parts of the habenular complex (Hb). Recent studies showed that MHb plays an important role in memory, and in the expression of ErbB4. However, the expression of MHb ErbB4 receptor and its role in fear memory is not well understood. In this study, western blotting and quantitative real-time polymerase chain reaction were used to assess the protein and mRNA levels of ErbB4 in the process of contextual fear conditioning. A pharmacological approach was used to block and stimulate the ErbB4 receptor. Contextual fear conditioning tests induced a significant increase on the expression of ErbB4 at various times in the Hb and the MHb. Moreover, the blockade and stimulation of MHb ErbB4 receptors did not affect the fear formation but impaired and improved the contextual-dependent fear expression. Furthermore, in vitro electrophysiological recordings showed that the blockade of the MHb ErbB4 receptor reduced the presynaptic gamma-amino butyric acid release. ErbB4 is a susceptible gene for schizophrenia and the above findings may provide new insights into the mechanisms of fear-related responses.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular Ca2+ stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD., Astrocytes contribute to autism spectrum disorder (ASD) pathophysiology. Here, the authors show that IP3R2 conditional KO mice show ASD-like behaviours and identify astrocyte-derived ATP as a modulator of these behaviours in mice.

Background Although several studies have focused on the associations between particle size and constituents and blood pressure, results have been inconsistent. Methods and Results We conducted a panel study, between December 2017 and January 2018, in 88 healthy university students in Guangzhou, China. Weekly systolic blood pressure and diastolic blood pressure were measured for each participant for 5 consecutive weeks, resulting in a total of 440 visits. Mass concentrations of particles with an aerodynamic diameter of ≤2.5 µm (PM 2.5 ), ≤1.0 µm (PM 1.0 ), ≤0.5 µm (PM 0.5 ), ≤0.2 µm (PM 0.2 ), and number concentrations of airborne particulates of diameter ≤0.1 μm were measured. Linear mixed‐effect models were used to estimate the associations between blood pressure and particles and PM 2.5 constituents 0 to 48 hours before blood pressure measurement. PM of all the fractions in the 0.2‐ to 2.5‐μm range were positively associated with systolic blood pressure in the first 24 hours, with the percent changes of effect estimates ranging from 3.5% to 8.8% for an interquartile range increment of PM. PM 0.2 was also positively associated with diastolic blood pressure, with an increase of 5.9% (95% CI, 1.0%–11.0%) for an interquartile range increment (5.8 μg/m 3 ) at lag 0 to 24 hours. For PM 2.5 constituents, we found positive associations between chloride and diastolic blood pressure (1.7% [95% CI, 0.1%–3.3%]), and negative associations between vanadium and diastolic blood pressure (−1.6% [95% CI, −3.0% to −0.1%]). Conclusions Both particle size and constituent exposure are significantly associated with blood pressure in the first 24 hours following exposure in healthy Chinese adults.

Reduced knee weight-bearing from prescription or sedentary lifestyles are associated with cartilage degradation; effects on the meniscus are unclear. Rodents exposed to spaceflight or hind limb unloading (HLU) represent unique opportunities to evaluate this question. This study evaluated arthritic changes in the medial knee compartment that bears the highest loads across the knee after actual and simulated spaceflight, and recovery with subsequent full weight-bearing. Cartilage and meniscal degradation in mice were measured via microCT, histology, and proteomics and/or biochemically after: (1) ~ 35 days on the International Space Station (ISS); (2) 13-days aboard the Space Shuttle Atlantis; or (3) 30 days of HLU, followed by a 49-day weight-bearing readaptation with/without exercise. Cartilage degradation post-ISS and HLU occurred at similar spatial locations, the tibial-femoral cartilage-cartilage contact point, with meniscal volume decline. Cartilage and meniscal glycosaminoglycan content were decreased in unloaded mice, with elevated catabolic enzymes (e.g., matrix metalloproteinases), and elevated oxidative stress and catabolic molecular pathway responses in menisci. After the 13-day Shuttle flight, meniscal degradation was observed. During readaptation, recovery of cartilage volume and thickness occurred with exercise. Reduced weight-bearing from either spaceflight or HLU induced an arthritic phenotype in cartilage and menisci, and exercise promoted recovery.

Neuroplasticity in the medial prefrontal cortex (mPFC) is essential for fear extinction, the process of which forms the basis of the general therapeutic process used to treat human fear disorders. However, the underlying molecules and local circuit elements controlling neuronal activity and concomitant induction of plasticity remain unclear. Here we show that sustained plasticity of the parvalbumin (PV) neuronal network in the infralimbic (IL) mPFC is required for fear extinction in adult male mice and identify the involvement of neuregulin 1-ErbB4 signalling in PV network plasticity-mediated fear extinction. Moreover, regulation of fear extinction by basal medial amygdala (BMA)-projecting IL neurons is dependent on PV network configuration. Together, these results uncover the local molecular circuit mechanisms underlying mPFC-mediated top-down control of fear extinction, suggesting alterative therapeutic approaches to treat fear disorders.

OBJECTIVE: To study the clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). METHODS: A retrospective analysis was performed on the medical data of 14 children who were diagnosed with AML-MRC from June 2014 to March 2020, including clinical features, laboratory examination results, and prognosis. RESULTS: Among the 14 children with AML-MRC, there were 9 boys and 5 girls, with a median age of 11 years (range: 1-17 years), a median leukocyte count of 8.3×10(9)/L [range: (2.0-191.0)×10(9)/L], a median hemoglobin level of 73 g/L (range: 44-86 g/L), and a median platelet count of 75×10(9)/L [range: (4-213)×10(9)/L] at diagnosis. According to the FAB classification, the children with AML-M5 accounted for 71% (10/14). Among the 14 children, 4 had multi-lineage dysplasia (MLD), 2 had a history of myelodysplastic syndrome (MDS), 5 had MDS-related cytogenetic changes, 2 had MLD with MDS-related cytogenetic changes, and 1 had a history of MDS with MLD. The median follow-up time was 10.6 months (range: 0.4-54.4 months) for 14 children, among whom 2 gave up treatment immediately after diagnosis and 12 had an evaluable treatment outcome. The 2-year overall survival (OS) rate was 50%±15%, and the 2-year disease-free survival (DFS) rate was 33%±13%. Of the 12 children, 7 underwent haploidentical hematopoietic stem cell transplantation (HSCT), among whom 5 achieved DFS and 2 died, with a 2-year OS rate of 71%±17% and a 2-year DFS rate of 43%±19%; 5 children underwent chemotherapy alone, among whom 1 achieved DFS, 3 died, and 1 was lost to follow-up, with a 2-year OS rate of 40%±30% and a 2-year DFS rate of 30%±24%. There was no significant difference in the survival condition between the transplantation and chemotherapy groups (P > 0.05). CONCLUSIONS: Childhood AML-MRC is often observed in boys, and AML-M5 is the most common type based on FAB classification. Such children tend to have a poor prognosis. HSCT is expected to improve the poor prognosis of children with AML-MRC. However due to the small number of cases, it is necessary to increase the number of cases for further observation.

Background Urban greenness may protect against obesity, but very few studies have assessed ‘street view’ (SV) greenness metrics, which may better capture people's actual exposure to greenness compared to commonly-used satellite-derived metrics. We aimed to investigate these associations further in a Chinese adult study. Methods Our analysis included 24,845 adults in the 33 Chinese Community Health Study in 2009. SV images from Tencent Map, segmented by machine learning algorithms, were used to determine the average proportion of green vegetation in SV images at community level in 800m road network buffer. Sensitivity analyses were performed with an alternative buffer size. Overall greenness was assessed as normalized difference vegetation index (NDVI) in 800 m buffer. We used predicted PM2.5 and monitored NO2 as proxies of air pollution. Body mass index (BMI), waist circumference (WC) and hip circumference (HC) were regressed on SV greenness by generalized linear mixed models, with adjustment for covariates. Mediation analyses were performed to assess the mediation effects of air pollution. Results Each interquartile range (IQR = 3.6%) increase in street view greenness was associated with a 0.15 kg/m2 (95% CI: −0.22, −0.09) decrease in BMI and 0.23 cm (95% CI: −0.35, −0.11) reduction in HC, and was associated with 7% lower odds of overweight (OR = 0.93, 95% CI:0.90, 0.96) and 18% lower odds of obesity (OR = 0.82, 95% CI:0.76, 0.89). Similar effect estimation was observed compared with commonly-used NDVI measures. PM2.5 and NO2 mediated 15.5% and 6.1% of the effects of SV greenness with BMI, respectively. Conclusions Our findings suggest beneficial associations between community-level SV greenness and lower body weight in Chinese adults. The effects were observed in women but not in men. Air pollution may partially mediate the association. These findings may have implications to support efforts to promote greening in urban areas.

Zinc finger E-box-binding homeobox 1 (ZEB1), a functional protein of zinc finger family, was aberrant expressed in many kinds of liver disease including hepatic fibrosis and Hepatitis C virus. Bioinformatics results showed that ZEB1 was abnormally expressed in HCC tissues. However, to date, the potential regulatory role and molecular mechanisms of ZEB1 are still unclear in the occurrence and development of HCC. This study demonstrated that the expression level of ZEB1 was significantly elevated both in liver tissues of HCC patients and cell lines (HepG2 and SMMC-7721 cells). Moreover, ZEB1 could promote the proliferation, migration, and invasion of HCC cells. On the downstream regulation mechanism, ZEB1 could activate the Wnt/β-catenin signaling pathway by upregulating the protein expression levels of β-catenin, c-Myc, and cyclin D1. Novel studies showed that miR-708 particularly targeted ZEB1 3′-UTR regions and inhibited the HCC cell proliferation, migration, and invasion. Furthermore, results of nude mice experiments of HCC model indicated that miR-708 could inhibit tumor growth and xenograft metastasis model was established to validate that miR-708 could inhibit HCC cell metastasis through tail-vein injection in vivo. Together, the study suggested that ZEB1 modulated by miR-708 might be a potential therapeutic target for HCC therapy. [Image: see text]