Regulatory T cells protect against diabetic cardiomyopathy in db/db mice.

AIMS/INTRODUCTION: Regulatory T cells (Tregs) have protected against many cardiovascular diseases. This study was intended to explore the effect of Tregs on diabetic cardiomyopathy (DCM) using a db/db mouse model. MATERIALS AND METHODS: Eight-week-old male db/db mice were randomly divided into four groups: the control group, administered 200 µL phosphate-buffered saline; the small-dose Treg group, administered 105 Tregs; the large-dose Treg group, administered 106 Tregs; and the PC group, administered 100 µg anti-CD25 specific antibody (PC61) and 106 Tregs. After 12 weeks, mice were euthanized. Transthoracic echocardiography was carried out at the beginning and end of the experiment. Relevant basic experiments to evaluate the effects of Tregs on DCM were carried out. RESULTS: Echocardiography showed that the impaired diastolic and systolic functions were significantly improved in mice administered large-dose Tregs. Large-dose Tregs significantly ameliorated myocardial hypertrophy and fibrosis, and decreased hypertrophic gene expression and collagen deposition. The protective effects of Tregs on diabetic hearts were associated with decreased oxidative stress, inflammatory response and apoptosis. In addition, Tregs promoted the activation of the phosphatidylinositol 3-kinase-protein kinase B signaling pathway, whereas they inhibited extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase phosphorylation, which might be responsible for the cardioprotective role of Tregs against DCM. CONCLUSIONS: Tregs ameliorated myocardial hypertrophy and fibrosis, improved cardiac dysfunction, and protected against DCM progression in db/db mice. The mechanisms involved a decrease of inflammatory response, oxidative stress and apoptosis, which might be mediated by phosphatidylinositol 3-kinase-protein kinase B and mitogen-activated protein kinase pathways. Hence, Tregs might serve as a promising therapeutic approach for DCM treatment.

Paraspeckle protein NONO attenuates vascular calcification by inhibiting bone morphogenetic protein 2 transcription.

Vascular calcification is a pathological process commonly associated with atherosclerosis, chronic kidney disease, and diabetes. Paraspeckle protein NONO is a multifunctional RNA/DNA binding protein involved in many nuclear biological processes but its role in vascular calcification remains unclear. Here, we observed that NONO expression was decreased in calcified arteries of mice and patients with CKD. We generated smooth muscle-specific NONO-knockout mice and established three different mouse models of vascular calcification by means of 5/6 nephrectomy, adenine diet to induce chronic kidney failure, or vitamin D injection. The knockout mice were more susceptible to the development of vascular calcification relative to control mice, as verified by an increased calcification severity and calcium deposition. Likewise, aortic rings from knockout mice showed more significant vascular calcification than those from control mice ex vivo. In vitro, NONO deficiency aggravated high phosphate-induced vascular smooth muscle cell osteogenic differentiation and apoptosis, whereas NONO overexpression had a protective effect. Mechanistically, we demonstrated that the regulation of vascular calcification by NONO was mediated by bone morphogenetic protein 2 (BMP2). NONO directly bound to the BMP2 promoter using its C-terminal region, exerting an inhibitory effect on the transcription of BMP2. Thus, our study reveals that NONO is a novel negative regulator of vascular calcification, which inhibits osteogenic differentiation of vascular smooth muscle cell and vascular calcification via negatively regulating BMP2 transcription. Hence, NONO may provide a promising target for the prevention and treatment of vascular calcification.

Angiotensin II type 2 receptor agonist attenuates LPS-induced acute lung injury through modulating THP-1-derived macrophage reprogramming.

Acute respiratory distress syndrome (ARDS) is a devastating respiratory disorder, characterized by overwhelming inflammation in the alveoli without effective pharmacological treatment. We aimed to investigate the effect and mechanism of angiotensin II type 2 receptor (AT2R) agonist, Compound 21 (C21), on the lipopolysaccharide (LPS)-induced acute lung injury (ALI) model. The protective effect of C21 was evaluated via enzyme-linked immunosorbent assay (ELISA), Western blot (WB), real-time PCR, and fluorescence microscopy in LPS-challenged THP1-derived macrophages. Besides, the in vivo efficacy of C21 was assessed using cell counting, ELISA, protein quantification, hematoxylin-eosin (H&E) staining, and WB in an LPS-induced ALI mouse model. The results showed that C21 significantly inhibited the secretion of pro-inflammatory cytokines (CCL-2, IL-6), overproduction of intracellular ROS, and activation of inflammatory pathways (NF-κB/NLRP3, p38/MAPK) in THP-1 cell-derived macrophages stimulated by LPS. In in vivo study, intraperitoneal injection of C21 could reduce airway leukocytes accumulation and chemokine/cytokine (keratinocyte chemoattractant (KC), IL-6) generation, as well as alleviate diffuse alveolar damage induced by LPS. Conclusively, the AT2R agonist C21 significantly inhibited LPS-stimulated excess inflammatory responses and oxidative stress in macrophages. Meanwhile, C21 could effectively alleviate acute inflammation and tissue damage in the lungs of ALI mice challenged by LPS. The results of this study bring new hope for the early treatment of ALI/ARDS.

L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome.

NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-ß1/Smad pathways.

Cardiac fibrosis plays a key role in the progression of diabetic cardiomyopathy (DCM). Previous studies demonstrated the cardioprotective effects of natriuretic peptides. However, the effects of natriuretic peptide receptor C (NPRC) on cardiac fibrosis in DCM remains unknown. Here, we observed that myocardial NPRC expression was increased in mice and patients with DCM. NPRC-/- diabetic mice showed alleviated cardiac fibrosis, as well as improved cardiac function and remodeling. NPRC knockdown in both cardiac fibroblasts and cardiomyocytes decreased collagen synthesis and proliferation of cardiac fibroblasts. RNA sequencing identified that NPRC deletion up-regulated the expression of TGF-ß-induced factor homeobox 1 (TGIF1), which inhibited the phosphorylation of Smad2/3. Furthermore, TGIF1 up-regulation was mediated by the activation of cAMP/PKA and cGMP/PKG signaling induced by NPRC deletion. These findings suggest that NPRC deletion attenuated cardiac fibrosis and improved cardiac remodeling and function in diabetic mice, providing a promising approach to the treatment of diabetic cardiac fibrosis.

NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis in ApoE knockout mice.

Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease, but the role of natriuretic peptide receptor C (NPRC) in the pathogenesis of atherosclerosis (AS) remains unknown. This study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress, inflammation, and apoptosis via protein kinase A (PKA) signaling. ApoE-/- mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice. Systemic NPRC knockout mice were crossed with ApoE-/- mice to generate ApoE-/-NPRC-/- mice, and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE-/-NPRC-/- versus ApoE-/- mice. In addition, endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in mice. In contrast, endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in mice. Experiments in vitro showed that NPRC knockdown in human aortic endothelial cells (HAECs) inhibited ROS production, pro-inflammatory cytokine expression and endothelial cell apoptosis, and increased eNOS expression. Furthermore, NPRC knockdown in HAECs suppressed macrophage migration, cytokine expression, and phagocytosis via its effects on endothelial cells. On the contrary, NPRC overexpression in endothelial cells resulted in opposite effects. Mechanistically, the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway, leading to downstream upregulated AKT1 pathway and downregulated NF-κB pathway. In conclusion, NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE-/- mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB pathways. Thus, targeting NPRC may provide a promising approach to the prevention and treatment of atherosclerosis.

PTPN2 targets TAK1 for dephosphorylation to improve cellular senescence and promote adipose tissue browning in T2DM.

Introduction: The energy imbalance when energy intake exceeds expenditure acts as an essential factor in the development of insulin resistance (IR). The activity of brown adipose tissue, which is involved in the dissipation of energy via heat expenditure decreases under type 2 diabetic mellitus (T2DM) state when the number of pathological aging adipocytes increases. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates several biological processes by dephosphorylating several cellular substrates; however, whether PTPN2 regulates cellular senescence in adipocytes and the underlying mechanism has not been reported. Methods: We constructed a model of type 2 diabetic mice with PTPN2 overexpression to explore the role of PTPN2 in T2DM. Results: We revealed that PTPN2 facilitated adipose tissue browning by alleviating pathological senescence, thus improving glucose tolerance and IR in T2DM. Mechanistically, we are the first to report that PTPN2 could bind with transforming growth factor-activated kinase 1 (TAK1) directly for dephosphorylation to inhibit the downstream MAPK/NF-κB pathway in adipocytes and regulate cellular senescence and the browning process subsequently. Discussion: Our study revealed a critical mechanism of adipocytes browning progression and provided a potential target for the treatment of related diseases.

Dopamine D1 receptor agonist alleviates acute lung injury via modulating inflammatory responses in macrophages and barrier function in airway epithelial cells.

Acute lung injury (ALI) or its severe form, acute respiratory distress syndrome (ARDS) is a life-threatening illness without effective therapeutic interventions currently. Multiple lines of evidence indicated that overwhelming inflammatory responses and impaired epithelial barrier contributed to the pathogenesis of ALI/ARDS. Recently, dopamine (DA) system was identified to participate in various pulmonary diseases. Here, we discovered that dopamine D1-like receptors mainly expressed in macrophages and airway epithelial cells (AECs), which were downregulated by lipopolysaccharide (LPS) challenge in ALI mouse lung. SKF38393 (SKF) is a selective agonist for D1-like receptors and was demonstrated to inhibit excessive inflammatory responses and oxidative stress in THP-1 cell-derived macrophages and Beas-2B cells, as well as improve airway epithelial barrier dysfunction induced by LPS stimulation. Moreover, SKF administration could effectively decrease pulmonary inflammation, ameliorate tissue damage in the LPS-triggered ALI mice. The broad protective actions of SKF might be attributed to the activation of Nrf2 antioxidative system by use of the specific inhibitor, ML385. This study offers evidence of potent immunoregulatory activity of SKF in macrophages, AECs as well as ALI mouse model, which opens novel therapeutic avenues for the intervention of ALI/ARDS.

Circulating miR-143 and miR-145 as promising biomarkers for evaluating severity of coronary artery stenosis in patients with acute coronary syndrome.

BACKGROUND: Multiple studies have provided evidence that miR-143 and miR-145 play a crucial role in the pathogenesis and progression of atherosclerosis. In the present study, we aim to investigate the expression of plasma miR-143 and miR-145 in patients with acute coronary syndrome (ACS) and their association with the severity of coronary artery stenosis. METHODS: The study enrolled 279 patients with ACS, including 201 patients with unstable angina (UA) and 78 patients with acute myocardial infarction (AMI), and 65 matched subjects as the control group. The plasma levels of miR-143 and miR-145 were detected by quantitative real-time PCR (qRT-PCR). Gensini score was applied to evaluate the severity of coronary artery stenosis. RESULTS: Plasma levels of miR-143 and miR-145 in patients with ACS were both decreased compared with the control group (p < 0.001). Plasma levels of miR-143 and miR-145 were negatively correlated with Gensini score (miR-143: r = -0.246, p < 0.001; miR-145: r = -0.222, p < 0.001). Logistic regression analysis showed that miR-143 and miR-145 were protective factors for the onset of ACS, UA, or AMI separately. MiR-143 (AUC: 0.786, p < 0.001) and miR-145 (AUC: 0.793, p < 0.001) were able to predict the degree of coronary artery stenosis greater than 50 %. CONCLUSION: The plasma levels of miR-143 and miR-145 were significantly decreased in ACS patients and were negatively correlated with coronary stenosis. In conclusion, plasma miR-143 and miR-145 levels can be used as noninvasive biomarkers for evaluating coronary artery stenosis.

L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome.

Pharmacologic therapies of ARDS: From natural herb to nanomedicine.

Acute respiratory distress syndrome (ARDS) is a common critical illness in respiratory care units with a huge public health burden. Despite tremendous advances in the prevention and treatment of ARDS, it remains the main cause of intensive care unit (ICU) management, and the mortality rate of ARDS remains unacceptably high. The poor performance of ARDS is closely related to its heterogeneous clinical syndrome caused by complicated pathophysiology. Based on the different pathophysiology phases, drugs, protective mechanical ventilation, conservative fluid therapy, and other treatment have been developed to serve as the ARDS therapeutic methods. In recent years, there has been a rapid development in nanomedicine, in which nanoparticles as drug delivery vehicles have been extensively studied in the treatment of ARDS. This study provides an overview of pharmacologic therapies for ARDS, including conventional drugs, natural medicine therapy, and nanomedicine. Particularly, we discuss the unique mechanism and strength of nanomedicine which may provide great promises in treating ARDS in the future.

ATRX status in patients with gliomas: Radiomics analysis.

MATERIAL AND METHODS: A cohort of 123 patients diagnosed with gliomas (World Health Organization grades II-IV) who underwent surgery and was treated at our center between January 2016 and July 2020, was enrolled in this retrospective study. Radiomics features were extracted from MR T1WI, T2WI, T2FLAIR, CE-T1WI, and ADC images. Patients were randomly split into training and validation sets at a ratio of 4:1. A radiomics signature was constructed using the least absolute shrinkage and selection operator (LASSO) to train the SVM model using the training set. The prediction accuracy and area under curve and other evaluation indexes were used to explore the performance of the model established in this study for predicting the ATRX mutation state. RESULTS: Fifteen radiomic features were selected to generate an ATRX-associated radiomic signature using the LASSO logistic regression model. The area under curve for ATRX mutation (ATRX(-)) on training set was 0.93 (95% confidence interval [CI]: 0.87-1.0), with the sensitivity, specificity and accuracy being 0.91, 0.82 and 0.88, while on the validation set were 0.84 (95% CI: 0.63-0.91), with the sensitivity, specificity and accuracy of 0.73, 0.86, and 0.79, respectively. CONCLUSIONS: These results indicate that radiomic features derived from preoperative MRI facilitat efficient prediction of ATRX status in gliomas, thus providing a novel evaluation method for noninvasive imaging biomarkers.

Statin therapy protects against abdominal aortic aneurysms by inducing the accumulation of regulatory T cells in ApoE-/- mice.

CD4+CD25+ regulatory T cells (Tregs) have been shown to protect against abdominal aortic aneurysm (AAA) progression. Statins have immunomodulatory properties, and their effect on AAA partly depends on immune-related mechanisms. In this study, we aimed to explore whether there is an association between statins and Tregs in AAA progression. Sixty ApoE-/- mice were randomly divided into four groups (n = 15 per group): A, saline group; B, control group; C, simvastatin group (intragastric administration of simvastatin); and D, PC61 group (simvastatin combined with an intraperitoneal injection of 100 µg CD25-depleting antibody PC61). After 2 weeks of simvastatin treatment, the mice received a continuous subcutaneous infusion of angiotensin II (Ang II; B, C, and D groups) or saline (A group) for 28 days. Simvastatin therapy for 6 weeks significantly decreased the incidence and severity of AAA and inhibited the apoptosis of smooth muscle cells and generation of reactive oxygen species, which was partly abolished after the injection of PC61 antibody. Importantly, simvastatin increased the number of Tregs and the levels of Treg-associated cytokines (TGF-ß and IL-10) and decreased the level of IL-17 both in aortic tissues and serum. Interestingly, simvastatin attenuated Ang II-induced gut microbial dysbiosis, which might be associated with the accumulation of Tregs. In conclusion, simvastatin therapy prevented the development of AAA induced by Ang II in ApoE-/- mice, which might be partly due to the induction of Treg accumulation. In addition, simvastatin regulated gut microbial dysbiosis, which might also be associated with Treg generation.

The Acute Toxicities and Efficacy of Concurrent Chemotherapy With Docetaxel Plus Cisplatin, or Docetaxel, or Cisplatin and Helical Tomotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Single-Center Phase II Trial.

Objective: The objective of this trial is to evaluate and compare the acute toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with docetaxel plus cisplatin, or docetaxel, or cisplatin concurrently with helical tomotherapy during concurrent chemoradiotherapy (CCRT). Methods: In a prospective, single-center, open-label, randomized phase II study, after 2 cycles of induction chemotherapy with docetaxel plus cisplatin regimen, 125 patients with LA-NPC (stage III and IVA, UICC eighth) diagnosed pathologically from June 2017 to November 2019 were randomized into CCRT with docetaxel plus cisplatin group (25 patients), CCRT with docetaxel group (50 patients), and CCRT with cisplatin group (50 patients). The incidence of grade 3 or 4 acute toxicities and clinical efficacy were analyzed among the 3 groups. Results: Safety evaluation was completed in all the 125 patients, during the CCRT period, 66.4% of patients completed 3 cycles of chemotherapy, 24.0% completed 2 cycles of chemotherapy, and 9.6% completed 1 cycle of chemotherapy according to the research plan. The incidence of grade 3 or 4 acute toxicity in CCRT with docetaxel plus cisplatin (DP), docetaxel (D), and cisplatin (P) groups was 88.0%, 72.0%, and 56.0%, respectively. The incidence of grade 3 or 4 acute toxicities in the DP group was significantly higher than that in the D and P groups (P = .015), no significant difference was detected between the D and P groups (P = .096). The most common toxicities were mucositis (40.0%), leukopenia (29.6%), neutropenia (26.4%), and pharyngo-esophagitis (12.0%); compared to D and P groups, DP group did not significantly improved the 3-year overall survival (96.0% vs 87.0% and 87.6%), progression-free survival (92.0% vs 79.7% and,76.9%), locoregional failure-free survival (96.0% vs 91.8% and 92.7%), and distant failure-free survival (100% vs 90.0% and 89.0%), there were no significant difference in survival data among the 3 groups (all P > .05). Conclusions: Higher survival benefits did not achieve from intensified CCRT with DP, CCRT with P or D obtained similar short-term survival outcomes with similar acceptable toxicities in LA-NPC patients.

The Psychosocial Correlates of Non-suicidal Self-Injury Within a Sample of Adolescents With Mood Disorder.

Background: According to the integrated theoretical model, adolescents' behaviors were the outcome of the complex interplay between multiple levels. Non-suicidal self-injury (NSSI) is a serious and high prevalent problem among adolescents with mood disorders. However, a systematic perspective on psychosocial correlates among Chinese clinical adolescents is still rare. Method: The impact of several factors at the individual (i.e., sex, age, self-esteem, and psychological distress), family (i.e., family structure, family income, and family support), and social level (i.e., living environment, peer support, and teacher support) on the frequency of NSSI behaviors were investigated in the current study. This research included 621 Chinese adolescents with mood disorders from 20 hospitals. Results: Three-steps hierarchical regression analyses indicated that lower levels of psychological distress and higher levels of self-esteem were most associated with less frequency of NSSI behaviors. In addition, family support was negatively associated with the frequency of NSSI behaviors. After controlling the factors at individual and family levels, no significant association was found between the factors at the social level and the frequency of NSSI behaviors. Conclusion: These findings provide preliminary support for the notion that adolescent self-esteem and family support may effectively shield them from problematic behavior; nevertheless, adolescents suffering from more emotional pain can be even riskier. Thus, further intervention strategies should consider the non-independence of individual capacities, co-combinatory effects of mood disorder, and family environment in treating those vulnerable Chinese adolescents.

The psychological characteristics and risk factors of suicidal attempt among mood disorders adolescents accompany with non-suicidal self-injury: A multi-center study.

BACKGROUND: Identifying the risk factors of suicide attempts(SA) in adolescents with mood disorders(MD) who engage in non-suicidal self-injury(NSSI) is of great significance for suicide prevention. The aim of the present study was to explore the psychological characteristics and risk factors of SA among MD adolescents engaged in NSSI. METHODS: We recruited MD outpatients accompany with NSSI aged 12-18 years. SA, NSSI methods and function, suicidal ideation(SI), psychological distress(PD), self-esteem, stress mindset and perceived social support were assessed by valid scales. Classification and regression tree analysis (CART) was employed to explore the characteristics and risk factors of SA among MD adolescent with NSSI. RESULTS: We included 658 participants in this study. Of 58.1% participants reported SA during the past 12 months. Compared with the adolescents without SA, the attempters used more different NSSI methods and reported more frequent NSSI. SA, SI, PD, self-esteem and amount of thinking time before engaging in self-injury were risk factors of SA among MD adolescents. Interactions between the four risk factors resulted in varying degrees of risk of SA. Compared to adolescents with the characteristics of low level of SI - little consideration before self-injury, adolescents who having multiple characteristics of the high level of SI -high level of PD - low self-esteem were associated with a 15.1-fold increased risk of SA(P < 0.001), and those with the characteristics of high SI - deliberated before engaging in self-injury were associated with a 28.1-fold increased risk of attempted suicide(P < 0.001). CONCLUSIONS: Our findings identify multiple correlates for SA in MD adolescents accompany with NSSI, including SI, PD, self-esteem and deliberate time they thought before self-injury, which may contribute to the development of suicidal behaviors in an interactive manner.

Relapsing cerebral atypical teratoid/rhabdoid tumor after trimodality therapy: A case report.

INTRODUCTION: Atypical teratoid rhabdoid tumor (AT/RT) is a high-grade embryonal malignant neoplasm of the central nervous system. It is rare and most often diagnosed in children <4 years of age. The biological manifestations of AT/RTs are highly malignant and have a very poor prognosis. Here, we present the case of a 16-year-old boy with AT/RT in the right parietal lobe and with a dismal outcome. PATIENT CONCERNS: A 16-year-old male boy presented with a headache after waking up for 1 year without obvious cause. The pain was persistent and dull, mainly in the right orbital, and was slightly relieved after pressing the orbital. Occasionally, nausea and vomiting occurred, and the vomiting was gastric contents. Examination and head computed tomography performed at a local hospital revealed a space-occupying lesion in the right parietal lobe. The patient was then transferred to our hospital for further diagnosis and treatment. DIAGNOSIS: The patient underwent craniotomy and gross total excision of the tumor. Further histologic examination of the tumor was identified (space-occupying lesion in the right parietal lobe) AT/RT, World Health Organization grade IV. INTERVENTIONS: The patient was transferred to the oncology department for radiotherapy and chemotherapy after surgery recovery. OUTCOMES: The patient did not comply with the advice for adjuvant chemotherapy regularly and the tumor recurred rapidly. Finally, the patient died after 18 months after the definitive surgery. CONCLUSION: In conclusion, in the presence of a tumor with peripheral cystic components or hemorrhage in young children, a diagnosis of AT/RT must always be considered. Patients must follow the doctor's advice for active treatment. All relevant data are within the paper and its Supporting Information files.

Carnitine Palmitoyltransferase System: A New Target for Anti-Inflammatory and Anticancer Therapy?

Lipid metabolism involves multiple biological processes. As one of the most important lipid metabolic pathways, fatty acid oxidation (FAO) and its key rate-limiting enzyme, the carnitine palmitoyltransferase (CPT) system, regulate host immune responses and thus are of great clinical significance. The effect of the CPT system on different tissues or organs is complex: the deficiency or over-activation of CPT disrupts the immune homeostasis by causing energy metabolism disorder and inflammatory oxidative damage and therefore contributes to the development of various acute and chronic inflammatory disorders and cancer. Accordingly, agonists or antagonists targeting the CPT system may become novel approaches for the treatment of diseases. In this review, we first briefly describe the structure, distribution, and physiological action of the CPT system. We then summarize the pathophysiological role of the CPT system in chronic obstructive pulmonary disease, bronchial asthma, acute lung injury, chronic granulomatous disease, nonalcoholic fatty liver disease, hepatic ischemia-reperfusion injury, kidney fibrosis, acute kidney injury, cardiovascular disorders, and cancer. We are also concerned with the current knowledge in either preclinical or clinical studies of various CPT activators/inhibitors for the management of diseases. These compounds range from traditional Chinese medicines to novel nanodevices. Although great efforts have been made in studying the different kinds of CPT agonists/antagonists, only a few pharmaceuticals have been applied for clinical uses. Nevertheless, research on CPT activation or inhibition highlights the pharmacological modulation of CPT-dependent FAO, especially on different CPT isoforms, as a promising anti-inflammatory/antitumor therapeutic strategy for numerous disorders.

Association Between Stent Implantation and Progression of Nontarget Lesions in a Rabbit Model of Atherosclerosis.

BACKGROUND: Progression of nontarget lesions (NTLs) after percutaneous coronary intervention (PCI) has been reported. However, it remains unknown whether progression of NTLs was causally related to stenting. This study was undertaken to test the hypothesis that stent implantation triggers acute phase response and systemic inflammation which may be associated with progression of NTLs. METHODS: Thirty New Zealand rabbits receiving endothelial denudation and atherogenic diet were randomly divided into stenting, sham, and control groups. Angiography and intravascular ultrasonography were performed in the stenting and sham groups, and stent implantation performed only in the stenting group. Histopathologic study was conducted and serum levels of APPs (acute phase proteins) measured in all rabbits. Proteomics analysis was performed to screen the potential proteins related to NTLs progression after stent implantation. The serum levels of APPs and inflammatory cytokines were measured in 147 patients undergoing coronary angiography or PCI. RESULTS: Plaque burden in the NTLs was significantly increased 12 weeks after stent implantation in the stenting group versus sham group. Serum levels of APPs and their protein expression in NTLs were significantly increased and responsible for stenting-triggered inflammation. In patients receiving PCI, serum levels of SAA-1 (serum amyloid A protein 1), CRP (C-reactive protein), TNF (tumor necrosis factor)-α, and IL (interleukin)-6 were substantially elevated up to 1 month post-PCI. CONCLUSIONS: In a rabbit model of atherosclerosis, stent implantation triggered acute phase response and systemic inflammation, which was associated with increased plaque burden and pathological features of unstable plaque in NTLs. The potential mechanism involved vessel injury-triggered acute phase response manifested as increased serum levels of SAA-1, CRP, and LBP (lipopolysaccharide-binding protein) and their protein expression in NTLs. These findings provided a new insight into the relation between stent implantation and progression of NTLs, and further studies are warranted to clarify the detailed mechanism and clinical significance of these preliminary results. Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900026393. Graphic Abstract: A graphic abstract is available for this article.