Artificial intelligence differentiates abdominal Henoch-Schönlein purpura from acute appendicitis in children.

OBJECTIVE: This study aims to construct an artificial intelligence (AI) model capable of effectively discriminating between abdominal Henoch-Schönlein purpura (AHSP) and acute appendicitis (AA) in pediatric patients. METHODS: A total of 6965 participants, comprising 2201 individuals with AHSP and 4764 patients with AA, were enrolled in the study. Additionally, 53 laboratory indicators were taken into consideration. Five distinct artificial intelligence (AI) models were developed employing machine learning algorithms, namely XGBoost, AdaBoost, Gaussian Naïve Bayes (GNB), MLPClassifier (MLP), and support vector machine (SVM). The performance of these prediction models was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve assessment, and decision curve analysis (DCA). RESULTS: We identified 32 discriminative indicators (p < .05) between AHSP and AA. Five indicators, namely the lymphocyte ratio (LYMPH ratio), eosinophil ratio (EO ratio), eosinophil count (EO count), neutrophil ratio (NEUT ratio), and C-reactive protein (CRP), exhibited strong performance in distinguishing AHSP from AA (AUC ≥ 0.80). Among the various prediction models, the XGBoost model displayed superior performance evidenced by the highest AUC (XGBoost = 0.895, other models < 0.89), accuracy (XGBoost = 0.824, other models < 0.81), and Kappa value (XGBoost = 0.621, other models < 0.60) in the validation set. After optimization, the XGBoost model demonstrated remarkable diagnostic performance for AHSP and AA (AUC > 0.95). Both the calibration curve and decision curve analysis suggested the promising clinical utility and net benefits of the XGBoost model. CONCLUSION: The AI-based machine learning model exhibits high prediction accuracy and can differentiate AHSP and AA from a data-driven perspective.

Finite Element Parametric Design of Hallux Valgus Orthosis Based on Orthogonal Analysis.

OBJECTIVE: To design appropriate orthosis for hallux valgus, a difficult foot condition that affects a quarter of the body's bones, we need to clarify the numerical biomechanical features, which have not been established in previous biomechanical studies. Therefore, we constructed a finite element model of the bunion foot to investigate the orthopaedic force compensation mechanism. METHODS: A patient with moderate hallux valgus was recruited. CT imaging data in DICOM format were extracted for three-dimensional foot model reconstruction. In conjunction with the need for rapid design of bunion orthosis, a metatarsal force application sizing method based on an orthogonal test design was investigated. The orthogonal test design was used to obtain the hallux valgus angle (HVA) and the inter metatarsal angle (IMA) data for different force combinations. Based on the extreme difference analysis and analysis of variance of the test results, the influence of different force combinations on the bunion angle was quickly determined. RESULTS: The results showed that the stress concentration occurred mainly in the first metatarsal bone. The distribution trend was in the medial and lateral middle of the bone and gradually decreased to the dorsal base of the bone body. The greatest stress occurs in the cartilage between the phalanges and metatarsals. In 25 groups of simulation experiments, HVA was reduced from 27.7° to 13°, and IMA was reduced from 12.5° to 7.3°. CONCLUSION: Applying detailed orthopaedic force collocation to the first metatarsal column can effectively restore the mechanics and kinematics of hallux valgus, and provide a reference for the treatment of bunion valgus and the design of orthopaedic devices.

Label-free optical metabolic imaging of adipose tissues for prediabetes diagnosis.

Rationale: Prediabetes can be reversed through lifestyle intervention, but its main pathologic hallmark, insulin resistance (IR), cannot be detected as conveniently as blood glucose testing. In consequence, the diagnosis of prediabetes is often delayed until patients have hyperglycemia. Therefore, developing a less invasive diagnostic method for rapid IR evaluation will contribute to the prognosis of prediabetes. Adipose tissue is an endocrine organ that plays a crucial role in the development and progression of prediabetes. Label-free visualizing the prediabetic microenvironment of adipose tissues provides a less invasive alternative for the characterization of IR and inflammatory pathology. Methods: Here, we successfully identified the differentiable features of prediabetic adipose tissues by employing the metabolic imaging of three endogenous fluorophores NAD(P)H, FAD, and lipofuscin-like pigments. Results: We discovered that 1040-nm excited lipofuscin-like autofluorescence could mark the location of macrophages. This unique feature helps separate the metabolic fluorescence signals of macrophages from those of adipocytes. In prediabetes fat tissues with IR, we found only adipocytes exhibited a low redox ratio of metabolic fluorescence and high free NAD(P)H fraction a1. This differential signature disappears for mice who quit the high-fat diet or high-fat-high-sucrose diet and recover from IR. When mice have diabetic hyperglycemia and inflamed fat tissues, both adipocytes and macrophages possess this kind of metabolic change. As confirmed with RNA-seq analysis and histopathology evidence, the change in adipocyte's metabolic fluorescence could be an indicator or risk factor of prediabetic IR. Conclusion: Our study provides an innovative approach to diagnosing prediabetes, which sheds light on the strategy for diabetes prevention.

Preliminary Investigation of Essentially Derived Variety of Tea Tree and Development of SNP Markers.

The continuous emergence of Essentially Derived Varieties (EDVs) in the process of tea tree breeding will endanger and affect the innovation ability and development potential of tea tree breeding. In this study, genotyping by sequencing (GBS) technology was used to screen high-quality genomic SNPs for the first time to investigate the derived relationships of 349 tea trees from 12 provinces in China. A total of 973 SNPs uniformly covering 15 tea tree chromosomes with high discrimination capacity were screened as the core SNP set. A genetic similarity analysis showed that 136 pairs of tea trees had a genetic similarity coefficient (GS) > 90%, among which 60 varieties/strains were identified as EDVs, including 22 registered varieties (19 were indisputably EDVs). Furthermore, 21 SNPs with 100% identification of 349 tea trees were selected as rapid identification markers, of which 14 SNP markers could be used for 100% identification of non-EDV. These results provide the basis for the analysis of the genetic background of tea trees in molecular-assisted breeding.

Mouse Strain- and Charge-Dependent Vessel Permeability of Nanoparticles at the Lower Size Limit.

Remarkable advancement has been made in the application of nanoparticles (NPs) for cancer therapy. Although NPs have been favorably delivered into tumors by taking advantage of the enhanced permeation and retention (EPR) effect, several physiological barriers present within tumors tend to restrict the diffusion of NPs. To overcome this, one of the strategies is to design NPs that can reach lower size limits to improve tumor penetration without being rapidly cleared out by the body. Several attempts have been made to achieve this, such as selecting appropriate nanocarriers and modifying surface properties. While many studies focus on the optimal design of NPs, the influence of mouse strains on the effectiveness of NPs remains unknown. Therefore, this study aimed to assess whether the vascular permeability of NPs near the lower size limit differs among mouse strains. We found that the vessel permeability of dextran NPs was size-dependent and dextran NPs with a size below 15 nm exhibited leakage from postcapillary venules in all strains. Most importantly, the leakage rate of 8-nm fluorescein isothiocyanate dextran was significantly higher in the BALB/c mouse strain than in other strains. This strain dependence was not observed in slightly positive TRITC-dextran with comparable sizes. Our results indicate that the influence on mouse strains needs to be taken into account for the evaluation of NPs near the lower size limit.

Development and Validation of a Differential Diagnosis Model for Acute Appendicitis and Henoch-Schonlein Purpura in Children.

Objective: To study and develop a predictive model for the differential diagnosis of acute appendicitis (AA) and Henoch-Schonlein purpura (HSP) in children and to validate the model internally and externally. Methods: The complete data of AA and HSP cases were retrospectively analyzed and divided into internal and external verification groups. SPSS software was used for single-factor analysis and screening of independent variables, and R software was used for the development and verification of the diagnostic model. Lasso regression analysis was used to screen predictors and Lasso-logistic regression model was constructed, and K-fold cross-validation was used for the internal verification. In addition, nonfever patients were selected for model development and validation in the same way. Receiver operating characteristic (ROC) curves and calibration curves were drawn, respectively, to evaluate the 2 models. Results: Internal development and validation of the model showed that fever, neutrophil ratio (NEUT%), albumin (ALB), direct bilirubin (DBIL), C-reactive protein (CRP), and K were predictive factors for the diagnosis of HSP. The model was presented in the form of a nomogram, and the area under ROC curve of the development group and verification group was 0.9462 (95% confidence interval [CI] = 0.9402-0.9522) and 0.8931 (95% CI = 0.8724-0.9139), respectively. In the model of patients without fever, NEUT%, platelets (PLT), ALB, DBIL, alkaline phosphatase (ALP), CRP, and K were predictive factors for the diagnosis of HSP, and the area under ROC curve of the development group and verification group was 0.9186 (95% CI = 0.908-0.9293) and 0.8591 (95% CI = 0.8284-0.8897), respectively. Conclusion: In this study, 2 diagnostic models were constructed for fever or not, both of which had good discrimination and calibration, and were helpful to distinguish AA and HSP in children.

Radiomic features as a risk factor for early postoperative seizure in patients with meningioma.

PURPOSE: This study aim to identify the clinical risk factors of and to develop a radiomics-based predictive model for early postoperative seizure. METHODS: We retrospectively assessed 322 operative patients with meningioma who met the inclusion criteria from January 2014 to December 2016 at The First Affiliated Hospital of Wenzhou Medical University. Univariate and multivariate analyses were performed to determine the predictive value of clinical variables. Magnetic resonance imaging (MRI) was performed to obtain the radiomic score (Rscore) for early postoperative seizure. Radiological features were evaluated using the AK software. The minimal redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) methods were used to assess for radiomic features, and the Rscore was obtained based on radiomic characteristics using a specific formula. RESULTS: In total, 260 patients who met the inclusion criteria were finally enrolled in this study. Among them, 20 experienced early postoperative seizure. Logistic regression analysis showed that Rscore was associated with a significantly high risk of seizure (p<0.000). Receiver operating characteristic (ROC) curve analysis revealed that the area under the ROC curve of the Rscore was 0.92 (95% confidence interval: 0.853-0.987). The model had a high accuracy for predicting early postoperative seizure. CONCLUSIONS: The Rscore was found to be associated with a high risk of early postoperative seizures. Thus, a higher Rscore (>-1.644) can identify high-risk patients requiring intensive care.

Tumor stem-like cells isolated from MMQ cells resist to dopamine agonist treatment.

Although tumor stem-like cells (TSLCs) have been studied in a range of malignant tumors, evidence for the presence of these cells in pituitary adenomas needs further exploration. Here, we identified a small subset of sphere-forming cells possess tumor stem-like cell properties in rat prolactinoma MMQ cells, which resist to dopamine agonist treatment. Comparing to MMQ cells, sphere-forming cells showed higher cell viability after dopamine agonist (DA) treatment. Furthermore, the cells showed lower expression of prolactin (PRL) and dopamine 2 receptor (D2R). On the contrary, the daughter tumor cells differentiated from these cells restored the sensitivity to DA and showed high expression of PRL and D2R. The lower D2R expression and DA resistance might be due to DNA hypermethylation of D2R promoter. Our study demonstrates that the sphere-forming cells isolated from MMQ cells possess the trait of TSLCs and resist to DA treatment, which offers the opportunity to further investigate the mechanisms underlying tumor recurrence based on TSLCs.

Ciclopirox and bortezomib synergistically inhibits glioblastoma multiforme growth via simultaneously enhancing JNK/p38 MAPK and NF-κB signaling.

Ciclopirox (CPX) is an antifungal drug that has recently been reported to act as a potential anticancer drug. However, the effects and underlying molecular mechanisms of CPX on glioblastoma multiforme (GBM) remain unknown. Bortezomib (BTZ) is the first proteasome inhibitor-based anticancer drug approved to treat multiple myeloma and mantle cell lymphoma, as BTZ exhibits toxic effects on diverse tumor cells. Herein, we show that CPX displays strong anti-tumorigenic activity on GBM. Mechanistically, CPX inhibits GBM cellular migration and invasion by reducing N-Cadherin, MMP9 and Snail expression. Further analysis revealed that CPX suppresses the expression of several key subunits of mitochondrial enzyme complex, thus leading to the disruption of mitochondrial oxidative phosphorylation (OXPHOS) in GBM cells. In combination with BTZ, CPX promotes apoptosis in GBM cells through the induction of reactive oxygen species (ROS)-mediated c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling. Moreover, CPX and BTZ synergistically activates nuclear factor kappa B (NF-κB) signaling and induces cellular senescence. Our findings suggest that a combination of CPX and BTZ may serve as a novel therapeutic strategy to enhance the anticancer activity of CPX against GBM.

A Quantified Risk-Scoring System for the Recurrence of Meningiomas: Results From a Retrospective Study of 392 Patients.

Aim: This study aimed to identify the independent risk factors of recurrence in patients undergoing primary resection of meningioma and construct a scoring system for the prediction of the risk of postoperative recurrence. Materials and Methods: The clinical data of 591 patients who underwent primary surgical resection for meningioma at the First Affiliated Hospital of Wenzhou Medical University between November 2010 and December 2016 were retrospectively reviewed. The clinical, radiological, and pathological characteristics were evaluated, and the independent risk factors for recurrence were identified via receiver operating characteristic (ROC) curve and logistic analyses. A scoring system that included these independent risk factors was used to construct a risk-predicting model that was evaluated via a ROC curve analysis. The recurrences of different subgroups were observed by Kaplan-Meier's curves. Results: The clinical data of 392 patients with meningioma were used to construct the scoring system. The logistic analysis showed that sex (OR = 2.793, 95% CI = 1.076-7.249, P = 0.035), heterogeneous tumor enhancement (OR = 4.452, 95% CI = 1.714-11.559, P = 0.002), brain invasion (OR = 2.650, 95% CI = 1.043-6.733, P = 0.041), Simpson's removal grade (OR = 5.139, 95% CI = 1.355-19.489, P = 0.016), and pathological grade (OR = 3.282, 95% CI = 1.123-9.595, P = 0.030) were independent risk factors for recurrence. A scoring system was developed and used to divide the patients into the following four subgroups: subgroup 1 with scores of 0-75 (n = 249), subgroup 2 with scores of 76-154 (n = 88), subgroup 3 with scores of 155-215 (n = 46), and subgroup 4 with scores of 216-275 (n = 9). The incidences of recurrence in each subgroup were as follows: subgroup 1, 1.2%; subgroup 2, 5.7%; subgroup 3, 26.1%; and subgroup 4, 66.7% (P < 0.001). The scoring system reliably predicted the postoperative recurrence of meningioma with a high area under the ROC curve. Conclusions: Our scoring system is a simple and reliable instrument for identifying meningioma patients at risk of postoperative recurrence and could help in optimizing individualized clinical treatment.

A Fully Automated Multiplex Assay for Diagnosis of Lyme Disease with High Specificity and Improved Early Sensitivity.

Lyme borreliosis is a tick-borne disease caused by the Borrelia burgdorferisensu lato complex. Bio-Rad Laboratories has developed a fully automated multiplex bead-based assay for the detection of IgM and IgG antibodies to B. burgdorferi The BioPlex 2200 Lyme Total assay exhibits an improved rate of seropositivity in patients with early Lyme infection. Asymptomatic subjects from endemic and nonendemic origins demonstrated a seroreactivity rate of approximately 4% that was similar to other commercial assays evaluated in this study. Coupled to this result was the observation that the Lyme Total assay retained a high first-tier specificity of 96% while demonstrating a relatively high sensitivity of 91% among a well-characterized CDC Premarketing Lyme serum panel. The Lyme Total assay also performs well under a modified two-tier algorithm (sensitivity, 84.4 to 88.9%; specificity, 98.4 to 99.5%). Furthermore, the new assay is able to readily detect early Lyme infection in patient samples from outside North America.

Arca subcrenata Polypeptides Inhibit Human Colorectal Cancer HT-29 Cells Growth via Suppression of IGF-1R/Akt/mTOR Signaling and ATP Production.

Arca subcrenata Lischke, widely scattering offshore at neritic regions, is very popular on dining table due to its edible and medical functional meatball. This study aims to investigate the suppression of a polypeptide fraction from A. subcrenata (PAS) on human colorectal cancer HT-29 cells, and its underlying mechanism. The results showed that PAS inhibited the growth of HT-29 cells with an IC50 value of 117 µg/ml after 48 h treatment, and significantly suppressed the tumor growth in nude mice bearing-xenografted HT-29 cells at the dosage of 63 mg/kg, with little influence on normal colon cells and normal colonic mucosa. PAS was then inspiringly found to induce apoptosis and G2/M phase arrest in HT-29 cells. The effect mechanism was involved in the inhibition of IGF-1/IGF-1R signaling activation, which was responsible for inactivating downstream Akt/mTOR pathway. Immunofluorescence assay also showed that PAS could reduce phosphorylation of IGF-1R (Tyr1165/1166). IGF-1, an IGF-1R activator, could reverse the suppression of PAS on IGF-1R phosphorylation. Furthermore, PAS significantly inhibited ATP production of HT-29 cells both in vitro and in vivo. Our results provide positive evidence that A. subcrenata has the potential to be a candidate for the treatment of colorectal cancer.

Epigenetic Control of Rho-Associated Protein Kinase 2 in Neurodegeneration.

Upregulation of Rho-associated protein kinase 2 (ROCK2) hallmarks the progression of neurodegenerative diseases. However, the molecular mechanisms underlying the regulation of ROCK2 expression are not clear and thus addressed in the current study. We generated a subacute model of Parkinson's disease in mice with a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) method. The MPTP model was validated by impaired rotational behavior of the mice upon apomorphine exposure, astrocytic activation, and reduction in tyrosine-hydroxylase-positive neurons in the mouse striatum. Moreover, MPTP induced increases in ROCK2 protein but not in ROCK2 mRNA. Further analysis showed that MPTP inhibited the expression of microRNA-291 (miR-291), which suppressed ROCK2 mRNA via 3'-UTR-binding in neuronal cells to increase ROCK2 protein. Intracranial injection of miR-291 four days before MPTP alleviated the impaired rotational behavior of the mice upon apomorphine exposure, MPTP-induced astrocytic activation, and the reduction in tyrosine-hydroxylase-positive neurons in the mouse striatum. Together, these data suggest that miR-291 has a protective role in neurodegeneration, likely through regulation of ROCK2.

A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells.

The astonishing clinical success of CD19 chimeric antigen receptor (CAR) T-cell therapy has led to the approval of two second generation chimeric antigen receptors (CARs) for acute lymphoblastic leukemia (ALL) andnon-Hodgkin lymphoma (NHL). The focus of the field is now on emulating these successes in other hematological malignancies where less impressive complete response rates are observed. Further engineering of CAR T cells or co-administration of other treatment modalities may successfully overcome obstacles to successful therapy in other cancer settings. We therefore present a model in which others can conduct pre-clinical testing of CD19 CAR T cells. Results in this well tested B-cell lymphoma model are likely to be informative CAR T-cell therapy in general. This protocol allows the reproducible production of mouse CAR T cells through calcium phosphate transfection of Plat-E producer cells with MP71 retroviral constructs and pCL-Eco packaging plasmid followed by collection of secreted retroviral particles and transduction using recombinant human fibronectin fragment and centrifugation. Validation of retroviral transduction, and confirmation of the ability of CAR T cells to kill target lymphoma cells ex vivo, through the use of flow cytometry, luminometry and enzyme-linked immunosorbent assay (ELISA), is also described. Protocols for testing CAR T cells in vivo in lymphoreplete and lymphodepleted syngeneic mice, bearing established, systemic lymphoma are described. Anti-cancer activity is monitored by in vivo bioluminescence and disease progression. We show typical results of eradication of established B-cell lymphoma when utilizing 1st or 2nd generation CARs in combination with lymphodepleting pre-conditioning and a minority of mice achieving long term remissions when utilizing CAR T cells expressing IL-12 in lymphoreplete mice. These protocols can be used to evaluate CD19 CAR T cells with different additional modification, combinations of CAR T cells and other therapeutic agents or adapted for the use of CAR T cells against different target antigens.

MicroRNA-93 mediates cabergoline-resistance by targeting ATG7 in prolactinoma.

To date, the management of dopamine agonist (DA)-resistant prolactinomas remains a major clinical problem. Previously, we determined that miRNA-93 expression increases in DA-resistant prolactinomas; however, the role of miRNA-93 in the DA resistance remains largely unexplored. Hence, this study aimed to investigate the susceptibility of tumor cells to cabergoline (CAB) and the autophagy changes in MMQ and GH3 cells after miRNA-93 overexpression or inhibition. We used bioinformatics to identify the potential target of miRNA-93. Subsequently, we analyzed the correlation between miRNA-93 and autophagy-related 7 (ATG7) using protein expression analysis and luciferase assays. Furthermore, the change in the effect of miRNA-93 was measured after ATG7 overexpression. miRNA-93 expression was elevated in DA-resistant prolactinomas, whereas the expression of its identified target, ATG7, was downregulated. miRNA-93 overexpression suppressed the cytotoxic effect of CAB in MMQ and GH3 cells. In contrast, miRNA-93 downregulation enhanced CAB efficiency and promoted cell autophagy, eventually resulting in apoptosis. These results were further confirmed in vivo xenograft models in nude mice. ATG7 overexpression could reverse the inhibitory effect of miRNA-93 on CAB treatment. Taken together, our results suggest that miRNA-93 mediates CAB resistance via autophagy downregulation by targeting ATG7 and serves as a promising therapeutic target for prolactinoma.

RBM17 controls apoptosis and proliferation to promote Glioma progression.

The splicing factor SPF45 (RBM17) is a well-known component of the spliceosome that is involved in alternative splicing. RBM17 is frequently overexpressed in many tumors and plays a crucial role in cancer progression and drug resistance. However, the role of RBM17 in the development of glioma has not been thoroughly elucidated to date. In the present study, we found that RBM17 was overexpressed in glioma and that a high level of expression of RBM17 was closely associated with a poor prognosis in glioma patients. We investigated the effect of RBM17 on apoptosis, cell growth and cell cycle indexes and the activation of apoptosis signaling by shRNA in human U87 and U251 glioma cells. The downregulated expression of RBM17 mRNA was accompanied by the induction of cell cycle arrest, and apoptosis, reduced cell proliferation in the two cell lines, and reduced cell survival, as measured by the increased activation of caspase-3, caspase-9, and PARP (poly ADP-ribose polymerase). Furthermore, in subcutaneous U87 cell xenograft tumors in nude mice, intradermal administration of an shRNA targeting RBM17 significantly downregulated RBM17 expression in vivo and was accompanied by the suppressed growth of glioma. To the best of our knowledge, our results are the first to confirm that RBM17 functions in promoting cell proliferation, affecting the cell cycle, and inducing apoptosis in human glioma cells both in vitro and in vivo. These results indicate that RBM17 may be a therapeutic target in the clinical management of glioma.

CTRP9 ameliorates cellular senescence via PGC­1α/AMPK signaling in mesenchymal stem cells.

Stroke is the second most common cause of death worldwide, and thus, it imposes great financial burdens on both individuals and society. Mesenchymal stem cell (MSC) therapy is a promising approach for ischemic brain injury. However, MSC treatment potential is progressively reduced with age, limiting their therapeutic efficacy for brain repair post­stroke. C1q and tumor necrosis factor­related protein 9 (CTRP9) is a novel cytoprotective cytokine with antioxidant effects, which is highly expressed in brain tissue. The present study tested the hypothesis that CTRP9 might act as an antisenescence factor to promote the rejuvenation of aged MSCs. MSCs were isolated from the bone marrow of young (8­weeks­old) and aged (18­months­old) male C57BL/6 mice. Cell proliferation was measured by Cell Counting Kit­8 assay and cell viability was determined by MTT assay. Gene expression levels of interleukin (IL)­6 and IL­10 were evaluated with reverse transcription­quantitative polymerase chain reaction, and secretion of vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, and insulin­like growth factor were measured by ELISA. The expression levels of proteins in the peroxisome proliferator­activated receptor γcoactivator (PGC)­1α/AMP­activated protein kinase (AMPK) signaling pathway were investigated with western blotting. Oxidative stress was evaluated by detecting mitochondrial membrane potential, reactive oxygen species, superoxide dismutase activity and malondialdehyde. MSCs isolated from aged mice exhibited reduced proliferation and viability, and impaired immunoregulatory and paracrine abilities, compared with MSCs from younger mice. CTRP9 had a significant antisenescence effect in aged MSCs by activating PGC­1α/AMPK signaling and decreasing the oxidative response. Silencing either PGC­1α or AMPK abolished the above effects of CTRP9. These results suggest that CTRP9 may have a critical role in cellular senescence by facilitating stem cell rejuvenation, and may therefore have the potential to enhance the efficacy of stem cell therapy.

Notch1 Signaling Activation Contributes to Adult Hippocampal Neurogenesis Following Traumatic Brain Injury.

BACKGROUND Neural stem cells are reported to exist in the hippocampus of adult mammals and are important sources of neurons for repair. The Notch1 signaling pathway is considered as one of the important regulators of neural stem cells, but its role in adult brains is unclear. We aimed to describe the role of Notch1 signaling in the adult rat hippocampus after traumatic brain injury. MATERIAL AND METHODS The model rats were randomly divided into 4 groups as follows: sham, sham-TBI, sham-Ad-TBI, and NICD-Ad-TBI. We used adenovirus-mediated gene transfection to upregulate endogenous NICD in vivo. Firstly, a TBI rat model was constructed with lateral fluid percussion. Then, the hippocampus was collected to detect the expression of Notch1 markers and stem cell markers (DCX) by Western blot analysis, immunohistochemistry, and immunofluorescence. The prognosis after TBI treatment was evaluated by the Morris Water Maze test. RESULTS First, we found the expression of NICD in vivo was significantly increased by adenovirus-mediated gene transfection as assessed by Notch1 immunofluorescence and Western blot analysis. Second, enhancing NICD stimulated the regeneration of neural stem cells in the DG of the adult rat brain following traumatic brain injury, as evaluated by DCX and NeuN double-staining. Furthermore, Notch1 signaling activation can promote behavioral improvement after traumatic brain injury, including spatial learning and memory capacity. CONCLUSIONS Our findings suggest that targeted regulation of Notch1 signaling may have a useful effect on stem cell transformation. Notch1 signaling may have a potential brain-protection effect, which may result from neurogenesis.

HSP47 is associated with the prognosis of laryngeal squamous cell carcinoma by inhibiting cell viability and invasion and promoting apoptosis.

Heat shock protein 47 (HSP47) is a 47 kDa collagen binding protein that has a close relationship with the development and progression of tumours. However, little is known concerning the expression profile of HSP47 in laryngeal squamous cell carcinoma (LSCC) patients and there is still insufficient data concerning the underlying mechanisms. The aim of the present study was to explore the expression of HSP47 in LSCC and provide an overview of its association with tumourigenicity and clinical prognosis. The expression of HSP47 in LSCC and adjacent non-cancerous laryngeal tissues was assessed via western blotting and immunohistochemical studies. The prognostic significance of HSP47 expression was analysed using a Kaplan-Meier survival curve. To investigate the influence of HSP47 on the viability, invasion and apoptosis of a LSCC cell line, we performed an in vitro analysis with plasmid vectors and small interfering RNA (siRNA). Our results showed that HSP47 protein expression in the LSCC tissues was markedly decreased compared to that noted in the adjacent non-cancerous tissues, and low expression of HSP47 was correlated with poor prognosis in LSCC patients. Upregulation of HSP47 via plasmid vectors inhibited the proliferation, reduced the invasive ability, increased the sensitivity to cisplatin chemotherapy, promoted apoptosis, and induced the G1 phase arrest of LSCC cells in vitro. The expression of apoptosis-regulating proteins was also altered when HSP47 was upregulated, involving increased expression of cleaved caspase-7/-8/-9, PARP, and Bax and decreased expression of Bcl-2. Our present data suggest that HSP47 is an important prognostic factor and an attractive therapeutic target in LSCC due to its influence on the biological behaviour of LSCC cells.

Subdural Hemorrhage from Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage: A Risk Factor for Postoperative Hemorrhage.

OBJECTIVE: Surgical treatment for cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) is controversial. A subset of CAA-related ICH with associated subdural hemorrhage (SDH) has been reported. This study aimed to evaluate clinical results and surgical outcomes of this type of ICH with associated SDH. METHODS: Study participants included 98 patients with CAA-related ICH who met Boston criteria. Patients were divided into an SDH group and a control (no SDH) group. Clinical and neuroimaging features and surgical outcomes of the 2 groups were compared. RESULTS: Lobular shape of hematoma was found significantly more often in the SDH group (65.7% [23/35]) compared with the control group (25.4% [16/63]; P < 0.001). Subarachnoid hemorrhage was found significantly more often in the SDH group (34.3% [12/35]) compared with the control group (7.9% [5/63]; P = 0.001). The rate of postoperative hemorrhage was significantly higher in the SDH group (61.5% [8/13]) than in the control group (16.2% [6/37]; P = 0.006). The frequency of occurrence of postoperative hemorrhage was significantly higher in the SDH group (13/13) than in the control group (6/37; P = 0.017). A good surgical outcome occurred in none (0/12) of the patients in the SDH group, whereas a good surgical outcome occurred in 51.9% (14/27) of patients in the control group (P = 0.006). CONCLUSIONS: Patients with CAA-related ICH with associated SDH more frequently have postoperative hemorrhage and have a worse surgical outcome. These findings are useful in choosing therapeutic methods and preoperative planning of surgical strategy.