ObjectiveTo investigate the feasibility of multiparametric MRI （mpMRI） combined with histogram analysis of apparent diffusion coefficient （ADC） in the assessment of patients with variant histology （VH） of urothelial carcinoma （UC）. MethodWe retrospectively analyzed the data of patients pathologically diagnosed with UC who underwent mpMRI in the First Affiliated Hospital of Sun Yat-sen University between March 2015 and March 2023. The patients were divided into VH group （urothelial carcinoma mixed with other histologies） and non-VH group （pure urothelial carcinoma） according to pathological results. We performed propensity score 1：1 nearest-neighbor matching on the two groups based on age and gender and 49 patients were included in each group. The regions of interest （ROIs） of the whole tumor were delineated manually by using ITK-SNAP software and Pyradiomics was applied to extract ADC histogram parameters. We compared the clinicopathological data， MRI morphological features and ADC histogram parameters between the groups. Multivariate logistic regression was used to identify independent risk factors and construct the prediction model. Receiver operating characteristic （ROC） curve analyses were performed to evaluate the diagnostic performance of these parameters for determining VH of UC. ResultsMRI morphological features including the lesion shape， vesical imaging-reporting and data system （Ⅵ-RADS）score， enhancement pattern and suspicious lymph node metastasis were markedly different between the two groups （all P < 0.05）. ADC _mean， ADC _median， ADC_25th， ADC_75th， ADC_10th and ADC_90th were significantly lower in patients with VH than those in non-VH group （all P<0.05）. Multivariate logistic regression analysis showed enhancement pattern， ADC_25th， ADC_75th and ADC mean were independent predictors （P < 0.05）. The combined model yielded the best predictive performance， with an area under the ROC curve （AUC） of 0.91 （95% CI： 0.83-0.96）. ConclusionsMpMRI combined with whole-tumor histogram analysis of ADC can serve as a reliable method for evaluating the presence of VH in UC， further to assist the clinical decision making.

OBJECTIVES: To study the changes of protein levels in peripheral blood after it dried. METHODS: The proteins from whole blood and bloodstains were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and normalized by the label-free quantification (LFQ) method. The differential proteins were analyzed by using R 4.2.1 software, limma and edgeR package. The analysis of biological function, signaling pathway and subcellular localization for the differential proteins was then performed. RESULTS: A total of 623 and 596 proteins were detected in whole blood and bloodstains, respectively, of which 31 were statistically significant in the quantitative results, including 10 up-regulated and 21 down-regulated proteins in bloodstains. CONCLUSIONS The protein abundances in whole blood and bloodstains are highly correlated, and the variation of protein abundances may be related to the changes of endogenous and structural proteins in cells. The application of proteomics technology can assist the screening and identification of protein biomarkers, thereby introducing new biomarkers for forensic research.
Chromatography, Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Proteomics/methods* ; Blood Stains ; Biomarkers

Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca

Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca
Adenosine Triphosphate ; Animals ; Antidepressive Agents/therapeutic use* ; Caloric Restriction ; Mice ; Mice, Knockout ; Prefrontal Cortex

Objective:To explore the potential targets and related mechanism involved in the paclitaxel resistance to ovarian cancer. Method:Ovarian cancer A2780 cells and A2780 paclitaxel-resistant cells （A2780/T） were treated by 2， 4， 8， 16， 32， 64， 128， 256 μmol·L^-1 paclitaxel （PTX） for 24 h or 48 h respectively in vitro. The proliferation rate of A2780 cells and A2780/T cells treated with paclitaxel was determined by methyl thiazolyl tetrazolium （MTT） colorimetric method assay. A2780 and A2780/T cells were analyzed by LC-MS/MS Label-Free quantitative proteomics to identify and screen differentially expressed proteins in the two groups of cells. Gene ontology （GO） annotation and Kyoto encyclopedia of genes and genomes （KEGG） pathway analysis were used to determine the potential biomarkers of paclitaxel resistance in ovarian cancer. Conventionally cultured A2780 cells were used as a control group， and A2780/T cells were treated with 0， 1， 4 μmol·L^-1 PTX. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot methods were used to detect and verify the mRNA and protein expression levels of potential target transforming growth factor-β-activated kinase 1 binding protein 1 （TAB1） and its downstream related molecules transforming growth factor-β-activated kinase （TAK1） and p38. Result:After PTX treatment for 24 h and 48 h， the cell viability of A2780 and A2780/T cells decreased. The inhibitory rate of PTX on A2780 cells was significantly higher than that of A2780/T cells. In A2780 cells， the IC₅₀ of PTX treatment for 48 h was 0.002 μmol·L^-1， while in A2780/T cells， the IC₅₀ of PTX was greater than the maximum concentration of 128 μmol·L^-1， indicating that A2780/T cells were resistant to PTX compared with A2780 cells. 441 differentially expressed proteins and 421 special differentially expressed proteins between A2780/T and A2780 cells were screened by label-free quantitative proteomic analysis. GO function enrichment analysis showed that the binding proteins accounted for the majority （80%） among the differentially expressed proteins. According to the results of KEGG pathway analysis and expression site analysis， TAB1 might be a potential biomarker in paclitaxel-resistant ovarian cancer. Compared with A2780 cells， mRNA and protein expression levels of TAB1 in A2780/T cells were significantly reduced （P<0.01）. mRNA expression of TAK1 and p38 that interacted with TAB1 were also significantly reduced （P<0.05， P<0.01）， while there was no significant change in protein expression. Conclusion:TAB1 may be a potential biomarker of paclitaxel resistance to ovarian cancer ， and its mechanism may be related to the TAB1/TAK1/p38 MAPK pathway.

Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized. We generated a new astrocyte-specific Aldh1l1-CreER knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines (hGfap-CreER from The Jackson Laboratory and The Mutant Mouse Resource and Research Center, Glast-CreER, Cx30-CreER, and Fgfr3-iCreER) by crossing with Ai14 mice, which express tdTomato fluorescence following Cre-mediated recombination. In adult Aldh1l1-CreER:Ai14 transgenic mice, tdTomato was detected throughout the CNS, and five novel morphologically-defined types of astrocyte were described. Among the six evaluated lines, the specificity of Cre-mediated recombination was highest when driven by Aldh1l1 and lowest when driven by hGfap; in the latter mice, co-staining between tdTomato and NeuN was observed in the hippocampus and cortex. Notably, evident leakage was noted in Fgfr3-iCreER mice, and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30. Furthermore, tdTomato was clearly expressed in peripheral organs in four of the lines. Our results emphasize that the astrocyte-specific CreER transgenic lines used in functional studies should be carefully selected.

OBJECTIVE: To evaluate the changes of cardiac structure and function and their risk factors in elderly patients with obstructive sleep apnea syndrome (OSA) without cardiovascular complications. METHODS: Eighty-two elderly OSA patients without cardiovascular disease admitted between January, 2015 and October, 2016 were enrolled in this study. According to their apnea-hypopnea index (AHI, calculated as the average number of episodes of apnoea and hypopnoea per hour of sleep), the patients were divided into mild OSA group (AHI < 15) and moderate to severe OSA group (AHI ≥ 15). The demographic data and the general clinical data were recorded and fasting blood samples were collected from the patients on the next morning following polysomnographic monitoring for blood cell analysis and biochemical examination. Echocardiography was performed within one week after overnight polysomnography, and the cardiac structure, cardiac function and biochemical indexes were compared between the two groups. RESULTS: Compared with those with mild OSA group, the patients with moderate to severe OSA had significantly higher hematocrit (0.22±0.08 CONCLUSIONS Cardiac diastolic function impairment may occur in elderly patients with moderate or severe OSA who do not have hypertension or other cardiovascular diseases, and the severity of the impairment is positively correlated with AHI.
Aged ; Cardiovascular Diseases/etiology* ; Humans ; Risk Factors ; Severity of Illness Index ; Sleep Apnea, Obstructive/complications* ; Stroke Volume ; Ventricular Dysfunction, Left ; Ventricular Function, Left

Objective To study the diagnostic values of X-ray,CT and MRI for the hip joint lesion of the patient with ankylosing spondylitis (AS).Methods Totally 180 AS patients underwent the examinations of X-ray,CT and MRI from January 2014 to December 2015,and the hip joint lesion,clinical features and the efficacies of the three imaging techniques were observed.Results The rates for positive findings were 69.44％,71.11％ and 72.22％ respectively by X-ray,CT and MRI,and more than 90％ patients had the lesions occurred at the bilateral hip joints simultaneously.Hip joint lesion of AS had the imaging features of bone marrow and joint space changes,which related to the disease progress closely.Early positive signs consisted of medial joint space narrowing by X-ray,rear joint space narrowing by CT as well as bone marrow fat deposition (BMFD) and bone marrow edema (BME) by MRI.Conclusion X ray,CT and MRI all gain their advantages when used to diagnose the hip joint lesion of AS.X-ray behaves well in early diagnosis of medial joint space narrowing,while have disadvantages in displaying soft tissues and minute structures when compared with CT and MRI.CT displays the minute structure of hip joint clearly,and is not so good at soft tissue resolution as MRI.MRI gains the highest resolution for displaying soft tissues in the three techniques,and can show BMFD,BME and etc which can not be revealed by X-ray and CT.

BACKGROUNDCatheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT). However, the optimal dosage of a thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT.

METHODSA retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evaluated by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively.

RESULTSThe mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days. Prior to discharge, Grade III (complete lysis) was achieved in 154 (36%) patients; Grade II (50-99% lysis) in 222 (52%); and Grade I (50% lysis) in 51 (12%). The major complications included one intracranial hemorrhage, one hematochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study.

CONCLUSIONSTreatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.

Adolescent ; Adult ; Aged ; Drug Administration Schedule ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Urokinase-Type Plasminogen Activator ; administration & dosage ; adverse effects ; therapeutic use ; Venous Thrombosis ; drug therapy ; Young Adult

BACKGROUNDEpstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC.

METHODSUsing logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage association study was conducted to identify EBV variations associated with NPC risk. A protein degradation assay was performed to characterize the functional relevance of the RPMS1 variations.

RESULTSBased on EBV-encoded RPMS1 variations, a single nucleotide polymorphism (SNP) in the EBV genome (locus 155391: G>A, named G155391A) was associated with NPC in 157 cases and 319 healthy controls from an NPC endemic region in South China [P < 0.001, odds ratio (OR) = 4.47, 95% confidence interval (CI) 2.71-7.37]. The results were further validated in three independent cohorts from the NPC endemic region (P < 0.001, OR = 5.20, 95% CI 3.18-8.50 in 168 cases vs. 241 controls, and P < 0.001, OR = 5.27, 95% CI 4.06-6.85 in 726 cases vs. 880 controls) and a non-endemic region (P < 0.001, OR = 7.52, 95% CI 3.69-15.32 in 58 cases vs. 612 controls). The combined analysis in 1109 cases and 2052 controls revealed that the SNP G155391A was strongly associated with NPC (P(combined) < 0.001, OR = 5.27, 95% CI 4.31-6.44). Moreover, the frequency of the SNP G155391A was associated with NPC incidence but was not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assay showed that this SNP decreased the degradation of the oncogenic RPMS1 protein.

CONCLUSIONSOur study identified an EBV variation specifically and significantly associated with a high risk of NPC. These findings provide insights into the pathogenesis of NPC and strategies for prevention.

Adult ; Aged ; Carcinoma ; Case-Control Studies ; China ; epidemiology ; Epstein-Barr Virus Infections ; complications ; epidemiology ; virology ; Female ; Genetic Association Studies ; Genome, Viral ; Herpesvirus 4, Human ; genetics ; isolation & purification ; Humans ; Incidence ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; epidemiology ; virology ; Neoplasm Proteins ; genetics ; Pilot Projects ; Polymorphism, Single Nucleotide ; Risk Assessment ; methods ; Tumor Cells, Cultured ; Viral Proteins ; genetics