Objective To investigate the value of multimodal MRI radiomics in predicting muscle-invasive bladder cancer.Methods A total of 178 patients with pathology diagnosis of bladder cancer were retrospectively collected,including 31 cases of muscle invasive bladder cancer(MIBC)and 147 cases of non-muscle invasive bladder cancer(NMIBC).Patients were randomly divided into training group and testing group at a ratio of 7︰3.The range of bladder tumors in T2WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images were segmented as volume of interest(VOI)by using ITK-SNAP software.Radiomics features were extracted through A.K software.The optimal radiomics features were obtained through radiomics algorithm and least absolute shrinkage and selection operator(LASSO)method.Finally,the logistic regression analysis method and random forest model method were used to construct prediction models.The performance of prediction models was evaluated by the receiver operating characteristic(ROC)curve.Results This study constructed four groups of models containing T2WI prediction model,DWI prediction model,ADC prediction model,and T2WI+DWI+ADC prediction model.The area under the curve(AUC)of T2WI,DWI,and ADC prediction models for identifying MIBC and NMIBC were separately 0.920,0.914,and 0.954 in the training group while those were respectively 0.881,0.773,and 0.871 in the testing group.There was no statistical significance between T2WI,DWI,and ADC prediction models.In training and testing groups,the AUC of T2WI+DWI+ADC prediction model were respectively 0.959 and 0.909,which were higher than the single sequence prediction model.The sensitivity and specificity of the training group were 0.905 and 0.853 and the sensitivity and specificity of the testing group were 0.778 and 0.795.Conclusion MRI radiomics prediction model can effectively differentiate MIBC and NMIBC.The T2WI+DWI+ADC prediction model shows better prediction efficiency.

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L^-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L^-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L^-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L^-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L^-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L^-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 （T2DM） rats， and the mechanism based on liver peroxidase proliferators activate receptors-α （PPAR-α） and carnitine palmityl transferase-1 （CPT-1） proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet （HFD） + streptozocin（STZ）method. Rats with blood glucose ≥ 11.1 mmol·L^-1 were divided into three administration groups with the high dose （300 mg·kg^-1）， medium dose （150 mg·kg^-1）， and low dose （75 mg·kg^-1） of total flavonoids of mulberry leaves for 8 weeks， respectively， to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin （HE） staining. Biochemical method was used to detect the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein-cholesterol （LDL-C）， and high density lipoprotein-cholesterol （HDL-C） of blood lipid metabolism in rats. The messenger ribonucleic acid （mRNA） and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves， compared with the control group， the food intake， liver index， and fasting blood glucose of rats in the model group increased significantly （P<0.01）. Compared with the model group， the food intake， fasting blood glucose， and liver index of rats in the administration groups decreased significantly （P<0.01）. The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group， the levels of TC， TG， and LDL-C increased significantly （P<0.01）， but the level of HDL-C decreased significantly （P<0.01） in the model group. Compared with the model group， the levels of TC， TG， and LDL-C decreased significantly （P<0.05， P<0.01）， whereas the level of HDL-C increased significantly （P<0.01） in the administration groups. The results of Real-time PCR showed that compared with the control group， the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.01）. The results of Western blot showed that compared with the control group， the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.05， P<0.01）. ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.

The incidence of diabetes has been on the rise as the result of lifestyle changes， especially the high-fat diet and reduced exercise. Thus， it has become a global public health problem and it is an urgent task to explore effective therapy. There has been an explosion of research on the relationship of transforming growth factor-β （TGF-β） signaling pathways with diabetes complications and tumors， but the role of the pathways in the occurrence and progression of diabetes remains unclear. TGF-β signaling pathways can be activated by many factors， directly or indirectly leading to the apoptosis of islet β cells and insulin resistance （IR）， and thus they are expected to become new targets for the treatment of diabetes. TGF-β-related signaling pathways involve AMP-activated proteinkinase （AMPK）， protooncogene （c-Myc）， Ski-relatednovel protein N （SnoN）， Smad ubiquitination regulatory factor 1 （Smurf1）， miR-335-5p， and other signaling molecules. They participate in the occurrence and development of IR， apoptosis of islet β cells， insulin secretion disorder， fibrosis of adipocytes， and metabolic disorder of adipocytes， and inhibit the browning of white adipose tissue， playing an important part in the pathological process of human diabetes. According to traditional Chinese medicine （TCM）， the pathogenesis of diabetes is the deficiency of Qi and Yin， and the late stage is characterized by the syndrome of Qi deficiency， and Yang deficiency and blood stasis， which should be treated according to the principle of replenishing Qi and nourishing Yin， warming Yang and activating blood. It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways. This paper reviews TGF-β-associated signaling pathways， elucidating the roles of them in pathogenesis of diabetes， and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes. This study is expected to lay a theoretical basis for the research on the treatment diabetes.

Alternative polyadenylation(APA)is a crucial step in post-transcriptional regulation.Previous bioinformatic studies have mainly focused on the recognition of polyadenylation sites(PASs)in a given genomic sequence,which is a binary classification problem.Recently,computa-tional methods for predicting the usage level of alternative PASs in the same gene have been pro-posed.However,all of them cast the problem as a non-quantitative pairwise comparison task and do not take the competition among multiple PASs into account.To address this,here we propose a deep learning architecture,Deep Regulatory Code and Tools for Alternative Polyadenylation(DeeReCT-APA),to quantitatively predict the usage of all alternative PASs of a given gene.To accommodate different genes with potentially different numbers of PASs,DeeReCT-APA treats the problem as a regression task with a variable-length target.Based on a convolutional neural network-long short-term memory(CNN-LSTM)architecture,DeeReCT-APA extracts sequence features with CNN layers,uses bidirectional LSTM to explicitly model the interactions among com-peting PASs,and outputs percentage scores representing the usage levels of all PASs of a gene.In addition to the fact that only our method can quantitatively predict the usage of all the PASs within a gene,we show that our method consistently outperforms other existing methods on three different tasks for which they are trained:pairwise comparison task,highest usage prediction task,and rank-ing task.Finally,we demonstrate that our method can be used to predict the effect of genetic variations on APA patterns and sheds light on future mechanistic understanding in APA regulation.

In order to meet the requirements in the cooperation and competition experiments for an individual patient in clinical application, two human interactive behavior key-press models based on hidden Markov model (HMM) were proposed. To validate the cooperative and competitive models, a verification experimental task was designed and the data were collected. The correlation of the score and subjects' participation level has been used to analyze the reasonability verification. Behavior verification was conducted by comparing the statistical difference in response time for subjects between human-human and human-computer experiment. In order to verify the physiological validity of the models, we have utilized the coherence analysis to analyze the deep information of prefrontal brain area. Reasonability verification shows that the correlation coefficient for the training data and the testing data is 0.883 1 and 0.578 6 respectively based on cooperation model, and 0.813 1 and 0.617 8 respectively based on the competition model. The behavioral verification result shows that the cooperation and competition models have an accuracy of 71.43% respectively. The results of physiological validity show that the deep information of prefrontal brain area could been extracted based on the cooperation and competition models, and reveal the consistency of coherence between the double key-press cooperative and competitive experiments, respectively. Above all, the high consistency is obtained between the cooperatio/competition model and the double key-press experiment by the behavioral and physiological evaluation results. Consequently, the cooperation and competition models could be applied to clinical trials.

Objective Based on Chinese guidelines for the management of ischemic stroke, a standardized stroke management program was performed to provide intensive education and training for medical physicians, aiming to enhance their knowledge and ability for ischemic stroke prevention and treatment, thereby reducing patients′ in-hospital cost and length of stay, and improving patients′ clinical prognosis. Methods This study was conducted in 20 general hospitals throughout Hainan province. A total of 163 physicians from 20 hospitals involved in the management of stroke patients were trained by highly experienced physicians based on the Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2014 and the Chinese guidelines for secondary prevention of ischemic stroke and transient ischemic attack 2014. Prior to and post the standardized stroke management training, the data of 3218 and 3367 patients with ischemic stroke were respectively collected. Quality of life assessments including the Barthel index (BI) and the modified Rankin Scale (mRS) score of all patients were recorded at baseline and after discharge. The length of stay and in-hospital cost were directly collected from the hospital information system. Results Physicians′ knowledge and ability manifested as testing scores were significantly improved after training (78.2 ± 15.5 vs 55.6 ± 10.7, t=69.1, P<0.01). The average length of stay of post-training patients was significantly shorter than that of pre-training patients ((8.7 ± 0.9) vs (11.7 ± 1.5) days, t=97.9, P<0.01). The average in-hospital cost of post-training patients was significantly less than that of pre-training patients ((7681.7 ± 1397.7) vs (11846.2 ± 2514.6) Yuan, t=82.5, P<0.01). Both BI (68.2 ± 3.2 vs 43.5 ± 5.3, t=227.7, P<0.01) and mRS score (2.74±0.51 vs 3.65±0.71, t=59.5, P<0.01) were significantly improved for post-training patients. Multivariate linear regression analysis illustrated that standardized stroke management was negatively associated with in-hospital cost (r=-0.461, P<0.01), length of stay (r=-0.357, P<0.01) and mRS score (r=-0.298, P<0.01), and was positively associated with levels of BI (r=0.376, P<0.01). Conclusion Standardized stroke management program might be a cost-effective choice for the management of ischemic stroke as it reduces the in-hospital cost and improves patients′BI and mRS levels.

BACKGROUND:Monoaxial pedicle screws are not conducive to the instal ation during percutaneous pedicle screw technique, but it has better mechanical conductivity and stability than polyaxial pedicle screws. How to select and use these two kinds of screws in the clinic to exert their advantages and to further elevate efficacy has become a subject worthy of reflection. OBJECTIVE:To compare the clinical efficacy of percutaneous pedicle screw placement for thoracolumbar fracture using monoaxial and polyaxial pedicle screws at different placement selections. METHODS:A total of 46 cases of thoracolumbar fracture without neurological symptoms underwent minimal y invasive percutaneous pedicle screw fixation. 25 patients (monoaxial screw group) were treated with monoaxial pedicle screws and the other 21 ones (polyaxial screw group) with polyaxial pedicle screws. Kyphotic angle, correction rate, correction loss rate and height of injury vertebrae were compared before and after fixation in both groups. The therapeutic effects of monoaxial and polyaxial percutaneous pedicle screw fixation in the treatment of thoracolumbar fractures were evaluated. RESULTS AND CONCLUSION:(1) Fixation time, blood loss, complication and hospital stay were not significantly different in both groups (P>0.05). (2) Kyphotic angle and height of the fractured vertebra body were significantly different between the two groups (P<0.05). (3) The restoration of anterior height of injured vertebrae, kyphotic angle and correction rate were better in the monoaxial screw group than in the polyaxial screw group after treatment (P<0.05). The correction loss rate was significantly better in the monoaxial screw group than in the polyaxial screw group during last fol ow-up (P<0.05). However, there was no significant difference in the posterior height of injured vertebraeafter fixation (P>0.05). (4) These findings indicate that compared with the polyaxial percutaneous pedicle screw fixation, the monoaxial pedicle screw may be preferable in percutaneous pedicle screw fixation for thoracolumbar fractures, has more satisfactory fracture distraction reduction, and has less postoperative correction loss rate.

Objective To evaluate the clinical results of self-designed double-pivot extracorporeal reduction device in internal fixation with percutaneous pedicle screws for thoracolumbar fractures.Methods From January 2014 to May 2015,a total of 41 patients with thoracolumbar fracture without neurological symptoms underwent minimally invasive fixation with percutaneous pedicle screws.Of them,22 were treated with our self-designed double-pivot extracorporeal reduction device and the other 20 with common single-pivot extracorporeal reduction device.The 2 groups were compared in terms of pre-and postoperative kyphotic angles,correction rates and anterior,middle and posterior heights of injured vertebrae to evaluate the therapeutic effects of the self-designed double-pivot extracorporeal reduction device.Results The patients were followed up for 6 to 18 months (average,12.3 months).No iatrogenic impairment of nerve root,postoperative infection,or implant failure happened.Compared with preoperation,significant improvements were observed in all the patients regarding cobb's angle,anterior,middle and posterior heights of the fractured vertebral body (P ＜ 0.05).Compared with the single-pivot group,the double-pivot group were significantly superior in the kyphotic angle,correction rate,and anterior and middle heights of the injured vertebrae(P ＜ 0.05),but there was no significant difference between the 2 groups in the recovery of posterior height of the fractured vertebral body (P ＞ 0.05).Conclusion Compared with the single-pivot reduction device,the self-designed double-pivot reduction device may be preferable in percutaneous pedicle screw fixation for thoracolumbar fractures.