Objective To investigate the efficiency of Trichostatin A (TSA) in inducing cell apoptosis and altering the Notch pathway genes expression in PANC-1 cells line.Methods The survival rate and apoptosis of PANC-1 cells were measured by MTT assay and Hoechst 33258 staining,respectively.mRNA expression levels of the genes,numb,gcn512,dll3,hes6,eaf2,cytohesins,in PANC-1 cells were assessed by real-time quantitive PCR.Western blot was used to measure the expression of bcl-2,bax,actived caspase-3 and NICD protein which was the biologically active form of Notch-1.Results After culturing with 0.1,0.2,and 0.4 μmol/L TSA for 24 hours,the cellular survival rate of PANC-1 cells significantly decreased to 72％,58％ and 39％,respectively.The survival rate of PANC-1 was negatively correlated to time length of culture with TSA.Increased apoptosis of PANC-1 cells after 12,24 and 36 h culture with TSA was detected by Hoechst 33258 staining.Western blotting showed that the expression of bax,actived caspase-3 and NICD protein increased while the bcl-2 protein decreased after culture with TSA.In real time quantitive PCR assessment,the mRNA expression of numb and hes6 in PANC-1 cells were upregulated by TSA (P ＜ 0.05),while the mRNA expression of gcn512 and dll3 were down-regulated by TSA (P ＜ 0.05).While mRNA expressions of eaf2 and cytohesin1,2,3,4 were not affected by TSA.Conclusions TSA induces apoptosis of pancreatic cancer cell line PANC-1.The Notch signal pathway may be involved in inducing cellular apoptosis of PANC-1 when cultured with TSA.

BACKGROUND: Intra-articular injection is a classic strategy for the treatment of early osteoarthritis (OA). However, the local delivery of traditional therapeutic agents has limited benefits for alleviating OA. Exosomes, an important type of extracellular nanovesicle, show great potential for suppressing cartilage destruction in OA to replace drugs and stem cellbased administration. METHODS: In this study, we developed a thermosensitive, injectable hydrogel by in situ crosslinking of Pluronic F-127 and hyaluronic acid, which can be used as a slow-release carrier to durably retain primary chondrocyte-derived exosomes at damaged cartilage sites to effectively magnify their reparative effect. RESULTS: It was found that the hydrogel can sustainedly release exosomes, positively regulate chondrocytes on the proliferation, migration and differentiation, as well as efficiently induce polarization of M1 to M2 macrophages. Intraarticular injection of this exosomes-incorporated hydrogel significantly prevented cartilage destruction by promoting cartilage matrix formation. This strategy also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+ regenerative M2 macrophages over CD86+ M1 macrophages in synovial and chondral tissue, with a concomitant reduction in pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and increase in anti-inflammatory cytokine (IL-10) in synovial fluid. CONCLUSION Our results demonstrated that local sustained-release primary chondrocyte-derived exosomes may relieve OA by promoting the phenotypic transformation of macrophages from M1 to M2, which suggesting a great potential for the application in OA.

Objective:To develop a prediction model based on imaging features by contrast-enhanced MRI radiomics combined with clinical features for early recurrence of hepatocellular carcinoma (HCC) after radical resection.Methods:A retrospective study was carried out on 109 HCC patients who underwent radical resection at the Fifth Affiliated Hospital of Wenzhou Medical University from January 2015 to December 2020. Of 109 patients enrolled in this study, there were 96 males and 13 females, aged (58.3±10.7) years. Based on whether there was recurrence within 12 months after operation, the patients were divided into the early recurrence group ( n=31) and the control group ( n=78). These 109 patients were then randomly divided into the validation set ( n=23) and the training set ( n=86) at a ratio of 1∶4. Based on preoperative multi-phase contrast-enhanced MRI scanning, the tumor lesions were delineated on the Radcloud platform, and 1 409 quantitative radiomic features were extracted. Dimension reduction and screening of these features were carried out using variance threshold, SelectKBest and LASSO. Combined with clinical features (alpha fetoprotein, tumor size), several prediction model were established through machine learning. The predictive efficiencies of these models were evaluated using the area under the receiver operating characteristic (ROC) curve, accuracy rate, recall rate and balanced F score. Results:The proportions of irregular tumor shape and unclear tumor boundary, as well as maximum tumor diameter in the early recurrence group were significantly higher than that in the control group, but the proportion of pseudocapsule was significantly lower than that in the control group (all P<0.05). A total of 465 features were screened from the 1 409 features using the variance threshold method, followed by 38 features were screened using the method of SelectKBest. Finally 7 optimal radiomic features were screened based on the LASSO method. When combined with clinical features, 5 prediction models were established through machine learning. These models were support vector machine, Gaussian naive bayes, logistic regression, Multinomial naive bayes and K-nearest neighbor (KNN), respectively. Among these 5 models, the prediction efficiency of the KNN model was relatively highest, with the area under the ROC curve, accuracy rate, recall rate and balanced F score being 0.90, 0.98, 0.74 and 0.84 in the training set, and 0.76, 0.92, 0.75 and 0.83 in the verification set, respectively. Thus, the KNN model was selected as the best prediction model in this study. Conclusion:The prediction model of KNN was developed for early recurrence of HCC after radical resection based on preoperative contrast-enhanced MRI radiomics combined with clinical features.

Objective:To investigate the urodynamic characteristics in Parkinson's disease(PD)versus multiple system atrophy(MSA)patients with lower urinary tract symptoms(LUTS).Methods:We performed a retrospective study in PD and MSA patients admitted to the First Affiliated Hospital of Zhengzhou University and undergone urodynamic examinations from January 2016 to June 2019.A total of 178 patients, mean age(59.2±9.7)years were enrolled, with 64 PD patients, 74 MSA patients and 40 normal controls.Urodynamic parameters included maximum flow rate(Qmax), post-voided residual urine volume(PVR), bladder compliance(BC), overactive bladder(OAB), maximum cystometric capacity(MCC)and detrusor pressure at maximum flow rate(PdetQmax). Bladder function was assessed.Results:Frequent urination(68.8%)was the most common LUTS in PD patients, as opposed to urinary retention(91.9%)in MSA patients.The Qmax, PdetQmax and incidence of OAB were higher and the PVR were lower in PD patients than in MSA patients [free-flow(FF)-Qmax: (13.5±7.1)ml/s vs.(10.1±5.2)ml/s, U=26.98, P<0.01]; pressure-flow study(PFS)-Qmax: [(13.6±5.7)ml/s vs.(10.5±3.3)ml/s, U=34.90, P<0.01]; PFS-PdetQmax: [(23.9±11.3)cm H 2O vs.(16.3±8.6)cmH 2O, U=35.04, P<0.01]; OAB: (46.9% vs.27.0%, χ2=5.85, P<0.01); FF-PVR: [(30.4±20.0)ml vs.(161.7±79.8)ml, U=-71.81, P<0.01]; PFS-PVR: [(65.9±30.7)ml vs.(212.6±83.0)ml, U=-65.29, P<0.01]. Compared with the control group, the incidences of OAB and PFS-PVR were increased and the MCC and PdetQmax were decreased in the PD group(OAB: 46.9% vs.7.5%, χ2=6.15, P<0.018); PFS-PVR: [(65.9±30.7)ml vs.(22.2±10.4)ml, U=47.25, P<0.01]; MCC: [(305.1±79.7)ml vs.(389.6±65.2)ml, U=-52.13, P<0.01]; PdetQmax: [(23.9±11.3)cmH 2O vs.(37.3±10.3)cmH 2O, U=-49.88, P<0.01]. Compared also with the control group, the MSA group had a lower Qmax, PdetQmax and MCC, FF-Qmax: [(10.1±5.2)ml/s vs.(16.3±4.7)ml/s, U=-50.11, P<0.01]; PFS-Qmax: [(10.5±3.3)ml/s vs.(13.1±5.0)ml/s, U=-27.54, P<0.05]; PdetQmax: [(16.3±8.6)cmH 2O vs.(37.3±10.3)cmH 2O, U=-84.92, P<0.01]; MCC: [(284.3±71.8)ml vs.(389.6±65.2)ml, U=-39.31, P<0.01], a higher PVR, lower bladder compliance(BC)and a higher incidence of OAB(FF-PVR: [(161.7±79.8)ml vs.(22.0±13.0)ml, U=84.82, P<0.01]; PFS-PVR: [(212.6±83.0)ml vs.(22.2±10.4)ml, U=112.54, P<0.01]; BC: (28.4% vs.7.5%, χ2=6.81, P<0.01); OAB: (27.0% vs.7.5%, χ2=17.62, P<0.01). Conclusions:PD and MSA patients with LUTS have bladder dysfunction.MSA patients have more serious bladder dysfunction than PD patients.