Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To explore the value of preoperative diffusion tensor imaging (DTI) in predicting motor function outcomes in patients with moderate-volume basal ganglia cerebral hemorrhage after minimally invasive puncture and drainage.Methods:A retrospective study was performed; 54 patients with moderate-volume hypertensive basal ganglia hemorrhage (30-50 mL) admitted to Department of Neurosurgery, First People's Hospital of Chenzhou from March 2018 to December 2019 were enrolled. All patients accepted DTI within 24 h of onset; fractional anisotropy (FA) and mean diffusivity (MD) of the bilateral cerebral peduncles were measured and converted to relative FA (rFA) and relative MD (rMD). Patients accepted minimally invasive puncture and drainage within 24 h of DTI. Motor function score (MFS) was used to evaluate the prognoses of limb motor function 90 d after puncture and drainage; and these patients were divided into good motor function outcome group (MFS scores of 0-3) and poor motor function outcome group (MFS scores of 4-8). The clinical data and DTI indexes were compared between the 2 groups; receiver operating characteristic (ROC) curve was used to analyze the efficacy of rFA in preoperative DTI in predicting limb motor function 90 d after puncture and drainage.Results:Fifty-four patients successfully completed minimally invasive puncture and drainage, without intracranial infection or obvious rebleeding. Twenty-two patients (40.7%) had good motor function outcome and 32 (59.3%) had poor one 90 d after puncture and drainage. No significant difference in age, gender, Glasgow coma scale score at admission, preoperative hematoma volume or postoperative residual hematoma volume was noted between the good function outcome group and poor function outcome group ( P>0.05). Compared with the good function outcome group, the poor function outcome group had statistically lower FA and rFA in the affected side of cerebral peduncles ( P<0.05). ROC curve showed that the area under the curve of preoperative rFA in predicting motor function 90 d after puncture and drainage was 0.984, with cutoff value of 0.78, sensitivity of 100%, and specificity of 96.9%. Conclusion:Preoperative DTI can effectively predict limb motor function 90 d after minimally invasive puncture and drainage in patients with moderate-volume hypertensive basal ganglia hemorrhage.

Plasmids are the most commonly used gene carriers in the field of gene synthesis and sequencing. However, the main problems faced by traditional plasmid DNA extraction technology are low extraction throughput and high production cost, so they cannot meet the growing demand. In this study, a double-magnetic-bead method (DMBM) for plasmid extraction was developed based on the principle of plasmid extraction. The effects of the input of magnetic beads, the size of plasmid DNA fragments, and the volume of bacterial on plasmid DNA extraction were explored. In addition, the quality, throughput, and cost of plasmid DNA extraction were also compared between this technique and the commercial plasmid DNA extraction kits. The results showed that the DMBM can meet the needs of extracting plasmid DNA with different cell densities and fragment lengths. Moreover, the sensitivity and quality of plasmid extraction by the DMBM method were both superior to those of the centrifugal adsorption column method. In addition, this technique could be applied on a 96-channel automated nucleic acid extractor, resulting in higher purity of the extracted plasmid DNA, 80% reduction in extraction time, and 57.1% reduction in cost. It also reduces manual operations, achieving high-throughput and low-cost plasmid DNA extraction, thus may facilitate gene synthesis and sequencing.
Plasmids/genetics* ; DNA/genetics* ; Nucleic Acids ; Genetic Techniques ; Magnetic Phenomena

In recent years, the incidence rate of malignant tumors has been ever increased. As the persistent advancement of various therapeutic techniques, the therapeutic plans of cancer have been improved. Radiotherapy takes effect mainly by killing the topical tumor cells by radiation. During radiotherapy, the anti-tumor immune response can be induced or enhanced. Appropriate radiotherapy dose and segmentation model combined with certain immunotherapy plays a more and more significant role in the treatment of tumors. In this article, the underlying mechanisms of radiation-enhanced anti-tumor immune response and the current status and research prospects of radiotherapy combined with immunotherapy were reviewed.

Objective To explore whether therapeutic dosing timing of proteasome inhibitor bortezomib(BZ) would impact its clinical efficacy .Methods From 2012 to 2018 ,35 biopsy-confirmed cases of acute antibody-mediated kidney transplant rejection (AMR) were collected .They received intravenous immunoglobulin (IVIG) plus sirolimus (Sir) plus bortezomib (BZ) .Three groups were assigned according to dosing timing of BZ .After a diagnosis of AMR ,ET (early treatment ) group began BZ dosing within 7 days (n=16) while DT (delayed treatment) group within 8-14 days (n=11) and LT (late treatment) group > 14 days (n= 8).Their clinical parameters and incidence of complications were analyzed .Results DSA reversal rate of ET ,DT and LT groups was 87 .5％ , 45 .5％ and 25 .0％ (P=0 .006) while DSA declining rate 93 .8％ ,90 .9％ and 50％ respectively (P=0 .019);recurrent rate of AMR was lower in ET/DT group than LT group (6 .6％ vs 10％ vs 75％ , P=0 .042) .No significant differences existed in blood perfusion score of allograft at 1 month post-dosing among three groups .In three groups ,creatinine (Cr) of ET group was lower than DT group at month 1/3/12 while DT group was lower than LT group .No significant difference existed in the incidence of adverse reactions among 3 groups .Conclusions More likely to enter the window period , early dosing of BZ is more effective for treating acute AMR .An earlier intervention yields a better efficacy .

Objective:To examine the role of LY294002 in cardiac function and myocardial structure in dilated cardiomyopathy (DCM) rats.Methods:Fifty-two male SD rats were randomly assigned to a control group (n=16) and a DCM group (n=36).The DCM rats were induced by intraperitoneal injection of adriamycin,and the control rats were given normal saline.After observation for 2 weeks,6 rats from each group were killed randomly.In the end of the 8th week,the 24 DCM rats were randomly assigned to a DCM group (n=12) and a LY294002 group (n=12),which were given normal saline and LY294002,respectively.In the end of the 8th week and 16th week,the cardiac function was analyzed by ultrasonic cardiogram (UCG) and the plasma was collected to test the level of N-terminal pro-brain natriuretic peptide (NT-pro BNP).HE and Van Gieson (VG) staining were performed to calculate the collagen volume fraction (CVF).Results:Compared with the control group,the left ventricular end-diastolic dimension (LVEDD),left ventricular end-systolic dimension (LVESD) and NT-proBNP level of in the DCM rats were increased obviously,while the left ventricular ejection fraction (LVEF),left ventricular fractional shortening (LVFS) in the DCM rats were decreased obviously (P＜0.01).These changes were consistent with DCM characteristics.Compared with the DCM group,the LVEDD,LVESD and NT-proBNP levels in the LY294002 group were decreased,while the LVEF and LVFS were increased (P＜0.05).Histopathology showed that the myocardium in the DCM rats was fibrotic and the CVF was increased compared with the control rats (P＜0.01).The myocardial structure was improved in the LY294002 group compared to the DCM group.Conclusion:LY294002 can reduce the myocardial fibrosis in the DCM rats and improve the cardiac function.

Objective: To observe the expression level of microRNA-181 (miR-181) and importin-α3 in oxidized low density lipoprotein (ox-LDL) induced vascular endothelial cell injury models, and explore the effect and mechanism of miR-181 on endothelial cell injury. Methods: Human vein endothelial cell line CRL-1730 were cultured and vascular endothelial cell injury model was established by intervention with ox-LDL. The cells were divided into control group (intervened by double distilled water), low-dose group (intervened by 10 μg/ml ox-LDL) and high-dose group (intervened by 20 μg/ml ox-LDL). In addition, cells of low-dose group were divided into miR-181 mimic group (miR-181 mimic was transfected) and mimic control group (miR-181 mimic control was transfected). Cell viabilities, mRNA and protein expression level of interleukin-6 (IL-6), miR-181, importin-α3, and nuclear transcription factor-κB (NF-κB) were measured by methyl thiazolyl tetrazolium (MTT), real-time PCR and Western blot, respectively. Results: (1) The cell viabilities in low-dose group and high-dose group were lower than control group (0.207±0.012 and 0.204±0.007 vs. 0.323±0.018, all P<0.01). The relative IL-6 mRNA expression in low-dose group and high-dose group were higher than control group (1.24±0.16 and 1.36±0.23 vs. 0.22±0.03, all P<0.01). The relative miR-181 mRNA expression in low-dose group and high-dose group were lower than control group (0.91±0.11 and 0.88±0.07 vs. 2.20±0.13, all P<0.01). The relative importin-α3 mRNA expression in low-dose group and high-dose group were higher than control group (1.23±0.22 and 0.55±0.03 vs. 0.44±0.06, all P<0.01). The relative NF-κB mRNA expression in low-dose group and high-dose group were higher than control group (1.67±0.34 and 0.41±0.11 vs. 0.11±0.04, all P<0.01). The relative importin-α3 protein expression in low-dose group and high-dose group were higher than control group (1.44±0.23 and 1.31±0.22 vs. 0.29±0.08, all P<0.01). The relative NF-κB protein expression in low-dose group and high-dose group were higher than control group (0.43±0.05 and 0.37±0.04 vs. 0.16±0.03, all P<0.01). (2)The cell viabilities in miR-181 mimic group was higher than in mimic control group (0.262±0.008 vs. 0.211±0.021, P<0.01). The relative miR-181 mRNA expression level in miR-181 mimic group was higher than in mimic control group (4.23±0.34 vs. 0.88±0.16, P<0.01). The relative importin-α3 mRNA expression level in miR-181 mimic group was lower than in mimic control group (0.24±0.03 vs. 1.08±0.13, P<0.01). The relative NF-κB mRNA expression level was lower in miR-181 mimic group than in mimic control group (0.13±0.03 vs. 0.51±0.06, P<0.01). The relative importin-α3 protein expression level was lower in miR-181 mimic group than in mimic control group (0.34±0.06 vs. 1.67±0.26, P<0.01). The relative NF-κB protein expression level was lower in miR-181 mimic group than in mimic control group (0.43±0.02 vs. 1.53±0.36, P<0.01). Conclusions Lower miR-181 expression but higher importin-α3 and its downstream NF-κB signaling are associated with ox-LDL induced vascular endothelial cell injury and up-regulation of miR-181 could alleviate ox-LDL induced vascular endothelial cell injury possibly via importin-α3/NF-κB pathway.

Objective To explore the application value of three-dimensional (3D) visualization combined with portal vein (PV) arterialization technologies in pancreaticoduodenectomy.Methods The retrospective descriptive study was adopted.The clinical data of 1 patient with duodenal cancer who was admitted to the Chenggong Hospital of Xiamen University in August 2015 were collected.The preoperative plain scan images in the upper abdomen and enhanced scan images in the arterial and PV phases using 320-slice spiral CT were converted to the 3D images by 3D visualization technology.The 3D data were used for detecting tumor invading pancreatic head and organizational structure surrounding hepatic hilus,and making a preliminary surgical plan.Open exploration found that tumor involved pancreatic head and didn't invade superior mesenteric artery and vein,and then pancreaticoduodenectomy was applied to the patient during operation.Intraoperative proper hepatic artery-PV end-to-side anastomosis was used for increasing R0 resection rate.Operation time,volume of intraoperative blood loss,result of postoperative pathological examination,liver function and complication and vascular patency at postoperative week 1 and vascular patency at postoperative month 1 were observed.The patient underwent color Doppler ultrasound and digital subtraction angiography (DSA) at postoperative month 1 in order to detect blood vessels,and was followed up by outpatient examination for observing tumor till November 2015.Results There was a clear and solid 3D reconstruction model between anatomical position of tumor and blood vessels,and preoperative assessment was consistent with intraoperative finding.Operation time and volume of intraoperative blood loss were 6.5 hours and about 1 500 mL.The patient was confirmed as intestinal diffuse large B-cell lymphoma by postoperative pathological examination.The patient had normal liver function at postoperative week 1 and discharged from hospital at postoperative week 2,without abdominal secondary hemorrhage,infection,pancreatic fistula,intestinal fistula and other severe complications.PV blood flowing was normal by color Doppler ultrasonography at postoperative week 1 and month 1.DSA examination showed that there was no proper hepatic artery images and visible compensatory liver artery at postoperative month 1.During follow-up,no tumor recurrence was detected.Conclusion 3D reconstruction model can provide an accurate preoperative assessment,and PV arterialization technology for unreserved hepatic artery has a certain degree of clinical value in pancreaticoduodenectomy.

OBJECTIVE: To analyze the characteristics of left ventricular rotation and twist in patients with silent myocardial ischemia (SMI) by three-dimensional speckle tracking echocardiography (3D-STE), and to explore the diagnostic value of this method for SMI.
 METHODS: According to Gensini score, 66 patients with SMI were divided into 3 subgroups: a mild lesion group (n=16), a moderate lesion group (n=26) and a severe lesion group (n=24). Thirty patients with negative results in selective coronary angiography served as a control group. The parameters of wall motion score index (WMSI), left ventricular ejection fraction (LVEF), peak basal rotation (Ptw-B), peak apical rotation (Prot-A), left ventricular peak apical rotation (LVrot), left ventricular peak apical twist (LVtw) were measured.
 RESULTS: In the SMI group, with an increase in severity of myocardial ischemia, LVEF, Prot-A, Prot-B, LVrot, LVtw showed a decrease trend while WMSI exhibited an opposite phenomenon (P<0.05), and all of them displayed a significant corelation with Gensini score (P<0.05). In the diagnosis of SMI, all of the above-mentioned parameters were highly sensitive and specific. 3D-STE showed the highest diagnostic value for LVtw.
 CONCLUSION Left ventricular rotation and twisting motion monitered by 3D-STE can evaluate the severity of myocardial ischemia in patients with SMI.
Coronary Artery Disease ; Echocardiography, Three-Dimensional ; Heart Ventricles ; Humans ; Myocardial Ischemia ; Rotation ; Ventricular Function, Left

Objective To investigate the mechanism of protective effects of resveratrol on tissueengineered cartilage.Methods The chondrogenesis of alginate-encapsulated bone marrow mesenchymal stem cells (BMSCs) were evaluated by toluidine blue staining and immunostain.The morphology of BMSCs-derived chondrocytes cultured on chitosan-gelatin scaffolds (CGS) was evaluated by scanning electron microscope and laser confocal microscope.When these cells on CGS were pre-stimulated with interleukin-1β (IL-1β) or cotreated with IL-1β and resveratrol in the absence and presence of specific β1-integrin blocking antibody,collagen type Ⅱ,aggrecan,matrix metalloproteinase-13 (MMP-13) expression,and the translocation of nuclear factor kappaB (NF-κB) were analyzed by Western blotting.ANOVA was used for statistical analysis.Results Alginate bead culture plus conditional medium together could induce the cartilage-specific collagen type Ⅱ,aggrecan expression and extracellular matrix accumulation in differentiated chondrocytes.CGS supported differentiated cell attachment,proliferation,and migration.When those cells cultured on CGS were stimulated with IL-1β alone,collagen type Ⅱ and aggrecan expression was inhibited.However,MMP-13 expression increased.By Western blotting semi-quantitative analysis,the expression level of cartilage-specific collagen type Ⅱ of the control group was 0.484±0.006; the expression level of resveratrol intervention group was 0.474±0.014.The difference between these two groups was not statistically significant (P＞0.05).The expression level of the IL-1β intervention group reduced to 0.155±0.009,which was statistically significant different from the above two groups(P＜0.05).Resveratrol could antagonist the negative effect of IL-1β,and increase collagen type Ⅱ to 0.468±0.014,the difference between these two was statistically significant (P＜0.05),and no significant difference when compared to the control group (P＞0.05).Specific β1-integrin blocking antibody could abrogate these effects of resveratrol,decrease collagen Ⅱ expression to 0.169±0.011,the difference was significant (P＜0.05),but there was no difference when compared to the IL-1β group (P＞0.05).Aggrecan semi-quantitative expression has the same trend in the expression of type Ⅱ collagen while the expression of MMP-13,NF-κB had the reversal trend.These indicated that the resveratrol reversed the catabolic effects by reducing the nuclear translocation of NF-κB.Specific β1-integrin blocking antibody abrogated these effects of resveratrol.Conclusion Resveratrol,by regulating β1-integrin,acts as a NF-κB nuclear trans-location inhibitor to protect tissue-engineered cartilage.