BACKGROUND:Tyrosine kinase inhibitors,as well as other types of small-molecule cancer drugs,can cause severe cardiotoxicity. OBJECTIVE:To perform a heart safety re-evaluation by observing the effects of antitumor drugs on isolated heart electrocardiograph,cardiac action potential and associated ion channels and cytotoxicity. METHODS:Extracorporeal cardiac perfusion was given to the isolated rabbit heart using Langendorff perfusion:Sunitinib(0.3,3,10 μmol/L),Crizotinib(0.3,1,3 μmol/L),and Doxorubicin(1,30 μmol/L)were perfused sequentially for 120 minutes to record electrocardiograph and left ventricular pressure.A blank control group was set for comparison.Manual patch clamp was used to record the effects of Crizotinib,Sunitinib,Doxorubicin on hERG,Cav1.2,Nav1.5 channel currents and action potential in human induced pluripotent stem cell derived cardiomyocytes.Adenosine triphosphate level in human induced pluripotent stem cell derived cardiomyocytes was detected by CellTiter-Glo luminescent cell viability assay. RESULTS AND CONCLUSION:Isolated rabbit heart using Langendorff perfusion:Compared with the blank ontrol group,Sunitinib and Crizotinib at≥3 μmol/L decreased heart rate(P<0.01)and prolonged QT/QTc interval(P<0.01),and reduced left ventricular pressure to different extents.Manual patch clamp recording:Compared with the blank control group,Sunitinib and Crizotinib at 3 μmol/L inhibited the activities of hERG,Nav1.5 and Cav1.2 channels and significantly prolonged the duration of action potential(P<0.01).According to the analysis of the test article,the difference between the labeled concentration and the measured concentration of the recovered solution was not significant.Cell viability assays:Compared with the blank control group,adenosine triphosphate content in human induced pluripotent stem cell derived cardiomyocytes significantly decreased after treatment with Sunitinib(IC50=4.64 μmol/L),Doxorubicin(IC50=4.21 μmol/L)and Crizotinib(IC50=2.87 μmol/L),indicating that cell viability significantly decreased(P<0.01).To conclude,this study successfully established an early cardiac safety evaluation method for antitumor drugs,which provides good support and help for the subsequent development of antitumor drugs.

Purpose: To understand the recurrence risk perception of stroke patients and develop a chain mediation model of recurrence risk perception and health behavior. Methods: A cross-sectional study and convenience sampling were used. Stroke survivors were recruited from the neurology departments of three tertiary hospitals. Their recurrence risk perception, behavioral decision-making, social support, self-efficacy, recurrence worry, and health behavior were measured by relevant tools. Data was analyzed through one-way analysis and regression analysis, and the AMOS 21.0 software was used to explore the mediating relationships between variables. Results: Of the 419 participants, 74.7% were aware of stroke recurrence risk. However, only 28.2% could accurately estimate their own recurrence risk. Recurrence risk perception was significantly correlated with behavioral decision-making, social support, self-efficacy, and health behavior (r = .19 ∼ .50, p < .05). Social support and recurrence risk perception could affect health behavior indirectly through self-efficacy, behavioral decision-making, and worry. Behavioral decision-making acted as a main mediator between recurrence risk perception and health behavior, while the path coefficient was .47 and .37, respectively. The chain mediation effect between recurrence risk perception and health behavior was established with a total effect value of .19 (p < .01). Conclusion Most stroke survivors could be aware of recurrence risk but failed to accurately estimate their individual risk. In the mediation model of recurrence risk perception and health behavior, social support seemed to be an important external factor, while self-efficacy, behavioral decision-making, and worry seemed to act as key internal factors.

Purpose: To understand the recurrence risk perception of stroke patients and develop a chain mediation model of recurrence risk perception and health behavior. Methods: A cross-sectional study and convenience sampling were used. Stroke survivors were recruited from the neurology departments of three tertiary hospitals. Their recurrence risk perception, behavioral decision-making, social support, self-efficacy, recurrence worry, and health behavior were measured by relevant tools. Data was analyzed through one-way analysis and regression analysis, and the AMOS 21.0 software was used to explore the mediating relationships between variables. Results: Of the 419 participants, 74.7% were aware of stroke recurrence risk. However, only 28.2% could accurately estimate their own recurrence risk. Recurrence risk perception was significantly correlated with behavioral decision-making, social support, self-efficacy, and health behavior (r = .19 ∼ .50, p < .05). Social support and recurrence risk perception could affect health behavior indirectly through self-efficacy, behavioral decision-making, and worry. Behavioral decision-making acted as a main mediator between recurrence risk perception and health behavior, while the path coefficient was .47 and .37, respectively. The chain mediation effect between recurrence risk perception and health behavior was established with a total effect value of .19 (p < .01). Conclusion Most stroke survivors could be aware of recurrence risk but failed to accurately estimate their individual risk. In the mediation model of recurrence risk perception and health behavior, social support seemed to be an important external factor, while self-efficacy, behavioral decision-making, and worry seemed to act as key internal factors.

Purpose: To understand the recurrence risk perception of stroke patients and develop a chain mediation model of recurrence risk perception and health behavior. Methods: A cross-sectional study and convenience sampling were used. Stroke survivors were recruited from the neurology departments of three tertiary hospitals. Their recurrence risk perception, behavioral decision-making, social support, self-efficacy, recurrence worry, and health behavior were measured by relevant tools. Data was analyzed through one-way analysis and regression analysis, and the AMOS 21.0 software was used to explore the mediating relationships between variables. Results: Of the 419 participants, 74.7% were aware of stroke recurrence risk. However, only 28.2% could accurately estimate their own recurrence risk. Recurrence risk perception was significantly correlated with behavioral decision-making, social support, self-efficacy, and health behavior (r = .19 ∼ .50, p < .05). Social support and recurrence risk perception could affect health behavior indirectly through self-efficacy, behavioral decision-making, and worry. Behavioral decision-making acted as a main mediator between recurrence risk perception and health behavior, while the path coefficient was .47 and .37, respectively. The chain mediation effect between recurrence risk perception and health behavior was established with a total effect value of .19 (p < .01). Conclusion Most stroke survivors could be aware of recurrence risk but failed to accurately estimate their individual risk. In the mediation model of recurrence risk perception and health behavior, social support seemed to be an important external factor, while self-efficacy, behavioral decision-making, and worry seemed to act as key internal factors.

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

Objective:To explore the genetic etiology for a premature ovarian insufficiency (POI) patient from a consanguineous Chinese family, and to provide basis for genetic counseling and fertility counseling.Methods:Whole-exome sequencing was performed using DNA extracted from the blood sample of POI patient. Suspected pathogenic mutation was analyzed by bioinformatics methods and verified by Sanger sequencing. The pathogenicity of the variation was assessed according to the ACMG genetic variation classification criteria and guidelines.Results:A homozygous variation, c. 32G>T (p.G11V), of PSMC3IP was identified in the patient. Bioinformatics analysis revealed that the variation was conserved in different animal species, and this variation was classified as possible pathogenic variation according to the ACMG genetic variation classification criteria and guidelines.Conclusions:The homozygous missense variation of PSMC3IP is the cause of the POI patient in this family. We are reporting for the first time the missense variation in PSMC3IP gene caused POI, which enriched the mutation spectrum of PSMC3IP and provided the basis for genetic counseling and fertility guidance of this family.

Objective:To evaluate the effect of down-regulating lncRNA LINC00263 targeting miR-4458 on the proliferation, migration, invasion and radiosensitivity of breast cancer SK-BR-3 cells.Methods:The expression differences of LINC00263 in breast cancer tissues, adjacent tissues, normal breast epithelial cells and breast cancer cells were determined by qRT-PCR. Transfection of LINC00263 shRNA in breast cancer SK-BR-3 cells down-regulated the expression of LINC00263, and the cloning experiment was used to detect the radiosensitivity. Breast cancer SK-BR-3 cells were treated with 6 Gy irradiation. CCK-8 assay was employed to detect cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Transwell chamber test was performed to detect cell migration and invasion. Western blot was used to detect the expression levels of C-Caspase-3 and C-Caspase-9, MMP-2 and MMP-9 proteins. Bioinformatics software predicted that LINC00263 and miR-4458 had complementary binding sites, and the luciferase reporter system was utilized determine the targeting relationship between LINC00263 and miR-4458. LINC00263 shRNA and miR-4458 inhibitor were co-transfected into breast cancer SK-BR-3 cells, and 6 Gy irradiation was given to detect the changes in cell proliferation, apoptosis, invasion and migration.Results:The expression level of LINC00263 in breast cancer tissues was higher than that in adjacent tissues. The expression level of LINC00263 in breast cancer cells was higher compared with that in normal breast epithelial cells. The radiosensitivity of breast cancer SK-BR-3 cells was increased after transfection of LINC00263 shRNA. Transfection of LINC00263 shRNA and radiation exerted a synergistic effect, jointly inhibited breast cancer cell proliferation, migration and invasion, promoted cell apoptosis, up-regulated the expression levels of C-Caspase-3 and C-Caspase-9 proteins in cells, and down-regulated those of MMP-2 and MMP-9 proteins. Down-regulation of LINC00263 targetedly up-regulated miR-4458 expression. miR-4458 inhibitor reversed the inhibitory effect of LINC00263 shRNA combined with radiation on the proliferation, migration, invasion and apoptosis promotion of breast cancer SK-BR-3 cells.Conclusion:Down-regulating lncRNA LINC00263 targeting miR-4458 inhibits the proliferation, migration and invasion of breast cancer SK-BR-3 cells, and improves cell radiosensitivity.

Objective To investigate the clinical efficacy of vena cava-atrium anastomosis liver transplantation (VCAALT) for Budd-Chiari syndrome (BCS).Methods The retrospective descriptive study was conducted.The clinicopathological data of 18 BCS patients who underwent VCAALT in the Zhongnan Hospital of Wuhan University (6 cases),the Third Xiangya Hospital of Central South University (8 cases) and Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (4 cases) from May 1996 to December 2012 were collected.All the 18 patients were males,aged from 29 to 61 years,with an average age of 42 years.According to characteristics and invasion extent of hepatic vein and vena cava after preoperative examinations,patients were performed different surgical procedures of VCAALT,including bridge piggyback liver transplantation (BPBLT),hanging atrium liver transplantation (HALT) and cava vena resection bridge liver transplantation (CVRBLT).Observation indicators:(1) surgical and postoperative situations;(2) typical case analysis;(3) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival up to December 2018.Measurement data with normal distribution were represented as Mean±SD and measurement data with skewed distribution were described as M (range).Results (1) Surgical and postoperative situations:of 18 patients,11 underwent BPBLT,3 underwent HALT,4 underwent CVRBLT.The operation time and volume of intraoperative blood loss were (6.0± 1.3)hours and (1 264±435)mL.One patient died of bilateral pulmonary diffuse inflammation and sepsis due to severe infection.The duration of postoperative hospital stay was (18±5) days.(2) Typical case analysis:one 47-year-old male BCS patient was detected retrohepatic vena cava plaques and thrombus and hepatic venous thrombus by exploratory laparotomy,and underwent BPBLT.A 43-year-old male BCS patient was detected hepatic and retrohepatic vena cava plaques,thrombus,concomitant cavernous transformation,and underwent HALT.A 32-year-old male BCS patient was detected plaques and thrombus with red thrombus in the hepatic vein,from right renal vein to right atrium,and underwent CVRBLT.All the 3 patients underwent VCAALT successfully with a satisfactory recovery.(3) Followup situations:18 patients were followed up for 3.0-60.0 months,with a median time of 51.7 months.During the follow-up,3 patients died of acute rejection,biliary complications and chronic graft dysfunction at 1,3,5 years postoperatively.The 1-,3-,5-year survival rates were 16/18,15/18,14/18,respectively.Conclusion Different surgical procedures of VCAALT for BCS are selected according to different situations of patients,which are safe and feasible with a satisfactory efficacy and beneficial to long-term survival of patients.

Objective: To describe the molecular epidemiological characteristics of norovirus gastroenteritis outbreaks in Zhuhai from 2011 to 2016. Methods: Anal swab specimens were collected from 576 cases with 56 outbreaks of acute norovirus gastroenteritis from 2011 to 2016. Specimens were tested by real-time RT-PCR. Three to four of norovirus positive specimens were selected from every outbreak to amplify the VP1 gene by RT-PCR and one strain was chosen randomly from every outbreaks to determine the genotype by phylogenetic tree analysis. Results: Eight genotypes were identified from 56 outbreaks and all of them belonged to GⅡ genogroup. The genotype of norovirus strain changed with prevalence time. The GⅡ.4/2006b was dominant from 2011 to 2012, and replaced by GⅡ.4/Sydney _2012 during the 2012—2013 norovirus season, and both of them never appeared after Feb. 2013. GⅡ.17 was the only genotype during the 2014—2015 norovirus season. All the 7 outbreaks occurred from 2015 to 2016 were caused by GⅡ.3 norovirus. The GⅡ.17and GⅡ.3 were identified from Apr. to Sep. 2016; GⅡ.p16-GⅡ.2 were the only genotype in 12 outbreaks from Nov. to Dec. 2016. The GⅠ genogrope was never identified from 2011 to 2016 in Zhuhai. Conclusions The Norovirus GⅡ was the only pathogeny which caused the outbreaks of norovirus gastroenteritis. The recombinant norovirus strain GⅡ.p16-GⅡ.2 emerged and caused large outbreaks in the last two months of 2016 in Zhuhai; several recombinant strains of the GⅡ.p16 RdRp gene were found now, which suggests that attention should be focused on the prevalence and evolution of the recombinant norovirus.

Objective To establish a method for isoimperatorin in Fengshi Bitong capsule and to study the effects of different doses of 60Co irradiation on the content of isoimperatorin. Methods The Agilent C18 column(4.6 mm×150 mm, 5μm) was used with the mobile phase consisted of acetonitrile -water (41:59) ;The flow rate was 1.0 mL?min-1 ,the detection wavelength was at 310 nm,and the column temperature was at 30 ℃ . Results Isoimperatorin showed a good linear relationship within a range of 3.66896-183.448 μg? mL-1( r = 1.0000).The average rate of recovery was 96.42％, RSD = 2.61％.The content of isoimperatorin in Fengshi Bitong capsule did not change significantly when irradiated by 2, 5 and 10 kGy of 60Co. Conclusion The established methods can be used for isoimperatorin determination in Fengshi Bitong capsule with high specificity,accuration and feasibility.The influence was not significant when the irradiation dose was less than 10 kGy.