ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A （IDH3A） on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers （n=10） and patients with heart failure （HF） （n=10）， and in the myocardium of mice subjected to transverse aortic constriction （TAC） surgery and sham operation， as well as in phenylephrine （PE）-induced neonatal rat ventricular cardiomyocytes （NRVCs）， was assessed by real-time quantitative polymerase chain reaction （RT-qPCR） and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity， IDH3A_D208A， was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype， ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid （AKG） on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay， respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients， in the myocardium of TAC-operated mice， and in PE-induced NRVCs （P = 0.005 2，P = 0.026 6，P = 0.041 3 and P = 0.006 6， respectively）. Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs （P < 0.000 1， P = 0.000 1 and P = 0.000 2， respectively）. The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs （P = 0.001 2 and P<0.000 1， respectively）， whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could， but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level， providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1（SLC8A1） mRNA in the myocardium of healthy organ donors （n=24） and heart failure （HF） patients （n=21） were assessed by real-time quantitative polymerase chain reaction （RT-qPCR） assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts （mCFs） with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay， respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation （RIP） was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 （Idh2） mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients， while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression， and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA （siRNA） could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.

Objective:To investigate the clinical value of magnetic resonance imaging (MRI) plain scan and diffusion weighted imaging (DWI) in the diagnosis of brain metastases.Methods:The MRI plain imaging findings of 105 cases with brain metastases and 103 cases without brain metastases confirmed by enhanced MRI examination and clinical diagnosis were retrospectively analyzed. The comparisons of plain MRI findings including T1 weighted image (T1WI), T2WI, T2/fluid attenuated inversion recovery (T2/FLAIR), DWI and apparent diffusion coefficient (ADC) values were made between brain metastases and non-brain metastases.Results:The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T1WI in the brain metastatic group were 54, 23, 9 and 19, respectively, while the numbers of hypo-intensity and iso-intensity in the non-brain metastatic group were 52 and 51, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI in the brain metastatic group were 1, 9, 72 and 23, respectively, while the numbers of iso-intensity and hyper-intensity in the non-brain metastatic group were 11 and 92, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, hyper-intensity and heterogeneous signal intensity of DWI in the brain metastatic group were 4, 31 and 65, respectively, while the number of hyper-intensity in the non-brain metastatic group was 4 and others were iso-intensity, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI/FLAIR in the brain metastatic group were 4, 5, 60 and 36, respectively, while all cases in the non-brain metastatic group were hyper-intensity, with statistically significant difference ( P<0.001). The number of lesion accompanied with peripheral edema in the brain metastatic group were 69 cases, significantly higher than 0 cases in the non-brain metastatic group ( P<0.001). The mean ADC value in the brain metastatic group were (0.919±0.019)×10 -3 mm 2/s, significantly lower than (1.098±0.012)×10 -3 mm 2/s of non-brain metastatic group ( P<0.05). Conclusions:For patients with a history of primary malignancy, the MRI plain scan signals of T1WI, T2WI, T2WI/FLAIR and DWI are significantly different between brain metastatic tumor and non-metastatic tumor. The mixed signal, peripheral edema and the restriction of DWI diffusion indicate brain metastases. The combined application of the above parameters can improve the diagnostic efficacy of predicting brain metastases, and contrast enhancement MRI examination should be performed for the confirmation of diagnosis.

Objective:To investigate the clinical value of magnetic resonance imaging (MRI) plain scan and diffusion weighted imaging (DWI) in the diagnosis of brain metastases.Methods:The MRI plain imaging findings of 105 cases with brain metastases and 103 cases without brain metastases confirmed by enhanced MRI examination and clinical diagnosis were retrospectively analyzed. The comparisons of plain MRI findings including T1 weighted image (T1WI), T2WI, T2/fluid attenuated inversion recovery (T2/FLAIR), DWI and apparent diffusion coefficient (ADC) values were made between brain metastases and non-brain metastases.Results:The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T1WI in the brain metastatic group were 54, 23, 9 and 19, respectively, while the numbers of hypo-intensity and iso-intensity in the non-brain metastatic group were 52 and 51, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI in the brain metastatic group were 1, 9, 72 and 23, respectively, while the numbers of iso-intensity and hyper-intensity in the non-brain metastatic group were 11 and 92, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, hyper-intensity and heterogeneous signal intensity of DWI in the brain metastatic group were 4, 31 and 65, respectively, while the number of hyper-intensity in the non-brain metastatic group was 4 and others were iso-intensity, respectively, with statistically significant difference ( P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI/FLAIR in the brain metastatic group were 4, 5, 60 and 36, respectively, while all cases in the non-brain metastatic group were hyper-intensity, with statistically significant difference ( P<0.001). The number of lesion accompanied with peripheral edema in the brain metastatic group were 69 cases, significantly higher than 0 cases in the non-brain metastatic group ( P<0.001). The mean ADC value in the brain metastatic group were (0.919±0.019)×10 -3 mm 2/s, significantly lower than (1.098±0.012)×10 -3 mm 2/s of non-brain metastatic group ( P<0.05). Conclusions:For patients with a history of primary malignancy, the MRI plain scan signals of T1WI, T2WI, T2WI/FLAIR and DWI are significantly different between brain metastatic tumor and non-metastatic tumor. The mixed signal, peripheral edema and the restriction of DWI diffusion indicate brain metastases. The combined application of the above parameters can improve the diagnostic efficacy of predicting brain metastases, and contrast enhancement MRI examination should be performed for the confirmation of diagnosis.

Objective: To study laparoscopic ultrasound assisted hepatectomy in treatment of intrahepatic and extrahepatic bile duct stones. Methods: The data of 52 patients with hepatolithiasis who underwent laparoscopic hepatectomy from May 2014 to January 2019 at the Fuyang District First People's Hospital in Hangzhou were analyzed retrospectively. There were 28 men and 24 women. The median age was 56 years. Operative laparoscopic ultrasonography was used to detect the location, size, distribution of stones and their relations to blood vessels. A total of 43 patients underwent anatomic hepatectomy, while 38 patients underwent choledochoscopic stone extraction. A " T" tube was used according to intraoperative conditions. Results: Laparoscopic surgery was successfully carried out in 50 patients, while conversion to open surgery was required in 2 patients because of adhesions and bleeding. Laparoscopic ultrasonography revealed intrahepatic calcifications in 5 patients and choledochoscopy in 2 patients. Postoperative complications included 5 patients who devleoped abdominal abscesses. The operation time was (289.0±132.0) minutes. The intraoperative blood loss was (451.0±256.0) ml. The hospitalization after operation was (12.0±3.0) days. In 52 patients, 4 patients had residual stones and the residual rate was 7.7%. All of them were completely removed by T-tube sinus 8 weeks after operation. Conclusions Laparoscopic ultrasound helped to detect relevant bile ducts containing stones, reduced chance of bleeding in surgery, helped to clarify location and distribution of stones, improved accuracy of diagnosis, and reduced unnecessary hepatectomy by clearly defining intrahepatic bile duct stones intraoperatively. The residual intrahepatic and intrahepatic bile duct stones rates were reduced, and the safety and accuracy of the operations were improved.

PURPOSE: Although the effect of lysosome-associated protein transmembrane 4 beta (LAPTM4B) on the proliferation, migration, and invasion of breast cancer (BC) cells has already been studied, its specific role in BC progression is still elusive. Here, we evaluated the effect of different levels of LAPTM4B expression on the proliferation, invasion, adhesion, and tumor formation abilities of BC cells in vitro, as well as on breast tumor progression in vivo. METHODS: We investigated the influence of LAPTM4B expression on MCF-7 cell proliferation, invasion, adhesion, and tube formation abilities in vitro through its overexpression or knockdown and on breast tumor progression in vivo. RESULTS: Cell growth curves and colony formation assays showed that LAPTM4B promoted the proliferation of breast tumor cells. Cell cycle analysis results revealed that LAPTM4B promoted the entry of cells from the G1 into the S phase. Transwell invasion and cell extracellular matrix adhesion assays showed that LAPTM4B overexpression increased the invasion and adhesion capabilities of MCF-7 cells. More branches were observed in MCF-7 cells overexpressing LAPTM4B under an electron microscope. In comparison with LAPTM4B overexpression, LAPTM4B knockdown decreased the expression of vascular endothelial growth factor-A and significantly inhibited the vasculogenic tube formation ability of tumors. These results were also verified with western blot analysis. CONCLUSION: LAPTM4B promoted the proliferation of MCF-7 cells through the downregulation of p21 (WAF1/CIP1) and caspase-3, and induced cell invasion, adhesion, and angiogenesis through the upregulation of hypoxia-inducible factor 1 alpha, matrix metalloproteinase 2 (MMP2), and MMP9 expression. This specific role deems LAPTM4B as a potential therapeutic target for BC treatment.
Blotting, Western ; Breast Neoplasms ; Breast ; Caspase 3 ; Cell Cycle ; Disease Progression ; Down-Regulation ; Extracellular Matrix ; Hypoxia-Inducible Factor 1 ; In Vitro Techniques ; Matrix Metalloproteinase 2 ; MCF-7 Cells ; S Phase ; Up-Regulation ; Vascular Endothelial Growth Factor A

Objective To study epidemic of schistosomiasis in the Qiandao Lake reservoir area,and to provide a reference for prevention and control of schistosomiasis in the construction of large water conservancy projects in the epidemic area of schistosomiasis.Methods The data over the years of snail condition and monitoring of schistosomiasis before and after building the dam,and water conservancy project reconstruction related information were collected.Based on the survey results of the river channel,the lake beach and the dissipation zone in the reservoir area,the influence of Xin'an River water conservancy project on epidemic of schistosomiasis in the Qiandao Lake reservoir area was analyzed,and the epidemic factors of the schistosomiasis in the Three Gorges reservoir were compared and analyzed.Results Before the dam was built,an area of 38 144 000 m2 was examined but Oncomelania was undetected.The Qiandao Lake reservoir area belonged to a non epidemic area of schistosomiasis.After the dam was built,557 cases of schistosomiasis were found in 6 232 immigrants during 1962-1965,resulting in an imported epidemic.In 1970-1980,an area of 379 654 m2 in which Oncomelania was found was examined and snails were mainly distributed in some rice fields and ditches in the end of the reservoir.949 cases of local schistosomiasis were found in the snails.The condition and condition of the snail are gradually controlled through several decades of comprehensive prevention and control.Compared with the epidemic factors of schistosomiasis in Qiandao Lake and the Three Gorges reservoir,the environment of elevation beach and ecologically fragile fluctuation zone coexist in the two reservoir areas.Conclusion From the long-term longitudinal monitoring data of the Qiandao Lake reservoir area and the epidemic regularity of schistosomiasis and the comparison with the ecology of the Three Gorges reservoir,it is concluded that the two reservoir areas will not cause a large range of schistosomiasis epidemic in general,but it does not exclude the possibility of the breeding of the inputting Oncomelania.

Objective To analyze the related factors of donor′s donation reaction in first time apheresis platelets to provide a basis for formulating the preventive measures of donation reactions in apheresis platelets.Methods The donation data in 743 cases of first time apheresis platelet in this blood station were retrospectively analyzed,and the factors possible influencing the donation reaction occurrence in donors of the first time apheresis platelet were performed the univariate Logistic regression analysis,then observation indicators with statistical significance were performed the multivariate Logistic regression analysis.Results The univariate Logistic regression analysis showed that gender,age,body mass,whole blood donation history were the influencing factors of donors′ donation reaction in the first time apheresis platelets.In multivariate Logistic regression analysis,the main factors were age (OR=0.301,P<0.05),body mass (OR=0.411,P<0.05)and whole blood donation history(OR=0.441,P<0.05).Conclusion Age,body mass and whole blood donation history are the main influencing factors of donors′ donation reactions in the first time apheresis platelets.

Objective To study the effects of experiment-related factors on hematological parameters in SD rats, analyze the data difference and causes, understand the effects of anesthetics and stress responses on the physiological aspects of animals, and to provide a reference for the standardization of animal welfare and compound toxicity testing methods.Methods According to gender (A), fasting time (B), anesthesia (C) and blood collection mode (D), SPF SD rats were divided into 24 groups.Blood samples were collected from each group.Then, red blood cell count, hemoglobin levels, white blood cell count and classification indicators were measured.Results The primary and secondary order of the factors affecting the white blood cell count was D > C > A > B, and the levels of white blood cell count of each factor were male rats > female rats, and venous blood > arterial blood, chloral hydrate > pentobarbital sodium > no anesthesia.The primary and secondary order of the factors affecting the white blood cell classification was C > D=A=B, and factors affecting the levels of white blood cell classification were chloral hydrate > pentobarbital sodium > no anesthesia.The primary and secondary order of the effects of the factors on the red blood cell count and hemoglobin level was C > D=A=B, and the levels of red blood cell count and hemoglobin level were pentobarbital sodium > chloral hydrate> no anesthesia.There was no significant difference in the blood indexes between the different fasting time groups.Conclusions There is no effect of fasting on hematological parameters, but there are differences in the blood parameters between arteries and veins.The effect of chloral hydrate anesthesia on the count and classification of white blood cells is greater than that of pentobarbital sodium.The effect of chloral hydrate anesthesia on the red blood cell count and hemoglobin level is greater than that of pentobarbital sodium.The two kinds of anesthesia methods have their own advantages and disadvantages.

Objective To evaluate the effect of evidence-based bundle intervention strategy on reducing the inci-dence of central line-associated bloodstream infection (CLABSI).Methods Prospective and multicenter study was adopted,patients admitted to 54 intensive care units (ICUs)of 41 hospitals and with central venous catheters (CVCs)between October 1 ,2013 and September 30,2014 were monitored .Baseline data between October 2013 and March 2014 were collected as pre-intervention data;from April to September 2014,the participated hospitals performed intervention strategy,post-intervention data were compared with pre-intervention data.Results The usage rate of CVCs before and after intervention was significantly different (44.18% vs 44.63%,χ2 =5.526,P =0.019).Incidence of CLABSI before and after intervention was not significantly different(RR ,0.82[95%CI ,0.59-1 .13],P =0.10).Constituent ratio of catheter insertion sites between pre-and post-intervention was significantly different (χ2 =76.264,P <0.001),femoral vein catheterization rate as well as proportion of two and above catheter insertion sites after intervention decreased(17.25% VS 13.72%;2.27% VS 1 .44%,respectively);hand hygiene implementation rate and accuracy rate after intervention were both higher than before intervention (79.73% vs 76.14%,P <0.001 ;91 .47% vs 74.26%,P <0.001 ,respectively);constituent ratio of skin disinfectant applica-tion before and after intervention was significantly different(χ2 =3.861 ,P <0.001 ),proportion of chlorhexidine ethanol increased (29.62% VS 50.56%);except daily assessment and record,compliance to other prevention and control measures before and after intervention were all significantly different(all P <0.001);utilization rate of max-imal sterile barrier,qualified rate of dressing of operators,and port disinfection were all significantly enhanced. Conclusion Bundle intervention in intubation and maintenance are implemented effectively,but intervention effect on CLABSI needs further study.