The pattern of alternative splicing and DNA methylation alteration and their interaction in linseed (Linum usitatissimum L) response to repeated drought stresses

BACKGROUND: Drought stress has significantly hampered agricultural productivity worldwide and can also result in modifications to DNA methylation levels. However, the dynamics of DNA methylation and its association with the changes in gene transcription and alternative splicing (AS) under drought stress are unknown in linseed, which is frequently cultivated in arid and semiarid regions. RESULTS: We analysed AS events and DNA methylation patterns in drought-tolerant (Z141) and drought-sensitive (NY-17) linseed under drought stress (DS) and repeated drought stress (RD) treatments. We found that the number of intron-retention (IR) and alternative 3' splice site (Alt3'SS) events were significantly higher in Z141 and NY-17 under drought stress. We found that the linseed response to the DS treatment was mainly regulated by transcription, while the response to the RD treatment was coregulated by transcription and AS. Whole genome-wide DNA methylation analysis revealed that drought stress caused an increase in the overall methylation level of linseed. Although we did not observe any correlation between differentially methylated genes (DMGs) and differentially spliced genes (DSGs) in this study, we found that the DSGs whose gene body region was hypermethylated in Z141 and hypomethylated in NY-17 were enriched in abiotic stress response Gene Ontology (GO) terms. This finding implies that gene body methylation plays an important role in AS regulation in some specific genes. CONCLUSION: Our study is the first comprehensive genome-wide analysis of the relationship between linseed methylation changes and AS under drought and repeated drought stress. Our study revealed different interaction patterns between differentially expressed genes (DEGs) and DSGs under DS and RD treatments and differences between methylation and AS regulation in drought-tolerant and drought-sensitive linseed varieties. The findings will probably be of interest in the future. Our results provide interesting insights into the association between gene expression, AS, and DNA methylation in linseed under drought stress. Differences in these associations may account for the differences in linseed drought tolerance.

MicroRNA-141-3p expression in serum of patients with cerebral hemorrhage and its mechanism / 解剖学报

Objective To analyze the expression level of microRNA-141-3p (miR-141-3) in patients with intracerebral hemorrhage (ICH), and explore the effect and mechanism of miR-141-3p on cerebral hemorrhage injury in rats. Methods Forty patients with ICH and 40 healthy controls in total were enrolled in this study. The expression of miR- 141-3p in peripheral blood serum was determined by the Real-time PCR method. The target relationship between miR-141- 3p and NOD-like receptor 3 (NLRP3) 3′ UTR was confirmed by dual luciferase reporter assay. miR-141-3p agonist and agonist NC were injected into rats via the lateral ventricle, respectively. On day 7 after treatment, the neurological function score was evaluated, and then all rats were killed to obtain brain tissue. Brain water content was examined by the dried and wet mass. HE staining was conducted to observe the pathological changes of cerebral tissue. The mRNA expressions of NLRP3 and miR-141-3p were detected by Real-time PCR. The protein expression of interleukin (IL)-lβ, IL-6 and IL-18 were detected by Western blotting analysis. Results The expression of miR-141-3p in serum of ICH patients was significantly down-regulated compared to healthy controls and negatively correlated with the severity of edema around the hematoma [(0.068±0.038) vs (0.520±0.028), t = 15.93, P<0.001; r =-0.8948, -0.9434 to-0.8087, P<0.001 ]. The result of luciferase reporter assay showed that miR-141-3p was related to the regulation of NLRP3 gene expression. The relative expression levels of miR-141-3p in agonist group were significantly higher than those in the agonist NC group (P< 0.001), while the expression levels of NLRP3, IL-lβ, IL-6 and IL-18 were significantly lower than those in the agonist NC group (P< 0.001). Compared with the agonist NC group, the cerebral water content reduced significantly (P< 0.001), and the neurological function score was significantly improved on the day 7 after treatment in agonist group (P< 0.001). The result of HE staining showed that injection of miR-141-3p in ICH rats could reduced the severity of edema around the hematoma. Conclusion MiR-141-3p alleviates ICH-induced inflammatory injury in rat possibly by modulating miR-141-3p.

Effect of early continuous blood purification on the prognosis of children with septic shock: a prospective randomized controlled clinical trial / 中国当代儿科杂志

OBJECTIVE@#To study the effect of early continuous blood purification (CBP) on the prognosis of children with septic shock.@*METHODS@#A prospective analysis was performed for the children with septic shock who did not reach the 6-hour initial recovery target and/or had a fluid overload of >10%. According to the treatment time of CBP, they were divided into an early group with 30 children and a conventional group with 28 children. The two groups were compared in terms of the start time of CBP and 28-day mortality rate, as well as the related indexes in the children who were cured.@*RESULTS@#The early group had a significantly earlier start time of CBP than the conventional group (P0.05). The children who were cured in the early group had significantly shorter correction time of lactic acid, urine volume, and fluid overload than those in the conventional group (P10%, early CBP treatment can quickly control the disease, shorten the course of disease, and accelerate immune reconstruction.

Curative Effect of Simply Hormone and Combined Gamma Globulin and Thrombopoietin on Primary Immune Thrombocytopenia / 中国实验血液学杂志

OBJECTIVE@#To investigate the curative effect of simply hormone and combined gamma globulin and thrombopoietin(TPO) on primary immune thrombocytopenia(PITP).@*METHODS@#100 patients with PITP were divided into simply drug groups, and combined drug group each for 50 cases. The patients in single drug group were given simply hormone therapy, the patients in combined drug group were given gamma globulin and thrombopoietin. The levels of TPO, platelet activating factor (PAF) were detected by DAS-ELISA. The differences of clinical curative effect, clinical indicators, biochemical indexes and adverse reactions between the two groups were compared.@*RESULTS@#The total effective rate of combined drug group (90.00%) was obviously higher than that in single drug group (66.00%)(P0.05), however, the above-mentioned indexes of two groups after treatment were lower than those before treatment (P0.05), the recurrence rate in combined drug group(2%) was obviously lower than that in single group(14.00%) (P<0.05).@*CONCLUSION@#The curative effect of hormone, as well as gamma globulin combined with TPO to treat PITP are satisfying, can obviously improve the levels of TPO, PAF, and the drug safety is higher. but the efficacy of combined drug is surperior to single drug.

Design and Implementation of A Portable Mobile Controlled Transcranial Direct Current Stimulator / 中国康复理论与实践

Objective:To design and implement a low-power and portable transcranial direct current stimulator controlled by mobile phones. Methods:The constant current stimulation circuit was realized by a field effect transistor, which could output stable and adjustable low-intensity direct current, and the impedance detection circuit and the over-current protection circuit increased the effectiveness and safety of the stimulator. The control and real-time detection of the stimulation circuit was realized through a microcontroller, and the parameters' settings of the stimulator and the display and preservation of the actual stimulus information were realized through the Android software on the smartphone. Results:The output current strength and accuracy, maximum load, as well as the timing, device connection, stimulus information collection and display all achieved the expected goals. Conclusion:The design realized the mobile control of the stimulator, with portability, low cost and low power consumption, providing a new solution for wider applications.

Influence of CTPVB under ultrasound-guidance combined with general anesthesia on inflammatory reaction and homodynamic of patients with thoracotomy / 中国医学装备

Objective: To explore influence of continuous thoracic paravertebral block(CTPVB)under ultrasound-guidance combined with general anesthesia on inflammatory reaction and homodynamic of patients who underwent thoracotomy.Methods: 138 patients who underwent thoracotomy were prospectively selected and were divided into observation group(69 cases)and control group(69 cases)as random number table.Patients of observation group received CTPVB under ultrasound-guidance combined with general anesthesia and that of control group received general anesthesia.The changes of IL-6,IL-10 and TNF-α postoperative 48h and postoperative VAS score between the two groups were compared.And the VAS scores postoperative 2h,12h,24h and 48h also were observed.Besides,the mean arterial pressure and heart rate between the two groups at various time point included tranquillization time(T0),the 15 min(T1)after CTPVB combined with general anesthesia,the time post induced intubation(T2),5 min post skin incision(T3)and the time pre extubation(T4)were compared and analyzed so as to research its influence on hemodynamic.Results: The IL-6 and TNF-α postoperative 48h of observation group were significantly lower than that of control group(t=15.95,t=46.99,P＜0.05).And postoperative IL-10 of observation group was significantly higher than that of control group(t=134.3,P＜0.05).And the VAS scores of observation group at postoperative 2h,12h,24h and 48h were significantly lower than that of control group(t=13.91,t=17.1,t=2.321,t=9.231,P＜0.05),respectively.Conclusion: CTPVB under ultrasound-guidance combined with general anesthesia can improve postoperatively analgesic effect for patients,and it don't affect patients' blood pressure and heart rate,and it can reduce inflammatory reaction of patients who underwent thoracotomy and promote rehabilitation of patients.

Analysis of Correlation between IgG Titer of Pregnant Women and Neonatal Hemolytic Complications of Different Blood Groups / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the relationship between IgG titer of pregnant women and hemolytic disease of newborn(HDN) with different blood groups.</p><p><b>METHODS</b>Four hundred pregnant women, including pregnant women with type O blood, were selected from May 2014 to January 2015 in our hospital for inspection and a couple of different blood groups, the IgG titer of pregnant women were detected in the inspection process. According to neonatal HDN, newborns were divided into 2 groups: HDN group(85 cases) and non-HDN group(315 cases). The incidence of postpartum neonatal hemolytic disease was tracked and the correlation of IgG titers with HDN were systematically analyzed.</p><p><b>RESULTS</b>In the production and inspection process, the IgG titer in pregnant women was divided into <1:64, 1:64, 1:128, 1:256 and greater than or equal to 1:512 five groups. the comparison of HDN incidence rate in 4 groups of IgG titer >64 and IgG titer <1:64 group showed that the prevalence of ABO hemolytic disease of newborn were 96.9%, 79.6%, 63, 7% and 28.8%, there was a certain correlation of pregnant women IgG titers with ABO hemolytic disease of the newborn, that is, with the increase of IgG titer, the incidence of hemolytic disease of newborns increased in certain degree (r=0.8832), the risk in 4 groups of neonatal HDN was higher than that in IgG titer <1:64 of IgG titer >64 HDN group.</p><p><b>CONCLUSION</b>There is a certain corelation between prevalence of ABO-HDN and IgG titer of pregnant women. For these pregnant women, the control of the pregnant women IgG titer has a positive clinical significance to reduce the incidence of hemolytic disease of the newborn.</p>

Design and Realization of Independent Calling Device for Patients with Amyotrophic Lateral Sclerosis / 中国康复理论与实践

@#Objective To design a device for the patients with amyotrophic lateral sclerosis (ALS), who are disable to speak and move, to call for the nurses independently when necessary. Methods The electroencephalographic signals were collected and processed with TGAM, and the extracted attention characteristic values were transmitted to a computer with Bluetooth. The loudspeaker would call the nurses when the attention characteristic value exceeds the normal range. Results In the testing process of 20 participants in 10 tests, the success rate was 81.5%, and the average misjudged frequence was 0.2 within 20 min. Conclusion The device can be used in the nursing of the patients with ALS to meet the needs of daily nursing work.

A PKLR Gene Novel Complex Mutation in Erythrocyte Pyruvate Kinase Deficiency Detected by Targeted Sequence Capture and Next Generation Sequencing / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the molecular mechanism of erythrocyte pyruvate kinase deficiency (PKD).</p><p><b>METHODS</b>Targeted sequence capture and next-generation sequencing (NGS) were used to detect the regions of exon and exon-intron boundarie of PKLR gene in a clinical suspected PKD patient. The protein function of mutant gene was forecasted by the SIFT and PolyPhen-2 databank, after the mutation of PKLR gene in the patient was detected by the NGS technology, its genotype was confirmed by Sanger sequencing.</p><p><b>RESULTS</b>The patient was found to have peculiar double heterozygous mutations: 661 G>A (Asp221Asn) of exon 5 and 1528 C>T (Arg510Ter) of exon 10, resulting in amino acid substitution Asp221Asn and Arg510Ter, these mutations were also further confirmed by Sanger sequencing. The complex mutations were infrequent and each of them was able to cause diseases.</p><p><b>CONCLUSION</b>The complex mutations of both 661 G>A and 1528 C>T of PKLR gene are the molecular mechanism of PKD. Simultaneous existance of above-mentioned complex mutations in PDK patient was never been previously reported at home and abroad.</p>

Effects of obesity on peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test and obesity-related hormones in girls with central precocious puberty / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP).</p><p><b>METHODS</b>Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis.</p><p><b>RESULTS</b>There was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P<0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P<0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P<0.05), and positively correlated with the levels of leptin and neurokinin B (P<0.05).</p><p><b>CONCLUSIONS</b>The effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.</p>

Hemodynamics-based numerical comparison between two options of modified B-T shunt / 医用生物力学

Objective To analyze and compare hemodynamic features of two different options for modified B-T shunt (MBTS) surgery, namely end-to-side(ETS) and side-to-side (STS), so as to provide references for clinical treatment of single ventricle heart defect syndrome. MethodsThe real geometric model was reconstructed by medical images obtained from a patient with hypoplastic left heart syndrome (HLHS); MBTS surgery was simulated through virtual operations; a lumped parameter model (LPM) was constructed based on physiological data of the patient; the post-operational boundary conditions of computational fluid dynamics (CFD) models (namely STS model and ETS model) were predicted based on the LPM; numerical simulation was conducted on two CFD models by using finite volume method. Results Flow details and wall shear stress distributions were all obtained for two models. The mean oscillatory shear index (OSI) of ETS model and STS model in part of pulmonary arteries was 3.058×10-3 and 13.624×10-3, respectively, while the energy loss was 116.5 and 94.8 mW, respectively, and blood flow rate ratios of left pulmonary artery to right pulmonary artery (RRPA/LPA) were 0.8 and 1.72, respectively. Conclusions There were nearly no differences between two CFD models in energy loss, which led to a relatively small impact on the surgery. The STS model had a more balanced pulmonary artery blood perfusion and a smaller mean OSI in part of pulmonary arteries, therefore, the STS model was superior to the ETS model. This study provides an important theoretical support and reference for treating patients with HLHS.

Hemodynamics-based numerical comparison between modified B-T shunt and central shunt / 医用生物力学

Objective Modified B-T shunt (MBTS) and central shunt (CS) are two common surgical procedures for the treatment of tetralogy of fallot (TOF). The purpose is to analyze and compare the hemodynamic features of MBTS and CS. Methods 3D anatomy was reconstructed by medical images obtained from a patient with TOF, and two computational models were generated through virtual operations. A lumped parameter model was constructed to predict the post-operational boundary conditions. Computational fluid dynamics (CFD) was performed for the two models. Results A persistent pulmonary blood perfusion was observed in each model both during the systolic phase and diastolic phase, but the maximum velocities in the shunt were different for the two models. The pressure drop of the shunt in CS model was higher than that in MBTS model. The wall shear stress of the shunt in the MBTS model ranged unevenly from 0.025 to 340 Pa, while the wall shear stress in CS model ranged relatively evenly from 32.2 to 72.6 Pa. Conclusions Pulmonary artery blood was increased effectively for both options. The blood perfusion of right upper extremity was decreased in the MBTS model. More blood was directed into the pulmonary artery in CS model. Attention should be paid to the fact that the pressure gradient was large at the proximal anastomosis in both models in clinic. This study provides important theoretical references for surgeons to make choice from the surgery options in the treatment with TOF.

Recent development and application of hemodynamics / 医用生物力学

The study of hemodynamics, which refers to dynamics inside the blood circulation, mainly includes the flow rate, flow resistance, pressure, shear stress, disturbed flow, as well as their associations in between. Therefore, with its important significance in the clinical treatments of vessel curvature, arterial stenosis or occlusion, pathological artery branches and aneurism, study about hemodynamics is essential to human health. Currently, extensive researches on hemodynamics have been conducted with respect to artery bypass, coronary arterial stenosis, abdominal aortic aneurysm, atherosclerosis, cerebral aneurysm and swirling flow. With the development of such research on hemodynamics, surgical planning and interventional therapy have improved rapidly. The influence mechanism of hemodynamic parameters, including pressure, flow resistance, flow rate, wall shear stress, blood viscosity, flow separation, turbulent flow, vortex on the post-operation complications could be deeply explored with the help of more and more clinical apparatus and have gained some achievements.

Numerical study on multiscale simulation for hemodynamics of systemic-pulmonary shunt procedure based on lattice Boltzmann method / 医用生物力学

Objective Based on time-coupled multiscale coupling algorithm, to simulate the hemodynamics after systemic-pulmonary shunt procedure on single ventricular patient so as to obtain the local three-dimensional (3D) fluid field and global hemodynamic information before and after surgery. MethodsFirstly, the 0D-3D coupled multiscale hemodynamic model of systemic-pulmonary shunt procedure was established based on the lumped parameter model (0D) before surgery and the shunt model (3D), then the 0D-3D interface coupling condition and the time coupling algorithm were discussed. Secondly, the multiscale simulation of 3D CFD (computational fluid dynamics) model coupled with 0D lumped parameter model was realized based on lattice Boltzmann method. Finally, the multiscale simulation results were compared with patient’s 0D simulation results to study the hemodynamic changes before and after surgery. Results The global hemodynamic change and local 3D flow pattern were obtained by this multiscale simulation. The pulmonary blood flow distribution ratio was increased from 32.21% to 57.8%. Conclusions The systemic-pulmonary shunt procedure can effectively increase the blood supply of pulmonary circulation by implanting the shunt between the systematic circulation and pulmonary circulation. The geometrical multiscale method can effectively simulate both the coarse global and detailed local cardiovascular hemodynamic changes, which is of great significance in pre-operation planning of cardiovascular surgery.

Hemodynamic comparison between elastic and rigid vessels for the central shunt / 医用生物力学

Objective To study the hemodynamics of central shunt (CS) by numerical simulation and investigate the effects of the elastic and rigid vessel wall on distributions of hemodynamic parameters in the vessel. Methods Two idealized CS models were constructed, one with a rigid wall (the rigid model) and the other with an elastic wall (the elastic model). Numerical calculation was conducted by the finite element method, and the elastic model adopted the fluid structure interaction. Results The distribution of flow velocity and pressure in both models were generally the same. About 68.9% of the aortic blood was directed into the pulmonary artery for the rigid model, as compared to 70% for the elastic model. The pressure drops within the shunt for the elastic model and rigid model were about 7.668 8 kPa and 7.222 3 kPa, respectively. The maximum variation in the average cross sections along the shunt was about 2.2% for the elastic model, appearing at the proximal end to side (ETS) anastomosis. The maximum difference of wall shear stress (WSS) between the two models at five key regions of each was about 16.1%. Conclusions Generally, the global flow structure in both the CS models remains unchanged; the elasticity of the vessel wall slightly influenced the flow distributions and pressure drop of the shunt; the effect from elasticity of the vessel wall on average cross sections along the shunt was higher at the proximal ETS anastomosis than that at the distal ETS anastomosis; the hypothesis that the vessel wall is rigid is acceptable in CS numerical simulations for the treatment of tetralogy of Fallot (TOF). However, the coupling of flow dynamics and wall mechanics may lead to a more reliable simulation result in the CS.

Numerical simulation of a double-bypass-graft design for alleviating artery stenosis / 医用生物力学

Objective In order to improve the local hemodynamics of coronary artery bypass graft and reduce the incidence of restenosis, a double-bypass-graft design was proposed to alleviate artery stenosis. Methods Based on finite element method, the hemodynamics of the conventional bypass graft model and the double-bypass-graft model was adopted for numerical simulation. The distributions of hemodynamics such as flow field and wall shear stress in the vicinity of anastomosis were calculated. Results This new design provided better hemodynamics near the main anastomosis region, eliminated the vortex and flow stagnation, and increased the wall shear stress at the artery floor. The axial length of vortex near the assistant bypass graft by this new design was only 3 mm, which was shorter than that of 4.5 mm in the conventional design. Nearly 36% of the total blood was directed into the assistant bypass graft. Conclusions The new design could help to reduce the incidence of intimal hyperplasia.

A control strategy of intra aorta pump based on blood assist index / 医用生物力学

Objective A blood assist index (BAI), defined as ratio of the output power of LVAD (left ventricular assist device) to the total input power of circulatory system, was proposed in this paper to regulate the energy distribution between LVAD and natural heart. Methods A control strategy based on model free adaptive control (MFAC) algorithm was designed by using BAI as the control variable. The algorithm could track the desired BAI by regulating the pump speed to maintain the measured BAI. A mathematic model of cardiovascular system was used to verify the feasibility of the controller in presence of heart failure, slight physical active and recovery of cardiac function. Results The simulating results demonstrated that the proposed controller could automatically regulate the pump to respond to the reduced peripheral resistance (5 500 r/min vs. 6 000 r/min). When Emax increased from 80 to 240 Pa/mL to simulate the heart recovery, the blood flow rate could increase accordingly from 5 to 8 L/min.Conclusions The proposed control strategy can provide an adjustable and accurate energy distribution between LVAD and native heart by regulating the pump speed, which would be of benefit to promoting left ventricle reverse remodeling.

Model sculpture for virtual coronary artery bypass operation / 医用生物力学

Objective To conduct the operation of capture and deformation in virtual three-dimensional (3D) environment with force feedback device and simulate the coronary artery bypass operation. Methods Based on data collected from real CT images of the patient with heart disease, digitized visual model of the heart was reconstructed. Then the bypass vessel was built and the vessel model was sculptured by force feedback device to simulate the bypass surgery from pulmonary artery to ventriculus dexter in Fontan operation. Results Space structure of the heart was shown in the virtual 3D reconstructed environment. Bypass vessel with any diameter and angle was transformed to simulate the coronary artery bypass operation. Heart patch with any size was built to repair the heart model. The satisfactory model and parameters of the postoperative model were finally achieved. Conclusions The application of force feedback device in virtual coronary artery bypass operation sets the stage for cardiovascular surgery planning system with mechanical characteristics to simulate multiple modalities of such operation.

Numerical study on bilateral bidirectional Glenn shunt / 医用生物力学

Objective To predict the influence of connecting position between left superior vena cava (LSVC) and pulmonary artery on bilateral bidirectional Glenn (BBDG) shunt by numerical simulation. Methods Firstly, a 3D anatomical geometrical model was reconstructed by the medical images of a hypoplastic left heart syndrome (HLHS) patient with LSVC. Secondly, based on haptic deformations, several computational models were virtually generated, and computational fluid dynamics (CFD) numerical simulations were conducted using finite volume method. Finally, hemodynamic parameters were analyzed and evaluated. Results Flow recirculation was observed in the pulmonary artery between the LSVC and right superior vena cava (RSVC). The diameter of RSVC was defined as D. Varying the distance between LSVC and RSVC from 2D to 3.5D resulted in the least energy dissipation at 3D and the most at 2D. The blood flow rate ratios of left pulmonary artery to right pulmonary artery (LPA/RPA) ranged from 0.65-1.11. Conclusions Too close distance between LSVC and RSVC would bring out unfavorable hemodynamic distributions and consume more energy in the treatment of BBDG shunt. This study is of significance for surgeons to evaluate the optimal Fontan options in the treatment of HLHS accompanied by LSVC.