ObjectiveTo explore the effects and mechanisms of modified Dahuang Huanglian Xiexintang on hepatic oxidative stress injury in type 2 diabetes mellitus （T2DM） rats based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） axis. MethodSix ZDF （fa/+） rats were as assigned to the blank group， and 30 ZDF （fa/fa） rats were used to induce the T2DM model by feeding a high-fat diet. After successful modeling， the rats were randomly divided into the model group， metformin group （0.18 g·kg^-1）， and low， medium， and high dose groups of modified Dahuang Huanglian Xiexintang （0.54， 1.08， 2.16 g·kg^-1）， with six rats in each group. After 12 weeks of drug intervention， the body mass， liver mass， fasting blood glucose （FBG）， and oral glucose tolerance test （OGTT） levels were measured. Serum total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， low-density lipoprotein cholesterol （LDL）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） levels were detected using an automatic biochemical analyzer. The pathological changes of liver tissue were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the activity of superoxide dismutase （SOD）， reactive oxygen species （ROS）， glutathione peroxidase （GSH-Px）， and the level of malondialdehyde （MDA） in liver tissues. Immunohistochemistry was used to detect the expression of Nrf2 in the liver. Real time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of Nrf2 and HO-1 in liver tissues. ResultCompared with the normal group， the model group showed a significant increase in body mass， liver mass， and liver index （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed a significant decrease in body weight， liver mass， and liver index （P<0.01）. Compared with the normal group， the model group showed significantly increased TC， TG， and LDL levels （P<0.01）， and significantly decreased HDL levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced TC levels （P<0.01）， and significantly reduced TG levels （P<0.05）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced LDL levels （P<0.05）. The metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased HDL levels （P<0.05）. Compared with the normal group， the model group showed significantly increased ALT and AST activities （P<0.01）. Compared with the model group， all doses of modified Dahuang Huanglian Xiexintang and the metformin group showed significantly reduced ALT activities （P<0.05） and significantly reduced AST activities （P<0.01）. Compared with normal group， the model group showed significantly increased FBG at all time points （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced FBG at 8， 10， 12 weeks. The OGTT results showed that compared with the normal group， the model group had significantly increased blood glucose at all time points （P<0.01）. Compared with the model group， the metformin group showed significantly reduced blood glucose at all time points （P<0.01）， and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced blood glucose at 90， 120 min （P<0.01）. HE pathology showed clear and regular liver cell structure in the normal group， while the model group showed disordered liver cell structure with visible fat vacuoles and a large number of deformed necrotic cells. The liver tissue structure improved in the metformin group and all doses of modified Dahuang Huanglian Xiexintang， with fewer necrotic cells. Compared with the normal group， the model group showed significantly reduced SOD and GSH-Px levels （P<0.01）， and significantly increased ROS and MDA levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased SOD and GSH-Px levels （P<0.01）， and significantly reduced MDA levels （P<0.01）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced ROS levels （P<0.05）. Compared with the normal group， the model group showed significantly reduced Nrf2 and HO-1 mRNA expression levels （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly increased Nrf2 and HO-1 mRNA expression levels （P<0.05）. Immunohistochemistry showed that compared with the normal group， the model group had significantly reduced positive expression of Nrf2 and HO-1 （P<0.05）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed increased positive expression of Nrf2 and HO-1， with a significant increase in brown-yellow granules around the cell nucleus （P<0.05）. Western blot results showed that compared with the normal group， the model group had significantly reduced protein expression of Nrf2 and HO-1 （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased protein expression of Nrf2 and HO-1 （P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang can significantly improve the general condition and pathological changes of liver tissues in T2DM model rats. This improvement is likely achieved through ameliorating hepatic oxidative stress injury via regulating the Nrf2/HO-1 axis.

ObjectiveTo observe the effect of modified Dahuang Huanglian Xiexintang on mitochondrial autophagy and browning of visceral adipose tissue in obese type 2 diabetes mellitus （T2DM） model ZDF rats. MethodForty ZDF rats were induced with a high-fat diet to establish an obese T2DM model. The rats were randomly divided into five groups： Model group， metformin group （0.18 g·kg^-1）， and high， medium， and low dose groups of modified Dahuang Huanglian Xiexintang （2.16， 1.08， 0.54 g·kg^-1）， with eight rats in each group. Additionally， eight ZDF （fa/+） rats were assigned to the normal group. All groups received an intragastric volume of 10 mL·kg^-1， with the model and normal groups receiving the same volume of purified water once daily for 12 weeks. Fasting blood glucose （FBG） was regularly measured. After 12 weeks of intervention， the body weight， epididymal fat weight， and serum levels of glucose （GLU）， glycated serum protein （GSP）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in epididymal fat tissue. Transmission electron microscopy （TEM） was employed to observe mitochondrial autophagy in adipocytes. Real-time PCR was used to detect the mRNA expression of hypoxia-inducible factor-1α （HIF-1α）， Bcl-2/adenovirus E1B 19 kDa interacting protein 3 （BNIP3）， microtubule-associated protein 1 light chain 3B （LC3B）， p62/SQSTM1， uncoupling protein 1 （UCP1）， iodothyronine deiodinase 2 （Dio2）， and PR domain containing 16 （Prdm16） in epididymal fat. Western blot was used to detect the protein expression of HIF-1α， BNIP3， LC3B， p62， and UCP1 in epididymal fat. ResultCompared with the normal group， the model group showed pathological changes in epididymal fat， with adipocyte mitochondrial condensation and numerous autophagosomes indicating mitochondrial autophagy. The model group also exhibited significantly increased body weight， epididymal fat weight， FBG， GLU， GSP， TC， TG， and LDL-C levels （P<0.01）， significantly decreased HDL-C levels （P<0.01）， significantly elevated mRNA and protein expression of HIF-1α， BNIP3， and LC3B （P<0.01）， significantly reduced mRNA and protein expression of p62 and UCP1 （P<0.01）， and significantly reduced mRNA expression of Dio2 and Prdm16 （P<0.01）. Compared with the model group， all intervention groups showed varying degrees of improvement in epididymal fat pathology. The metformin group and high-dose modified Dahuang Huanglian Xiexintang group displayed intact mitochondrial morphology， clear cristae， uniform matrix， and few autophagosomes and autophagosomes in the adipocyte cytoplasm. The metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced body weight and epididymal fat weight （P<0.01）. The epididymal fat index was reduced in all intervention groups （P<0.05）， and FBG was lowered in all intervention groups （P<0.01）.Serum GSP， GLU， TG， and LDL-C levels were reduced in the metformin group and the high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The serum TC level was significantly reduced in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.01）， and HDL-C levels were significantly increased in all intervention groups （P<0.05， P<0.01）. The mRNA and protein expression of HIF-1α， BNIP3， and LC3B were significantly reduced， and UCP1 protein expression was significantly increased in the metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The mRNA and protein expression of p62， Dio2， and Prdm16 were significantly increased in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang may inhibit mitochondrial autophagy and promote the browning of visceral adipose tissue through the HIF-1α/BNIP3/LC3B pathway， thereby improving glucose and lipid metabolism in obese T2DM rats.

Objective:To investigate the effect of curcumin on skin wound healing and angiogenesis in rats and its possible mechanism.Methods:Rats with full-thickness dermal defect were prepared and randomly divided into model group, low-dose, medium-dose and high-dose groups of curcumin, with 10 rats in each group. Curcumin was injected intraperitoneally. The low-dose, medium-dose and high-dose groups of curcumin were given 5, 15, 45 mg/(kg·d) curcumin respectively. The rats in the model group were injected intraperitoneally with 0.5% sodium carboxymethyl cellulose for 14 days. The wound healing rate of rats in each group was measured; The wound tissue was stained with haematoxylin and eosin staining, Masson and immunohistochemistry; The levels of angiopoietin-1 (Ang-1) and basic fibroblast growth factor (bFGF) in the wound tissue of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA); The relative expression of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA in wound tissue was detected by real-time quantitative polymerase chain reaction (qRT-PCR); Western blot was used to detect the expression of VEGFA, VEGFR-2, Notch1, Jagged1, Hes1 protein in the wound tissue.Results:The wound healing rate, the vascular density and the level of Ang-1 and bFGF, the mRNA of VEGFA and VEGFR-2, the relative expression of Notch1, Jagged1, Hes1, VEGFA and VEGFR-2 protein in wound tissue of rats in low, medium and high dose groups of curcumin were higher than those in the model group (all P<0.05). Histological staining results showed that the reepithelialization of the wound tissue was not obvious in the model group, with severe infiltration of inflammatory cells and less collagen deposition; the reepithelialization of the wound tissue in the low-dose, medium-dose and high-dose groups of curcumin was gradually obvious, with thickened epidermis, reduced inflammatory cell infiltration and increased collagen deposition. The effect of curcumin on skin wounds in rats was enhanced in a dose-dependent manner (all P<0.05). Conclusions:Curcumin could promote wound healing and angiogenesis in rats, and its mechanism may be related to the activation of Notch signaling pathway.

Objective To study the characteristics of neural adaptation for resistance training of maximum voluntary contraction (MVC) of muscles at different joint angles. Methods Thirty healthy male college students were randomly divided into 3 groups, and each group was subjected to MVC isometric contraction resistance training at elbow joint angles of 45°, 90°, and 135°. Surface electromyography (sEMG) signals of the biceps brachii were measured before and after training, and the root mean square (RMS) and median frequency (MF) of the sEMG signals were also analyzed. ResultsThere were significant differences in normalized RMS of sEMG for the biceps brachii before and after training at 45°, 90°, and 135° elbow joints. Comparison of the RMS between different angles after training showed that 45° was significantly different from 90° and 135°. There were no significant differences between 90° and 135°. After training, no significant differences were found in normalized MF at all angles. Conclusions The RMS of sEMG shows angle-specific changes, while the MF of sEMG does not have angle-specific changes. When the biceps brachii is at the middle and large elbow joint angles, the neural adaptation effect produced by isometric resistance training is better.

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
A549 Cells ; Animals ; Apoptosis Regulatory Proteins/immunology* ; DEAD Box Protein 58/immunology* ; Dogs ; HEK293 Cells ; Humans ; Influenza A Virus, H1N1 Subtype/immunology* ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/pathology* ; Proteolysis ; RAW 264.7 Cells ; Signal Transduction/immunology* ; THP-1 Cells ; TNF Receptor-Associated Factor 3/immunology* ; Ubiquitination/immunology* ; Viral Proteins/immunology*

Objective To measure the body surface dose under different confinations of additional filters,tube voltage and tube current and discuss the lowest amount of different additional filters,tube voltage and tube current combination for crib side X-ray radiation dose while the quality of the image is guaranteed.Methods Japan Shimadzu wireless tablet mobile DR machine and Dutch Artinis CDRAD 2.0 phantom were used.The tube voltage and tube current for children's crib side X-ray normal work were 50 kV and 1.40 mAs to get the image quality figure inverse (IQFInv),respectively.Totally four filter combinations of 1 mm A1,2 mm A1,1+2 mm A1 and 0.3 mm Cu were added to the opening of collimator system by mobile DR machine.Phantom was shot by respectively combination of 50,66,83 and 100 kV tube voltages and different tube currents.All images to get the IQFInv value,Pearson correlation and regression analysis of the influence of tube voltage and current on IQFInv value were analyzed.The IQFInv value of the additional filter corresponds to the image quality of normal work.The combination of the additional filter with the tube voltage and the tube current was also found.Swedish RTI Barracuda diagnostic level dosimeter was used to measure the entrance surface dose of these combinations after filtration,20 times for each group.Results Comparisons among different filters,tube voltage and tube current combination with quality of daily work images:the tube voltage was positively correlated with IQFInv value in the test range(r=0.49,P＜0.05),and tube current was positively correlated with IQFInv value (r=0.36,P＜0.05).As the additional filters increase,it required greater tube current to acquire the desired value of images.Meanwhile,greater additional filters would increase the difference of IQFInv of tube voltage at each level.Comparisons among different filters,tube voltage and tube current combination with daily shooting dose,and after using additional filters,entrance surface dose changed from (30.58±0.21)to (10.49±0.09) μGy.There is a significant difference between each group (t=-15.306-514.585,P＜0.05).All additional filters effectively reduced entrance surface dose.Meanwhile,as the filter and tube voltage increased,entrance surface dose showed a more significant reduction.However,when the tube voltage exceeded 83 kV,all entrance surface dose of additional filters showed an increasing trend.Conclusions Additional filter is an effective method to reduce the crib side X-ray entrance surface dose.Under the premise of ensuring image quality,additional filter with high atomic number and second high kilovolt tube voltage with paired tube current is the best condition for crib side X-ray.

Objective? To summarize the nursing experience for 6 patients receiving wireless pacemaker implantation. Methods? The nursing experience for 6 patients who received wireless pacemaker implantation for the first time in Beijing Anzhen Hospital, Capital Medical University from August to October 2018. The nursing highlights included preoperative nursing, operative nursing, postoperative monitoring, nursing, follow-up and education. Results? 2 of the 6 patients sustained atrial fibrillation combined with long pause, and 4 sustained atrionector lesion combined with incidental long pause. The threshold value and perception of pace-making was sound and the impedance was ideal during operation. No complication was found during and post operation. The surgical time for implanting wireless pacemakers was short and the patients' appearance was not affected. Their mental burden was relatively light. Nursing procedures were simpler than the those for traditional pacemakers. Conclusion? Wireless pacemakers reduce airbag and wire-related complications and is promising in clinical use. But nursing experience needs to be observed clinically and summarized.

Objective To explore the feasibility and clinical significance of individualized formular administration of tacrolimus after renal transplantation based on the CYP3A5 and MDR1 gene polymorphism.Methods Total 129 renal transplantation recipients from Oct.1,2015 to July 30,2016 were included in this study and divided into 2 groups.In experimental group,tacrolimus was administrated by the individualized formula based on CYP3A5 and MDR1 gene polymorphism;in control group,tacrolimus was administrated by doctors' experience based on patient's body weight.The blood trough level of tacrolimus was determined 3 days after administration.The first blood trough level of tacrolimus,plasma creatinine level,acute rejection rate,and necessity for dialysis were compared between two groups.Results The first blood trough levels of tacrolimus in experimental and control groups were 9.24 ± 2.32 and 9.39 ± 3.47μg/L respectively (P＞0.05).The tacrolimus levels of 7 cases in experimental group and 18 cases in control group were not in normal range (P＜0.05).The plasma creatinine level at day 7 after surgery was 157.36 ± 110.55 μg/L in experimental group,and 174.01 ± 130.68μg/L in control group (P＞0.05).Acute rejection was found in both two groups:2 in experimental group and 5 in control group (P ＞ 0.05).There was significant difference in necessity for dialysis between two groups:4 in experimental group and 10 in control group (P＜0.05).Conclusion The individualized formular administration of tacrolimus based on the CYP3A5 and MDR1 gene polymorphism is more feasible and reasonable than experimental administration,which is more easier to come to an appropriate blood level and would benefit the early recovery of renal function.

Objective To explore the mechanisms of ligament of Marshall (LOM) initiat and sustain atrial fibrillation (AF).Methods The electrophysiologic properties of canine LOM were investigated using multipolar catheter mapping(normal canines,n =4,group A;AF canines,n =5,group B).The programmed stimulation were performed in the LOM,PV-left atrium(LA)junction and LA,respectively.Activations maps of LOM were analyzed from episodes of spontaneous onset of AF and initiation of induced AF by a single extrastimulus.The effectives refractory period of each part was compared and statistically analyzed among three parts in each group and between the two groups.LOM were cutted with surgical incision technology.The inducing rate of AF and the mapping rate of double potential and fragmented electrocardiogram were compared and statistically analyzed pro and post isolation of LOM.Results The incidence of abnormal potential of LOM in the two groups was significantly different(P ＜0.01),re-entry cycle(group A 25％ vs.B group 80％),tachycardia(group A 25％ vs.B 100％),double potential(group A 25％ vs.group B 80％),fragmentation potential(group A 25％ vs.group 80％).There was a significant difference in the rate of LOM tachycardia induction before and after LOM intervention in group B (P ＜ 0.05,before 100％ vs.after 20％).Conclusion There are two possible mechanisms of LOM involved in the occurrence and maintenance of AF:one is that LOM induces AF through spontaneous excitation,the other is that LOM participates in the reentry of left atrium and pulmonary vein in the form of bypass to induce and maintain AF.

A novel molecularly imprinted electrochemical sensor for direct detection of insulin was prepared based on epitope imprinting.C-Terminal polypeptide in insulin as template molecule was firstly self-assembled on the Au electrode.Then the molecularly imprinted polymer (MIP) was fabricated by electropolymerization with o-phenylenediamine (o-PD) as functional monomer on this Au electrode.After elution of template molecules by NaOH solution, the imprinting cavities were formed with the three-dimensional structure matched with the polypeptide in insulin molecules.The imprinting cavities could specifically recognize and rebind with insulin molecules.With K3[Fe(CN)6]/K4[Fe(CN)6] as a probe, the insulin was indirectly detected.There was a linear relationship between the response current and the insulin concentrations in the range of 1.0 × 10-14-5.0 × 10-13 mol/L, and the detection limit was 7.24×10-15 mol/L.The developed sensor exhibited good selectivity and stability, and could be applied to the determination of serum samples.