0.05).The ADCs of low-grade(gradeⅠ～Ⅱ) astrocytomas were significantly higher(P

Objective To investigate the effect of high mobility group box chromosomal protein 1 (HMGB-1) on the proliferation and inflammatory phenotype of human fibroblast like synoviocytes (FLS).Methods FLSs were isolated from the synovial tissues of rheumatoid arthritis (RA) patients undergoing joint replacement surgery.All the experiments described here utilize the FLSs between the third and sixth passages.FLS were incubated with HMGB1 at (100,500,2 000 ng/ml) or interleukin (IL)-1β (0.5 ng/ml) or lipopolysaccharide (LPS) (100 ng/ml) alone or HMGB1/IL-1β complexes or HMGB1/LPS complexes.Cell proliferation assay were used by CCK-8,IL-6,IL-8 and matrix metalloproteinase-3 (MMP-3) in culture supernatants were measured using enzyme-linked immunosorbent assays.The measurement data were compared with single factor analysis of variance.Results Stimulation with all concentrations of HMGB1,IL-1β and LPS alone did not affect the cell proliferation of FLS.HMGB1/IL-1β complexes and HMGB1/LPS complexes did not affect the cell proliferation of FLS,neither (F=0.415.P=0.915).Except high concentration of HMGB1 (2 000 ng/ml) could significantly stimulate the secretion of IL-6 from FLS [(23.0±1.1) ng/ml],HMGB1,IL-1β and LPS alone did not affect the production of IL-6,IL-8 and MMP-3.However,HMGB1/IL-1β complexes and HMGB1/LPS complexes increased IL-6,IL-8 and MMP-3 production from FLS (F=97.804,117.383,70.179,P=0.000).Conclusion Neither HMGB1,IL-1β,LPS alone nor HMGB1/IL-1β complexes or HMGB1/LPS complexes affect the cell proliferation of FLS.HMGB1 in complex with LPS or IL-1β boost IL-6,IL-8 and MMP-3 production in synovial fibroblasts from RA patients.

Polybrominated diphenyl ethers (PBDEs), a kind of important Brominated Flame Retardant (BFR), are widely used in electronic products, construction materials and textiles. PBDEs have been detected in many environmental media (including air, water, dust, sediment and food), many animal and human tissues. For their environmental persistence, high bioaccumulative and multiple biotoxicitiies, PBDEs have been viewed as one of the most concerned environmental Endocrine Disrupting Chemicals (EDCs) at present. Although detailed mechanisms are not clear, studies have found that PBDEs can induce toxicity to liver, endocrine system, nervous system, reproduction and immune system. What's more, lots of experiments indicate that PBDEs exposure can alter the levels of thyroid hormones. Recently, studies on the impact of PBDEs exposure on thyroid hormones have been quite a few and have not reached an agreement, especially on the alternation of thyroid hormones caused by PBDEs exposure, which has also been a hot issue. This paper reviews from the basic properties, usage, exposure and biotoxicity of PBDEs. We mainly introduce the impact PBDEs have on the thyroid and thyroid hormones in terms of biotoxicity, and attach importance to the endocrine disruption and neurodeveloptoxicity. We also give a preliminary introduction to hydroxylated and methoxylated polybrominated diphenyl ethers, structural analogs of PBDEs, which researchers start late to study. This paper can be a reference for the further research on PBDEs exposure and biotoxicity.

Objective:To assess the left ventricular (LV) myocardial mechanical dysfunction in patients with cirrhosis using ultrasonic layer-specific strain imaging and to explore its value in clinical application.Methods:A total of 80 consecutive cirrhosis patients without cardiovascular diseases were prospectively enrolled from October 2020 to March 2021 in Sichuan Provincial People′s Hospital, 39 of whom were assigned to the compensated group and 41 were assigned to the decompensated group according to the occurrence of portal hypertension. Forty-three healthy volunteers during the same period were randomly recruited as the control group. Transthoracic echocardiography was performed to assess the LV configuration and functional parameters. LV global longitudinal strain in endocardial, middle and epicardial myocardium (GLSendo, GLSmid, GLSepi), and longitudinal strain (LS) in basal, middle and apical segments, and peak strain dispersion (PSD) were obtained using ultrasonic layer-specific strain imaging. ΔLS was calculated by the formula of GLSendo-GLSepi. Then, the differences of related parameters among three groups were compared.Results:①Conventional echocardiography: compared with the control group, the interventricular septum end-diastolic thickness (IVSTd), left ventricular posterior wall end-diastolic thickness (LVPWd), left ventricular mass (LVM) and LVM index (LVMI) were increased in compensated and decompensated groups (all P<0.05), while no significant differences in conventional echocardiographic parameters were identified between the two cirrhosis groups (all P>0.05). ②Global layer-specific strain: compared with the control group, GLSendo, GLSmid, GLSepi and ΔLS were decreased and PSD was increased in compensated and decompensated groups (all P<0.05); Moreover, the decompensated group showed a more impaired GLSendo, GLSmid and GLSepi than compensated group (all P<0.05), whereas there were no significant differences of ΔLS and PSD between the two groups(all P>0.05). ③Segmental layer-specific strain: compared with the control group, LS values of three layers in compensated and decompensated groups were reduced at basal, middle and apical levels (all P<0.05); Compared with the compensated group, LS values of three layers in decompensated group tended to be reduced at above there levels, but only apical segments had significant differences (all P<0.05). Conclusions:There are different degrees of LV mechanical dysfunction in patients with variable severity of cirrhosis. Ultrasonic layer-specific strain imaging has the potential to quantitatively assess the state of cardiac involvement in patients with cirrhosis and to provide visual evidence for the early and accurate diagnosis of myocardial injuries.

Objective To observe the effects of electroacupuncture(EA)on glutamate(Glu),metabotropic glutamate receptor 2/3(mGluR2/3)and apoptosis related proteins expression in hippocampus in rats with acute myocardial ischemia(AMI);To explore the mechanism of EA against AMI.Methods Totally 50 SD rats were randomly divided into sham-operation group,model group,EA group and inhibitor group,with 10 rats in each group.Except for the sham-operation group,the rats were treated with ligation at the left anterior descending coronary artery to establish AMI model.The rats in the EA group was treated with EA at"Shenmen"and"Tongli",30 minutes each time,once a day for 3 consecutive days.The rats in the inhibitor group were treated with injection of LY341459 via the lateral ventricle 30 min after modeling.HE staining was used to observe myocardial tissue morphology,and ELISA was used to detect Caspase-3 activity in myocardial tissue and Glu content in hippocampal tissue,immunofluorescence staining was used to detect mGluR2/3 expression in hippocampal tissue,TUNEL staining was used to detect apoptosis in hippocampal tissue cells,Western blot was used to detect the expressions of PI3K,Akt,and Caspase-3 protein in hippocampal tissue.Results Compared with the sham-operation group,the myocardial cells of the model group rats showed sparse and swelling with severe infiltration of inflammatory cells;the activity of Caspase-3 in myocardial tissue significantly increased,and the Glu content,positive expression of mGluR2/3,number of apoptotic cells in hippocampal tissue significantly increased(P<0.01),and the expressions of PI3K and Akt proteins in hippocampal tissue were significantly decreased,while the expression of Caspase-3 protein significantly increased(P<0.01).Compared with the model group,myocardial cell edema and inflammatory cell infiltration were reduced in the EA group and inhibitor group,the activity of Caspase-3 in myocardial tissue was significantly decreased,the Glu content,positive expression of mGluR2/3,and number of apoptotic cells in hippocampal tissue were significantly reduced(P<0.01),the expressions of PI3K and Akt proteins in hippocampal tissue significantly increased,while the expression of Caspase-3 protein significantly decreased(P<0.01).Conclusion EA can improve myocardial injury in AMI rats,and its mechanism may be related to activation of PI3K/Akt signaling pathway,inhibition of hippocampal mGluR2/3 overexpression,reduction of Glu accumulation,inhibition of apoptosis of hippocampal neurons and reduction of neurotoxicity.

Objective:To analyze the trend relevant factors leading to death and their patterns over a 10-year period in inpatients with connective tissue diseases (CTDs).Methods:All clinical data about death in inpatients with CTDs were retrospectively reviewed between 2005 and 2014 at the Department of Rheumatology and Immunology in Xiangya Hospital of Central South University.Results:In the 10-year time period,the overall hospital mortality was 15.689‰.The disease itself accounted for 44.71% of the total causes of death,infection accounted for 42.94%,and comorbidities accounted for 12.35%.The constituent ratio of deaths and the average hospital mortality caused by the disease itself declined gradually year by year,and the constituent ratio of deaths caused by infection and comorbidities increased gradually year by year (P<0.05).In 2013-2014,infection was the leading cause of death,which accounted for 51.06%.The survival time for CTDs inpatients with interstitial lung disease (ILD) was shorter than that of CTDs inpatients without ILD,and even the risk of death was 1.722 times of the latter.The proportion of deaths caused by the disease itself was the highest in systemic sclerosis and systemic lupus erythematosus,that by infection was the highest in idiopathic inflammatory myopathy (IIM),and that by comorbidities was the highest in rheumatoid arthritis.Conclusion:The proportion of deaths and the hospital mortality in CTDs inpatients caused by the disease itself show a declining trend,while the proportion of deaths caused by infection and comorbidities increase.CTDs patients with ILD have shorter survival time and an increase in risk of death.

Objective:To observe the impact of core stability training in the sling exercise therapy pattern on the balance of stroke survivors.Methods:Sixty stroke survivors were randomly divided into a control group ( n=30) and an experimental group ( n=30). In addition to routine rehabilitation training, the control group received traditional core stability training, while the experimental group underwent core stability training applying the sling exercise therapy pattern. Before and after 4 weeks of training, the standing balance of both groups was evaluated using the Prokin balance trainer, with the length and area of motion recorded when performing the balance test with the eyes open and closed. Surface electromyography was used to record the average EMG (AEMG) values of the bilateral erector spinae and multifidus muscles during the balance testing. Results:After the 4 weeks of training the length and the area of progression of the center of the pressure were both significantly smaller for both groups than before the training with the eyes both open and closed. The average length and area in the experimental group were significantly less than among the controls. The AEMG values recorded during the balance tests were significantly higher than those before the intervention for both groups, with the multifidus muscle averages on the affected side significantly greater in the experimental group than among the controls when performing the balance test with the eyes closed.Conclusion:Core stability training in the sling exercise therapy pattern is superior to conventional core stability training because it can better improve the balance of stroke survivors.

Uridine-cytidine kinase, an important catalyst in the compensation pathway of nucleotide metabolism, can catalyze the phosphorylation reaction of cytidine to 5'-cytidine monophosphate (CMP), but the reaction needs NTP as the phosphate donor. To increase the production efficiency of CMP, uridine-cytidine kinase gene from Thermus thermophilus HB8 and polyphosphate kinase gene from Rhodobacter sphaeroides were cloned and expressed in Escherichia coli BL21(DE3). Uridine-cytidine kinase was used for the generation of CMP from cytidine and ATP, and polyphosphate kinase was used for the regeneration of ATP. Then, the D403 metal chelate resin was used to adsorb Ni²⁺ to form an immobilized carrier, and the immobilized carrier was specifically combined with the recombinant enzymes to form the immobilized enzymes. Finally, single-factor optimization experiment was carried out to determine the reaction conditions of the immobilized enzyme. At 30 °C and pH 8.0, 60 mmol/L cytidine and 0.5 mmol/L ATP were used as substrates to achieve 5 batches of high-efficiency continuous catalytic reaction, and the average molar yield of CMP reached 91.2%. The above method has the advantages of low reaction cost, high product yield and high enzyme utilization rate, and has good applied value for industrial production.
Cytidine Monophosphate ; metabolism ; Escherichia coli ; genetics ; Industrial Microbiology ; methods ; Phosphotransferases (Phosphate Group Acceptor) ; metabolism ; Uridine Kinase

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.