Objective To investigate the effect of mild hypothermia on the expression of hypoxia-inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) in a rat model of chronic cerebral ischemia-reperfusion.Methods Thirty-six female SD rats weighing 170-210 g were randomly divided into 3 groups (n = 12 each):sham operation group (group S), normal body temperature group (group NT ) and mild hypothermia group (group MH). Arterio-venous fistula was established by end-to-end anastomosis between the right common carotid artery and right external jugular vein for 6 weeks followed by reperfusion. In group MH, mild hypothermia was induced at the initiation of reperfusion and the rectal temperature was reduced to 31.5-32.5 ℃. In group S and NT, the rectal temperature was maintained at 37-38 ℃. Six rats in each group were sacrificed at 3 and 48 h of reperfusion. The brains were immediately removed for determination of the expression of HIF-1α, GLUT-1, HIF-1α mRNA and GLUT-1 mRNA and microscopic examination. Results Compared with group S, the expression of HIF-1α and HIF-1α mRNA at 3 and 48 h of reperfusion and GLUT-1 mRNA at 3 h of reperfusion was up-regulated, while the expression of GLUT-1 and GLUT-1 mRNA at 48 h of reperfusion was down-regulated in group NT (P ＜ 0.05).Compared with group NT, the expression of HIF-1α and HIF-1α mRNA at 48 h of reperfusion and HIF-1α mRNA and GLUT-1 mRNA at 3 h of reperfusion was down-regulated, while the expression of GLUT-1 and GLUT-1 mRNA at 48 h of reperfusion was up-regulated in group MH (P ＜ 0.05).Microscopic examination showed that the injury to the ultrastructure of blood-brain barrier was significantly attenuated in group MH compared with group NT. Conclusion Mild hypothermia can attenuate chronic ischemia-reperfusion injury by down-regulating the expression of HIF-1α and up-regulating the expression of GLUT-1.

Objective To compare the plasma volume expanding effect of hydroxyethyl starch (HES)130/0.4 and electrolyte solution (E-HES) and HES 130/0.4 and normal saline (NS-HES) in patients undergoing noncardiac surgery under general anesthesia.Methods A multicenter,prospective,randomized,double-blind,controlled clinical trial was conducted.Two hundred and forty-two ASA Ⅰ or Ⅱ patients aged 18-64 yr with body mass index 18-29 kg/m2 undergoing noncardiac surgery were randomly divided into 2 groups: group E-HES and group NS-HES.E-HES and NS-HES 15 ml/kg was infused iv over 1 h immediately after induction of anesthesia in groups E-HES and NS-HES respectively.Arterial blood samples were taken before (baseline) and at 15 min after the end of HES infusion for blood gas analysis (pH value,BE,HCO3-,K+,Na+,Cl-,Mg2+ ) and measurement of Hb,Hct,blood chemistry (ALT,AST,Cr,BUN,Glu) and coagulation function.The electrolyte abnormality,requirement for vasopressor,treatment-related adverse effects (prolonged prothrombin time,activated partial thromboplastin time and hyperchloremia) and fluid balance were recorded.Results Of the 242 patients,122received E-HES and 120 received NS-HES.Ninety-one patients in group E-HES and 95 in group NS-HES completed the trial.The pH value,BE,HCO3 -,K+,and Mg2+ were significantly higher and Na+ and Cl- lower at 15 min after HES infusion was finished in group E-HES than in group NS-HES.BE,HCO3-,Na+,Mg2+,Hb and Hct were significantly decreased while Cl- was significantly increased in group NS-HES while Na+,Mg2+,Hb and Hct were significantly decreased and Cl- was increased in group E-HES at 15 min after HES infusion as compared with the baseline values before infusion.The incidence of clinical significant abnormality in plasma K+ and Cl- was significantly lower in group E-HES than in group NS-HES.There were no significant differences in Hb,Hct,urine output,amount of HES infused,vasopressor requirement,the incidence of clinically significant abnormality in blood chemistry and treatment-related adverse effects between the 2 groups.Conclusion E-HES and NS-HES have the same plasma volume expanding effect,but E-HES maintains better electrolyte and acid-base balance than NS-HES.

Objective:To observe acid-base and biochemical changes in clinical orthotopic liver transplantation with veno-venous bypass.Method,Seven patients receiving orthotopic liver transplantation, veno-venous bypass was undergone in anheptic phase.The acid-base and biochemical parameters were monitored during operation. Result:Compared to preoperation,pH decreased a little in each phase,BE and SBC slightly decreased 60 min following bypass and during skin closure. Compared to before bypass,pH had no changes during bypass and new liver phases. The serum Ca~(2+) level decreased and serum glucose level elevated in each phase,The temperature gradually decreased during operation. The serum K~+ level was transiently elevated from 3.17mmol/L to 3.53 mmol/L early after the heptic revascularizaton. Conclusion:With the application of the veno-venous bypass technique,the hazard of acid-base and biochemical changes can be reduced during orthotopic heptic transplantation.

Objective To investigate the effect and potential mechanism of autophagy inhibitor chloroquine on the calcium oxalate crystals formation in rats.Methods From September 2016 to October 2016,Thirty healthy male SD rats were randomly divided into 3 groups:control group,model group and chloroquine intervention group.The method to establish calcium oxalate stone model was drinking water with 1％ ethylene and 1％ ammonium chloride freely.The rats of chloroquine intervention group were treat with chloroquine (40mg/kg · d) by intraperitoneal injection.Modeling was finished after 28 days.The amounts of renalcalcium oxalate crystals were detected by polarizing microscope.For all groups,the amounts of autophagosome were detected by transmission electron microscope.Twenty four hour urine compositions for stone risk factors were detected.The expressions of oxidative stress injury related molecular markers (SOD,MCP-1 and 8-OHdG) and the expressions of autophagy markers (LC3 and P62) were detected by immunohistochemistry.The RNA expressions of SLC26A6 in kidney were detected by Real-time PCR.Results Compared to the model group,the amounts of renal calcium oxalate crystals were significantly reduced in chloroquine intervention group (32.37 ± 5.14 vs.4.18 ± 0.25,P ＜ 0.05).Compared to the control group,the level of autophagy was increased in the model group.Compared to the model group,the level of autophagy was inhibited in the chloroquine intervention group.For control group,model group and chloroquine intervention group,the excretion of urinary oxalate were (3.1 ± 1.5) mmol,(22.5 ± 8.1) mmol,(2.8 ± 1.2) mmol,respectively;the excretion of urinary citrate were (63.4 ± 7.4) mmol,(45.9 ± 9.5)mmol,(15.6 ± 8.2) mmol,respectively.Compared to the control group,the amounts of urinary oxalate weresignificantly elevated in model group (P ＜ 0.05),but citrate were significantly reduced in the chloroquineintervention group(P ＜ 0.05).For control group,model group and chloroquine intervention group,theexpressions of SOD were 42.24 ±4.16,19.21 ± 2.25,39.08 3.53,respectively;the expressions of MCP-1 were 4.02 0.51,8.45 ± 0.55,5.52 ± 0.34,respectively;the expressions of 8-OHdG were 7.16 ± 0.54,11.21 ± 1.12,8.67 ±0.34,respectively;the RNA expressions of SLC26A6 were 0.35 ±0.07,1.02 ±0.17,0.70 ± 0.06,respectively.Compared to the control group,the expressions of SOD were significantly reduced in the model group,but the expressions of MCP-1,8-OHdG and SLC26A6 were significantly elevated(P ＜0.05).Compared to the model group,the expressions of SOD were significantly elevated chloroquine intervention group (P ＜ 0.05),but the expressions of MCP-1,8-OHdG and SLC26A6 were significantly elevated(P ＜ 0.05).Conclusions The autophagy inhibitor chloroquine could inhibit the formation of calcium oxalate crystals induced by ethylene in rat kidney via inhibit the renal autophagy level and expressions of the SLC26A6,reducing the renal oxidative stress injury and urinary oxalate excretion.

Objective:To investigate the effects of bisphenol A(BPA)on the proliferation activity and stemness characteristics of endometrial mesenchymal stem/stromal cells(eMSCs),and to elucidate the improvement effect of human umbilical cord mesenchymal stem cell-derived supernatant(hUCMSC-Sup)on the cell injury.Methods:The eMSCs were cultured in vitro and treated with different concentrations of BPA(0,200,250,300,350,and 400 μmol·L-1).The eMSCs were divided into control group(only cultured with culture solution),BPA group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA),BPA+hUCMSC-Sup group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 50%volumetric ratio of hUCMSC-Sup),and BPA+CHIR-99021 group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 10 μmol·L-1 CHIR-99021).The survival rates of eMSCs in various groups were detected by methyl thiazolyl tetrazolium(MTT)assay.The numbers and diameters of the spheroids in various groups were detected by spheroids formation assay,the proliferation activities of the cells in eMSCs stem cell spheroids in various groups were detected by CCK-8 assay;the percentage of CD73+cells in eMSCs in various groups were detected by flow cytometry;the expression levels of sex determining region Y-box 2(Sox2),octamer-binding transcription factor 4(Oct4),and Nanog mRNA in the eMSCs in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method,the expression levels of β-catenin protein in the eMSCs in various groups were detected by Western blotting method.Results:The MTT results showed that after treated with BPA for 24 and 48 h,compared with 0 μmol·L-1 BPA group,the survival rates of eMSCs in 200,250,300,350,and 400 μmol·L-1 BPA groups were significantly decreased(P<0.01).At 24 and 48 h after treatment,compared with control group,the survival rate of the eMSCs in BPA group was significantly decreased(P<0.01);at 48 h after treatment,compared with BPA group,the survival rate of the eMSCs in BPA+hUCMSC-Sup group was significantly inereased(P<0.05).The spheroids formation assay results showed that compared with culture 3 d group,the numbers and diameters of stem cell spheroids of the eMSCs in culture 4 d group and culture 5 d group were significantly increased(P<0.05 or P<0.01);compared with control group,after 48 h of culture,the number and diameter of the cells in eMSCs stem cell spheroids in BPA group were significantly decreased(P<0.05 or P<0.01).The CCK-8 results showed that after 24 and 48 h of treatment,compared with control group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA group was significantly decreased(P<0.01);compared with BPA group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The flow cytometry results showed that compared with control group,the percentage of the CD73+cells in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the percentage of the CD73+cells in eMSCs in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The RT-qPCR results showed that compared with control group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA group were significantly decreased(P<0.01);compared with BPA group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression level of β-catenin protein in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the expression levels of β-catenin protein in the eMSCs in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were signifrcantly inereased(P<0.01).Conclusion:BPA can inhibit the stemness characteristics of the eMSCs,and injury the self-renewal and repair of endometrium;its mechanism may be related to down-regulating the activity of Wnt/β-catenin signal pathway in the cells.hUCMSC-Sup can promote the proliferation of injured eMSCs,and has improvement effect on the stemness injury induced by BPA.

Rheumatic diseases, a typical kind of autoimmune disease, are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, which often leads to immune dysfunction in patients and increases the risk of activation of latent tuberculosis infection. To regulate the screening, diagnosis, and prophylactic treatment of latent tuberculosis infection in patients with rheumatic diseases, reduce the risk of developing active tuberculosis and improve the prognosis, Peking University Shenzhen Hospital, Shenzhen Third People′s Hospital and Peking Union Medical College Hospital jointly organized domestic experts in the field of rheumatology and tuberculosis to establish the expert consensus on the diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases. This consensus focuses on epidemiology, the importance of screening, screening methods, and prophylactic anti-tuberculosis treatment strategies for latent tuberculosis infection combined with rheumatic diseases.

In dentistry, orthodontic root resorption is a long-lasting issue with no effective treatment strategy, and its mechanisms, especially those related to senescent cells, remain largely unknown. Here, we used an orthodontic intrusion tooth movement model with an L-loop in rats to demonstrate that mechanical stress-induced senescent cells aggravate apical root resorption, which was prevented by administering senolytics (a dasatinib and quercetin cocktail). Our results indicated that cementoblasts and periodontal ligament cells underwent cellular senescence (p21⁺ or p16⁺) and strongly expressed receptor activator of nuclear factor-kappa B (RANKL) from day three, subsequently inducing tartrate-resistant acid phosphatase (TRAP)-positive odontoclasts and provoking apical root resorption. More p21⁺ senescent cells expressed RANKL than p16⁺ senescent cells. We observed only minor changes in the number of RANKL⁺ non-senescent cells, whereas RANKL⁺ senescent cells markedly increased from day seven. Intriguingly, we also found cathepsin K⁺p21⁺p16⁺ cells in the root resorption fossa, suggesting senescent odontoclasts. Oral administration of dasatinib and quercetin markedly reduced these senescent cells and TRAP⁺ cells, eventually alleviating root resorption. Altogether, these results unveil those aberrant stimuli in orthodontic intrusive tooth movement induced RANKL⁺ early senescent cells, which have a pivotal role in odontoclastogenesis and subsequent root resorption. These findings offer a new therapeutic target to prevent root resorption during orthodontic tooth movement.
Rats ; Animals ; Root Resorption/prevention & control* ; Senotherapeutics ; Stress, Mechanical ; Dasatinib/pharmacology* ; Quercetin/pharmacology* ; Osteoclasts ; Tooth Movement Techniques ; Periodontal Ligament ; RANK Ligand