ObjectiveTo establish the reference intervals of serum triiodothyronine (TT3),the thyroxine ( TT4 ),free triiodothyronine ( FT3 ),free thyroxine ( FT4 ) and thyroid-stimulating hormone (TSH)in the apparently healthy individuals of Beijing and Shanghai.Methods According to the requirement for laboratory support for the diagnosis and monitoring of thyroid diseases in the National Academy ofClinicalBiochemistry(NACB)laboratorymedicinepracticeguidelines, therewere 390 apparently healthy individuals tested (221 male,169 female,18 -65 years old) from Beijing and Shanghai for serum TT3,TT4,FT3,FT4 and TSH on American Beckman UniCel DXI 800 Automatic Chemiluminescent Analyzer.All markers were analyzed between gender,region,age group using t test and ANOVA.The reference intervals of all markers were determined by P2.5 - P97.5.ResultsTT3,TT4,FT3,FT4,TSH levels in the male group were ( 1.90 ± 0.32) nmol/L,( 116.77 ± 18.02) nmol/L,( 5.28 ±0.67) pmol/L,( 11.54 ± 1.97) pmol/L,( 1.92 ± 1.12 ) mIU/L,respectively,while the above indicators in the female group were ( 1.82 ± 0.32) nmol/L,( 115.73 ± 14.39 ) nmol/L,(5.04 ± 0.59 ) pmol/L,( 10.94 ± 1.45) pmol/L,( 2.37 ± 1.86 ) mIU/L,respectively.When comparing the results in genders,statistical significance was shown in TF3,FT3,FT4 and TSH of two gender groups( t =2.377,3.642,3.471,2.520,all P ＜ 0.05 ).When comparing different regions,statistical significance was only shown in FT3 ( t =6.410,P ＜ 0.05 ),in which Beijing group was (5.01 ± 0.63) pmol/L,and Shanghai group was (5.41 ±0.61 ) pmol/L,and no significant difference were shown in other four markers.Correlation analysis showed that TT4 was positively correlated with age (r =0.22,P ＜ 0.001 ) while TSH was negatively correlated with age ( r =- 0.12,P ＜ 0.05 ).TT3,TT4,FT3,FT4,TSH reference intervals were ( 1.22 - 2.50 ) nmol/L,(83.37 - 149.37 ) nmol/L,( 3.88 - 6.48 ) pmol/L,( 7.70 - 14.86) pmol/L,( 0.38 - 5.58 ) mIU/L,respectively.ConclusionDifferences of serum thyroid hormones were observed in different areas of China,It is important to establish reference intervals of the serum thyroid hormones in Chinese population.

Objective To reveal the role of inhibitor of nuclear factor kappa B kinase alpha (IKKα) in renal inflammation after renal ischemia-reperfusion (IR) injury and its potential associated mechanism.Methods Ischemia-reperfusion injury models were induced in a total of 24 healthy C57BL/6 male mice.Renal function and histological changes were estimated.The expression and site of IKKα,p52,RelB,IL-10 and IL-18 were determined by immunohistochemistry and Western blotting.After the short hairpin RNA(shRNA)targeting IKKα was injected into renal parenchyma,renal function and protein expressions of IKKα,p52,RelB,IL-10,IL-18 were detected.Results Compared with sham-operated group[Scr(7.30±0.13) μmol/L,BUN (8.39± 0.30) mmol/L],levels of Scr [(29.80± 2.10)μmol/L,(27.00±3.40) μmol/L,(23.00±3.70) μmol/L] and BUN [(9.47±3.50) mmol/L,(11.68 ±4.30)mmol/L,(13.12±2.10) mmol/L] were higher on day 1,3,7 and the injury of kidney was serious in IR injury group.Immunohistochemical expression of both IL-18 and IL-10 were increased.Markedly increased IKKα,p52 and RelB protein expression were noted in experiments from day 1 to day 7 during kidney recovery period,with a peak on day 3 and then decreasing toward baseline after day 7.Compared with IR injury group,low-expression of IKKα by injection of shRNA up-regulated the expression of IL-18 and down-regulated the expression of IKKα,p52,RelB and IL-10.Conclusions The NF-κB pathway is activated and IKKα expression is up-regulated during the kidney ischemiareperfusion injury,low-expression of IKKα may block inflammation resolution via down-regulation of alternative NF-κB pathway family members of both p52 and RelB.

The effectiveness and safety of acupuncture for the treatment of supraventricular tachycardia were systematically reviewed. The randomized controlled trials (RCTs) regarding acupuncture for supraventricular tachycardia were searched in domestic and overseas databases, and the evaluation tool of bias risk in Cochrane Handbook 5.1.0 software was used to perform the evaluation of bias risk in literature, and RevMan 5.2 software was applied for statistics and Meta-analysis. Five RCTs involving 323 patients were included. The results showed that compared with the blank control group, the acupuncture reduced the heart rate by 18.8 times/min [95% CI (12.68, 24.92)]; the clinical effective rate in the acupuncture group was superior to that in the diltiazem group [OR= 3.11, 95% CI (1.50, 6.46)]; the difference of immediate effect between propafenone and acupuncture was not significant. No reports regarding adverse events was described in 5 RCTs. As was shown in the present evidence, acupuncture is safe and effective for the treatment of supraventricular tachycardia, but the level of evidence was low and the intensity of conclusion needed to be improved.
Acupuncture Points ; Acupuncture Therapy ; adverse effects ; Humans ; Randomized Controlled Trials as Topic ; Tachycardia, Supraventricular ; physiopathology ; therapy ; Treatment Outcome

The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacokinetics ; Camptothecin ; analogs & derivatives ; pharmacokinetics ; Chromatography, Liquid ; Colon ; metabolism ; Half-Life ; Injections, Intravenous ; Lung ; metabolism ; Mice ; Nanoparticles ; administration & dosage ; Rats ; Tandem Mass Spectrometry ; Tissue Distribution

Objective To observe the expression of stromal cell-derived factor 1 (SDF-1) in the kidney after ischemic reperfusion injury (IRI),and explore its relationship with macrophage during the IRI kidney.Methods A total of 28 healthy C57BL/6 male mice were used to establish renal IRI model by clamping both pedicles for 35 min followed by reperfusion.Kidney tissue samples were collected at indicated time points.Renal histological changes were estimated.The expression of SDF-1 was determined by immunohistochemistry,ELISA and real-time PCR.After the liposomal clodronate was injected intraperitoneally,the location of CD68 was observed by immunofluorescence.Renal histology and protein expression of SDF-1 were also detected.Results Compared with sham-operated group,classical tubular damage was found in IRI group,accompanied by a large number of inflammatory cells.The expression of total renal SDF-1 peaked on day 1 and decreased to control levels in the following days.SDF-1 in healthy kidney was localized at cortex,but spread to the corticomedullary area of the kidney during IRI.Compared with IRI groups,elimination of macrophage by injection of liposomal clodronate alleviated renal IRI and down-regulated the expressions of CD68 while up-regulating SDF-1.Conclusions SDF-1 expression is up-regulated in IRI kidney and is associated with macrophage.SDF-1 may play a role in the early phase of acute kidney injury and it may be a new marker in diagnosis of AKI.

Objective To study the effect of interleukin (IL)-10 knockout (IL-10-/-) on renal repair after renal ischemia-reperfusion injury in mice.Methods Eighteen IL-10-/-mice (KO) aged 8-10 weeks and 18 C57BL/6 wild type mice (WT) aged 8-10 weeks were divided into control group (Sham) and renal ischemia-reperfusion injury (IRI) group.The renal tissue morphology change was observed by Hematoxylin and eosin (HE) staining and Masson staining.The expressions of IL-18, Ki67 and TGF-β1 were detected by immunohistochemistry.The expression of TGF-beta1 and IL-18 were detected by Western blotting.Results Compared with that in WT-IRI group, in KO-IRI group renal pathological damage was more severe, renal interstitial fibrosis was visible, Ki67 expression of renal tubular epithelial cells decreased distinctly (P＜0.01), the expression of TGF-betal increased significantly (P＜0.01).Conclusion Repair slows down significantly after kidney ischemia-reperfusion injury and fibrosis occurs gradually in IL-10-/-mice, eventually progressing to chronic kidney disease.

Objective Effectiveness of two kinds of thermochemotherapy infusion from intraarterial approach were studied in the grafted liver VX2 tumors of rabbit.Methods VX2 tumor model was established in 30 Newzland rabbit's livers.Percutaneous transfemoral hepatic arterial catheterization with fixation of the cathether tip inside the feeding vessel was carried out under DSA guidance.All 30 rabbits were divided into three groups(n=10 in each group),normal temperature 100 ml saline+Adriamycin(ADM)infusion(group 1),60℃100 ml saline+ADM continuous perfusion(group 2)and 60℃100 ml saline+ADM intermittent perfusion(group 3).After the perfusion,the lasting time periods of 43-45℃for tumor tissue of group 2 and 3 together with the concentrations of ADM within tumor's tissue were measured.Results Concentrations of ADM were shown as(12.013?2.237)?g/ml,(17.622?1.368)?g/ml,and(11.519?1.225)?g/ml for group 2, group 3 and group 1 respectively.60℃intermittent perfusion vs 60℃continuous perfusion showed P＜0.05, 60℃continuous pefusion vs normal temperature perfusion also showed P＞0.05. 43-45℃period lasting time (min)for 60℃continuous pefusion vs 60℃intermittent pefusion were(4.1?2.7)min and(11.3?3.3)min respectively,the latter was three times more than the former.There were no differences shown betwen the temperature,respiration and heart rate of group 2 and group 3.Conclusion Intermittent intraarterial perfusion thermochemotherapy is a more effective interventional management among all thermochemotherapies.

Objective:To investigate the significance and mechanism of ten-eleven translocation (Tet1) against Mycobacterium marinum ( Mm) infection in mice. Methods:SPF wild-type C57BL/6 and Tet1-knockout (Tet1KO) mice were injected intravenously with Mm. All mice were monitored and the abscesses formed in tail were observed and quantified. Pathological changes in mouse tail tissues were observed using hematoxylin and eosin (HE) staining and transmission electron microscopy and the differences between the two groups were analyzed. Immunohistochemistry staining was used to detect the expression and distribution of TNF-α and TGF-β in mouse tail tissues. Moreover, mouse tail tissues were cultured on 7H10 plates for bacterial counting. The expression of NF-κBp65 and TGF-β was detected by Western blot. Results:Obvious lesions including abscesses and ulcers were formed in the Mm-infected C57BL/6, but only scattered small abscesses were observed in Mm-infected Tet1KO mice. During Mm infection, the bacterial load was gradually increased in C57BL/6 mice, but decreased in Tet1KO mice. Histopathological examination showed that obvious inflammatory cell infiltration and typical granulomatous lesions were found in Mm-infected C57BL/6 mice, while no significant inflammatory cell infiltration was detected in Mm-infected Tet1KO mice. Immunohistochemistry staining demonstrated that the expression of TNF-α and TGF-β was lower in Mm-infected Tet1KO mice than in Mm-infected C57BL/6 mice. Moreover, the expression of phosphorylated NF-κBp65 and TGF-β was significantly reduced in Mm-infected Tet1KO mice as compared with that in Mm-infected C57BL/6 mice. Conclusions:Deletion of Tet1 could alleviate the inflammatory damage mediated by Mm and enhance the host immune response to bacteria.

Tumor brings great threat to human public health. In recent years, incidence rate and mortality of tumor were rapidly increased in the world. Anti-tumor therapies have undergone the development of cytotoxic therapy, targeted therapy, and immunotherapy. Among them, tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years, although it also brings some related side effects. Tumor microenvironment (TME) is composed of immune cells, vascular vessels, fibroblasts, the extracellular matrix, etc. TME significantly affects the efficacy of immunotherapy. Macrophages in the TME are named as tumor associated macrophages (TAMs). Recently, increasing studies have shown that TAMs play an important role in the regulation of tumor immunity, especially in tumor immune surveillance and immune escape. Currently, more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage. Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy, we first reviewed the subtypes and functions of TAMs, as well as the roles of TAMs in tumors. Furthermore, we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs. The current review will provide new ideas and novel insights for tumor immunotherapy.

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.
Administration, Oral ; Animals ; Anticholesteremic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Atorvastatin Calcium ; administration & dosage ; blood ; pharmacokinetics ; Biological Availability ; Cross-Over Studies ; Dogs ; Drug Interactions ; Female ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; blood ; pharmacokinetics ; Hypoglycemic Agents ; administration & dosage ; blood ; pharmacokinetics ; Male ; Random Allocation ; Thiazolidinediones ; administration & dosage ; blood ; pharmacokinetics