Objective:To develop a chemiluminescent microparticle immunoassay ( CMIA) method for the determination of meco-balamin in human serum to investigate the pharmacokinetics and bioequivalence of mecobalamin. Methods:A single oral dose of two kinds of mecobalamin was given to 19 healthy volunteers in a randomized three-period crossover study. The concentrations of mecobal-amin in serum were assayed by CMIA, the main pharmacokinetic parameters were analyzed by DAS 3. 0 software, and the bioequiva-lence was evaluated. Results: The main pharmacokinetic parameters of test and reference mecobalamin tablets were as follows: tmax were (4.2 ±1.9)h and (4.4 ±2.4)h,Cmax were (322.0 ±145.4) ng·L-1 and (282.2 ±108.1) ng·L-1,t1/2 were (19.2 ±5.3) h and (20.0 ±6.3)h,AUC0-72 were (6 769.1 ±2 169.4) ng·h·L-1 and (6 400.6 ±1 921.5) ng·h·L-1. F(0-72) and F(0-∞) of the test tablets was 105. 9% ± 13. 2% and 104. 9% ± 12. 6%,respectively. Conclusion:The method is simple and precise. The two tablets are bioequivalent.

Objective To observe the effect of light emitting diode (LED) red light irradiation on serum lipid in experimental hyperlipidemia rats. Methods 36 healthy male Sprague-Dawley rats were randomly divided into normal control group (n=12) and hyperlipidemic model group (n=24). The normal group was fed with normal diet while the hyperlipidemic model group with fat-rich forage for 6 weeks. The hyperlipidemic model group rats were randomly divided into the hyperlipidemic control group (n=12) and LED treatment group (n=12), and the latter accepted LED red light irradiation for 28 d. The levels of serum lipid including total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), and the activities of lipoproteinesterase (LPL) and hepatic lipase (HL) were detected with biochemical assay. The expression of 3-hydroxy-3-methylglutaryl coenzyme A reducase (HMG-CR) of hepatic tissue were measured with immunohistochemical staining. Results Compared with the hyperlipidemic control group, the levels of serum TC, TG and LDL-C decreased while the serum HDL-C increased significantly in the LED treatment group (P<0.01) after treated with LED. The levels of LPL and HL in serum increased (P<0.01) while the activity of HMG-CR decreased (P<0.05). Conclusion LED red light irradiation might play a regulating effect on serum lipid by enhancing the activities of LPL and HL and inhibiting the expression of HMG-CR to interfere the metabolism of TC, TG, LDL-C and HDL-C.

Objective To explore the effects of the extracellular regulated protein kinase’s (ERK1/2) inhibitor PD98059 and ino-sitol triphosphate kinase (PI3K/PKB) signaling pathway’s inhibitor LY294002 on extracellular matrix (ECM) deposition in pulmonary arterial smooth muscle cells (PASMCs) stimulated by connective tissue growth factor (CTGF). Methods PASMCs of SD rat were cul-tured in vitro. The PASMCs were divided into control group, CTGF group, CP (CTGF+PD98059) group, CL (CTGF+LY294002) group and CPL (CTGF+PD98059+LY294002) group. Real-time lfuorescent quantitative RT-PCR was used to detect the expression of colla-gen III and ifbronectin mRNA of PASMCs, and the expression of collagenШprotein of PASMCs was detected by immunohistochem-istry and western-blot. Results The expressions of collagenШand ifbronectin mRNA of PASMCs stimulated with CTGF (50 ng/ml) for 48 h were signiifcantly higher than those in control group, and the collagen proteinШof PASMCs was decreased signiifcantly after stimulation with CTGF (50 ng/ml) for 72 h (P<0.05). The expressions of collagenШand ifbronectin mRNA in PASMCs cultured with PD98059 (20μmol/L) and/or LY294002 (10μmol/L) for 48 h was signiifcantly lower than those in CTGF group (P<0.05). The collagen proteinШin PASMCs cultured with PD98059 (20μmol/L) and/or LY294002 (10μmol/L) for 72 h was increased (P<0.05). The expres-sions of collagenШand ifbronectin mRNA of PASMCs stimulated with both PD98059 and LY294002 were more signiifcant. Conclu-sions CTGF may increase the expression of collagenШand ifbronectin mRNA in PASMCs, which may contribute to the deposition of ECM in PASMCs during pulmonary vascular remodeling. PD98059 and LY294002 may repress ERK1/2 and PI3K/PKB signaling pathways and interfere with the biological effect of CTGF.

Objective To explore the mechanisms of integrin β1 on connective tissue growth factor(CTGF)-induced proliferation,migration,change of cytoskeleton of pulmonary arterial smooth muscle cell(PASMC) in vitro,and to investigate the effects of CTGF-integrin β1 signal pathway on pulmonary vascular remodeling in pulmonary arterial hypertension (PAH).Methods Pulmonary artery smooth muscle cells of SD rats were cultured in vitro.WST-1 assay was used to detect the effects of anti-integrin β1 antibody on CTGF-induced proliferation of PASMC.Transwell chambers were used to observe the effects of anti-integrin β1 antibody on CTGF-induced migration of PASMC.The cytoskeletal rearrangement was observed with coomassie brilliant blue R250 staining and Confocal Lasar Scanning Microscopy (CLSM).Results Different concentration of anti-integrin β1 antibody could inhibit the proliferation of PASMC induced by CTGF,which presents concentration dependent pattern (P ＜ 0.05).The higher the concentration of anti-integrin β1 antibody,the more severity the proliferation of PASMC induced by CTGF was inhibited.and inhibition rate of PASMC proliferation was the highest at 72 hours.Anti-integrin β1 antibody(15 mg/L) decreased significantly the number of PASMC passing through Transwell induced by CTGF,compared with CTGF group (P ＜ 0.01).Meanwhile,antiintegrin β1 antibody could change cytoskeletal rearrangement of PASMC induced by CTGF.Conclusions Integrin β1mediates the proliferation,migration,cytoskeletal rearrangement of PASMC induced by CTGF.The CTGF-integrin β1signal pathway may play a key role in proliferation,migration,cytoskeletal rearrangement PASMC.

OBJECTIVE:To study the bioequiavailability of domestic roxithromycin tablets and imported ones.METH?ODS:20male healthy volunteers took single dose of150mg roxithromycin tablet orally in a random crossover design,blood concentrations were determined by LC-MS.RESULTS:The main pharmacokinetic parameters of domestic and imported tablets were determined respectively as follows,AUC 0～72 were(72.81?23.85)(mg?n)/L and(72.63?20.86)(mg?h)/L,AUC 0～∞ were(74.41?24.45)(mg?h)/L and(74.42?24.45)(mg?h)/L,C max were(6.46?1.51)mg/L and(6.58?1.55)mg/L,t max were(1.9?0.5)h and(1.8?0.5)h,t 1/2 were(13.56?1.35)h and(14.18?1.50)h,the relative bioavailability of the homemade tablet to imported one was(99.8?11.2)%.CONCLUSIONS:Domestic and imported roxithromycin are bioequivalent.

AIM: To compare the pharmacokinetics and relative bioavailability of the domestic and imported sustained-release tablets of gliclazide in healthy volunteers. METHODS:The study was performed by an four-period crossover design with singledose and multiple-dose administration. The plasmadrug concentrations of twenty male healthy volunteers were determined by liquid chromatography with mass spectrum detector method (LC-MS). RESULTS:The pharmacokinetic parameters after a single oral dose of the domestic and imported gliclazide tablets were (7.2+s 1.5) h and (6.9 +1.4) h for tmax, (13.4 ±1.2) h and (13.7 +1.3) h for t1/2, (2.4 +0.8) mg ·L-1and (2.3 ±0.6) mg· L-1 forcmax, (48 ±14)mg · h · L-1 and (48 +14) mg· h · L-1 forAUC0-60,(51+15) mg· h· L-1 and (50±14) mg· h· L-1for AUC0-∞, (22.4 ± 1.9 ) h and (22.8 ± 1.9 ) h for MRT, respectively. The steady state pharmacokinetic parameters after multiple doses of the domestic and imported gliclazide tablets were (6. 1 ± 1.4) h and (6.5+1.4) h for tmax, (4.6±0.9) mg· L-1 and (4.7±1.1) mg· L-1 for cmax, (0.23 ±0.08) mg ·L-1and (0.26±0.08) mg· L-1 forcmin, (1.6±0.3) mg·L-1 and (1.6±0.3) mg · L-1 for mean value of steady plasma-drug concentration (cav),(94±19) mg· h · L-1 and (95 ±20) mg · h · L-1forAUCss, (282 ±33)% and (283 ±43)% for degree of fluctuation DF ), respectively. The relative bioavailability of the domestic gliclazide tablet to the imported gliclazide tablet following a single and multiple dose were ( 102 ± 9) % and (99 ± 10 ) %, respectively. Main pharmacokinetic parameters between the two formulations in both single and multiples dose studies showed no statistical difference ( P >0.05 ). CONCLUSION: The result of two one side t-test shows that the two formulations are bioequivalent.

Objective To observe the changes of adiponectin (APN),chemerin and tumor necrosis factor-α (TNF-α) in subclinical hypothyroidism (SCH) rats,and to clarify the effect of L-thyroxine (L-T4) replacement therapy.Methods Sixty-five male Wistar rats were randomly divided into five groups via the random number table method:control group (n =10),SCH group A (n =15),SCH group B (n =15),SCH group C (n =15) and L-T4 treatment group (SCH + L-T4,n =10).Rats in groups SCH A,B and C were fed with 5,15 and 20 mg·kg-1·d-1 methimazole (MMI) once daily by gavage.The rats in SCH + L-T4 group were given 20 mg·kg-1·d-1 MMI once daily through gavage,after 8 weeks,6 μg·kg-1· d-1 of L-T4 was intragastrically added (50 μg/tablet) and the model was completed at the 16th week.The levels of serum APN,chemerin and TNF-α were measured via the enzyme linked immunosorbent assay (ELISA) method.The mRNA and protein levels of APN,chemerin and TNF-α in visceral adipose tissue of 5 groups were determined by real-time PCR (RT-PCR) and Western blotting,respectively.Results Compared with the control group [(202.20 + 17.27) ng/L,(143.70 ± 18.46) ng/L,(114.69 ± 4.18) μg/L],the serum chemerin levels in the SCH A,B,C groups were significantly higher [(314.33 ± 16.80),(355.00 ± 17.10),(365.00 ± 11.63) ng/L,P ＜0.05] and TNF-α levels also increased significantly [(222.60 ± 14.13),(279.20 ± 12.79),(288.30 ± 15.89) ng/L,P ＜0.05],and APN levels were significantly decreased [(77.21 ± 3.08),(68.58 ± 2.92),(59.45 ± 2.41) μg/L,P ＜0.05];but compared with SCH group C,the levels of chemerin and TNF-α in the SCH + L-T4 group were decreased [(260.07 ± 10.80),(178.40 ± 10.29) ng/L] and the level of APN [(102.35 ± 3.17) μg/L] was increased (P＜ 0.05).The mRNA and protein levels of APN in SCH A,B,C groups were significantly lower than those in the control group (P ＜0.05).The APN mRNA and protein levels in the SCH + L-T4 group were significantly higher than those in the SCH group C (P ＜ 0.05).The mRNA and protein levels of chemerin and TNF-α in the SCH A,B,C groups were higher than those in the control group (P ＜ 0.05).However,the mRNA and protein levels of chemerin and TNF-α in the SCH + L-T4 group were significantly lower than those in the SCH group C (P ＜ 0.05).Conclusion The expression levels of serum chemerin and TNF-α in SCH rats have increased,and APN levels decreased,but L-T4 can ameliorate these changes.

Pathogen detection is very important to improve the prognosis of patients with peritoneal dialysis-associated peritonitis. The paper reported a case of peritonitis caused by Ureaplasma parvum diagnosed by metagenomics next-generation sequencing（mNGS）technology. The patient was a middle-aged woman and hospitalized due to abdominal pain and muddy effluent. Anti-infective treatments such as ceftazidime and vancomycin were given but the effect was poor. The result of traditional culture was negative. Ureaplasma parvum was detected by mNGS. After using doxycycline，the patient's inflammation was controlled. It is suggested that mNGS plays an important role in the detection of the pathogens in peritoneal dialysis-associated peritonitis patients with negative culture. Through this case report and literature review，clinical experience is provided for the diagnosis and treatment in such patients.

Objective:To determine whether the early stage platelet count can predict the outcome of peritoneal dialysis-associated peritonitis (PDAP).Methods:A retrospective cohort study was conducted by selecting PDAP patients who were hospitalized in the First People's Hospital of Foshan from January 2012 to January 2019. According to the final treatment outcome, the patients were divided into cured group and withdrawn group. The withdrawn group included patients who transferred to hemodialysis or died. Basic data on demography, blood routine examination, peritoneal fluid, biochemical indicators were compared between the two groups. Logistic regression analysis was used to analyze the withdrawn risk factors of PDAP.Results:There were 180 patients included in the study, including 112 cases in the cured group and 68 cases in the withdrawn group. Compared with the cured group, there were older age [(53.38±14.17) years old vs (48.41±13.04) years old, t=2.407, P=0.017], longer age of dialysis [(49.20±26.05) months vs (30.36±32.97) months, t=4.034, P<0.001], longer hospital stay [(23.88±11.50) d vs (17.80±3.95) d, t=5.133, P<0.001] and higher platelet count [(285.55±107.23)×10 9/L vs (234.90±74.03)×10 9/L, t=3.450, P=0.001], lower serum albumin [(31.72±7.47) g/L vs (35.40±4.93) g/L, t=-3.972, P<0.001] in the withdrawn group. Multivariate logistic regression analysis showed that longer dialysis age ( OR=1.012, 95% CI 1.007-1.024, P=0.015) and higher platelet count ( OR=1.013, 95% CI 1.004-1.026, P=0.008) were independent risk factors, and higher serum albumin ( OR=0.941, 95% CI 0.896-0.988, P=0.005) was an independent protective factor of withdrawal from peritoneal dialysis in PDAP patients. Conclusions:The long dialysis age, early high platelet count are independent risk factors and high serum albumin level is an independent protective factor for withdrawal from peritoneal dialysis in PDAP patients.

Objective:To investigate the effect of salvianolic acid on depressive behavior in depression model rats induced by chronic mild stress (CMS) and its mechanism.Methods:Fifty healthy male clean grade Sprague-Dawley(SD) rats were divided into five groups according to a random number table with 10 in each group: control group (nCMS+ Nal group), CMS+ normal saline group (CMS+ Nal group), CMS+ fluoxetine group (CMS+ Flu group), CMS+ salvia acid group (CMS+ Sal group), CMS+ fluoxetine+ Salvia acid group (CMS+ Flu+ Sal group). Except the control group, the rats in the other four groups were all received CMS modeling for 21 days. Twenty-one days after CMS modeling, rats were intraperitoneally injected with 0.9% normal saline (10 mg·kg -1·d -1), fluoxetine (20 mg·kg -1·d -1), salvia acid(40 mg·kg -1·d -1), fluoxetine(20 mg·kg -1·d -1)+ salvia acid(40 mg·kg -1·d -1)for 21 days. During the administration period, rats in the other four groups continued to receive CMS intervention for 21 days. Forced swimming test and sucrose preference test were conducted at baseline (day 0), after modeling (day 21) and after intervention (day 42) so as to evaluate depression like behavior. Then the rats were sacrificed and the hippocampus and prefrontal cortex were taken. The mRNA levels of Toll like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) were detected by RT-qPCR. The cytokines including interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by Luminex technique.SPSS 21.0 was used for statistical analysis.Repeated measurement ANOVA was used for behavioral data analysis, one-way ANOVA was used for molecular index data analysis, and Spearman was used for correlation analysis. Results:The results of repeated measurement ANOVA showed that the interaction effects between group and time of body mass, sucrose preference, forced swimming immobility time were significant at baseline, after modeling and after intervention ( F=18.238, 6.921, 7.591, all P<0.05). After modeling, compared with nCMS+ Nal group, the rats in CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and CMS+ Nal group had lower body weight, lower sucrose preference rate and longer forced swimming immobility time (all P<0.05). After intervention, compared with CMS+ Nal group(body weight (350.15±41.65)g, sucrose preference(52.95±11.13)%, static time(91.40±15.22)s), the body weight((378.21±30.78)g, (385.12±43.19)g, (391.41±31.21)g, (402.33±18.67)g, all P<0.05) and sucrose preference((69.30±15.56)%, (68.12±10.99)%, (71.18±9.51)%, (75.47±11.55)%, all P<0.05) of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all increased, while the forced swimming immobility time ((68.81±21.74)s, (66.10±25.51)s, (63.53±22.32)s, (71.21±21.41)s, all P<0.05) were shorter (all P<0.05). After intervention, among the body weight, sucrose preference and the immobility time of CMS+ Flu group、CMS+ Sal group and CMS+ Flu+ Sal group, there were no differences between each two groups(all P>0.05). After intervention, the levels of TLR4 mRNA and MyD88 mRNA in prefrontal cortex and hippocampus of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all lower than those in CMS+ Nal group (all P<0.05). In prefrontal cortex, the levels of TLR4 mRNA (0.715±0.358) and MyD88 mRNA (0.739±0.233) in CMS+ Flu+ Sal group were lower than those in CMS+ Sal group (1.943±0.606, 1.815±0.897) (both P<0.05). The level of TLR4 mRNA in prefrontal cortex and hippocampus of rats were positively correlated with the level of MyD88 mRNA and TNF-α level and forced swimming immobility time and negatively correlated with sucrose preference rate (prefrontal cortex r=0.915, 0.041, 0.027, -0.178, all P<0.05; hippocampus r=0.810, 0.070, 0.011, -0.153, all P<0.05). Conclusion:The antidepressant effect of salvianolic acid is presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CMS rats.