Objective To establish a method to isolate and cultivate rat bone marrow mesenchymal stem cells (BMSCs),and explore the feasibility of labeling in vitro,and tracing in vivo,BMSCs with chloromethyl-benzamidodialkylcarbocyanine (CM-Dil). Methods BMSCs were obtained and subsequently cultured with whole bone marrow cell culture system,and the third generation of BMSCs was harvested. The positive rates of CD34,CD44 and CD29 were detected by flow cytometry. CM-Dil was used to label BMSCs in vitro and the efficiency of labeling after 24 hours and at day 21 and 30 were examined under fluorescent microscope. Moreover,the growth curves were sketched to determine the negative effects of CM-Dil on the vitality and proliferation of BMSCs cultured in vitro. Rat model of focal cerebral ischemia was reproduced,CM-Dil labeled BMSCs were implanted into corpus striatum of rats' brain with computer-guided stereotaxis thereafter. Brain tissues were obtained to prepare frozen sections at 7th,14th and 21st day post-implantation,and the survival and distribution of labeled cells were observed with fluorescent microscopy. Results The third generation passage of cultured BMSCs grew orderly,with shape of desmocytes,and homogeneous in morphology. The positive rates of CD34,CD44 and CD29 expressions in BMSCs were 1.71%,80.32% and 84.89%,respectively. Red fluorescence was observed in CM-Dil labeled BMSCs in vivo 24 hours after labeling,with a positive rate of 100%. The fluorescence intensity of passage cultured BMSCs observed on day 21 was similar to that observed at 24 hours after labeling,but diminished on day 30. The growth,proliferation and morphology of BMSCs,were not influenced by CM-Dil labeling. On day 7,14 and 21 post-implantation,BMSCs decreased in quantity,appearing in oval or irregular shapes,and most of the cells were found around the needle tract,with a tendency of diffusion to peripheral area. Conclusion High purity of BMSCs may be obtained with whole bone marrow cell culture system from bone marrow of rats. CM-Dil labeling is easy to handle and effective,with no cytotoxicity to cells. The latest labeling period of CM-Dil is 21 days in vitro,therefore it seems to be an effective method for in vivo tracing of BMSCs in brain after implantation.

Aim The relative bioavalability of hydrochloride eperisone granule in 10 healthy volunteers was studied. Methods The time-plasma concentrations of hydrochloride eperisone granule, as test drug, and myonal, as reference drug, were determined by GC-MS, with tolperisone senuing as internal standard.The pharmacokinetic parameters of both reference and test drug were calculated and analyzed with two-one side test and confidential interval test. Results The results showed that the AUC0-8, AUC0-∞, Cmax, Tpeak, t1/2(?) and t1/2(?) were (17.9?1.3)ng?h?ml-1 and(18.6?1.6)ng?h?ml-1, (19.1?1.2)ng?h?ml-1 and (20.2?1.6)ng?h?ml-1, (5.2?0.5)ng?ml-1 and (5.4?0.5) ng?ml-1, (1.05?0.18)h and (1.08?0.23)h, (0.78? 0.13)h and ( 0.82?0.14)h,( 1.8?0.3)h and (1.8?0.3)h, respectively. The relative bioavalability of test drug was (105? 5)%. Conclusion It can be concluded that the test and reference are bioequivalented between individuals, preparations and periods.

OBJECTIVEThe aims of this study were to evaluate whether the presence of -2518A/G polymorphism in the distal regulatory region of the monocyte chemotactic protein-1 (MCP-1) was associated with tuberculosis (TB) in Chongqing Han population and to find whether it has a significant impact on the pediatric patient.

METHODOne hundred children [ < or = 15 years old, mean age (7.3+/-4.6) years, 53 male, 47 female] and one hundred adults [51 male, 49 female, age (44.6+/-13.5) years with TB] and 200 healthy controls of comparable age were screened for genotype by PCR-sequence-specific primer (SSP) method. MCP-1 levels in the sera were detected by ELISA.

RESULT(1) TB patients and controls showed different single nucleotide polymorphism (SNP) distribution patterns (58%, 36%). MCP-1 alleles -2518G was associated with increased TB susceptibility (P<0.01). (2) The -2518 GG genotypes was associated with increased TB susceptibility (32% in TB patients and 13% in non-TB controls respectively, P<0.01). (3) The odds of developing TB in genotypes GG were higher than those in homozygous AA, and the risk was higher in children than in adult (7.0-fold in children and 5.1-fold in adults, respectively). (4) Cases of homozygous GG had the highest plasma levels of MCP-1, which increased the likelihood of developing TB. Furthermore, higher levels were observed in children than in adults.

CONCLUSIONThese findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which increases the risk of active TB infection in Chongqing Han people. These findings are more significant in child patients than in adult patients with TB.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Chemokine CCL2 ; blood ; genetics ; Child ; Child, Preschool ; DNA Primers ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Tuberculosis ; ethnology ; genetics ; metabolism

Angioimmunoblastic T-cell lymphoma (AITL) is a rare, distinct subtype of peripheral T-cell lymphoma, possessing an aggressive course and poor prognosis with no standard therapy. Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine (CsA), prednisone (PDN), and monthly, high-dose intravenous immunoglobulin (HDIVIG). The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function. All patients were examined for response, toxicity and survival. The most significant toxicities (≥ grade 2) were infection (16.7%), renal insufficiency (8.3%), hypertension (8.3%), diabetes (8.3%) and insomnia (16.7%). Discontinuation of treatment occurred in one patient (8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection. Treatment-related death was not observed. The overall response rate was 75.0% (complete response, 33.3%; partial response, 41.7%). With a median follow-up of 25.5 months, the median duration of response was 20 months (range, 12 to 49 months) and the median progression-free survival (PFS) was 25.5 months (range, 10 to 56 months). The 2-year PFS rate was 81.5%. Our findings indicate the combination of CsA, PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Combined Modality Therapy ; Cyclophosphamide ; therapeutic use ; Disease-Free Survival ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Immunoglobulins ; administration & dosage ; therapeutic use ; Infusions, Intravenous ; Lymphoma, T-Cell, Peripheral ; drug therapy ; therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Prednisolone ; therapeutic use ; Remission Induction ; Salvage Therapy ; Vincristine ; therapeutic use

Objective To study a method for monitoring multichannel electrode-scalp contact impedances in electrical impedance tomography (EIT), and to provide support for exploring the impact of contact impedances on imaging and the suppression method.Methods A reference electrode was introduced for the system,placed on the back of the neck or the top of the head. In the spare time of boundary voltage signal acquisition phase, the method of two electrodes was adopted to measure the electrical impedance between each imaging electrode and reference electrode, which was used to analyze the characteristics of multichannel contact impedances.Based on the existing EIT hardware system,the module for monitoring multichannel contact impedance was implemented.Results The calibration board test showed that the measurement error of this method was less than 1‰,and the maximum relative fluctuation of the measurement result within 10 hours was less than 1‰. Preliminary human test indicated that this method had the ability to obtain two kinds of information about spatial consistency and temporal stability of 16-channel contact impedances. Conclusion This method has high accuracy and stability,so it meets the requirements of monitoring multichannel contact impedances in brain EIT.

Objective To study the tolerability and safety of single and multiple doses of Picika oral solution in healthy volunteers.Methods A single center, randomized, single -blind, placebo -controlled, dose -escalation study was designed.50 patients were given single dose, and 10 cases were given multiple doses.All of them had half male and fe-male.Single -dose group: 20 mL(4 subjects), 40 mL(6 subjects), 60 mL(10 subjects; 2 using placebo), 90 mL(10 subjects; 2 using place-bo), 120 mL (10 subjects ; 2 using placebo), 160 mL (10 subjects; 2 using placebo); multiple doses group: 10 subjects(2 using placebo), 40 mL? times-1 , tid, continuous medication for 10 days.Results Of the sixty healthy subjects enrolled , 58 finally completed the trial, and two shed.One case (female) of adverse event in single -dose 160 mL group was reported: her ctivated partial thromboplastin time (APTT) was ab-normal with clinical significance.It may not be associated with the medi-cation.In multiple doses group, one case of abdominal pain (female) was reported, may not be associated with the medication.Conclusion Single and multiple doses of Picika oral solution are safe and well tolera -ted in healthy subjects.

Objective To study the influence of diet on the pharmacoki-netic of Picika oral solution in healthy subjects.Methods This study taken random , before and after self-control design.Twelve subjects were randomly divided into 2 groups, each group was 6 cases, then they were given Picika oral solution 60 mL respectively before and after meal.Before and after administration , blood and urine samples were collected at different points , the plasma and urine concentration was measured and pharmacokinetic parameters were calculated.Results Before and after administration of Picika oral solution 60 mL, the drug pharmacokinetic parameters of active ingredients -CKL-A03 were listed as follows:t1/2 was ( 126.13 ± 74.04 ) , ( 104.81 ± 68.44 ) min; tmax were (53.75 ±10.03 ) and (58.75 ±11.89 ) min;Cmax were (3.06 ±0.86 ) and ( 3.81 ±2.82 )μg· L-1; AUC0-t were ( 268.81 ±84.25 ) and (355.03 ±177.82 )μg· L-1 · min in plasma respectively.t1/2 was (1.14 ± 0.12 ), ( 1.24 ± 0.16 ) h in the urine respectively.Conclusion Diet may affect the absorption and eliminate speed of the drug.

Objective To evaluate the pharmacokinetic changes of Picika oral solution in healthy subjects after single dose.Methods This study taken random , three cross experiment design , 12 subjects were randomly divided into 6 groups, each group was 2 cases, then they were respec-tively given single oral doseof Picika oral solution (60, 90, 120 mL) in each cycle.Before and after administration , biological samples were col-lected for detection of blood drug concentration and urine drug concentra-tion, furthermore, calculation of blood and urine drug pharmacokinetic parameters.Results After single oral dose of 60, 90, 120 mL Picika oral solution, the main pharmacokinetic parameters of plasma CKL -A03, Cmax were (3.08 ±0.92), (3.63 ±0.75), (4.29 ±1.00)μg· L-1, tmax were (57.50 ±17.90 ), (52.50 ±20.73 ), (56.25 ±19.32 ) min, t1/2 were (197.51 ±106.35 ), (233.86 ±196.75 ), (141.34 ±65.16 ) min, AUC0-t were ( 383.28 ± 86.42 ) , ( 479.00 ± 136.25 ) , (540.59 ±102.87)μg · L-1 · min, AUC0-∞ were (710.06 ±233.03 ), (916.59 ±378.62 ), (782.65 ±130.40 )μg· L-1 · min, respectively. The main pharmacokinetic parameters of urine CKL -A03, t1/2 were (1.29 ±0.33), (1.23 ±0.20), (1.11 ±0.11) h, total urine discharge rates were (0.28 ±0.22)%, (0.20 ±0.11)%, (0.18 ±0.09)%, urine discharge amount were (74486.02 ±57923.42 ), (80015.14 ±43379.01 ), (93017.33 ±46658.61 ) mg.Conclusion The maximum oral absorption amount of Picika oral solution is possible 90 mL.And there is no apparent proportional relationship between the total urine discharge rate , urine discharge amount and the increased doses.

This study discussed whether the current pharmacokinetic study method of compound Chinese medicine could meet its research ob-jectives in drug development process.The conclusion were that, firstly, because the single or multiple active ingredient often do not represent the true effect of compound Chinese medicine, its findings may be biased. Secondly, drug accumulation method, pharmacological effect method, serum pharmacological method and integration of multi-effect component classifier method often draw pharmacokinetic results by pharmacodynamic study with thrust reversers method, but these methods can not accurately reflect the true pharmacokinetics in vivo.It might be more clinical value to make pharmacodynamic studies with pharmacodynamic markers.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.