Objective To improve the recognition of nervous system symptoms of inborn errors.Methods Five patients with organic acidemias were screened by urine organic acid analysis(gas chromotography-mass spectrometry,GC/MS),3 cases of methylmalolic acidemias(MMA) and 2 cases of propionic acidemias(PA) were confirmed.They were treated with special diet and medicine after diagnosis.Result The improvement of mental development was observed after treatment.Conclusions Most of organic acidemias involve nervous systems,causing non-specific symptoms of nervous system as lethergy,seizures,mental retardation.Inborn errors of metabolism shall be kept in mind when causes of the symtoms of acidosis,seisures,mental retardation and lethergy are investigated.GC/MS is a very important method in diagnosis of organic acidemias.Early diagnosis and early treatment can improve the mental prognosis.

Carcinoma, Renal Cell ; Humans ; Kidney Neoplasms ; Nomograms ; Prognosis ; Progression-Free Survival ; Retrospective Studies

Adult ; Fatty Liver ; diagnostic imaging ; physiopathology ; Female ; Humans ; Liver ; diagnostic imaging ; Liver Circulation ; Male ; Middle Aged ; Ultrasonography, Doppler, Color

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.
Animals ; Chromatography, Liquid ; Dexamethasone ; blood ; Dipeptidyl-Peptidase IV Inhibitors ; blood ; pharmacokinetics ; Linagliptin ; blood ; Rats ; Rats, Wistar ; Tandem Mass Spectrometry

AIM:To observe the tear film and corneal endothelial cell density in cataract patients with high myopia.METHODS:From January 2016 to December 2016,38 cases (38 eyes) with high myopia and cataract were selected as study group,24 males (24 eyes) and 14 females (14 eyes),average 65.2±2.37(60-72) years old.Age-related cataract patients without high myopia were as control group,22 males (22 eyes) and 16 females (16 eyes),average 64.4±2.43 (61-70) years old.The tear film and corneal endothelial cell density of the two groups were observed at 3,7,14d and 1mo after operations.RESULTS:Between the two groups of preoperative S I t,BUT,FL,subjective rating,corneal endothelial cell density comparison,there were no statistically significant difference (P＞0.05).In the two groups at 3,7,14d and 1mo after operations,BUT,FL,corneal endothelial cell density,subjective score comparison,the difference had statistical significance (P＜0.01).Two groups after 3,7,14d comparative differences of S Ⅰ t were statistically significant (P ＜ 0.01),not statistical significant at postoperative 1mo (P＞0.05).At postoperative 3,7,14d,1mo,FL,subjective rating,corneal endothelial cell density of the two groups were compared with preoperative,the difference was statistically significant (P＜0.01).In the two groups at 3,7,14d after operation,S I t compared with the same group preoperative difference was statistically significant (P ＜ 0.01),no statistical significance when postoperative 1mo compared with preoperative (P＞0.05).BUT of high myopia patients with age-related cataract surgery,at 3,7,14d and 1mo after operations decreased than preoperative,the difference was statistically significant (P＜ 0.01).Age-related cataract patients without high myopia at 3,7,14d after operation decreased than preoperative,the difference was statistically significant (P＜0.01),there was no statistically significant difference between preoperative and postoperative 1 mo (P＞0.05).CONCLUSION:Phacoemulsification cataract surgery in the treatment of high myopia cataract patients is safe and reliable,and less influence on tear film and corneal endothelial cell density.

Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg^-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between C_max and AUC_0-5d in the two groups. The liquid preparation was the reference preparation, with C_max ratio of 101.6% and AUC_0-5d ratio of 101.9%, the 90% confidence interval of C_max was 79.42%-129.92%, and the 90% confidence interval of AUC_0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

BACKGROUNDPrevious prognosis analyses of colorectal cancer (CRC) patients with stage II and III disease were done as separate categories. The purpose of this study was to analyze prognostic factors associated with survival in a group of patients who underwent radical resection of stages II and III CRC.

METHODSA retrospective review was performed for 141 consecutive stages II and III patients who had undergone radical resection of colorectal adenocarcinoma between May 2003 and November 2003. Univariate and multivariate analyses were performed to assess the effect of record variables on disease free survival and overall survival.

RESULTSThe median follow-up time was 59 months, and the 3- and 5-year survival rates were 76% and 68%, respectively. Four factors were independently associated with a worse disease-free survival: diabetes (hazard ratio (HR) 2.338; 95% confidence interval (CI) 1.011 - 5.407), expression of cyclooxygenase-2 (Cox-2) (HR 0.335; 95%CI 0.126 - 0.888), expression of matrix metalloproteinases 2 (MMP-2) (HR 0.233; 95%CI 0.101 - 0.541), expression of vascular endothelial growth factor (VEGF) (HR 0.295; 95%CI 0.088 - 0.996). Four factors were independently associated with a worse overall survival: lymph nodes metastasis (HR 1.67; 95%CI 1.29 - 2.14), Cox-2 positive (HR 0.056; 95%CI 0.247 - 0.731), MMP-2 positive (HR 0.398; 95%CI 0.190 - 0.836), VEGF (HR 0.364; 95%CI 0.090 - 0.716).

CONCLUSIONSDiabetes, expression of Cox-2, MMP-2 and VEGF were independently associated with a worse disease- free survival. Lymph nodes metastasis, expression of Cox-2, MMP-2 and high level of VEGF predicted a poor overall survival.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Colorectal Neoplasms ; metabolism ; pathology ; Cyclooxygenase 2 ; metabolism ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; pathology ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

OBJECTIVETo study the correlation between the expression of Fcgamma receptor II b (FcgammaRII b) on B cells and rheumatoid arthritis (RA) patients of Shen deficiency syndrome (SDS).

METHODSThere were 43 RA patients, including 26 of SDS and 17 of non-SDS. The expression levels of FcgammaRII b on naive B cells, memory B cells, and plasma blasts in the peripheral blood were detected by flow cytometry. The numbers of tender joints, numbers of swollen joints, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and disease activity score (DAS28), the correlation between the distribution of B cells and the expression level of FcgammaRII b in RA patients were analyzed. Besides, another 21 healthy volunteers were recruited as the control group.

RESULTSThe expression level of FcgammaRII b was 49.65% +/- 15.86% on memory B cells and 43.69% +/- 22.57% on plasma blasts in RA patients of SDS, significantly down-regulated when compared with those of the control group (64.03% +/- 6.01%, 66.59% +/- 10.18%, P < 0.01). The expression level of FcgammaRII b on memory B cells of RA patients of non-SDS was down-regulated more obviously when compared with that of the control group (52.70% +/- 9.52% versus 64.03% +/- 6.01%, P < 0.01). The expression level of FcgammaRII b on plasma blasts was obviously lower in RA patients of SDS than in RA patients of non-SDS (56.10% +/- 17.05%, P < 0.05). The expression level of FcgammaRII b on memory B cells was not correlated with numbers of tender joints, numbers of swollen joints, ESR, RF, or DAS28.

CONCLUSIONSThe defective immunological tolerance of B cells in RA patients of SDS might be closely correlated with down-regulation of FcgammaRII b on memory B cells and plasma blasts. There might exist genetic abnormality of FcgammaRII b gene in RA patients of SDS, thus inducing loss of autoimmunity tolerance.

Adult ; Arthritis, Rheumatoid ; blood ; diagnosis ; immunology ; B-Lymphocytes ; immunology ; metabolism ; Case-Control Studies ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Receptors, IgG ; immunology ; metabolism

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.
Animals ; Area Under Curve ; Batroxobin ; administration & dosage ; blood ; pharmacokinetics ; pharmacology ; Dogs ; Enzyme-Linked Immunosorbent Assay ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Fibrinolytic Agents ; administration & dosage ; blood ; pharmacokinetics ; pharmacology ; Infusions, Intravenous ; Male ; Partial Thromboplastin Time ; Prothrombin Time ; Thrombin Time

This study was aimed to investigate the effect of multikinase inhibitor sorafenib on the proliferation and apoptosis of U937 cells and its possible mechanism. U937 cells were treated with different concentrations of sorafenib for 48 hours. Cell viability was determined by Cell Counting Kit-8; cell apoptosis and cell ratio in cell cycle were detected by flow cytometry with Annexin V/PI staining and PI staining respectively; expressions of GSK-3β, β-catenin and cyclin-D1 were assayed by Western blot. The results showed that the proliferation of U937 cells was inhibited by sorafenib in a dose-dependent manner (p < 0.05). Sorafenib induced cell apoptosis and cell cycle G(1)/G(0) arrest. Compared with results of Western blot before treatment, expression of inactivated GSK-3β, β-catenin and Cyclin-D1 down-regulated in a dose-dependent manner after treatment with sorafenib, this same changes were observed after up-regulation of inactivated GSK-3β by LiCl (p < 0.05). It is concluded that sorafenib inhibits the proliferation of U937 cells and induces cell apoptosis through reducing negative regulation of WNT signal pathway on inactivated GSK-3β and down-regulating β-catenin and cyclin-D1 level, which result in U937 cell cycle G(1)/G(0) arrest.
Apoptosis ; drug effects ; Benzenesulfonates ; pharmacology ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; pharmacology ; U937 Cells ; Wnt Signaling Pathway ; beta Catenin ; metabolism