Chlorogenic acid (5-CQA) is one of the major components in some Chinese herbal injections. However, the metabolism of 5-CQA in rats after intravenous injection has not been determined. An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) method was applied to identify the metabolites in bile, urine, feces and plasma after a single intravenous administration of 10 mg x kg(-1) 5-CQA to rats. Using MSE and mass defect filter techniques, a total of 35 metabolites were detected in bile, urine, feces and plasma. The predominant metabolites in bile were glutathione conjugates of O-methyl-5-CQA, accounting for approximately 80% of the metabolites excreted in bile. The major components in urine were parent drug, O-methyl-5-CQA, hydrolyzed metabolites and glucuronide conjugates. The major components in feces were O-methyl-5-CQA and its cysteine conjugates. The major component in plasma was the parent drug. The urinary and fecal excretion pathways were equally important to 5-CQA in rats. These results demonstrate that 5-CQA undergoes extensively metabolism in rats and are highly reactive to nucleophiles such as GSH. This finding indicates that attention should be paid on the injections containing 5-CQA, which may covalently bind to proteins, leading to allergenic drug reactions.

To evaluate the efficacy and safety of compound Decumbent Corydalis Rhizome (DCR) in treating patients with knee osteoarthritis (OA). Totally 79 patients with knee osteoarthritis were selected from out-patient and inpatient departments of West China Hospital and randomly divided into the test group and the control group. The test group (n = 41) was given Compound DCR with the dosage of 1.8 g · d(-1), while the control group (n = 38) was administered with diclofenac sodium with the dosage of 75 mg · d(-1). After 12 weeks of treatment, the total efficacy rates based on patients/physicians evaluation for experimental and control groups were 68.29%, 63.41% and 71.05%, 63.16%, respectively, without significant difference between the two groups. Both of the two groups showed significant improvements in the main efficacy indexes (pain on walking 20 m) and minor indexes (tenderness on palpation, Western Ontario and McMaster Universities OA index (WOMAC) and Short-Form Health Survey (SF-36 ), but without significant difference in efficacy between them. The incidence of related adverse events was 24.39% in the test group and 47.37% in the control group, respectively, with significant differences between the two groups (P < 0.05). In the controlled study, compound DCR is as efficient as diclofenac sodium but more tolerable, with a good clinical application prospect.
Adult ; Aged ; Corydalis ; chemistry ; Diclofenac ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy ; Rhizome ; chemistry ; Treatment Outcome

Objective To investigate the expression of P-21 activated kinase 1 (PAK1) and v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutation in papillary thyroid carcinoma (PTC)and their relationship with clinicopathological characteristics.Methods Immunohistochemistry was used to detect the expression of BRAF V600E mutation and P-21 activated kinase 1 (PAK1) in 55 PTC tissues and 25 benign thyroid tissues.The correlation between their expression and clinicopathological characteristics were analyzed.Results BRAF V600E mutation and PAK1 expressed differently between PTC and benign thyroid (respectively,x2 =12.121,9.950,all P ＜ 0.01).The expression of PAK1 and BRAF V600E mutation was positively and significantly correlated with tumor invasion,grades and lymph node metastasis(P ＜ 0.05),but it had no correlation with age,gender,tumor size,multiple tumor foci and bilateral tumor foci in PTC (P ＞ 0.05).Expression of PAK1 in BRAF V600E negative PTC was higher than that in BRAF V600E positive PTC,and expression of PAK1 and BRAF V600E mutation in PTC were negatively correlated(r =-0.284,P ＜ 0.05).Conclusion Overexpression of either BRAF V600E mutation or PAK1 predicts poor prognosis of PTC patients.

To study the role of BK virus(BK polyomavirus)in the development of the hemorrhagic cystitis(HC)after hematopoietic stem cell transplantation(HSCT)and analyze the risk fators for BK viruri4a and HC.Methods From August 2006 to November 2007,blood and urine samples were collected from 80 patients undergoing HSCT.BK virus DNA was detected with PCR.Cytomegalovirus (CMV)antigen was detected with immunofluorescence histochemical examination.A control group including 20 healthy individuals was established.Results Late-onset HC occurred in 15 of the 80 HSCT patients with an incidence of 18.8%.The median onset time of HC was 44(13-150)days after transplantation.BK viruria was detected in 30 of the 80 HSCT patients(37.5%)and the positive rate of viruria in the HC patients was 86.7%(13/15).The median time of BK viruria detection in HC patients wag 23(0-56)days after transplantation,being earlier than the onset time of HC.The persistence time of BK viruria was 7(2-14) weeks,being much longer than that of HC(11 days).CMV antigen viremia was detected in 12 of the 80 transplanted patients.with a positive rate of 36.7% in patients with BK viruria and 40.0% in HC patients.Nine of the 30 HC patients developed acute graft versus host disease(Agvhd)of grade Ⅱ-Ⅳ(30.0%).BK virus was not detected in the urine of the remainimg two HC patients and the 20 control subjects as well as in all the blood samples.Univariate analysis indicated that CMV viremia and Agvhd of grade Ⅱ-Ⅳ were agsociated with the occurrence of BK viruria.Condusions BK viruria is the main cauge of the late-onset HC after HSCT.CMV infection and Agvhd may contribute to the occurrence of HC agsociatieg with BK virus.

Objective To explore the prevalence of sialorrhea and its clinical correlation with dysphagia in Chinese patients with Parkinson′s disease ( PD ).Methods One hundred and sixteen consecutive patients with a clinical diagnosis of PD were selected.Demographic data included sex , age, years of education, age at onset of PD, clinical genotype, disease duration, treatment, Hoehn and Yahr (H&Y) stage.Sialorrhea was assessed using the Unified Parkinson′s Disease Rating Scale (UPDRS) Ⅱitem number 6.All patients were studied with videofluoroscopic study of swallowing ( VFSS).Results The prevalence rate of sialorrhea in PD was 59.5% (69/116, 95% CI 50.6%-68.4%).Males were more likely to develop sialorrhea than females (47/70 vs 22/46,χ2 =4.298, P=0.038).PD patients′sialorrhea correlated with oral dysphagia:with food leaking from the mouth ( liquid r=0.229, P=0.014; juice r=0.197, P=0.034;pudding viscosities r=0.231, P=0.013;solid food r=0.255, P=0.006), with more than 1 ml of oral food residues (liquid r=0.319, P<0.01;solid food r=0.185, P=0.047), with delay in food transfer to the root of the tongue (liquid r=0.279, P=0.002; juice r=0.209, P=0.024), and delayed swallow transfer ( pudding viscosities r=0.257, P=0.005).Sialorrhea score was not related to H&Y stage, clinical course and levodopa equivalent doses (LED).The prevalence rate of dysphagia in PD was 87.1%(95% CI 81.0% -93.2%).Liquid was more likely to cause pharyngeal dysphagia ( P=0.03).With the increase in H&Y stage , so did the oral and pharyngeal stages of dysphagia.Late and mid-course was more likely to develop oral and pharyngeal dysphagia than those with early clinical course .Conclusions Sialorrhea and dysphagia are common non-motor symptoms in PD patients.Sialorrhea is more prevalent in males and correlates with oral phase of dysphagia.Liquid is more likely to cause pharyngeal dysphagia.With increase in H&Y stage , so did oral and pharyngeal dysphagia.Even though late clinical course is more likely to develop oral and pharyngeal dysphagia than early clinical course , the comparison between late and intermediate clinical courses does not reach statistical significance .

Chlorogenic acid (5-CQA) is one of the major components in some Chinese herbal injections. However, the metabolism of 5-CQA in rats after intravenous injection has not been determined. An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) method was applied to identify the metabolites in bile, urine, feces and plasma after a single intravenous administration of 10 mg x kg(-1) 5-CQA to rats. Using MSE and mass defect filter techniques, a total of 35 metabolites were detected in bile, urine, feces and plasma. The predominant metabolites in bile were glutathione conjugates of O-methyl-5-CQA, accounting for approximately 80% of the metabolites excreted in bile. The major components in urine were parent drug, O-methyl-5-CQA, hydrolyzed metabolites and glucuronide conjugates. The major components in feces were O-methyl-5-CQA and its cysteine conjugates. The major component in plasma was the parent drug. The urinary and fecal excretion pathways were equally important to 5-CQA in rats. These results demonstrate that 5-CQA undergoes extensively metabolism in rats and are highly reactive to nucleophiles such as GSH. This finding indicates that attention should be paid on the injections containing 5-CQA, which may covalently bind to proteins, leading to allergenic drug reactions.
Animals ; Bile ; metabolism ; Biotransformation ; Chlorogenic Acid ; administration & dosage ; blood ; pharmacokinetics ; urine ; Chromatography, High Pressure Liquid ; methods ; Cysteine ; metabolism ; Feces ; chemistry ; Glucuronides ; metabolism ; Glutathione ; metabolism ; Injections, Intravenous ; Male ; Protein Binding ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

Objective To investigate the characteristics of activation-induced cytidine deaminase (AID) expression level in de novo acute leukemia (AL) patients, chronic myeloid leukemia chronic phase (CML-CP), chronic myeloid leukemia blastic crisis (CML-BC) patients and leukemia cell lines. Methods The expression level of AID mRNA was measured in 89 cases of newly-diagnosed acute lymphoblastic leukemia (ALL) patients, 79 cases of de novo acute myeloid leukemia (AML) patients, 5 cases of CML-BC patients, 5 cases of CML-CP patients and leukemia cell lines NB4, THP-1, KG-1, Raji, K562 by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), bone marrow mononuclear cells of 16 normal healthy donors were used as the control group. Results The expression levels of AID mRNA in 89 cases of ALL and 79 cases of AML were 0.006-7 463.175 and 0.005-69.107, the median expression levels were 3.785 and 1.812, the expression level of AID mRNA in the normal control group was 0.146-4.707, and the median expression level was 1.483, respectively. The AID expression levels of ALL, B-ALL, Burkitt leukemia, M4 patients and Raji cells were significantly higher than those of the normal control group (all P <0.05). Nevertheless, the AID mRNA expression levels of M3 patients and NB4, KG-1 cells were lower than those of the normal control group (all P <0.05). Furthermore, the AID mRNA expression levels of K562 cell were strikingly higher than that of the CML-CP patients (P<0.001), so were those of CML-BC, chronic myeloid leukemia myeloid blast crisis (CML-MBC), chronic myeloid leukemia lymphoblastic blast crisis (CML-LBC) patients. Conclusion AID gene shows high expression level in B-ALL, Burkitt leukemia and M4, low expression level in M3 and KG-1 cells, and obvious high expression level in CML-BC.

Adult ; Humans ; Male ; Myoclonic Epilepsies, Progressive ; diagnostic imaging ; genetics ; therapy ; Nerve Tissue Proteins ; genetics ; Pedigree

Adult ; Aged ; Chromosome Aberrations ; Epilepsies, Myoclonic ; diagnosis ; genetics ; Female ; Humans ; Male ; Middle Aged ; Pedigree

OBJECTIVE: To explore the genetic basis for a Chinese pedigree where three siblings were affected with Parkinson's disease. METHODS: Multiple ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS) were employed to detect the causative mutation. Sanger sequencing of cDNA was also used for verify the effect of mutation on the transcription of RNA. RESULTS: Heterozygous deletion of exon 3 of the PARK2 gene was detected by MLPA, while a heterozygous splice site variant c.619-3G>C was detected by NGS. Both mutations were shown to result in aberrant transcripts of the PARK2 gene (loss of exons 3 and 6, respectively) by Sanger sequencing of cDNA. Both mutations have co-segregated with the disease in the pedigree. CONCLUSION Compound heterozygous mutations of the PARK2 gene probably underlie the disease in this pedigree. Identification of the splice site variant c.619-3G>C has expanded the mutation spectrum of the PARK2 gene.
Asian Continental Ancestry Group ; China ; DNA Mutational Analysis ; Exons ; Heterozygote ; Humans ; Mutation ; Parkinson Disease ; genetics ; Pedigree ; Ubiquitin-Protein Ligases ; genetics