Peoples Hospital of Lishui
Peoples Hospital of Lishui
Dai D.-P.,Beijing Hospital and Beijing Institute of Geriatrics |
Wang S.-H.,Peoples Hospital of Lishui |
Li C.-B.,Clinical Laboratory of Beijing Hospital |
Geng P.-W.,Peoples Hospital of Lishui |
And 5 more authors.
Drug Metabolism and Disposition | Year: 2015
CYP2C9, one of the most important drug-metabolizing enzymes, is responsible for metabolizing approximately 15% of clinically important drugs, including warfarin, diclofenac, and losartan. Similar to other CYP members, human CYP2C9 exhibits marked genetic polymorphisms among individuals of different ethnicities. In this study, a novel missense mutation (1300A>T) was identified in a warfarin-sensitive patient after a genetic screen of three candidate genes related to high variability in response to warfarin doses. This base transversion leads to an Ile-to- Phe amino acid substitution at codon 434 within the CYP2C9 protein, and this new variant has been named a novel allele, CYP2C9∗59, by the Human CYP Allele Nomenclature Committee (http://www.cypalleles.ki. se/cyp2c9.htm). The exogenous expression of CYP2C9.59 in insect cell microsomes revealed that, despite a similar protein expression level as wild-type CYP2C9, variant CYP2C9.59 exhibited significantly reduced maximal velocity, Vmax, and/or increased Michaelis constant, Km, values toward three CYP2C9-specific substrates. Our data suggest that the 1300A>T mutation can greatly decrease the enzymatic activity of the CYP2C9 protein both in vitro and in vivo. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
Dai D.-P.,Beijing Hospital and Beijing Institute of Geriatrics |
Wang S.-H.,Wenzhou University |
Wang S.-H.,Peoples Hospital of Lishui |
Geng P.-W.,Wenzhou University |
And 2 more authors.
Basic and Clinical Pharmacology and Toxicology | Year: 2014
Of the 57 reported CYP2C9 alleles, to date, 36 of them have been identified in the Chinese population. The aim of this study was to assess the catalytic characteristics of these allelic isoforms and their effects on the metabolism of glimepiride in vitro. Baculovirus-mediated expressing system was used to highly express wild-type and the 35 CYP2C9 allelic variants in insect cell microsomes. Then, the enzymatic characteristics of each variant were evaluated using glimepiride as the substrate. Reactions were performed at 37°C with the insect microsomes and 0.125-10 μM glimepiride for 40 min. After termination, the products were extracted and used for signal collection by LC-MS/MS. Of the 36 tested CYP2C9 allelic isoforms, only four variants (CYP2C9.40, CYP2C9.47, CYP2C9.51 and CYP2C9.54) exhibited similar relative clearance values to that of wild-type CYP2C9.1. In addition, one variant (CYP2C9.36) showed a higher intrinsic clearance value than the wild-type protein, while the remaining 30 CYP2C9 allelic isoforms exhibited significantly decreased clearance values (from 0.1% to 87.2%) compared to CYP2C9.1. This study provided the most comprehensive data on the enzymatic activities of all reported CYP2C9 variants in the Chinese population with regard to the commonly used antidiabetic drug, glimepiride. Our results indicate that most of the tested rare alleles significantly decrease the catalytic activity of CYP2C9 variants towards glimepiride hydroxylation in vitro. © 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Lin D.,Xi'an Jiaotong University |
Lin D.,Wenzhou University |
Wang Z.,Wenzhou University |
Li J.,Wenzhou University |
And 4 more authors.
Pharmacology | Year: 2016
Background: In light of the growing number of cancer survivors, the incidence of cardiovascular complications in these patients had also increased, while the effect of apatinib on the pharmacokinetic of cardioprotective drug (carvedilol) in rats or human is still unknown. The present work was to study the impact of apatinib on the metabolism of carvedilol both in vitro and vivo. Methods: A specific and sensitive ultra-performance liquid-chromatography tandem mass spectrometry method was applied to determine the concentration of carvedilol and its metabolites (4′-hydroxyphenyl carvedilol [4′-HPC], 5′-hydroxyphenyl carvedilol [5′-HPC] and o-desmethyl carvedilol [o-DMC]). Results: The inhibition ratios in human liver microsomes were 10.28, 10.89 and 5.94% for 4′-HPC, 5′-HPC and o-DMC, respectively, while in rat liver microsomes, they were 3.22, 1.58 and 1.81%, respectively. The data in vitro of rat microsomes were consistent with the data in vivo that the inhibition of 4′-HPC and 5′-HPC formation was higher than the control group. Conclusion: Our study showed that apatinib could significantly inhibit the formation of carvedilol metabolites both in human and rat liver microsomes. It is recommended that the effect of apatinib on the metabolism of carvedilol should be noted and carvedilol plasma concentration should be monitored. © 2015 S. Karger AG.
Zhang S.,Lishui University |
He X.,Peoples Hospital of Lishui |
Liu H.,Peoples Hospital of Lishui
NeuroReport | Year: 2015
The aim of the study was to assess the relationship between procalcitonin (PCT) serum levels and acute ischemic stroke (AIS) in a Chinese sample. All consecutive patients with first-ever AIS between January 2012 and December 2013 were recruited to participate in the study. PCT levels and National Institutes of Health Stroke Scale scores were evaluated at the time of admission. Logistic regression analysis was used to evaluate the risk for stroke according to serum PCT levels. The results indicated that serum PCT levels were significantly higher in AIS patients as compared with normal controls (P<0.0001). PCT levels increased with increasing severity of stroke, as defined by the National Institutes of Health Stroke Scale score. After adjusting for all other possible covariates, PCT level was found to be associated with an increased risk for AIS, with an adjusted odds ratio of 2.244 (95% confidence interval 1.563-3.756, P<0.0001). On the basis of the receiver operating characteristic curve, the optimal cutoff value of serum PCT levels as an indicator for auxiliary diagnosis of AIS was projected to be 1.20 ng/ml, which yielded a sensitivity of 79.6% and a specificity of 72.1%, with the area under the curve at 0.801 (95% confidence interval 0.762-0.844). An elevated serum level of PCT was a novel, independent diagnostic marker of AIS in the Chinese sample. Further study is needed to confirm these results. © 2014 Wolters Kluwer Health.
Liu H.,Peoples Hospital of Lishui |
Zhang N.,People's Care |
Tian D.,Peoples Hospital of Lishui
Cellular and Molecular Biology Letters | Year: 2014
Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMC) is a major contributor to the pathogenesis of peritoneal fibrosis. EMT is at least in part caused by repeated exposure to glucose degradation products (GDPs), such as methylglyoxal (MGO). MiRNA contributes greatly to the EMT of PMCs. In this study, we tried to profile whether differences exist between the peritoneal membrane (PM) miRNA expression seen in control rats and that seen in rats injected intraperitoneally with MGO. We assessed whether miR-30b has a possible role in MGO-induced EMT of PMCs in rats. Comparative miRNA expression array and real-time PCR analyses were conducted for the control group at the start of the experiment and for the MGO group after 1 and 2 weeks. During the second week, the MGO rats were treated with: a chemically modified antisense RNA oligonucleotide (ASO) complementary to the mature miR-30b (ASO group); an miR-30b mismatch control sequence (MIS group); or a citrate buffer (EMT group). Bioinformatic analyses indicated that the 3′ untranslated region (3′-UTR) of bone morphogenetic protein 7 (BMP7) mRNA did contain a putative binding site for miR-30b. We also tried to investigate whether miR-30b targeted BMP7 in vitro by transfection. Of the upregulated miRNAs, miR-30b expression demonstrated the greatest increase. The administration of miR-30b ASO for two weeks significantly reduced α-SMA excretion and upregulated E-cadherin and BMP-7 expression. Our in vitro study showed that miR-30b directly targeted and inhibited BMP7 by binding to its 3'-UTR. Our results revealed that miR-30b is involved in MGO-induced EMT of PMCs in rats. © 2013 Versita Warsaw and Springer-Verlag Wien.
Dong X.Y.,Wenzhou University |
He S.,No118Th Hospital Of Pla |
Zhu L.,Wenzhou University |
Dong T.Y.,Peoples Hospital of Haining |
And 3 more authors.
International Journal of Oral and Maxillofacial Surgery | Year: 2015
The study aimed to assess the diagnostic value of high-resolution ultrasonography (HR-US) in the detection of anterior disc displacement (ADD) of the temporomandibular joint. Relevant trials reported in MEDLINE, the Chinese National Knowledge Infrastructure Database, the Chinese Biomedical Literature Database, and Embase were identified. A manual search was also performed. The quality of retrieved data was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. Data were extracted and cross-checked, and a statistically rigorous meta-analysis was performed using a hierarchical summary receiver operating characteristic model (HSROC). The clinical utility of results was assessed using Fagan nomograms (Bayes theory). All data were evaluated using Stata software. A total 11 studies including 1096 subjects were included in the analysis; all reported the utility of HR-US for the diagnosis of ADD with reduction (ADDWR) and without reduction (ADDWoR). For ADDWR, the weighted sensitivity and specificity were 0.83 (95% confidence interval (CI) 0.78-0.88) and 0.85 (95% CI 0.76-0.92) respectively. The lambda value was 3.41 (95% CI 2.37-4.46) and the Fagan nomogram pre-test probability 58%, with a positive likelihood ratio (LR) of 6.01. The positive post-test probability was 89%, with a negative LR of 0.20. The negative post-test probability was 21%. The positive increase in diagnostic utility was 31% and the negative decrement in that value 37%. For ADDWoR, the weighted sensitivity and specificity values were 0.72 (95% CI 0.59-0.81) and 0.90 (95% CI 0.86-0.93), respectively. The lambda value was 3.69 (95% CI 2.39-4.99) and the Fagan nomogram pre-test probability 38%, with a positive LR of 7.00. The positive post-test probability was 82%, with a negative LR of 0.32. The negative post-test probability was 16%. The increase in diagnostic utility was 44% and the negative decrement in that value 22%. HR-US delivers acceptable performance when used to diagnose ADD, being superior for the detection of ADDWoR than ADDWR, and exhibiting a lower negative diagnostic value in the detection of ADDWoR than ADDWR. HR-US may serve as a new method for the rapid diagnosis of ADD. The method has the advantages of simplicity and low cost. Given the uncertainty in some of the estimated values, more high-quality studies are needed to assess that diagnostic efficacy. © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Mei J.,Wenzhou Medical College |
Morris S.F.,Health science Center |
Ji W.,Peoples Hospital of Lishui |
Li H.,Peoples Hospital of Lishui |
And 2 more authors.
Surgical and Radiologic Anatomy | Year: 2013
Purpose: The posterior forearm is an excellent donor site for the vascular pedicled cutaneous flaps; yet, there is surprisingly little detailed anatomical information based on clinical decision making. This study was undertaken to evaluate the anatomical basis of the dorsal forearm perforator flaps and to provide anatomical landmarks to facilitate flap elevation. Methods: Thirty cadavers were available to perform this anatomical study after arterial injection. Twenty fresh cadavers were injected with a modified lead oxide-gelatin mixture, selected for 3-dimensional reconstruction using special software (MIMICS) and the arterial territory measured with Scion Image. Other ten were injected with red latex preparation, and perforators were identified through dissection. Results: (1) The average number of posterior interosseous artery cutaneous perforators in the dorsal forearm was 5 ± 2, the average diameter was (0.5 ± 0.1) mm, and the pedicle length was (2.5 ± 0.2) cm. The average cutaneous vascular territory was (22 ± 15) cm 2. Cutaneous perforators could be found along the line extending from the lateral epicondyle to the radial border of the head of ulna. (2) Dorsal branch of anterior interosseous artery supplied blood to distal third of dorsal forearm; its average diameter was 0.8 mm. Conclusion: The free transplantation of the posterior interosseous perforator artery flaps or rotary flap pedicled by dorsal branch of anterior interosseous artery for defect reconstruction is feasible. © 2013 Springer-Verlag France.
Yan J.,Peoples Hospital of Lishui |
Jiang Y.,Peoples Hospital of Lishui |
Ye M.,Peoples Hospital of Lishui |
Liu W.,Peoples Hospital of Lishui |
Feng L.,Harbin Medical University
Journal of Cancer Research and Therapeutics | Year: 2014
Background: Oral tongue squamous cell carcinoma (OTSCC) is an oral carcinoma prone to lymphatic metastasis. Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) as important adhesion molecules play roles in regulating cell-cell adhesion and tumor cells metastasis.Materials and Methods: Lymphatic vessel density (LVD) was evaluated by immunohistochemistry using anti-human D2-40 antibody. The expression of ICAM-1 or VCAM-1 in lymphatic vessels were measured by double immunofluorescence staining. Then both of the LVD and the expression of ICAM-1 or VCAM-1 were compared between in normal tongue and in OTSCC lymphatic vessels. In OTSCC, statistical analyses were performed to determine the prognostic correlation of ICAM-1 or VCAM-1 levels.Results: LVD and expression of ICAM-1 or VCAM-1 in OTSCC lymphatic vessels was higher than those in normal tongue lymphatic vessels (LVD: 21.454 ± 7.022, 8.498 ± 1.679; ICAM-1: 30.241 ± 5.639%, 5.050 ± 1.227%; VCAM-1: 33.134 ± 5.127%, 2.113 ± 0.446%, in OTSCC, normal tongue tissues, respectively). High LVD and high ICAM-1 or VCAM-1 expression in lymphatic vessels was significantly associated with lymphatic node metastasis. Overall survival was significantly shorter in patients with high LVD and ICAM-1 or VCAM-1 expression in lymphatic vessels.Conclusions: LVD and expression of ICAM-1 or VCAM-1 in OTSCC was higher than that in normal tongue lymphatic vessels. Monitoring changes in the expression of ICAM-1 or VCAM-1 in lymphatic vessels may be a useful technique for assessing prognoses in OTSCC patients.
Zhan S.,Peoples Hospital Of Lishui
Journal of Craniofacial Surgery | Year: 2014
PURPOSE: The purpose of this meta-analysis was to evaluate the efficacy of the 2.0-mm locking miniplate/screw system in comparison with the 2.0-mm nonlocking miniplate/screw system in treatment of mandible fractures.METHODS: Articles published until March 2013 were searched in the PubMed and EMBASE electronic databases. Eligible studies were restricted to comparative controlled trials.RESULTS: Four studies with 220 patients and 420 fracture sites were enrolled into the analysis. The results showed that there were no significant differences in overall complications (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.24–1.36; P = 0.21), postoperative infection (OR, 0.43; 95% CI, 0.13–1.41, P = 0.17), and postoperative pain (P > 0.05) when comparing 2.0-mm locking miniplates with 2.0-mm nonlocking miniplates in treating mandible fractures. However, the use of 2.0-mm locking miniplates had a lower postoperative maxillomandibular fixation (MMF) rate than the use of 2.0-mm nonlocking miniplates (OR, 0.18; 95% CI, 0.08–0.41; P < 0.0001).CONCLUSIONS: Mandible fractures treated with 2.0-mm locking miniplates and nonlocking 2.0-mm miniplates present similar short-term complication rates, and the low postoperative maxillomandibular fixation rate of using 2.0-mm locking miniplates also indicates that the 2.0-mm locking miniplate has a promising application in treatment of mandibular fractures. © 2014 by Mutaz B. Habal, MD.
PubMed | Peoples Hospital of Lishui
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016
The role and clinical implication of the WWP2 E3 ubiquitin ligase in liver cancer are poorly understood. In the current study, we investigated the expression level of WWP2 and its functions in cell adhesion, invasion, and migration in liver cancer. We used real-time PCR to detect the expression of WWP2 in liver cancer and adjacent samples from the Peoples Hospital of Lishui and also analyzed The Cancer Genome Atlas (TCGA) RNA-seq data by bioinformatics. Migration and invasion were detected by transwell analysis. We detected a strong WWP2 expression in tumor tissues of the Peoples Hospital of Lishui, and the survival rate was significantly higher in patients with lower WWP2-expressing tumors. WWP2 small hairpin RNA (shRNA) lentivirus stably infected cells (shWWP2), Huh7, showed slower growth speed compared with scramble control-infected cells in a xenograft mouse model. Knockdown of WWP2 Huh7 and BEL-7404 cells demonstrated a reduction in adhesion, invasion, and migration. Gene set enrichment analysis (GSEA) showed that WWP2 is positively correlated to cancer-related pathways including the chemokine signaling pathway. WWP2 also regulated MMP-9, caspase-9, CXCR3, and CCR5 expression in liver cancer cells. In addition, knockdown of CXCR3 and CCR5 significantly inhibited cell proliferation, adhesion, invasion, and migration in Huh7 and BEL-7404 cells. Our data suggest that targeting of WWP2 may be a therapeutic strategy for liver cancer treatment.