Search

Aims: Some study found that ATP‐binding cassette (ABC) efflux transporters play an important role in antiepileptic drug resistance, especially ABCB1 and ABCC2. The aims of this study were to evaluate the relationship between the genetic polymorphisms of ABCC2 and ABCB1 and the therapeutic efficacy of antiepileptic drugs (AEDs) in Chinese epileptic patients. Methods: ABCB1 rs1045642 (3435C>T) and ABCC2 rs717620 (−24C>T), rs3740066 (3972C>T), and rs2273697 (1249G>A) polymorphisms loci in 537 Chinese epilepsy patients (217 drug resistant patients and 320 drug responders) were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Results: ABCC2 rs717620 −24TT genotype was significantly associated with drug resistant epilepsy (odds ratio [OR]= 4.06 [1.79–9.20], P= 0.001). The OR values of ABCC2 rs717620 −24 CT+TT genotypes and ABCC2 rs3740066 (3972C>T) CT+TT genotypes were markedly higher in drug resistant patients (OR = 1.57 [1.08–2.29], P= 0.018; OR = 1.49 [1.02–2.18], P= 0.038, respectively) compared with responsive patients. ABCC2 rs2273697 (1249G>A) and ABCB1 rs1045642 (3435C>T) polymorphisms were not associated with drug resistant epilepsy. Linkage disequilibrium (LD) test showed that the ABCC2 rs717620 were in strong LD with rs2273697 (D’= 0.694) and rs3740066 (D’= 0.699). The frequencies of haplotypes TGT (ABCC2 −24C>T/ABCC2 1249G>A/ABCC2 3972C>T) in resistant patients was significantly higher than those in responsive patients (21.0% vs. 14.2%, P < 0.05). Conclusion: ABCC2−24C>T, 3972C>T polymorphisms and one ABCC2 haplotype is associated with AED resistance; ABCC2 1249G>A and ABCB1 3435C>T polymorphisms are not associated with AED resistance in our study. These data suggest that ABCC2 polymorphisms and haplotype may affect the response of antiepileptic drugs.

We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients.Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty-three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day(-1)). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment.The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P0.01, odds ratios = 2.342 (1.365, 4.019), P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1) , P0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (-2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1), P0.01) (-3.53, -1.84 vs.-1.99, -0.13) and postprandial plasma glucose (-6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1), P0.01) (-9.28, -4.62 vs.-4.34, -0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (-6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1), P0.05) (-8.20, -4.89 vs.-3.92, -1.20).The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.

1. The aim of this study was to investigate the association of the serine racemase (SRR) rs391300 G/A polymorphism with the risk of diabetes mellitus type 2 (T2DM) and to assess the impacts of the polymorphism on the therapeutic efficacy of metformin in Chinese patients. 2. A case-control study of 402 patients with T2DM and 171 healthy controls was conducted. The SRR rs391300 polymorphism was genotyped in all participants using the ABI 3700 automated sequencer. Forty-four recent-onset T2DM patients with different rs391300 genotypes were selected to receive 500 mg metformin orally daily for 12 consecutive weeks as monotherapy. Serum fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated haemoglobin (HbA1c), fasting serum insulin (FINS), postprandial serum insulin (PINS), triglycerol (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), homeostasis model assessment for insulin resistance (HOMA-IR), and body mass index (BMI) were determined before and after metformin treatment. 3. The distribution frequencies of rs391300 were in agreement with Hardy-Weinberg equilibrium (P0.05). After treatment with metformin, the values of BMI, FPG, PPG, PINS, HbA1c, CHO, and TG decreased significantly (P0.01), whereas FINS increased (P0.001), in patients with T2DM. Patients with the GA or AA genotype of rs391300 showed better improvements in the levels of FPG, PPG, and CHO (P0.05) than individuals with the GG genotype. 4. The SRR rs391300 polymorphism was associated with the therapeutic efficacy of metformin in Chinese patients with T2DM.

With the increasing advocacy for total disc replacement (TDR) as a potential alternative to fusion in the management of lumbar degenerative disc disease, intradiscal pressures (IDPs) and facet joint stresses at the adjacent levels of spine have generated considerable interest. The purpose of this study was to compare adjacent-level IDPs and facet joint stresses among TDR, discectomy, and fusion.Ten fresh human cadaveric lumbar specimens (L2-S1) were subjected to an unconstrained load in axial torsion, lateral bending, flexion, and extension by using multidirectional flexibility test. Four surgical treatment modes-control (disc intact), discectomy, TDR, and fusion-were tested in sequential order at L4-5. During testing, the IDPs and facet forces following each treatment were calculated at the adjacent vertebral levels (L3-4 and L5-S1).Intradiscal pressures and facet force pressures were similar between the intact condition and the TDR reconstruction at the L3-4 and L5-S1 levels under all loading conditions (p0.05). Compared with the intact and TDR groups, the discectomy and fusion groups had higher IDPs at the L3-4 and L5-S1 levels under all loading conditions (p0.05). No significant difference in the facet force pressure was noted among the intact, discectomy, and TDR groups at the L3-4 and L5-S1 levels under any loading conditions (p0.05). However, the facet force pressure produced for fusion was significantly higher than the mean values obtained for the intact, discectomy, and TDR groups at the L3-4 and L5-S1 levels under all loading conditions (p0.05).Lumbar TDR maintained adjacent-level IDPs and facet force pressures near the values for intact spines, whereas adjacent-level IDPs tended to increase after discectomy or fusion and facet forces tended to increase after fusion.

1. In the present study, we investigated the associations of nicotinamide phosphoribosyltransferase (NAMPT)-3186 C/T and -948G/T polymorphisms with the risk of Type 2 diabetes mellitus (T2DM) and their impact on the efficacy of repaglinide in Chinese Han T2DM patients. 2. In all, 170 patients with T2DM and 129 healthy controls were genotyped for NAMPT-948GT and -3186CT polymorphisms. Thirty-five patients with different NAMPT -3186 C/T genotypes and the same organic anion-transporting polypeptide 1B1 (OATP1B1521) T/C genotype were randomly selected to undergo 8 weeks preprandial repaglinide treatment (1 mg, three times daily). Serum fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), glycated haemoglobin (HbAlc), fasting serum insulin (FINS), post-prandial serum insulin (PINS), triglyceride (TG), total cholesterol (CHO), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were determined before and after repaglinide treatment. 3. After repaglinide treatment for 8 consecutive weeks, there were significantly decreases in PFG, PPG, HbAlc, CHO and LDL-C, and increases in FINS, HDL-C and the HDL-C : LDL-C ratio, in T2DM patients. The elevated PINS value in patients with CT genotypes was significantly lower than that in patients with the CC and TT genotypes (P0.05) and there were significant differences in CHO between patients with the CT genotype and the CC or TT genotype (P0.05). 4. The data suggest that the NAMPT -3186CT polymorphism is significantly associated with plasma levels of PINS and CHO in Chinese T2DM patients with repaglinide monotherapy.

The goal of this study was to evaluate the array of causative organisms for septic arthritis in children and their antibiotic resistance patterns over a 20-year period at a single medical center. The medical records of children younger than 16 years with septic arthritis admitted to a hospital in China from 1989 to 2008 were retrospectively reviewed. A total of 158 cases of septic arthritis were studied, 70 from 1989 to 1998 and 88 from 1999 to 2008. Between the first and second decades, occurrence of serious illnesses decreased significantly from 44.3% to 28.4% ( P Staphylococcus aureus (MRSA) increasing significantly. Staphylococci remained the major causative organisms for joint infection. The percentage of Staphylococcus aureus resistance to various antibiotics increased: 85% to 100% for penicillin, 58.8% to 75% for erythromycin, 0% to 31.3% for cefazolin, and 15% to 29.4% for multi-resistance. In the second decade, 4 MRSA stains were multi-resistant. However, gentamincin resistance remained at the same level. Antibiotic resistance of coagulase-negative staphylococci and gram-negative bacilli changed little. The incidences of osteomyelitis and joint dislocation decreased significantly, from 15.7% to 6% and 28.6% to 14.8%, respectively ( P

To develop a new internal fixation device and the matching tools for subtrochanteric fracture, investigate the biomechanical features thereof, and compare its effects with those of other instruments.A new internal fixation device, static three dimensional screw-plate system: (STDSP) was developed based on the anatomical parameters and the biomechanical characteristics of proximal femur and combined with the biomechanical advantages of the model of three-dimensional plate and multiple-screws plate fixation. Sixteen paired cadaveric adult femurs were randomly divided into 2 equal groups: fracture healing group undergoing insertion of implant and then taking out thereof with a nail left, and fracture group with a trapezoid defect to mimic subtrochanteric fracture 4 of which were fixed with dynamic hip screw (DHS) and STDSP or Gamma nail and STDSP. All the specimens underwent A-P position four point bending test, axial compression test, torsion test, and destroyable test.(1) In the fracture group, A-P position four point bending test showed that the stretch displacement of STDSP group was (0.221 +/- 0.089) mm, significantly smaller than that of the Gamma nails group [(0.506 +/- 0.086) mm, t = 38.278 P = 0.000]; Axial compression test showed that the inferior displacement of the STDSP group was (2.804 +/- 0.585) mm, significantly larger than that of the Gamma nail group [(1.874 +/- 0.549) mm, t = -5.454, P = 0.012]; Torsion test showed that the torque values at 50 and 100 of the STDSP group were (3.78 +/- 0.84) J and (2.3 +/- 1.08) J, both significantly larger than those of the Gamma nail groups [(2.3 +/- 1.08) J and (4.35 +/- 1.81) J, t = -4.729 P = 0.018, and t = -3.227 P = 0.048] and those of the DHS group [(7.3 +/- 1.273) J and (4.325 +/- 0.88) J respectively, t = -3.242 P = 0.048]; and torsion destroyable test showed that the torque values at 200 of the STDSP group was (21.88 +/- 2.51) J, significantly larger than those of the Gamma nail and DHS groups, [(14.36 +/- 5.01) J and (15.475 +/- 1.924) J and (12.075 +/- 1.179) J, t = -3.323 P = 0.048, t = - 3.732 P = 0.034]. (2) In the fracture healing specimens, A-P position four point bending test showed that the radial degree displacement of the STDSP group was (1. 050 +/- 0.316) mm, significantly smaller than that of the DHS group [(1.261 +/- 0.364) mm, t = 3.4 P = 0.042].More capable of resisting bending than DHS and less capable of resisting axial compression, STDSP is an excellent internal fixator with good biomechanical feature in treating subtrochanteric femoral fracture.

To investigate clinical features of the traumatic cervical disc herniation and through retrospective analysis 62 cases of traumatic cervical disc herniation.Among 62 patients with traumatic cervical disc herniation, 46 patients were male and 16 patients were female, with an average ages of 36.4 years. According to the clinical manifestation, there were 30 cases of symmetrical limb palsy, 19 cases of upper motor palsy serious than lower, 13 cases of unilateral palsy and contralateral disorder of algesthesia and thermesthesia. There were 58 patients treated with operation and 4 patients treated with conservative method.All of the incisions were with primary healing. Twenty-four patients recovered to normal, and other 34 cases improved obviously and the duration of follow-up ranged from 6 to 28 months. The average time was 11 months. JOA scores increased from preoperative 5.6 to postoperative 12.7.Operative treatment is effective for different types of the traumatic cervical disc herniation.

To design and manufacture a new type instrument and its matching tools for the proximal femur.A new type instrument of subtrochanterical fracture-static 3-dimensional screw-plate system(STDSP)was designed and manufactured. The different types of accessory instruments which adapted to STDSP,the aiming guide, and the accessory tools were also designed and manufactured, and they were tested on bones.STDSP included 3 special lag screws and 1 anatomic plate. The lag screws distributed in femoral neck like "or"shape. There was 135 degree between the lag screws and femoral shaft. The shape of the plate was similar to the anatomic structure of the proximal thighbone. The posterior screw was stably connected to the plate. The plate was affixed crosswise to the lateral and anterior side by bicortical screws. The aiming guides and all kinds of accessory tools could help to install STDSP exactly and conveniently,which was verified on cadavers and X-ray photographs.STDSP has the function of dynamic compressing in 3-dimensional space, and can match with the structure of the proximal femur preferably. STDSP may be a suitable instrument to the subtrochanteric fractures. The accessory apparatus of STDSP has simple configuration,and can let the STDSP be installed accurately, conveniently and rapidly.

To analyze the relation between the clinical outcome and the integrity of the facets after a lumbar operation,and to provide a reference for choosing operative method and clinical prognosis.Forty-three patients with complete data underwent uni-segment discectomy were enrolled. There were 3 surgical interventions: open-window discectomy, full or semi-laminectomy. Groups were divided based on the integrity of the facets after the operation, and the clinical symptoms and signs were evaluated using the Japanese Orthopaedic Association Back (JOA) scores at 24-month follow-up.Preoperative JOA scores were not significantly different among the groups (P0.05). Compared with the facet intact group at 24-month follow-up,JOA scores were descended statistically in total uni-facetectomy group and total uni-facetectomy plus partial opposite facetectomy group (P0.01).Keeping facets integrated plays an important role in achieving good clinical results,and the damage of facet should be avoided in the lumbar operation.

To detect the mutations of EXT2 gene in hereditary multiple exostoses (HME) families and to investigate the sensitivity of denaturant gradient gel electrophoresis (DGGE) in screening the mutations in EXT2 gene.Five HME families and 3 sporadic patients were screened for the mutation detection in all exons of EXT2 gene covering the coding sequence and the flanking intronic sequence by DGGE, and DNA sequencing was performed for products with abnormal conformation.Among these HME patients, we found 2 disease-causing mutations: A313T (nonsense mutation) and 319 insGT (frameshift mutation).Two mutations of EXT2 gene are identified in the sample. DGGE can be an ideal choice for gene diagnoses of HME.

To detect the changes of mitochondrion DNA (mtDNA) sequence in articular chondrocytes of cartilage affected by osteoarthritis and to clarified the pathogenetic mechanism of osteoarthritis.We analyzed the mtDNA 4,977 bp deletion mutations of articular chondrocytes in 10 patients with osteoarthritis and 3 normal cartilages using the gap-PCR amplification method. We designed a two round PCR detection method, in which total DNA was isolated from articular chondrocytes as the template of the first round PCR reaction and products from the first round were the template in the second round reaction.The results of the first rounds of PCR reaction showed the mtDNA 524 bp amplified products in the osteoarthritis group and in the corresponding peripheral blood samples were not detected, but the 533 bp products were detected. However,the results of the second round reaction revealed that the 524 bp zones were detected in 2 of the 10 osteoarthritis patients and the corresponding peripheral blood samples were not detected. The 533 bp products were detected in all specimens. The mtDNA 524 bp amplified products in all the normal articular chondrocytes and the corresponding peripheral white blood cells contrast were not detected in both rounds PCR.This was the first study to evaluate the mtDNA 4799 bp large fragment deletion mutational accumulation between nt8,470 - nt13,447 of articular chondrocytes in osteoarthritic cartilage. Osteoarthritis may be related to mtDNA mutation of articular chondrocytes.

To determine the influence of artificial disc replacement on the stability of lumbar.Ten fresh human cadaveric lumbar spine specimens (9 males, 1 female) were tested. The donors had a mean age of 29.3 years old. The segments were fixed on a special testing device mounted in a universal testing machine. Physiological load with a maximum of 10 Nm was applied in the flexion, extension, right and left side bending. Moments were applied in 6 load steps: 0, 2, 4, 6, 8, and 10 Nm. Linearity migration and angle migration were recorded,and the mean flexibility coefficients were calculated. Four procedures of measurement were performed in every specimen: intact segments, segments after discectomy, segments after the artificial disc replacement, and segments after the artificial disc replacement with cutting posterior longitudinal ligament locally.The indexes we calculated of the segments after the discectomy were statistically different compared with the intact segments (P0.05, P0.01). The linearity migration,angle migration and mean flexibility coefficient in flexion/extension direction of the segments after the artificial disc replacement were statistically different compared with the segments after the discectomy (P0.05, P0.01), and there was a statistically significant increase in angle migration and mean flexibility coefficient in the extension direction compared with the intact situation (P0.05). There was no statistically significant difference in 4 directions between the segments after the artificial disc replacement and the segments after the artificial disc replacement with cutting posterior longitudinal ligament locally (P0.05).Artificial intervertebral disc replacement could keep the stability of the lumbar functional spine unit. There was no harmful effect of cutting posterior longitudinal ligament locally on the stability of lumbar while performing artificial intervertebral disc replacement when it is necessary.

To evaluate the therapeutic effects of intraarticular injection of ligustrazine on knee osteoarthritis (OA).Seventy-one cases of knee osteoarthritis (82 knees) were randomly divided into ligustrazine (LI) group and sodium hyaluronate (SH) group. The patients were intraarticularly injected ligustrazine or sodium hyaluronate once a week for 5 consecutive weeks, and were followed-up for 3 months. Lequesneos protocol for the evaluation of OA severity and activity was used. The therapeutic effects and changes of Lequesneos index were observed after the treatment.There was significant decrease in Lequesneos index in SH group after the treatment (P0.01), but not in LI group (P0.05). Three weeks later, there was significant decrease in Lequesneos index in both groups after the treatment (P0.01), with no significant difference between SH and LI group (P0.05). After the 5-week treatment, the efficacy rate of the LI group was 82.1%, and that of the SH group was 87.2%. No serious toxic or side effect was observed during the treatment and the follow-up.Intraarticular injection of ligustrazine has a therapeutic effect on knee OA. No adverse effect is observed, but it needs long time to take effect.

To evaluate the clinical outcome of ZEPHIR plate in treating cervical spondylotic myelopathy(CSM).We retrospectively analyzed 18 patients undergoing anterior decompression fusion and internal fixation with ZEPHIR plate. Follow-up period ranged from 3 to 12 months (an average of 9 months). The bone graft fusion rate, rehabilitation of neurological deficits, and the complications of the hardware were observed. We assessed the clinical effect with JOA score.Rehabilitation of neurological deficits were observed in 16 patients, The JOA score after the operation significantly increased than before the operation. The fusion rate was 100%, the intervertebral height were maintained, and no complications related to the plate were found.ZEPHIR plate in the treatment of cervical spondylotic myelopathy may increase the fusion rate of the bone graft significantly with low incidence of complication.

To observe the effect of nicotine on the secretion of TNF of human peripheral blood mononuclear cells (PBMC) in vitro, and explore the possible mechanism of the high level of TNF caused by smoking.Twenty-one non-smokers and 19 smokers were studied. The PBMCs isolated from each volunteer's blood sample were distributed to three groups, and cultured for 72 hours in supplemented RMPI 1640 alone or in supplemented RPMI 1640 containing 50 ng.ml-1 nicotine or 500 ng.ml-1 nicotine respectively. The level of TNF in supernate was quantified with the immuno-radioassay, and PBMC proliferation was observed.The level of TNF spontaneously secreted by PBMCs in smokers was significantly higher than that in non-smokers (P0.05). When the concentrations of nicotine were 50 ng.ml-1 and 500 ng.ml-1, the level of TNF increased significantly in non-smokers (P0.05, P0.01). In smokers, the level of TNF significantly increased when the concentration of nicotine was 50 ng.ml-1; however, the level of TNF significantly decreased (P0.05), and the proliferation of PBMCs was inhibited when the concentration of nicotine was 500 ng.ml-1 (P0.05, P0.05). The level of TNF was positively correlated to the multiple of PBMC proliferation (r = 0.93, P0.05). The linear regression equation was Y = 2.913X - 2.955.Nicotine can induce PBMCs to secrete more TNF, and the magnitude of the effect is strongly related to the dosage of nicotine, but a great dose of nicotine will inhibit the production of TNF.