AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorp...AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival. METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 ageand sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ 2 test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ 2 test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC. RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ 2 = 3.589, P = 0.166) and alleles (χ 2 = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ 2 = 5.449, P = 0.020), well differentiated (log rank χ 2 = 12.798, P = 0.000), T1 or T2 stage (log rank χ 2 = 4.745, P = 0.029), without lymph node involvement (log rank χ 2 = 6.647, P = 0.010), and at an early clinical stage (log rank χ 2 = 4.615, P = 0.032). CONCLUSION: Our results suggest that the FGFR4 Gly388Arg polymorphism is not a risk factor for GC cancer initiation but that it is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or at an early clinical stage.展开更多
Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a si...Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a significantly decreased level of ERs of the brain.The aim of our study was to investigate whether valproic acid(VPA)can enhance the beneficial effects of estrogen on cognitive function through restoration of ERαand ERβexpression in the brain.We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA(30 mg/kg,intraperitoneal injection,once daily),17β-estradiol(E2)(2.4μg,intraperitoneal injection,once daily),liquiritigenin(LG)(50μg/kg,intragastric infusion,once daily),VPA+E2,or VPA+LG for 4 successive weeks.Compared with treatment with a single drug,treatment with VPA+E2 or VPA+LG significantly increased the level of glycogen synthase kinase 3β,increased the expression of estrogen receptorα,reduced the expression of small ubiquitin-like modifiers,and increased the level of estrogen receptorβ.This resulted in enhanced sensitivity to estrogen therapy,reduced amyloidβaggregation,reduced abnormal phosphorylation of the tau protein,reduced neuronal loss,increased dendritic spine and postsynaptic density,and significantly alleviated memory loss and learning impairment in Alzheimer’s disease.This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee,China on March 6,2013.展开更多
For the treatment of an intertrochanteric fracture combined with femoral head necrosis in middle-age patients,it has been controversial whether to perform fracture reduction and fixation first then total hip replaceme...For the treatment of an intertrochanteric fracture combined with femoral head necrosis in middle-age patients,it has been controversial whether to perform fracture reduction and fixation first then total hip replacement,or direct total hip replacement.We present a rare case of 53-year-old male patient suffered from bilateral intertrochanteric fracture caused by a road traffic injury.The patient had a history of femoral head necrosis for eight years,and the Harris score was 30.We performed total hip replacement with prolonged biologic shank prostheses for primary repair.One year after the surgery,nearly full range of motion was achieved without instability(active flexion angle of 110°,extension angle of 20°,adduction angle of 40°,abduction angle of 40°,internal rotation angle of 25°,and external rotation angle of 40°).The Harris score was 85.For the middle-aged patient with unstable intertrochanteric fractures and osteonecrosis of the femoral head,we can choose primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement.展开更多
Some veterinary drug residues in food products and environment have been widely regarded as severe threats to human health.Rapid and simultaneous detection methods are crucial to monitor and control veterinary drug us...Some veterinary drug residues in food products and environment have been widely regarded as severe threats to human health.Rapid and simultaneous detection methods are crucial to monitor and control veterinary drug usage.Here,we propose a fluorescence biosensor utilizing immunomagnetic beads(IMBs)and quantum dots(QDs)for the rapid and simultaneous detection of 1-adamantylamine(ADA),enrofloxacin(ENR)and tilmicosin(TIL)in raw chicken meat.A pretreatment method using sodium phosphotungstate–magnesium as extraction reagent was developed to simultaneously extract ADA,ENR and TIL from chicken meat with minor interference in background or response.By adding the IMBs modified with three types of antibodies and the QD-antigens modified with three types of BSA-antigens to sample,IMBs competitively conjugated to target antigens in a sample or QD-antigens.After magnetic separation,the residual QD-antigens were adopted to collect signals using fluorescence spectroscopy.Using QDs with well separated emission peaks,the detection of one type of targets was minorly interfered by the others.Under the optimum conditions,the biosensor exhibited the limit of detection of 0.96,3.32,and 3.17 ng/mL for ADA,ENR and TIL in chicken samples,respectively,as well as good specificity.Due to the way of direct collection of signals in extracts,the tedious and complicated multiple magnetic separation and signal amplification procedures in conventional methods were avoided,thus the procedures were significantly simplified,and the reduction of the operation time of 30 min for sample pretreatment and 40 min for detection part was achieved.The biosensor might be promising in the rapid,in-field and sensitive screening of multiple veterinary drugs to ensure agriculture and food safety.展开更多
文摘AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival. METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 ageand sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ 2 test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ 2 test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC. RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ 2 = 3.589, P = 0.166) and alleles (χ 2 = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ 2 = 5.449, P = 0.020), well differentiated (log rank χ 2 = 12.798, P = 0.000), T1 or T2 stage (log rank χ 2 = 4.745, P = 0.029), without lymph node involvement (log rank χ 2 = 6.647, P = 0.010), and at an early clinical stage (log rank χ 2 = 4.615, P = 0.032). CONCLUSION: Our results suggest that the FGFR4 Gly388Arg polymorphism is not a risk factor for GC cancer initiation but that it is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or at an early clinical stage.
基金This study was supported by the National Natural Science Foundation of China,Nos.81671257,81371221,31600825(all to GQH).
文摘Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a significantly decreased level of ERs of the brain.The aim of our study was to investigate whether valproic acid(VPA)can enhance the beneficial effects of estrogen on cognitive function through restoration of ERαand ERβexpression in the brain.We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA(30 mg/kg,intraperitoneal injection,once daily),17β-estradiol(E2)(2.4μg,intraperitoneal injection,once daily),liquiritigenin(LG)(50μg/kg,intragastric infusion,once daily),VPA+E2,or VPA+LG for 4 successive weeks.Compared with treatment with a single drug,treatment with VPA+E2 or VPA+LG significantly increased the level of glycogen synthase kinase 3β,increased the expression of estrogen receptorα,reduced the expression of small ubiquitin-like modifiers,and increased the level of estrogen receptorβ.This resulted in enhanced sensitivity to estrogen therapy,reduced amyloidβaggregation,reduced abnormal phosphorylation of the tau protein,reduced neuronal loss,increased dendritic spine and postsynaptic density,and significantly alleviated memory loss and learning impairment in Alzheimer’s disease.This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee,China on March 6,2013.
文摘For the treatment of an intertrochanteric fracture combined with femoral head necrosis in middle-age patients,it has been controversial whether to perform fracture reduction and fixation first then total hip replacement,or direct total hip replacement.We present a rare case of 53-year-old male patient suffered from bilateral intertrochanteric fracture caused by a road traffic injury.The patient had a history of femoral head necrosis for eight years,and the Harris score was 30.We performed total hip replacement with prolonged biologic shank prostheses for primary repair.One year after the surgery,nearly full range of motion was achieved without instability(active flexion angle of 110°,extension angle of 20°,adduction angle of 40°,abduction angle of 40°,internal rotation angle of 25°,and external rotation angle of 40°).The Harris score was 85.For the middle-aged patient with unstable intertrochanteric fractures and osteonecrosis of the femoral head,we can choose primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement.
基金funded by the Walmart Foundation(0402-70013-21-0000)supported by the Walmart Food Safety Collaboration Center
文摘Some veterinary drug residues in food products and environment have been widely regarded as severe threats to human health.Rapid and simultaneous detection methods are crucial to monitor and control veterinary drug usage.Here,we propose a fluorescence biosensor utilizing immunomagnetic beads(IMBs)and quantum dots(QDs)for the rapid and simultaneous detection of 1-adamantylamine(ADA),enrofloxacin(ENR)and tilmicosin(TIL)in raw chicken meat.A pretreatment method using sodium phosphotungstate–magnesium as extraction reagent was developed to simultaneously extract ADA,ENR and TIL from chicken meat with minor interference in background or response.By adding the IMBs modified with three types of antibodies and the QD-antigens modified with three types of BSA-antigens to sample,IMBs competitively conjugated to target antigens in a sample or QD-antigens.After magnetic separation,the residual QD-antigens were adopted to collect signals using fluorescence spectroscopy.Using QDs with well separated emission peaks,the detection of one type of targets was minorly interfered by the others.Under the optimum conditions,the biosensor exhibited the limit of detection of 0.96,3.32,and 3.17 ng/mL for ADA,ENR and TIL in chicken samples,respectively,as well as good specificity.Due to the way of direct collection of signals in extracts,the tedious and complicated multiple magnetic separation and signal amplification procedures in conventional methods were avoided,thus the procedures were significantly simplified,and the reduction of the operation time of 30 min for sample pretreatment and 40 min for detection part was achieved.The biosensor might be promising in the rapid,in-field and sensitive screening of multiple veterinary drugs to ensure agriculture and food safety.
