In order to overcome the defects that the analysis of multi-well typical curves of shale gas reservoirs is rarely applied to engineering,this study proposes a robust production data analysis method based on deconvolut...In order to overcome the defects that the analysis of multi-well typical curves of shale gas reservoirs is rarely applied to engineering,this study proposes a robust production data analysis method based on deconvolution,which is used for multi-well inter-well interference research.In this study,a multi-well conceptual trilinear seepage model for multi-stage fractured horizontal wells was established,and its Laplace solutions under two different outer boundary conditions were obtained.Then,an improved pressure deconvolution algorithm was used to normalize the scattered production data.Furthermore,the typical curve fitting was carried out using the production data and the seepage model solution.Finally,some reservoir parameters and fracturing parameters were interpreted,and the intensity of inter-well interference was compared.The effectiveness of the method was verified by analyzing the production dynamic data of six shale gas wells in Duvernay area.The results showed that the fitting effect of typical curves was greatly improved due to the mutual restriction between deconvolution calculation parameter debugging and seepage model parameter debugging.Besides,by using the morphological characteristics of the log-log typical curves and the time corresponding to the intersection point of the log-log typical curves of two models under different outer boundary conditions,the strength of the interference between wells on the same well platform was well judged.This work can provide a reference for the optimization of well spacing and hydraulic fracturing measures for shale gas wells.展开更多
As opposed to the prototypical MoS2 with centroasymmetry,Janus ferrovalley materials such as H-VSSe are less symmetric with the mirror symmetry and time reversal symmetry broken,and hence possess spontaneous valley po...As opposed to the prototypical MoS2 with centroasymmetry,Janus ferrovalley materials such as H-VSSe are less symmetric with the mirror symmetry and time reversal symmetry broken,and hence possess spontaneous valley polarization and strong ferroelasticity.The optical transition is an important means to excite the valley carriers.We investigate the optical spectrum of H-VSSe by using the many-body perturbation-based GW approach and solving the Bethe–Salpeter equation(BSE)to include the electron–hole interactions.It is found that after the GW correction,the band gaps of the quasiparticle bands are much larger than those obtained by the normal density functional theory.The system is ferromagnetic and the valley gaps become non-degenerate due to spin–orbit coupling(SOC).The position of the lowest BSE peak is much lower than the quasiparticle band gap,indicating that the excitonic effect is large.The peak is split into two peaks by the SOC.The binding energy difference between these two BSE peaks is about the same as the difference between the inequivalent valley gaps.Our results show that in Janus H-VSSe the two lowest exciton peaks are from the two inequivalent valleys with different gaps,in contrast to the A and B exciton peaks of MoS2 which are from the same valley.展开更多
Based on Huang's accurate tri-sectional nonlin- ear kinematic equation (1997), a dimensionless simplified mathematical model for nonlinear flow in one-dimensional semi-infinite long porous media with low permeabili...Based on Huang's accurate tri-sectional nonlin- ear kinematic equation (1997), a dimensionless simplified mathematical model for nonlinear flow in one-dimensional semi-infinite long porous media with low permeability is presented for the case of a constant flow rate on the inner boundary. This model contains double moving boundaries, including an internal moving boundary and an external mov- ing boundary, which are different from the classical Stefan problem in heat conduction: The velocity of the external moving boundary is proportional to the second derivative of the unknown pressure function with respect to the distance parameter on this boundary. Through a similarity transfor- mation, the nonlinear partial differential equation (PDE) sys- tem is transformed into a linear PDE system. Then an ana- lytical solution is obtained for the dimensionless simplified mathematical model. This solution can be used for strictly checking the validity of numerical methods in solving such nonlinear mathematical models for flows in low-permeable porous media for petroleum engineering applications. Finally, through plotted comparison curves from the exact an- alytical solution, the sensitive effects of three characteristic parameters are discussed. It is concluded that with a decrease in the dimensionless critical pressure gradient, the sensi- tive effects of the dimensionless variable on the dimension- less pressure distribution and dimensionless pressure gradi- ent distribution become more serious; with an increase in the dimensionless pseudo threshold pressure gradient, the sensi- tive effects of the dimensionless variable become more serious; the dimensionless threshold pressure gradient (TPG) has a great effect on the external moving boundary but has little effect on the internal moving boundary.展开更多
BACKGROUND Eosinophilia is an increase of more than 0.5×109/L in the number of eosinophils;it is a systemic condition with an unknown etiology and is often accompanied by multiple impaired organ functions.The cli...BACKGROUND Eosinophilia is an increase of more than 0.5×109/L in the number of eosinophils;it is a systemic condition with an unknown etiology and is often accompanied by multiple impaired organ functions.The clinical manifestations of the disease are highly variable and diverse,rendering identification of the diagnosis challenging;hence,diagnosis and treatment are often delayed.Very few reports of this disease exist globally,especially with rare manifestations of cerebral venous sinus thrombosis and hemorrhage.CASE SUMMARY A 32-year-old woman with eosinophilia presented to the hospital with bilateral lower-limb edema as the first clinical manifestation,followed by an extensive maculopapular rash throughout the body.She subsequently developed cerebral venous sinus thrombosis along with bilateral lower-limb deep vein thrombosis.Two weeks earlier,she had received a single course of antibiotics from a local hospital for a low-grade fever and sore throat.After various treatments were administered for anticoagulation,maintaining blood circulation,and relieving blood stasis,the lower extremity edema improved significantly;however,the patient’s eosinophil count gradually increased.She experienced cerebral venous sinus thrombosis,cerebral hemorrhage,and deep vein thrombosis of the lower limbs before being declared brain dead.In this case report,we have elaborated the diagnosis and management of deep vein thrombosis manifested as eosinophilia,thrombocytopenia,and elevated D-dimer levels.CONCLUSION Because proper diagnosis is challenging,clinical vigilance is required for patients with eosinophilia,as it can lead to thrombus formation.展开更多
AIM: To compare the effect, adverse events, cost-effectiveness and dose intensity (DI) of oral Xeloda vs calcium folinate (CF)/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies...AIM: To compare the effect, adverse events, cost-effectiveness and dose intensity (DI) of oral Xeloda vs calcium folinate (CF)/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy.METHODS: A total of 131 patients were enrolled and randomly selected to receive either oral Xeloda (X group) or CF/5-FU (control group). Oral Xeloda 1 000 mg/m^2 was administered twice daily from d 1 to 14 in X group, while CF 200 mg/m^2 was taken as a 2-h intravenous infusion followed by 5-FU 600 mg/m^2 intravenously for 4-6 h on d 1-5 in control group. Cisplatin and oxaliplatin were administered in the same way to both the groups: cisplatin 60-80 mg/m^2 by hyperthermic intraperitoneal administration, and oxaliplatin 130 mg/m^2 intravenouslyfor 2 h on d 1. All the drugs were recycled every 21 d, with at least two cycles. Pyridoxine 50 mg was given t.i.d. orally for prophylaxis of the hand-foot syndrome (HFS). Then the effect, adverse events, cost-effectiveness and DI of the two groups were evaluated.RESULTS: Hundred and fourteen cases (87.0%) finished more than two chemotherapy cycles. The overall response rate of them was 52.5% (X group) and 42.4% (control group) respectively. Tumor progression time (TTP) was 7.35 mo vs5.95 too, and 1-year survival rate was 53.1% vs 44.5%. There was a remarkable statistical significance of TTP and 1-year survival between the two groups. The main Xelocla-related adverse events were myelosuppression, gastrointestinal toxicity, neurotoxicity and HFS, which were mild and well tolerable. Therefore, no patients withdrew from the study due to side effects before two chemotherapy cycles were finished. Both groups finished pre-arranged DI and the relative DI was nearly 1.0. The average cost for 1 patient in one cycle was ¥9 137.35 (X group) and ¥8 961.72 (control group), or US $1 100.89 in X group and $1 079.73 in control group. To add 1% to the response rate costs ¥ 161.44 vs ¥210.37 respectively (US $19.45 vs $25.35). One-month prolongation of TTP costs ¥1 243.18 vs ¥1 506.17 (US $149.78 vs $181.47). Escalation of 1% of 1-year survival costs ¥172.74 vs ¥201.64 (US $20.75 vs $24.29). CONCLUSION: Oral Xeloda combined with bi-platinu two-way combination chemotherapy is efficient and tolerable for patients with advanced gastrointestinal malignancies; meanwhile the expenditure is similar to that of CF/5-FU combined with bi-platinu chemotherapy, and will be cheaper if we are concerned about the increase of the response rate, TTP or 1-year-survival rate pharmacoeconomically.展开更多
Seaweeds possess a wide range of bioactive compounds which have been play a vital role in production of novel pharmaceutical and nutraceutical products resources.The present study employed in silico molecular docking ...Seaweeds possess a wide range of bioactive compounds which have been play a vital role in production of novel pharmaceutical and nutraceutical products resources.The present study employed in silico molecular docking to characterize the biomedical potential of brown seaweed Lobophora variegata through antibacterial,antibiofilm,antioxidant and anticancer activities.The antibacterial activity of L.variegata extracts was analyzed against Escherichia coli,Enterococcus faecalis,Staphylococcus aureus,and Pseudomonas aeruginosa strains producing biofilms.The antioxidant activity was assessed using(2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)),superoxide,and hydroxyl radical scavenging assays.Further,the anticancer,antibacterial,and antioxidant activities of the bioactive compounds were evaluated through molecular docking using GLIDE ligand docking module and prime MM-GBSA module in the Schrodinger software.The phytochemical analysis of the methanolic extract of L.variegata found more phycocompounds which was confirmed by FT-IR and GC-MS.The significant level of phenol and flavonoid were expressed in methanolic extract of L.variegata.In addition,the potent antioxidant activity of the methanolic extract was efficiently expressed during the free radical scavenging assays of ABTS,hydroxyl,and superoxide denoted as 34.94,26.64,and 29.86 mg/g,respectively.The antibacterial and biofilm activities of the methanolic extract of L.variegata had significant results.Moreover,the methanolic extract exhibited cytotoxicity against human colon cancer HT-29 cell lines at an inhibitory concentration is 193.65μg/mL.Through the computational analysis,glyceryl monostearate,2-palmitoylglycerol,phthalic acid,2-chloropropyl ethyl ester,phthalic acid,5-methylhex-2-yl ethyl ester,and l-(+)-ascorbic acid 2,6-dihexadecanoate results as top ranked molecules and shown to be a promising compounds,which were evaluated for anticancer,antioxidant,and antibacterial properties against multi-target proteins.Based on the experimental results,L.variegata could be a valuable marine source for developing novel pharmaceutical applications.展开更多
Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons and has no effective treatment. Recently, Iida et al. identified a single-nucleotide polymor...Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons and has no effective treatment. Recently, Iida et al. identified a single-nucleotide polymorphism (SNP) rs2275294 in the ZNF512B gene that is significantly associated with susceptibility to ALS in the Japanese population. Here, we performed a case-control study examining the possible association of rs2275294 with risk of sporadic ALS (SALS) in a large Chinese cohort. Methods: To assess this association, we performed a replication study in 953 SALS patients and 1039 age- and gender-matched healthy control subjects, who were recruited from Peking University Third Hospital and the First Affiliated Hospital of Anhui Medical University from January 2004 to December 2013 throughout China. We genotyped the rs2275294 SNP using polymerase chain reaction and direct sequencing. Results: The allele frequency of rs2275294 in ZNF512B was different between Japanese and Chinese. The association in Chinese between ALS patients and controls did not reach statistical significance (P = 0.54; odds ratio = 0.94; 95% confidence interval = 0.76-1.15). Conclusions: The SNP rs2275294 in ZNF512B is not considered to be associated with ALS susceptibility in the Chinese population. Our study highlights genetic heterogeneity in ALS susceptibility in different population. Given our negative results, further replication study involving larger and more homogeneous samples in different ethnicities should be performed in the future.展开更多
Background:Investigations of the pathogenic mechanisms in motor neurons(MNs)derived from amyotrophic lateral sclerosis(ALS)disease-specific induced pluripotent stem(iPS)cell lines could improve understanding of the is...Background:Investigations of the pathogenic mechanisms in motor neurons(MNs)derived from amyotrophic lateral sclerosis(ALS)disease-specific induced pluripotent stem(iPS)cell lines could improve understanding of the issues affecting MNs.Therefore,in this study we explored mutant superoxide dismutase 1(SOD1)protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations.Methods:We generated induced pluripotent stem cell(iPSC)lines from two familial ALS(FALS)patients withSOD1-V14M andSOD1-C111Y mutations,and then differentiated them into MNs.We investigated levels of the SOD1 protein in iPSCs and MNs,the intracellular Ca2+levels in MNs,and the lactate dehydrogenase(LDH)activity in the process of differentiation into the MNs derived from the controls and ALS patients’iPSCs.Results:The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers.We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the twoSOD1 mutant patients.However,at no time did we observe stronger LDH activity in the patient lines compared with the control lines.Conclusions:MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis,providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy.Incremental mutant expressions of SOD1 in MNs may have disrupted MN function,either causing or contributing to the intracellular calcium disturbances,which could lead to the occurrence and development of the disease.展开更多
基金financial support from PetroChina Innovation Foundation。
文摘In order to overcome the defects that the analysis of multi-well typical curves of shale gas reservoirs is rarely applied to engineering,this study proposes a robust production data analysis method based on deconvolution,which is used for multi-well inter-well interference research.In this study,a multi-well conceptual trilinear seepage model for multi-stage fractured horizontal wells was established,and its Laplace solutions under two different outer boundary conditions were obtained.Then,an improved pressure deconvolution algorithm was used to normalize the scattered production data.Furthermore,the typical curve fitting was carried out using the production data and the seepage model solution.Finally,some reservoir parameters and fracturing parameters were interpreted,and the intensity of inter-well interference was compared.The effectiveness of the method was verified by analyzing the production dynamic data of six shale gas wells in Duvernay area.The results showed that the fitting effect of typical curves was greatly improved due to the mutual restriction between deconvolution calculation parameter debugging and seepage model parameter debugging.Besides,by using the morphological characteristics of the log-log typical curves and the time corresponding to the intersection point of the log-log typical curves of two models under different outer boundary conditions,the strength of the interference between wells on the same well platform was well judged.This work can provide a reference for the optimization of well spacing and hydraulic fracturing measures for shale gas wells.
基金Project supported by the National Natural Science Foundation of China (Grant No.11874315)the Postgraduate Scientific Research Innovation Project of Hunan Province of China (Grant No.CX20220663)。
文摘As opposed to the prototypical MoS2 with centroasymmetry,Janus ferrovalley materials such as H-VSSe are less symmetric with the mirror symmetry and time reversal symmetry broken,and hence possess spontaneous valley polarization and strong ferroelasticity.The optical transition is an important means to excite the valley carriers.We investigate the optical spectrum of H-VSSe by using the many-body perturbation-based GW approach and solving the Bethe–Salpeter equation(BSE)to include the electron–hole interactions.It is found that after the GW correction,the band gaps of the quasiparticle bands are much larger than those obtained by the normal density functional theory.The system is ferromagnetic and the valley gaps become non-degenerate due to spin–orbit coupling(SOC).The position of the lowest BSE peak is much lower than the quasiparticle band gap,indicating that the excitonic effect is large.The peak is split into two peaks by the SOC.The binding energy difference between these two BSE peaks is about the same as the difference between the inequivalent valley gaps.Our results show that in Janus H-VSSe the two lowest exciton peaks are from the two inequivalent valleys with different gaps,in contrast to the A and B exciton peaks of MoS2 which are from the same valley.
基金supported by the National Natural Science Foundation of China(11102237)Program for Changjiang Scholars and Innovative Research Team in University(IRT1294)+1 种基金Specialized Research Fund for the Doctoral Program of Higher Education(20110133120012)China Scholarship Council(CSC)
文摘Based on Huang's accurate tri-sectional nonlin- ear kinematic equation (1997), a dimensionless simplified mathematical model for nonlinear flow in one-dimensional semi-infinite long porous media with low permeability is presented for the case of a constant flow rate on the inner boundary. This model contains double moving boundaries, including an internal moving boundary and an external mov- ing boundary, which are different from the classical Stefan problem in heat conduction: The velocity of the external moving boundary is proportional to the second derivative of the unknown pressure function with respect to the distance parameter on this boundary. Through a similarity transfor- mation, the nonlinear partial differential equation (PDE) sys- tem is transformed into a linear PDE system. Then an ana- lytical solution is obtained for the dimensionless simplified mathematical model. This solution can be used for strictly checking the validity of numerical methods in solving such nonlinear mathematical models for flows in low-permeable porous media for petroleum engineering applications. Finally, through plotted comparison curves from the exact an- alytical solution, the sensitive effects of three characteristic parameters are discussed. It is concluded that with a decrease in the dimensionless critical pressure gradient, the sensi- tive effects of the dimensionless variable on the dimension- less pressure distribution and dimensionless pressure gradi- ent distribution become more serious; with an increase in the dimensionless pseudo threshold pressure gradient, the sensi- tive effects of the dimensionless variable become more serious; the dimensionless threshold pressure gradient (TPG) has a great effect on the external moving boundary but has little effect on the internal moving boundary.
文摘BACKGROUND Eosinophilia is an increase of more than 0.5×109/L in the number of eosinophils;it is a systemic condition with an unknown etiology and is often accompanied by multiple impaired organ functions.The clinical manifestations of the disease are highly variable and diverse,rendering identification of the diagnosis challenging;hence,diagnosis and treatment are often delayed.Very few reports of this disease exist globally,especially with rare manifestations of cerebral venous sinus thrombosis and hemorrhage.CASE SUMMARY A 32-year-old woman with eosinophilia presented to the hospital with bilateral lower-limb edema as the first clinical manifestation,followed by an extensive maculopapular rash throughout the body.She subsequently developed cerebral venous sinus thrombosis along with bilateral lower-limb deep vein thrombosis.Two weeks earlier,she had received a single course of antibiotics from a local hospital for a low-grade fever and sore throat.After various treatments were administered for anticoagulation,maintaining blood circulation,and relieving blood stasis,the lower extremity edema improved significantly;however,the patient’s eosinophil count gradually increased.She experienced cerebral venous sinus thrombosis,cerebral hemorrhage,and deep vein thrombosis of the lower limbs before being declared brain dead.In this case report,we have elaborated the diagnosis and management of deep vein thrombosis manifested as eosinophilia,thrombocytopenia,and elevated D-dimer levels.CONCLUSION Because proper diagnosis is challenging,clinical vigilance is required for patients with eosinophilia,as it can lead to thrombus formation.
基金Supported by the Funds of Clinical New Technology from Xijing Hospital, Fourth Military Medical University, No. XJGXO4018M13
文摘AIM: To compare the effect, adverse events, cost-effectiveness and dose intensity (DI) of oral Xeloda vs calcium folinate (CF)/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy.METHODS: A total of 131 patients were enrolled and randomly selected to receive either oral Xeloda (X group) or CF/5-FU (control group). Oral Xeloda 1 000 mg/m^2 was administered twice daily from d 1 to 14 in X group, while CF 200 mg/m^2 was taken as a 2-h intravenous infusion followed by 5-FU 600 mg/m^2 intravenously for 4-6 h on d 1-5 in control group. Cisplatin and oxaliplatin were administered in the same way to both the groups: cisplatin 60-80 mg/m^2 by hyperthermic intraperitoneal administration, and oxaliplatin 130 mg/m^2 intravenouslyfor 2 h on d 1. All the drugs were recycled every 21 d, with at least two cycles. Pyridoxine 50 mg was given t.i.d. orally for prophylaxis of the hand-foot syndrome (HFS). Then the effect, adverse events, cost-effectiveness and DI of the two groups were evaluated.RESULTS: Hundred and fourteen cases (87.0%) finished more than two chemotherapy cycles. The overall response rate of them was 52.5% (X group) and 42.4% (control group) respectively. Tumor progression time (TTP) was 7.35 mo vs5.95 too, and 1-year survival rate was 53.1% vs 44.5%. There was a remarkable statistical significance of TTP and 1-year survival between the two groups. The main Xelocla-related adverse events were myelosuppression, gastrointestinal toxicity, neurotoxicity and HFS, which were mild and well tolerable. Therefore, no patients withdrew from the study due to side effects before two chemotherapy cycles were finished. Both groups finished pre-arranged DI and the relative DI was nearly 1.0. The average cost for 1 patient in one cycle was ¥9 137.35 (X group) and ¥8 961.72 (control group), or US $1 100.89 in X group and $1 079.73 in control group. To add 1% to the response rate costs ¥ 161.44 vs ¥210.37 respectively (US $19.45 vs $25.35). One-month prolongation of TTP costs ¥1 243.18 vs ¥1 506.17 (US $149.78 vs $181.47). Escalation of 1% of 1-year survival costs ¥172.74 vs ¥201.64 (US $20.75 vs $24.29). CONCLUSION: Oral Xeloda combined with bi-platinu two-way combination chemotherapy is efficient and tolerable for patients with advanced gastrointestinal malignancies; meanwhile the expenditure is similar to that of CF/5-FU combined with bi-platinu chemotherapy, and will be cheaper if we are concerned about the increase of the response rate, TTP or 1-year-survival rate pharmacoeconomically.
文摘Seaweeds possess a wide range of bioactive compounds which have been play a vital role in production of novel pharmaceutical and nutraceutical products resources.The present study employed in silico molecular docking to characterize the biomedical potential of brown seaweed Lobophora variegata through antibacterial,antibiofilm,antioxidant and anticancer activities.The antibacterial activity of L.variegata extracts was analyzed against Escherichia coli,Enterococcus faecalis,Staphylococcus aureus,and Pseudomonas aeruginosa strains producing biofilms.The antioxidant activity was assessed using(2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)),superoxide,and hydroxyl radical scavenging assays.Further,the anticancer,antibacterial,and antioxidant activities of the bioactive compounds were evaluated through molecular docking using GLIDE ligand docking module and prime MM-GBSA module in the Schrodinger software.The phytochemical analysis of the methanolic extract of L.variegata found more phycocompounds which was confirmed by FT-IR and GC-MS.The significant level of phenol and flavonoid were expressed in methanolic extract of L.variegata.In addition,the potent antioxidant activity of the methanolic extract was efficiently expressed during the free radical scavenging assays of ABTS,hydroxyl,and superoxide denoted as 34.94,26.64,and 29.86 mg/g,respectively.The antibacterial and biofilm activities of the methanolic extract of L.variegata had significant results.Moreover,the methanolic extract exhibited cytotoxicity against human colon cancer HT-29 cell lines at an inhibitory concentration is 193.65μg/mL.Through the computational analysis,glyceryl monostearate,2-palmitoylglycerol,phthalic acid,2-chloropropyl ethyl ester,phthalic acid,5-methylhex-2-yl ethyl ester,and l-(+)-ascorbic acid 2,6-dihexadecanoate results as top ranked molecules and shown to be a promising compounds,which were evaluated for anticancer,antioxidant,and antibacterial properties against multi-target proteins.Based on the experimental results,L.variegata could be a valuable marine source for developing novel pharmaceutical applications.
基金The research was supported by grants from the National Natural Science Foundation of China
文摘Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons and has no effective treatment. Recently, Iida et al. identified a single-nucleotide polymorphism (SNP) rs2275294 in the ZNF512B gene that is significantly associated with susceptibility to ALS in the Japanese population. Here, we performed a case-control study examining the possible association of rs2275294 with risk of sporadic ALS (SALS) in a large Chinese cohort. Methods: To assess this association, we performed a replication study in 953 SALS patients and 1039 age- and gender-matched healthy control subjects, who were recruited from Peking University Third Hospital and the First Affiliated Hospital of Anhui Medical University from January 2004 to December 2013 throughout China. We genotyped the rs2275294 SNP using polymerase chain reaction and direct sequencing. Results: The allele frequency of rs2275294 in ZNF512B was different between Japanese and Chinese. The association in Chinese between ALS patients and controls did not reach statistical significance (P = 0.54; odds ratio = 0.94; 95% confidence interval = 0.76-1.15). Conclusions: The SNP rs2275294 in ZNF512B is not considered to be associated with ALS susceptibility in the Chinese population. Our study highlights genetic heterogeneity in ALS susceptibility in different population. Given our negative results, further replication study involving larger and more homogeneous samples in different ethnicities should be performed in the future.
基金supported by grants from National Natural Science Foundation of China(No.31670987)Beijing Science Foundation(No.7192223)。
文摘Background:Investigations of the pathogenic mechanisms in motor neurons(MNs)derived from amyotrophic lateral sclerosis(ALS)disease-specific induced pluripotent stem(iPS)cell lines could improve understanding of the issues affecting MNs.Therefore,in this study we explored mutant superoxide dismutase 1(SOD1)protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations.Methods:We generated induced pluripotent stem cell(iPSC)lines from two familial ALS(FALS)patients withSOD1-V14M andSOD1-C111Y mutations,and then differentiated them into MNs.We investigated levels of the SOD1 protein in iPSCs and MNs,the intracellular Ca2+levels in MNs,and the lactate dehydrogenase(LDH)activity in the process of differentiation into the MNs derived from the controls and ALS patients’iPSCs.Results:The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers.We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the twoSOD1 mutant patients.However,at no time did we observe stronger LDH activity in the patient lines compared with the control lines.Conclusions:MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis,providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy.Incremental mutant expressions of SOD1 in MNs may have disrupted MN function,either causing or contributing to the intracellular calcium disturbances,which could lead to the occurrence and development of the disease.