Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was tre...Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34) 20 μg daily for 18 months,and the elcalonin group(CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months.Bone mineral density(BMD) of the lumbar spine 2-4(L_(2-4))and femoral neck,serum calcium and phosphorus,urinary calcium,serum hone specific alkaline phosphatase(BSAP).and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ /Cn were tested at baseline,and 6.12.and 18 months after treatment.Results:In PTH group.HMD of L_(2-4),at 6,12.and 18 months,BDM of Femoral neck at 18 month,BSAP at 6 and 12 months and uCTX- Ⅰ /Cr at 6.12 and 18 months were all significantly raised.In CT group.HMD of L_(2-4) at12 month and that of femoral neck at 12 and 18 months were significantly elevated,while HSAP was significantly decreased at 12 and 18 months,and no significant difference on CTX- Ⅰ /Cr was observed.When BMD growth and growth rate between two groups were compared.PTH group had better improvement in L_(2-4) BMD and growth rate than CT group at 6.12.and 18 months.BMD growth and growth rale of femoral neck al 12 month and its growth at 18 month in CT group were higher than in PTH group,hut there was no significant difference between two groups regarding the growth rates at 18 month.Besides,there were no significant differences regarding the rales ol adverse reactions between two groups.Conclusions:rhPTH(1—34),is safe and effective in the treatment of primary OP.It is superior to elcatonin in improving vertebral HMD at onset time,growth rate and growth range,but inferior to elcatonin at HMD of femoral neck.展开更多
AIM:To investigate the acetylcholinesterase(AChE)expression involved in retina pigment epithelial(RPE)apoptosis induced by higher concentrations H2O2.METHODS:The human retinal pigment epithelium cell line ARPE-19 ...AIM:To investigate the acetylcholinesterase(AChE)expression involved in retina pigment epithelial(RPE)apoptosis induced by higher concentrations H2O2.METHODS:The human retinal pigment epithelium cell line ARPE-19 was from ATCC(Rockville,MD).Cultured ARPE-19 cells were treated with H2O2 at 0,250,500,1000,2 000μmol/L and cell viability was measured with MTT assay.AChE expression and DNA fragments were analyzed by immunocytochemistry,TUNEL and PARP-1Western blotting.RESULTS:Immunofluorescence detected AChE exist in the normal human retinal tissue.When H2O2】500μmol/L,AChE expression showed an increase after 2h,and this concentration was selected for the present study.RPE cell was induced with 1 000μmoI/L H2O2 for 2h,compared to the control group,cell activity decline detected by MTT,AChE and PARP-1 protein expression was significantly increased detected by Western blotting.AChE immunofluorescence staining was positive in RPE cell after HO2 incubate 2h.In addition,pretreatment with100|jmol/L epigallocatechin gallate(EGCG),cell viability increased from 31.20%±3.90%to 70.23%±12.96%.CONCLUSION:AChE is weakly expressed in normal human RPE cells.Stimulation with H2O2 caused the stable increase of AChE expression in RPE cells,which may indicate that AChE may be an important role in AMD.展开更多
Organic matter(OM) is preserved as different occurrences in mudstones, which can affect the hydrocarbon generation process. However, little research has focused on hydrocarbon generation as a function of different occ...Organic matter(OM) is preserved as different occurrences in mudstones, which can affect the hydrocarbon generation process. However, little research has focused on hydrocarbon generation as a function of different occurrences of OM. This study collected a suite of mudstones in the Dongying Sag, Bohai Bay Basin, and conducted Rock-Eval Ⅵ pyrolysis after Soxhlet extraction and Na_(2)S_(2)O_(8) oxidation, aiming to quantify the OM with different occurrences and figure out the contributions of each occurrence of OM to the hydrocarbon generation. There are three types of occurrences of OM: soluble organic matter(SOM),mineral-bound organic matter(MOM), and particulate organic matter(POM). MOM is the most abundant among the three occurrence types of OM. SOM and MOM are the main hydrocarbon precursors, and their hydrocarbon contributions alternate with different kerogen types and layers. Additionally, MOMcontributed hydrocarbons are numerous at shallow depths;SOM-contributed hydrocarbons mainly occur at deep depths;and POM-contributed hydrocarbons change little with depth. These results demonstrate that MOM should be the main hydrocarbon precursor in shallow formations and that SOM is the main hydrocarbon contributor at deep depths.展开更多
The AlSi7Mg alloy was fabricated by selective laser melting(SLM),and its microstructure and properties at different building directions after heat treatment were analyzed.Results show that the microstructure of SLM Al...The AlSi7Mg alloy was fabricated by selective laser melting(SLM),and its microstructure and properties at different building directions after heat treatment were analyzed.Results show that the microstructure of SLM AlSi7Mg samples containes three zones:fine grain zone,coarse grain zone,and heat affected zone.The fine-grain regions locate inside the molten pool,and the grains are equiaxed.The coarse-grain regions locate in the overlap of molten pools.After T6 treatment,the microstructure at the molten pool boundary is still the network eutectic Si,but the network structure becomes discrete,and is composed of intermittent,chain-like eutectic Si particles.The yield strength at three directions(xy,45°,z direction)of the AlSi7Mg alloy samples fabricated by SLM is improved after T6 heat treatment.The fracture mechanism of the samples is a mixed ductile and brittle fracture before heat treatment and ductile fracture after heat treatment.展开更多
BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)...BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.展开更多
The increasingly frequent and severe regional-scale compound heatwave-drought extreme events(CHDEs),driven by global warming,present formidable challenges to ecosystems,residential livelihoods,and economic conditions....The increasingly frequent and severe regional-scale compound heatwave-drought extreme events(CHDEs),driven by global warming,present formidable challenges to ecosystems,residential livelihoods,and economic conditions.However,uncertainty persists regarding the future trend of CHDEs and their insights into regional spatiotemporal heterogeneity.By integrating daily meteorological data from observations in 1961-2022 and global climate models(GCMs)based on the Shared Socioeconomic Pathways,the evolution patterns of CHDEs were compared and examined among three sub-catchments of the Yangtze River Basin,and the return periods of CHDE in 2050s and 210Os were projected.The findings indicate that the climate during the 2022 CHDE period was the warmest and driest recorded in 1961-2022,with precipitation less than 154.5 mm and a mean daily maximum temperature 3.4°C higher than the average of 1981-2010,whereas the char-acteristics in the sub-catchments exhibited temporal and spatial variation.In July-August 2022,the most notable feature of CHDE was its extremeness since 1961,with return periods of~200-year in upstream,80-year in midstream,and 40-year in downstream,respectively.By 2050,the return periods witnessed 2022 CHDE would likely be reduced by one-third.Looking towards 2100,under the highest emission scenario of SSP585,it was projected to substantially increase the frequency of CHDEs,with return periods reduced to one-third in the upstream and downstream,as well as halved in the midstream.These findings provide valuable insights into the changing risks associated with forthcoming climate extremes,emphasizing the urgency of addressing these challenges in regional management and sustainable development.展开更多
Psoriasis is a chronic,recurrent,inflammatory systemic disease that is not only characterized by skin manifestations but may also be accompanied by various comorbidities,imposing a heavy burden on patients’physical a...Psoriasis is a chronic,recurrent,inflammatory systemic disease that is not only characterized by skin manifestations but may also be accompanied by various comorbidities,imposing a heavy burden on patients’physical and mental health and affecting their quality of life.Although the continuous approval of various biological agents for clinical use has provided more effective treatment options to patients with psoriasis,no consensus on the evaluation of comprehensive treatment goals has yet been established.The treat-to-target(T2T)strategy requires consideration of multiple dimensions of treatment outcomes,the development of long-term management goals,and regular assessments of treatment conditions,which are often used in the management of chronic diseases.Therefore,based on the latest consensuses and guidelines,research data,and clinical experience as well as the combination of survey results and expert group discussions,the present consensus focuses on 4 dimensions of short-and long-term integrated management goals for biological agents:alleviating skin lesions,improving quality of life,screening and managing psoriasis comorbidities,and ensuring drug safety.The implementation methods,evaluation time,treatment monitoring,and program adjustments are also herein described to achieve comprehensive management of psoriasis to the maximum extent.This consensus provides a reference for clinical practice.展开更多
Objective:To observe the effect of electroacupuncture at"Zusanli(ST36)"on 5-fluorouracil(5-FU)-induced renal injury in colorectal cancer-bearing mice,and to further investigate its effects on oxidative stres...Objective:To observe the effect of electroacupuncture at"Zusanli(ST36)"on 5-fluorouracil(5-FU)-induced renal injury in colorectal cancer-bearing mice,and to further investigate its effects on oxidative stress,inflammatory responses,and cell apoptosis in mouse renal tissue.Methods:Thirty-five male BALB/c mice were randomly divided into five groups of seven mice each,namely the control,CT26,5-FU,sham point(SP),and ST36(which received EA at the"ST36")groups.With the exception of the control group,each group was subjected to establishment of a subcutaneous implantation tumor model using the murine CT26 colorectal cancer cell line.Once the models were successfully established,the 5-FU,SP,and ST36 groups received 5-FU injection solution intraperitoneally at a dose of 5 mg/mL once every three days over a 21-day period.Mice in the SP and ST36 groups additionally received an EA intervention after each intraperitoneal 5-FU injection.EA were performed on mice of the SP group at bilateral sham acupoints and on mice of the ST36 group at the bilateral"ST36"using the continuous wave mode at a frequency of 2 Hz for a duration of 5 min,intervention was administered once every two days for a duration of 21 days.Samples were collected from the mice at the end of the experiment.The pathological morphology of the renal tissue was observed using hematoxylin and eosin(HE)staining;the contents of creatine(Cre),blood urea nitrogen(BUN)and malondialdehyde(MDA),and superoxide dismutase(SOD)activity were measured using biochemical assays;the expression and nuclear translocation of nuclear factor kappa B p65 subunit(NF-kB p65)were measured by immunofluorescence;the expression levels of tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in serum were measured by ELISA;cell apoptosis in renal tissue was detected using the TUNEL assay;and the expression levels of the anti-B-cell lymphoma/leukemia 2(Bcl-2),Bcl-2-associated X protein(Bax),cleaved caspase-3,cleaved caspase-9,and cytochrome C(cyt c)in renal tissue weremeasuredbyWesternblotting.Results:Compared with the control group,mice of the CT26 group showed a significant increase in serum Cre content(P<0.01),but the difference in BUN content was not statistically significant(P>0.05).HE staining of renal tissue revealed clear structures with normal glomerular and renal tubular morphology.SOD activity was decreased(P<0.01);MDA content was increased,but the increase was not statistically significant(P>0.05).Differences in NF-kB p65 protein expression in the cytoplasm of renal tissue and serum levels of TNF-α,IL-6,and IL-1βwere not statistically significant(all P>0.05).Results of immunofluorescent TUNEL staining indicated an absence of significant cell apoptosis.In the renal tissue,Bcl-2 protein expression was slightly increased(P<0.05),and the expression levels of Bax(P<0.01),cleaved caspase-3(P>0.05),cleaved caspase-9(P<0.01),and cyt c(P>0.05)were increased.Compared with the CT26 group,mice of the 5-FU group exhibited an increase in Cre(P<0.01)and BUN(P<0.05)content.HE staining of renal tissue revealed the presence of glomerular atrophy and dilated Bowman's capsular spaces.SOD activity was significantly decreased(P<0.01),while the increase of MDA content was not significant(P>0.05).The expression of NF-kB p65 in the nucleus and serum TNF-α,IL-6,and IL-1βlevels showed significant increases(P<0.05).The cell apoptosis level was significantly increased.The protein expression of Bcl-2(P<0.05),Bax(P<0.01),cleaved caspase-9(P<0.01),and cyt c(P<0.05)was significantly increased.Compared with the 5-FU group,the ST36 group showed decreased serum Cre and BUN levels(both P<0.01).HE staining of renal tissue showed less renal tissue injury and less dilation of renal capsular cavities.SOD activity was significantly higher(P<0.01),while MDA content was lower(P<0.05).Nuclear expression of NF-kB p65 and serum TNF-α(P<0.05),IL-6(P<0.05),and IL-1β(P<0.01)levels were lower.The cell apoptosis level was decreased relative to the 5-FU group.Bcl-2 protein expression was significantly increased(P<0.01),while the protein expression levels of Bax(P<0.01),cleaved caspase-3(P<0.01),cleaved caspase-9(P<0.01),and cyt c(P<0.05)also were reduced.Conclusion:EA at"ST36"attenuated 5-FU-induced renal injury in colorectal cancer-bearing mice.The mechanism may be related to the regulation of renal oxidative stress,alleviation of inflammatory responses,and inhibition of cell apoptosis.展开更多
Background:Spider nevi (SN) are quite common in children. SN are treated via different techniques, and complete removal often requires multiple treatments. However, few studies have evaluated the treatment of SN. The ...Background:Spider nevi (SN) are quite common in children. SN are treated via different techniques, and complete removal often requires multiple treatments. However, few studies have evaluated the treatment of SN. The present study aimed to evaluate the therapeutic effect and safety of a 595-nm pulsed-dye laser (PDL) for treating facial SN in children.Methods:A total of 110 children aged 0.2 to 12 years with facial SN were treated with a 595-nm PDL in a single institution from January 2016 to February 2018. In accordance with the treatment method, the patients were retrospectively divided into the small-spot-combined-with-large-spot group (SL-group) and the large-spot group (L-group). Patients with poor therapeutic results were retreated every 6 weeks until the lesions disappeared. The minimum follow-up period was 1 year. The groups were compared using independent-samples t tests, Mann-Whitney U test, Chi-square test, and Fisher exact probability test.Results:The therapeutic efficacy was significantly higher in the SL-group than in the L-group, with clearance rates of 90.9% and 53.0% after the primary treatment, respectively (χ2= 17.937, P < 0.001). For skin lesions with a central spider body diameter ≥1 mm, the once-treatment cure rates were 100% in the SL-group and 34.8% in the L-group (χ2 = 20.780, P < 0.001). For skin lesions with a central spider body diameter <1 mm, the once-treatment cure rates were 82.6% in the SL-group and 62.8% in the L-group (χ2 = 3.961, P = 0.138). The rates of adverse reactions and recurrence did not differ between the two groups (P = 0.141 and P = 1.000, respectively).Conclusions:The 595-nm PDL might be a safe and effective treatment option for facial SN in children. The small-spot-combined-with-large-spot method is especially suitable for SN with a central spider body diameter ≥1 mm.展开更多
The persistence infection of low-risk type (type 6 or type 11) of human papillomavirus (HPV) is the main cause of genital warts. Given the high rate of recurrence after treatment, the use of a new molecular agent ...The persistence infection of low-risk type (type 6 or type 11) of human papillomavirus (HPV) is the main cause of genital warts. Given the high rate of recurrence after treatment, the use of a new molecular agent is certain to be of value. The aim of this study was to achieve targeted inactivation of viral E7 gene in keratinocytes using the reprogrammed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system. To accomplish this, a universal CRISPR-Cas9 system for targeting both HPV6/11 E7 genes was constructed by using a dual guide RNA vector. After transfection of the vector into E7-transfromed keratinocytes, the expression level of E7 protein was measured using western-blot analysis and the sequence of the E7 gene was determined using Sanger sequencing. Cell proliferation was analyzed by CCK-8 assay, and cell apoptosis was evaluated by Hoechst 33258 staining, flow cytometry analysis and ELISA assay. The results indicated that both HPV6/11 E7 genes can be inactivated by the single CRISPR-Cas9 system. Furthermore, silencing of E7 led to inhibition of cell proliferation and induction of apoptosis in E7-transfromed keratinocytes but not in normal keratinocytes. Our data suggested that the reprogrammed CRISPR-Cas9 system has the potential for the development of an adjuvant therapy for genital warts.展开更多
The threats and challenges of unmanned aerial vehicle(UAV) invasion defense due to rapid UAV development have attracted increased attention recently. One of the important UAV invasion defense methods is radar network ...The threats and challenges of unmanned aerial vehicle(UAV) invasion defense due to rapid UAV development have attracted increased attention recently. One of the important UAV invasion defense methods is radar network detection. To form a tight and reliable radar surveillance network with limited resources, it is essential to investigate optimized radar network deployment. This optimization problem is difficult to solve due to its nonlinear features and strong coupling of multiple constraints. To address these issues, we propose an improved firefly algorithm that employs a neighborhood learning strategy with a feedback mechanism and chaotic local search by elite fireflies to obtain a trade-off between exploration and exploitation abilities. Moreover, a chaotic sequence is used to generate initial firefly positions to improve population diversity. Experiments have been conducted on 12 famous benchmark functions and in a classical radar deployment scenario. Results indicate that our approach achieves much better performance than the classical firefly algorithm(FA) and four recently proposed FA variants.展开更多
In this paper, a novel system using direct contact heat transfer between air and water solution was proposed to generate ice slurry. The heat transfer process and the system performance were studied; energy efficiency...In this paper, a novel system using direct contact heat transfer between air and water solution was proposed to generate ice slurry. The heat transfer process and the system performance were studied; energy efficiency coefficients of 0.038, 0.053, and 0.064 were obtained using different solutions. An empirical relationship between the volumetric heat transfer coefficient U v and the main parameters was obtained by fitting the experimental data. The U v calculated from the empirical formula agreed with the experimental U v quite well with a relative error of less than 15%. Based on the empirical formula, a laboratory-scale direct contact ice slurry generator was then constructed, with practical application in mind. If the air flow rate is fixed at 200 m 3 /h, the ice production rate will be 0.091 kg/min. The experimental results also showed that the cold energy consumption of the air compressor accounted for more than half of the total amount. To improve the system energy efficiency coefficient, it is necessary to increase the air pipes insulation and the solution's thermal capacity, and also it is appropriate to utilize the free cold energy of liquefied natural gas (LNG).展开更多
Acetylcholinesterase(AChE)is emerging as an important contributor to apoptosis in various cell types.However,overexpression of AChE does not initiate apoptosis,and cells which express AChE at basal levels grow normall...Acetylcholinesterase(AChE)is emerging as an important contributor to apoptosis in various cell types.However,overexpression of AChE does not initiate apoptosis,and cells which express AChE at basal levels grow normally,suggesting that AChE may function differently between normal and apoptotic conditions.In this study,we determined that an AChE-derived protein(∼55 kDa)positively correlated with cellular apoptotic levels.The 55 kDa AChE protein was not a result of a novel splice variant of the AChE primary transcript.Instead,it was determined to be a cleaved fragment of the full-length 68 kDa AChE protein that could not be inhibited by cycloheximide(CHX)but could be suppressed by caspase inhibitors in apoptotic PC-12 cells.Furthermore,activation of the Akt cascade abolished the 55 kDa protein,and both AChE protein forms(68 and 55 kDa)accumulated in the nucleus during apoptosis.In a mouse model for ischemia/reperfusion(I/R)-induced acute renal failure,the 55 kDa AChE protein was detected in the impaired organs but not in the normal ones,and its levels correlated with the genotype of the mice.In summary,a 55 kDa AChE protein resulting from the cleavage of 68 kDa AChE is induced during apoptosis,and it is negatively regulated by the Akt pathway.This study suggests that an alternative form of AChE may play a role in apoptosis.展开更多
Let μ and v be normal functions and let Tg be the extended Ceshso operator in terms of the symbol g. In this paper, we will characterize those g so that Tg is bounded (or compact) from mixed norm spaces H(p, q, μ...Let μ and v be normal functions and let Tg be the extended Ceshso operator in terms of the symbol g. In this paper, we will characterize those g so that Tg is bounded (or compact) from mixed norm spaces H(p, q, μ) to H(p, q, v) in the unit ball of C^n, Furthermore, as applications, some analogous results are also given on weighted Bergman spaces and Dirichlet type spaces.展开更多
Psoriasis is an immune-mediated chronic,recurrent,systemic inflammatory disease induced by the combination of hereditary and environmental factors.The etiology of psoriasis involves hereditary,immune,environmental,and...Psoriasis is an immune-mediated chronic,recurrent,systemic inflammatory disease induced by the combination of hereditary and environmental factors.The etiology of psoriasis involves hereditary,immune,environmental,and other factors,and its pathogenesis is considered to involve excessive proliferation of keratinocytes or inflammatory activation of synovial cells and chondrocytes within joints;these processes are caused by an immune response that is mainly mediated by T lymphocytes and various other immune cells.Psoriasis is an incurable disease,and the goal of treatment is to control the progression of disease and maintain long-term efficacy.Treatment protocols should be based on the patients’conditions.Patients with mild psoriasis can be mainly treated with topical agents,and those with moderate to severe psoriasis can be treated with systemic medications.Targeted biological agents can be appropriately chosen for cases of psoriasis that are resistant to traditional systemic treatment.New drugs and treatments for psoriasis continue to evolve and emerge,and our updated guidelines are designed to deliver new achievements from China and physicians worldwide and to keep pace with global progress on psoriasis research.Compared with the previous two editions,part of contents have been modified and revised in the present guidelines;this will further facilitate standardization and increase the efficiency of the diagnosis and treatment of psoriasis in China,and improve patients’quality of life.展开更多
Background:Single-nucleotide polymorphisms(SNPs)-associated genes and long non-coding RNAs(lncRNAs)can contribute to human disease.To comprehensively investigate the contribution of lncRNAs to breast cancer,we perform...Background:Single-nucleotide polymorphisms(SNPs)-associated genes and long non-coding RNAs(lncRNAs)can contribute to human disease.To comprehensively investigate the contribution of lncRNAs to breast cancer,we performed the first genome-wide lncRNA association study on Han Chinese women.Methods:We designed an lncRNA array containing>800,000 SNPs,which was incorporated into a 96-array plate by Affymetrix(CapitalBio Technology,China).Subsequently,we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals(5634 breast cancer patients and 6308 healthy controls).Additionally,in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene.Results:We identified a novel breast cancer-associated susceptibility SNP,rs11066150(P_(meta)=2.34×10^(-8)),and a previously reported SNP,rs9397435(P_(meta)=4.32×10^(-38)),in Han Chinese women.rs11066150 is located in NONHSAT164009.1(lncHSAT164),which is highly expressed in breast cancer tissues and cell lines.lncHSAT164 overexpression promoted colony formation,whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle.Conclusions:Based on our lncRNA array,we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle.These findings suggest a potential therapeutic target in breast cancer.展开更多
The wide adoption of genome-wide association study (GWAS) has dramatically changed the landscape of the genetic studies of human diseases.Banking on the study design that employs large and multiple-independent sampl...The wide adoption of genome-wide association study (GWAS) has dramatically changed the landscape of the genetic studies of human diseases.Banking on the study design that employs large and multiple-independent samples,linkage disequilibrium(LD) -based systematic genome-wide interrogation, and vigorous statistical standard for declaring genetic展开更多
基金supported by Clinical Special Funds of China University Medical Journals(No:11321375)
文摘Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34) 20 μg daily for 18 months,and the elcalonin group(CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months.Bone mineral density(BMD) of the lumbar spine 2-4(L_(2-4))and femoral neck,serum calcium and phosphorus,urinary calcium,serum hone specific alkaline phosphatase(BSAP).and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ /Cn were tested at baseline,and 6.12.and 18 months after treatment.Results:In PTH group.HMD of L_(2-4),at 6,12.and 18 months,BDM of Femoral neck at 18 month,BSAP at 6 and 12 months and uCTX- Ⅰ /Cr at 6.12 and 18 months were all significantly raised.In CT group.HMD of L_(2-4) at12 month and that of femoral neck at 12 and 18 months were significantly elevated,while HSAP was significantly decreased at 12 and 18 months,and no significant difference on CTX- Ⅰ /Cr was observed.When BMD growth and growth rate between two groups were compared.PTH group had better improvement in L_(2-4) BMD and growth rate than CT group at 6.12.and 18 months.BMD growth and growth rale of femoral neck al 12 month and its growth at 18 month in CT group were higher than in PTH group,hut there was no significant difference between two groups regarding the growth rates at 18 month.Besides,there were no significant differences regarding the rales ol adverse reactions between two groups.Conclusions:rhPTH(1—34),is safe and effective in the treatment of primary OP.It is superior to elcatonin in improving vertebral HMD at onset time,growth rate and growth range,but inferior to elcatonin at HMD of femoral neck.
基金National Natural Science Foundation of China(No.31071213,81101479,30971481,81260148,81271425 and 81160118)Clinical Medicine Research Special-purpose Foundation of China(No.L2012052)+3 种基金Natural Science Foundation of Jiangxi Province,China(No.20114BAB215029)Technology Foundation of Jiangxi Province,China(No 20111BBG70026-2)Health Department Science and Technology Foundation of Jiangxi Province,China(No.20121026)Education Department Youth Scientific Research Foundation of Jiangxi Province,China(No.GJJ12158)
文摘AIM:To investigate the acetylcholinesterase(AChE)expression involved in retina pigment epithelial(RPE)apoptosis induced by higher concentrations H2O2.METHODS:The human retinal pigment epithelium cell line ARPE-19 was from ATCC(Rockville,MD).Cultured ARPE-19 cells were treated with H2O2 at 0,250,500,1000,2 000μmol/L and cell viability was measured with MTT assay.AChE expression and DNA fragments were analyzed by immunocytochemistry,TUNEL and PARP-1Western blotting.RESULTS:Immunofluorescence detected AChE exist in the normal human retinal tissue.When H2O2】500μmol/L,AChE expression showed an increase after 2h,and this concentration was selected for the present study.RPE cell was induced with 1 000μmoI/L H2O2 for 2h,compared to the control group,cell activity decline detected by MTT,AChE and PARP-1 protein expression was significantly increased detected by Western blotting.AChE immunofluorescence staining was positive in RPE cell after HO2 incubate 2h.In addition,pretreatment with100|jmol/L epigallocatechin gallate(EGCG),cell viability increased from 31.20%±3.90%to 70.23%±12.96%.CONCLUSION:AChE is weakly expressed in normal human RPE cells.Stimulation with H2O2 caused the stable increase of AChE expression in RPE cells,which may indicate that AChE may be an important role in AMD.
基金financially supported by the National Natural Science Foundation of China (Grant Nos. 41672115 and 41972126)the National Science and Technology Major Project of China(Grant No. 2016ZX05006001-003)。
文摘Organic matter(OM) is preserved as different occurrences in mudstones, which can affect the hydrocarbon generation process. However, little research has focused on hydrocarbon generation as a function of different occurrences of OM. This study collected a suite of mudstones in the Dongying Sag, Bohai Bay Basin, and conducted Rock-Eval Ⅵ pyrolysis after Soxhlet extraction and Na_(2)S_(2)O_(8) oxidation, aiming to quantify the OM with different occurrences and figure out the contributions of each occurrence of OM to the hydrocarbon generation. There are three types of occurrences of OM: soluble organic matter(SOM),mineral-bound organic matter(MOM), and particulate organic matter(POM). MOM is the most abundant among the three occurrence types of OM. SOM and MOM are the main hydrocarbon precursors, and their hydrocarbon contributions alternate with different kerogen types and layers. Additionally, MOMcontributed hydrocarbons are numerous at shallow depths;SOM-contributed hydrocarbons mainly occur at deep depths;and POM-contributed hydrocarbons change little with depth. These results demonstrate that MOM should be the main hydrocarbon precursor in shallow formations and that SOM is the main hydrocarbon contributor at deep depths.
基金the fund of Beijing Municipal Science and Technology Commission(Z181100003318001)。
文摘The AlSi7Mg alloy was fabricated by selective laser melting(SLM),and its microstructure and properties at different building directions after heat treatment were analyzed.Results show that the microstructure of SLM AlSi7Mg samples containes three zones:fine grain zone,coarse grain zone,and heat affected zone.The fine-grain regions locate inside the molten pool,and the grains are equiaxed.The coarse-grain regions locate in the overlap of molten pools.After T6 treatment,the microstructure at the molten pool boundary is still the network eutectic Si,but the network structure becomes discrete,and is composed of intermittent,chain-like eutectic Si particles.The yield strength at three directions(xy,45°,z direction)of the AlSi7Mg alloy samples fabricated by SLM is improved after T6 heat treatment.The fracture mechanism of the samples is a mixed ductile and brittle fracture before heat treatment and ductile fracture after heat treatment.
文摘BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.
基金the National Natural Science Foundation of China(42371084,42101311,41975100)。
文摘The increasingly frequent and severe regional-scale compound heatwave-drought extreme events(CHDEs),driven by global warming,present formidable challenges to ecosystems,residential livelihoods,and economic conditions.However,uncertainty persists regarding the future trend of CHDEs and their insights into regional spatiotemporal heterogeneity.By integrating daily meteorological data from observations in 1961-2022 and global climate models(GCMs)based on the Shared Socioeconomic Pathways,the evolution patterns of CHDEs were compared and examined among three sub-catchments of the Yangtze River Basin,and the return periods of CHDE in 2050s and 210Os were projected.The findings indicate that the climate during the 2022 CHDE period was the warmest and driest recorded in 1961-2022,with precipitation less than 154.5 mm and a mean daily maximum temperature 3.4°C higher than the average of 1981-2010,whereas the char-acteristics in the sub-catchments exhibited temporal and spatial variation.In July-August 2022,the most notable feature of CHDE was its extremeness since 1961,with return periods of~200-year in upstream,80-year in midstream,and 40-year in downstream,respectively.By 2050,the return periods witnessed 2022 CHDE would likely be reduced by one-third.Looking towards 2100,under the highest emission scenario of SSP585,it was projected to substantially increase the frequency of CHDEs,with return periods reduced to one-third in the upstream and downstream,as well as halved in the midstream.These findings provide valuable insights into the changing risks associated with forthcoming climate extremes,emphasizing the urgency of addressing these challenges in regional management and sustainable development.
文摘Psoriasis is a chronic,recurrent,inflammatory systemic disease that is not only characterized by skin manifestations but may also be accompanied by various comorbidities,imposing a heavy burden on patients’physical and mental health and affecting their quality of life.Although the continuous approval of various biological agents for clinical use has provided more effective treatment options to patients with psoriasis,no consensus on the evaluation of comprehensive treatment goals has yet been established.The treat-to-target(T2T)strategy requires consideration of multiple dimensions of treatment outcomes,the development of long-term management goals,and regular assessments of treatment conditions,which are often used in the management of chronic diseases.Therefore,based on the latest consensuses and guidelines,research data,and clinical experience as well as the combination of survey results and expert group discussions,the present consensus focuses on 4 dimensions of short-and long-term integrated management goals for biological agents:alleviating skin lesions,improving quality of life,screening and managing psoriasis comorbidities,and ensuring drug safety.The implementation methods,evaluation time,treatment monitoring,and program adjustments are also herein described to achieve comprehensive management of psoriasis to the maximum extent.This consensus provides a reference for clinical practice.
基金Supported by Open Project Of Acupuncture And Moxibustion In Fujian University Of Traditional Chinese Medicine:XZJ2022001。
文摘Objective:To observe the effect of electroacupuncture at"Zusanli(ST36)"on 5-fluorouracil(5-FU)-induced renal injury in colorectal cancer-bearing mice,and to further investigate its effects on oxidative stress,inflammatory responses,and cell apoptosis in mouse renal tissue.Methods:Thirty-five male BALB/c mice were randomly divided into five groups of seven mice each,namely the control,CT26,5-FU,sham point(SP),and ST36(which received EA at the"ST36")groups.With the exception of the control group,each group was subjected to establishment of a subcutaneous implantation tumor model using the murine CT26 colorectal cancer cell line.Once the models were successfully established,the 5-FU,SP,and ST36 groups received 5-FU injection solution intraperitoneally at a dose of 5 mg/mL once every three days over a 21-day period.Mice in the SP and ST36 groups additionally received an EA intervention after each intraperitoneal 5-FU injection.EA were performed on mice of the SP group at bilateral sham acupoints and on mice of the ST36 group at the bilateral"ST36"using the continuous wave mode at a frequency of 2 Hz for a duration of 5 min,intervention was administered once every two days for a duration of 21 days.Samples were collected from the mice at the end of the experiment.The pathological morphology of the renal tissue was observed using hematoxylin and eosin(HE)staining;the contents of creatine(Cre),blood urea nitrogen(BUN)and malondialdehyde(MDA),and superoxide dismutase(SOD)activity were measured using biochemical assays;the expression and nuclear translocation of nuclear factor kappa B p65 subunit(NF-kB p65)were measured by immunofluorescence;the expression levels of tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in serum were measured by ELISA;cell apoptosis in renal tissue was detected using the TUNEL assay;and the expression levels of the anti-B-cell lymphoma/leukemia 2(Bcl-2),Bcl-2-associated X protein(Bax),cleaved caspase-3,cleaved caspase-9,and cytochrome C(cyt c)in renal tissue weremeasuredbyWesternblotting.Results:Compared with the control group,mice of the CT26 group showed a significant increase in serum Cre content(P<0.01),but the difference in BUN content was not statistically significant(P>0.05).HE staining of renal tissue revealed clear structures with normal glomerular and renal tubular morphology.SOD activity was decreased(P<0.01);MDA content was increased,but the increase was not statistically significant(P>0.05).Differences in NF-kB p65 protein expression in the cytoplasm of renal tissue and serum levels of TNF-α,IL-6,and IL-1βwere not statistically significant(all P>0.05).Results of immunofluorescent TUNEL staining indicated an absence of significant cell apoptosis.In the renal tissue,Bcl-2 protein expression was slightly increased(P<0.05),and the expression levels of Bax(P<0.01),cleaved caspase-3(P>0.05),cleaved caspase-9(P<0.01),and cyt c(P>0.05)were increased.Compared with the CT26 group,mice of the 5-FU group exhibited an increase in Cre(P<0.01)and BUN(P<0.05)content.HE staining of renal tissue revealed the presence of glomerular atrophy and dilated Bowman's capsular spaces.SOD activity was significantly decreased(P<0.01),while the increase of MDA content was not significant(P>0.05).The expression of NF-kB p65 in the nucleus and serum TNF-α,IL-6,and IL-1βlevels showed significant increases(P<0.05).The cell apoptosis level was significantly increased.The protein expression of Bcl-2(P<0.05),Bax(P<0.01),cleaved caspase-9(P<0.01),and cyt c(P<0.05)was significantly increased.Compared with the 5-FU group,the ST36 group showed decreased serum Cre and BUN levels(both P<0.01).HE staining of renal tissue showed less renal tissue injury and less dilation of renal capsular cavities.SOD activity was significantly higher(P<0.01),while MDA content was lower(P<0.05).Nuclear expression of NF-kB p65 and serum TNF-α(P<0.05),IL-6(P<0.05),and IL-1β(P<0.01)levels were lower.The cell apoptosis level was decreased relative to the 5-FU group.Bcl-2 protein expression was significantly increased(P<0.01),while the protein expression levels of Bax(P<0.01),cleaved caspase-3(P<0.01),cleaved caspase-9(P<0.01),and cyt c(P<0.05)also were reduced.Conclusion:EA at"ST36"attenuated 5-FU-induced renal injury in colorectal cancer-bearing mice.The mechanism may be related to the regulation of renal oxidative stress,alleviation of inflammatory responses,and inhibition of cell apoptosis.
文摘Background:Spider nevi (SN) are quite common in children. SN are treated via different techniques, and complete removal often requires multiple treatments. However, few studies have evaluated the treatment of SN. The present study aimed to evaluate the therapeutic effect and safety of a 595-nm pulsed-dye laser (PDL) for treating facial SN in children.Methods:A total of 110 children aged 0.2 to 12 years with facial SN were treated with a 595-nm PDL in a single institution from January 2016 to February 2018. In accordance with the treatment method, the patients were retrospectively divided into the small-spot-combined-with-large-spot group (SL-group) and the large-spot group (L-group). Patients with poor therapeutic results were retreated every 6 weeks until the lesions disappeared. The minimum follow-up period was 1 year. The groups were compared using independent-samples t tests, Mann-Whitney U test, Chi-square test, and Fisher exact probability test.Results:The therapeutic efficacy was significantly higher in the SL-group than in the L-group, with clearance rates of 90.9% and 53.0% after the primary treatment, respectively (χ2= 17.937, P < 0.001). For skin lesions with a central spider body diameter ≥1 mm, the once-treatment cure rates were 100% in the SL-group and 34.8% in the L-group (χ2 = 20.780, P < 0.001). For skin lesions with a central spider body diameter <1 mm, the once-treatment cure rates were 82.6% in the SL-group and 62.8% in the L-group (χ2 = 3.961, P = 0.138). The rates of adverse reactions and recurrence did not differ between the two groups (P = 0.141 and P = 1.000, respectively).Conclusions:The 595-nm PDL might be a safe and effective treatment option for facial SN in children. The small-spot-combined-with-large-spot method is especially suitable for SN with a central spider body diameter ≥1 mm.
文摘The persistence infection of low-risk type (type 6 or type 11) of human papillomavirus (HPV) is the main cause of genital warts. Given the high rate of recurrence after treatment, the use of a new molecular agent is certain to be of value. The aim of this study was to achieve targeted inactivation of viral E7 gene in keratinocytes using the reprogrammed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system. To accomplish this, a universal CRISPR-Cas9 system for targeting both HPV6/11 E7 genes was constructed by using a dual guide RNA vector. After transfection of the vector into E7-transfromed keratinocytes, the expression level of E7 protein was measured using western-blot analysis and the sequence of the E7 gene was determined using Sanger sequencing. Cell proliferation was analyzed by CCK-8 assay, and cell apoptosis was evaluated by Hoechst 33258 staining, flow cytometry analysis and ELISA assay. The results indicated that both HPV6/11 E7 genes can be inactivated by the single CRISPR-Cas9 system. Furthermore, silencing of E7 led to inhibition of cell proliferation and induction of apoptosis in E7-transfromed keratinocytes but not in normal keratinocytes. Our data suggested that the reprogrammed CRISPR-Cas9 system has the potential for the development of an adjuvant therapy for genital warts.
基金Project supported by the National Key Laboratory of CNS/ATMBeijing Key Laboratory for Network-Based Cooperative Air Traffic Managementthe National Natural Science Foundation of China(No.71731001)
文摘The threats and challenges of unmanned aerial vehicle(UAV) invasion defense due to rapid UAV development have attracted increased attention recently. One of the important UAV invasion defense methods is radar network detection. To form a tight and reliable radar surveillance network with limited resources, it is essential to investigate optimized radar network deployment. This optimization problem is difficult to solve due to its nonlinear features and strong coupling of multiple constraints. To address these issues, we propose an improved firefly algorithm that employs a neighborhood learning strategy with a feedback mechanism and chaotic local search by elite fireflies to obtain a trade-off between exploration and exploitation abilities. Moreover, a chaotic sequence is used to generate initial firefly positions to improve population diversity. Experiments have been conducted on 12 famous benchmark functions and in a classical radar deployment scenario. Results indicate that our approach achieves much better performance than the classical firefly algorithm(FA) and four recently proposed FA variants.
基金Project (No. 51176164) supported by the National Natural Science Foundation of China
文摘In this paper, a novel system using direct contact heat transfer between air and water solution was proposed to generate ice slurry. The heat transfer process and the system performance were studied; energy efficiency coefficients of 0.038, 0.053, and 0.064 were obtained using different solutions. An empirical relationship between the volumetric heat transfer coefficient U v and the main parameters was obtained by fitting the experimental data. The U v calculated from the empirical formula agreed with the experimental U v quite well with a relative error of less than 15%. Based on the empirical formula, a laboratory-scale direct contact ice slurry generator was then constructed, with practical application in mind. If the air flow rate is fixed at 200 m 3 /h, the ice production rate will be 0.091 kg/min. The experimental results also showed that the cold energy consumption of the air compressor accounted for more than half of the total amount. To improve the system energy efficiency coefficient, it is necessary to increase the air pipes insulation and the solution's thermal capacity, and also it is appropriate to utilize the free cold energy of liquefied natural gas (LNG).
基金supported in part by the grants from the National Natural Science Foundation of China(Nos.30971481 and 31071213)the Major State Basic Research Development Program of China(973 Program)(No.2007CB947901)the Third Phase Creative Program of Chinese Academy of Sciences(No.KSCX2-YW-R-13).
文摘Acetylcholinesterase(AChE)is emerging as an important contributor to apoptosis in various cell types.However,overexpression of AChE does not initiate apoptosis,and cells which express AChE at basal levels grow normally,suggesting that AChE may function differently between normal and apoptotic conditions.In this study,we determined that an AChE-derived protein(∼55 kDa)positively correlated with cellular apoptotic levels.The 55 kDa AChE protein was not a result of a novel splice variant of the AChE primary transcript.Instead,it was determined to be a cleaved fragment of the full-length 68 kDa AChE protein that could not be inhibited by cycloheximide(CHX)but could be suppressed by caspase inhibitors in apoptotic PC-12 cells.Furthermore,activation of the Akt cascade abolished the 55 kDa protein,and both AChE protein forms(68 and 55 kDa)accumulated in the nucleus during apoptosis.In a mouse model for ischemia/reperfusion(I/R)-induced acute renal failure,the 55 kDa AChE protein was detected in the impaired organs but not in the normal ones,and its levels correlated with the genotype of the mice.In summary,a 55 kDa AChE protein resulting from the cleavage of 68 kDa AChE is induced during apoptosis,and it is negatively regulated by the Akt pathway.This study suggests that an alternative form of AChE may play a role in apoptosis.
基金Supported by the National Natural Science Foundation of China (No.10571049, 10471039), the Natural Scicnce Foundation of Zhejiang Province (No. M103085).
文摘Let μ and v be normal functions and let Tg be the extended Ceshso operator in terms of the symbol g. In this paper, we will characterize those g so that Tg is bounded (or compact) from mixed norm spaces H(p, q, μ) to H(p, q, v) in the unit ball of C^n, Furthermore, as applications, some analogous results are also given on weighted Bergman spaces and Dirichlet type spaces.
文摘Psoriasis is an immune-mediated chronic,recurrent,systemic inflammatory disease induced by the combination of hereditary and environmental factors.The etiology of psoriasis involves hereditary,immune,environmental,and other factors,and its pathogenesis is considered to involve excessive proliferation of keratinocytes or inflammatory activation of synovial cells and chondrocytes within joints;these processes are caused by an immune response that is mainly mediated by T lymphocytes and various other immune cells.Psoriasis is an incurable disease,and the goal of treatment is to control the progression of disease and maintain long-term efficacy.Treatment protocols should be based on the patients’conditions.Patients with mild psoriasis can be mainly treated with topical agents,and those with moderate to severe psoriasis can be treated with systemic medications.Targeted biological agents can be appropriately chosen for cases of psoriasis that are resistant to traditional systemic treatment.New drugs and treatments for psoriasis continue to evolve and emerge,and our updated guidelines are designed to deliver new achievements from China and physicians worldwide and to keep pace with global progress on psoriasis research.Compared with the previous two editions,part of contents have been modified and revised in the present guidelines;this will further facilitate standardization and increase the efficiency of the diagnosis and treatment of psoriasis in China,and improve patients’quality of life.
基金supported by the National Natural Science Foundation of China(No.81320108016)the Natural Science Foundation of Higher Education of Anhui Province of China(No.KJ2017A181)。
文摘Background:Single-nucleotide polymorphisms(SNPs)-associated genes and long non-coding RNAs(lncRNAs)can contribute to human disease.To comprehensively investigate the contribution of lncRNAs to breast cancer,we performed the first genome-wide lncRNA association study on Han Chinese women.Methods:We designed an lncRNA array containing>800,000 SNPs,which was incorporated into a 96-array plate by Affymetrix(CapitalBio Technology,China).Subsequently,we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals(5634 breast cancer patients and 6308 healthy controls).Additionally,in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene.Results:We identified a novel breast cancer-associated susceptibility SNP,rs11066150(P_(meta)=2.34×10^(-8)),and a previously reported SNP,rs9397435(P_(meta)=4.32×10^(-38)),in Han Chinese women.rs11066150 is located in NONHSAT164009.1(lncHSAT164),which is highly expressed in breast cancer tissues and cell lines.lncHSAT164 overexpression promoted colony formation,whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle.Conclusions:Based on our lncRNA array,we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle.These findings suggest a potential therapeutic target in breast cancer.
文摘The wide adoption of genome-wide association study (GWAS) has dramatically changed the landscape of the genetic studies of human diseases.Banking on the study design that employs large and multiple-independent samples,linkage disequilibrium(LD) -based systematic genome-wide interrogation, and vigorous statistical standard for declaring genetic