In this paper,6 mm thick 2219-T6 aluminum alloy was joined by means of variable polarity tungsten-arc welding( VP-TIG) and the influence of gradient mismatches on VP-TIG joints is investigated. The average tensile str...In this paper,6 mm thick 2219-T6 aluminum alloy was joined by means of variable polarity tungsten-arc welding( VP-TIG) and the influence of gradient mismatches on VP-TIG joints is investigated. The average tensile strength of the joints reduces 32%,53% and 59%,when the mismatch of the joint was 0. 635 mm,1. 44 mm,1. 83 mm,respectively.Incomplete penetration,additional bending moment( Ma) and decrease of effective load region area are considered to explain this phenomenon. The fracture location of tensile specimens occurred at the weld zone( WZ) close to partial melt zone( PMZ),corresponding to a sharp decline of microhardness from PMZ to WZ. The original position of fracture is found at weld toe,where incomplete penetration forms due to the introduction of gradient mismatches.展开更多
The effect of system mismatches on an adaptive linear constrained generalized sidelobe canceller (LC-GSC) is discussed in this paper. Based on the array gain index, two classic system mismatches, the direction of ar...The effect of system mismatches on an adaptive linear constrained generalized sidelobe canceller (LC-GSC) is discussed in this paper. Based on the array gain index, two classic system mismatches, the direction of arrival (DOA) mismatch and the mismatches arising from array disturbance, are studied, respectively. To obtain the effective methods for compensating for the system mismatches, we analyze the performance of the improved LC-GSC with the diagonal loading and additional constraints (such as the directional constraints and derivative constraints). The computer simulations show that the techniques of diagonal loading and additional constraints can effectively compensate for the system mismatches. The loss of array gains can be controlled within 3 dB in the presence of 20% of array disturbances or DOA mismatch when the signal-to-noise ratio is less than 10 dB. The analysis illustrates that the proposed compensation methods are valid and feasible.展开更多
G-A mismatches are non-canonical base pairs that widely occur in native nucleic acids. They have been found to be functionally important in adopting unusual structures. In this paper, G-A mispairing was studied by Ram...G-A mismatches are non-canonical base pairs that widely occur in native nucleic acids. They have been found to be functionally important in adopting unusual structures. In this paper, G-A mispairing was studied by Raman spectral characterization of Polyadenylic acid (PolyA), Polyguanylic acid (PolyG) and their equimolar mixture in solution of 0.08 mol/L Na^+, pH7.0. The experiment showed the following three results. (1) At the experimental conditions used in the present work, PolyA and G A complexes existed as single-stranded and double-stranded helix of A form, respectively. And PolyG mainly occurred to be anti-parallel quadruplex conformers. (2) The formation of G A complexes, on one hand strengthened parts of base stacking interactions especially for PolyG, leading to Raman hypochromism effect with some corresponding bands shifting, and on the other hand weakened other base stacking interactions especially for PolyA to a certain degree. During this process, the backbone of PolyG underwent a significant change, but PolyA still conserved its main chain conformation. (3) The formation of G A complexes was stabilized by two interbase hydrogen- bond interactions (i.e. N6H2(A)-N3 (G) and N7 (A)--N2H2(G)) and a third hydrogen bond between O2^+ (G) and N6 (A). The third hydrogen bond was responsible for the remarkable changes of PolyG backbone conformation.展开更多
Event-related potential (ERP) studies demonstrated that emotional state immediately affects the processing of different linguistic mismatches (e.g., semantic and syntactic mismatches) in sentences. Furthermore, mood h...Event-related potential (ERP) studies demonstrated that emotional state immediately affects the processing of different linguistic mismatches (e.g., semantic and syntactic mismatches) in sentences. Furthermore, mood has been shown to impact discourse processing. In these studies, a strong expectancy was evoked by a linguistic context. In the present study, a strong expectancy was induced by a visual (non-linguistic) context paired with a sentence. A spatial array was followed by a sentence that matched (□○—The square stands in front of the circle) or mismatched the picture (intra-dimensional mismatch: □○—The square stands behind the circle;extra-dimensional mismatch: □○—The square stands above the circle). The main question was whether mood effects on the processing of visually induced expectancies are similar or different from mood effects on the processing of linguistically induced expectancies. To this aim, we presented conceptual (mis)matches that differed in saliency: intra-dimensional vs. extra-dimensional mismatches which are both reported to elicit an N2b/N400 and P600, reflecting reanalysis. EEG was recorded while participants read for comprehension. Mood (happy vs. sad) was effectively induced by film clips. Neither for N2b/N400 nor for P600, an interaction between mood and match was observed. Thus, in contrast with studies investigating the effects of pure linguistic mismatches (linguistic context paired with unexpected lexical item), mood did not modulate the processing of conceptual mismatches. However, a main effect of match revealed different ERP patterns for the two mismatches. While an increase in N2b/ N400 occurred for the intra-dimensional and extra-dimensional mismatches, a P600 only occurred to the extra-dimensional (more salient) mismatches. This finding is taken as support that being in an emotional state (positive or negative mood) influences processes of reanalysis. That is, when being in an emotional state, a reanalysis (monitoring) process is exclusively triggered by salient mismatches.展开更多
A correlation-based digital background calibration algorithm for pipelined Analog-to- Digital Converters (ADCs) is presented in this paper. The merit of the calibration algorithm is that the main errors information, w...A correlation-based digital background calibration algorithm for pipelined Analog-to- Digital Converters (ADCs) is presented in this paper. The merit of the calibration algorithm is that the main errors information, which include the capacitor mismatches and residue amplifier distortion, are extracted integrally. A modified 1st pipelined stage is adopted to solve the signal overflow caused by the Pseudo-random Noise (PN) sequences. Behavioral simulation results verify the effectiveness of the algorithm. It improves the Signal-to-Noise-plus-Distortion Ratio (SNDR) and Spurious-Free-Dynamic-Range (SFDR) of the pipelined ADC from 41.8 dB to 78.3 dB and 55.6 dB to 98.6 dB, respectively, which is comparable to the prior arts.展开更多
It is well known that primates,including humans,hardly recover motor function after spinal cord injury(SCI)when compared with non-primate mammals such as rodents.This limited functional recovery is in part due to a ...It is well known that primates,including humans,hardly recover motor function after spinal cord injury(SCI)when compared with non-primate mammals such as rodents.This limited functional recovery is in part due to a non-permissive environment of the central nervous system(CNS)inhibiting axonal regrowth.展开更多
BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-imm...BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.展开更多
BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing f...BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.展开更多
Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-de...Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.展开更多
The coordinated development of tourism resources and tourism economy is vital improve the quality and efficiency of regional tourism.Taking the ice and snow tourism in Altay region as an example,this study constructed...The coordinated development of tourism resources and tourism economy is vital improve the quality and efficiency of regional tourism.Taking the ice and snow tourism in Altay region as an example,this study constructed an evaluation indicator system and used the methods of gravity center model,spatial mismatch index model and obstacle degree model to calculate the spatial mismatch index and influencing factors of ice and snow tourism resources and tourism economy in Altay region as a whole and in each county and city.It found in the study period:(i)the ice and snow tourism resources and tourism economy in Altay region was synchronous in the development of time sequence,while the spatial distribution pattern was characterized by regional imbalance;(ii)at the macro scale,the spatial mismatch degree of the ice-snow tourism resource center and the tourism economic center in Altay region was gradually reduced,but they were always separated from the spatial geometric center of Altay region;(iii)at the micro scale,the spatial mismatch index of counties and cities in Altay region was mainly negative mismatch,and the types of spatial mismatch changed in different degrees;(iv)the factors showed certain spatial differentiation characteristics in different counties of Altay region,and there were some differences in the obstacles of different mismatch level areas,and the economic basis was the most frequent obstacle in different mismatch level areas of Altay region.展开更多
Extremely large-scale hybrid reconfigurable intelligence surface(XL-HRIS),an improved version of the RIS,can receive the incident signal and enhance communication performance.However,as the RIS size increases,the phas...Extremely large-scale hybrid reconfigurable intelligence surface(XL-HRIS),an improved version of the RIS,can receive the incident signal and enhance communication performance.However,as the RIS size increases,the phase variations of the received signal across the whole array are nonnegligible in the near-field region,and the channel model mismatch,which will decrease the estimation accuracy,must be considered.In this paper,the lower bound(LB)of the estimated parameter is studied and the impacts of the distance and signal-tonoise ratio(SNR)on LB are then evaluated.Moreover,the impacts of the array scale on LB and spectral efficiency(SE)are also studied.Simulation results verify that even in extremely large-scale array systems with infinite SNR,channel model mismatch can still limit estimation accuracy.However,this impact decreases with increasing distance.展开更多
The photoluminescence (PL) and Raman spectra of undoped ZnO films deposited directly on Si substrate (sample A),on Si substrate through a SiC buffer layer (sample B),and on a ZnO crystal wafer (sample C) are i...The photoluminescence (PL) and Raman spectra of undoped ZnO films deposited directly on Si substrate (sample A),on Si substrate through a SiC buffer layer (sample B),and on a ZnO crystal wafer (sample C) are investigated. There are emission peaks centered at 3.18eV (ultraviolet,UV) and 2.38eV (green) in these sampies. Comparing the Raman spectra and the variation of the PL peak intensities with annealing atmosphere, we conclude that the luminescence of the samples is related to the tensile strain in the ZnO film due to the lattice mismatch between the film and the substrate. In particular, the tensile strain reduces the formation energy of OZn antisite oxygen defects,which generate the green emission center. After annealing in oxygen-rich atmosphere, many OZn defects are generated. Thus, the intensity of green emission in ZnO/Si hetero-structure materials increases due to tensile strain in ZnO films.展开更多
AIM:To investigate gene mutations and DNA mismatch repair(MMR) protein abnormality in Chinese colorectalcarcinoma(CRC) patients and their correlations with clinicopathologic features.METHODS:Clinical and pathological ...AIM:To investigate gene mutations and DNA mismatch repair(MMR) protein abnormality in Chinese colorectalcarcinoma(CRC) patients and their correlations with clinicopathologic features.METHODS:Clinical and pathological information for 535 patients including 538 tumors was reviewed and recorded.Mutation analyses for exon 2 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was used.Expression of MMR proteins including MHL1,MSH2,MSH6 and PMS2 was evaluated by immunohistochemistry.Correlations of KRAS and BRAF mutation status and the expression status of MMR proteins with age,gender,cancer stage,location,and histology were analyzed.Correlations between KRAS or BRAF mutations and MMR protein expression were also explored.RESULTS:The overall frequencies of KRAS and BRAF mutations were 37.9% and 4.4%,respectively.KRAS mutations were more common in patients ≥ 50 years old(39.8% vs 22% in patients < 50 years old,P < 0.05).The frequencies of BRAF mutants were higher in tumors from females(6.6% vs males 2.8%,P < 0.05),located in the right colon(9.6% vs 2.1% in the left colon,1.8% in the rectum,P < 0.01),with mucinous differentiation(9.8% vs 2.8% without mucinous differentiation,P < 0.01),or being poorly differentiated(9.5% vs 3.4% well/moderately differentiated,P < 0.05).MMR deficiency was strongly associated with proximal location(20.5% in the right colon vs 9.2% in the left colon and 5.1% in the rectum,P < 0.001),early cancer stage(15.0% in stages Ⅰ-Ⅱ vs 7.7% in stages Ⅲ-Ⅳ,P < 0.05),and mucinous differentiation(20.2% vs 9.2% without mucin,P < 0.01).A higher frequency of MLH1/PMS2 loss was found in females(9.2% vs 4.4% in males,P < 0.05),and MSH2/MSH6 loss tended to be seen in younger(<50 years old) patients(12.0% vs 4.0% ≥ 50 years old,P < 0.05).MMR deficient tumors were less likely to have KRAS mutations(18.8% vs 41.7% in MMR proficient tumors,P < 0.05) and tumorswith abnormal MLH1/PMS2 tended to harbor BRAF mutations(15.4% vs 4.2% in MMR proficient tumors,P < 0.05).CONCLUSION:The frequency of sporadic CRCs having BRAF mutation,MLH1 deficiency and MSI in Chinese population may be lower than that in the Western population.展开更多
AIM:To analyze the mismatch repair(MMR)status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas.METHODS:We examined the expressions of MMR proteins and ARID1A by im...AIM:To analyze the mismatch repair(MMR)status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas.METHODS:We examined the expressions of MMR proteins and ARID1A by immunohistochemistry in consecutive 489 primary gastric adenocarcinomas.The results were further correlated with clinicopathological variables.RESULTS:The loss of any MMR protein expression,indicative of MMR deficiency,was observed in 38cases(7.8%)and was significantly associated with an older age(68.6±9.2 vs 60.4±11.7,P<0.001),a female sex(55.3%vs 31.3%,P=0.004),an antral location(44.7%vs 25.7%,P=0.021),and a differentiated histology(57.9%vs 39.7%,P=0.023).Abnormal ARID1A expression,including reduced or loss of ARID1A expression,was observed in 109 cases(22.3%)and was significantly correlated with lymphatic invasion(80.7%vs 69.5%,P=0.022)and lymph node metastasis(83.5%vs 73.7%,P=0.042).The tumors with abnormal ARID1A expression more frequently indicated MMR deficiency(47.4%vs 20.2%,P<0.001).A multivariate analysis identified abnormal ARID1A expression as an independent poor prognostic factor(HR=1.36,95%CI:1.01-1.84;P=0.040).CONCLUSION:Our observations suggest that the AIRD1A inactivation is associated with lymphatic invasion,lymph node metastasis,poor prognosis,and MMR deficiency in gastric adenocarcinomas.展开更多
AIM:To determine the prognostic significance of deficient mismatch repair(d MMR) and BRAF V600 E in Thai sporadic colorectal cancer(CRC) patients.METHODS:We studied a total of 211 out of 405 specimens obtained from ne...AIM:To determine the prognostic significance of deficient mismatch repair(d MMR) and BRAF V600 E in Thai sporadic colorectal cancer(CRC) patients.METHODS:We studied a total of 211 out of 405 specimens obtained from newly diagnosed CRC patients between October 1,2006 and December 31,2007 at Siriraj Hospital,Mahidol University.Formalinfixed paraffin-embedded blocks of CRC tissue samples w e re a n a l y ze d fo r d M M R b y d e t e c t i o n o f M M R protein expression loss by immunohistochemistry or microsatellite instability using polymerase chain reaction(PCR)-DHPLC.BRAF V600 E mutational analysis was performed in DNA extracted from the same archival tissues by two-round allele-specific PCR and analyzed by high sensitivity DHPLC.Associations between patient characteristics,MMR and BRAF status with diseasefree survival(DFS) and overall survival(OS) were determined by Kaplan-Meier survival plots and log-rank test together with Cox's proportional hazard regression.RESULTS:d MMR and BRAF V600 E mutations were identified in 31 of 208(14.9%) and 23 of 211(10.9%) tumors,respectively.d MMR was more commonly found in patients with primary colon tumors rather than rectal cancer(20.4% vs 7.6%,P =0.01),but there was no difference in MMR status between the right-sided and left-sided colon tumors(20.8% vs 34.6%,P = 0.24).d MMR was associated with early-stage rather than metastatic disease(17.3% vs 0%,P = 0.015).No clinicopathological features such primary site or tumor differentiation were associated with the BRAF mutation.Six of 31(19.3%) samples with d MMR carried the BRAFmutation,while 17 of 177(9.6%) with proficient MMR(p MMR) harbored the mutation(P = 0.11).Notably,patients with d MMR tumors had significantly superior DFS(HR = 0.30,95%CI:0.15-0.77; P = 0.01) and OS(HR = 0.29,95%CI:0.10-0.84; P = 0.02) compared with patients with p MMR tumors.By contrast,the BRAF V600 E mutation had no prognostic impact on DFS and OS.CONCLUSION:The prevalence of d MMR and BRAF V600 E in Thai sporadic CRC patients was 15% and 11%,respectively.The d MMR phenotype was associated with a favorable outcome.展开更多
In this experiment, 97 patients with obstructive sleep apnea hypopnea syndrome were divided into three groups (mild, moderate, severe) according to minimum oxygen saturation, and 35 healthy subjects were examined as...In this experiment, 97 patients with obstructive sleep apnea hypopnea syndrome were divided into three groups (mild, moderate, severe) according to minimum oxygen saturation, and 35 healthy subjects were examined as controls. Cognitive function was determined using the mismatch negativity paradigm and the Montreal Cognitive Assessment. The results revealed that as the disease worsened, the mismatch negativity latency was gradually extended, and the amplitude gradually declined in patients with obstructive sleep apnea hypopnea syndrome. Importantly, mismatch negativity latency in severe patients with a persistent time of minimum oxygen saturation 〈 60 seconds was significantly shorter than that with a persistent time of minimum oxygen saturation 〉 60 seconds. Correlation analysis revealed a negative correlation between minimum oxygen saturation latency and Montreal Cognitive Assessment scores. These findings indicate that intermittent night-time hypoxemia affects mismatch negativity waveforms and Montrea Cognitive Assessment scores. As indicators for detecting the cognitive functional status of obstructive sleep apnea hypopnea syndrome patients, the sensitivity of mismatch negativity is 82.93%, the specificity is 73.33%, the accuracy rate is 81.52%, the positive predictive value is 85.00%, the negative predictive value is 70.21%, the positive likelihood ratio is 3, and the negative likelihood ratio is 0.23. These results indicate that mismatch negativity can be used as an effective tool for diagnosis of cognitive dysfunction in obstructive sleep apnea hypopnea syndrome patients.展开更多
To develop a quantitative method for methylation analysis of the p16 gene based on mismatch hybridization and chemiluminescence. Methods Genomic DNA was modified by sodium bisulfite to convert all unmethylated but no...To develop a quantitative method for methylation analysis of the p16 gene based on mismatch hybridization and chemiluminescence. Methods Genomic DNA was modified by sodium bisulfite to convert all unmethylated but not methylated cytosines to uracil, and subsequently a pair of primer having no CpG sites was designed for amplification target DNA containing methylated or unmethylated CpG sites. The PCR product spanning CpG sites were hybridized with two oligonucleotide probes which perfectly matched the methylated and unmethylated CpG sequences respectively, and the hybrids were detected by chemiluminescent method. The percentage of methylated target sequences could be estimated by calculating the ratio of signals obtained with two probes. Results The percentage of methylation of artificial mixtures DNA showed a linear relation. There was a negative correlation between the methyaltion index with p16 transcriptional mRNA of p16 gene in tumor cell lines. Conclusion Compared with existing methods, this assay is nonisotopic, rapid, simple, and can be widely applied to the study of DNA methylation.展开更多
AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies.METHODS:Articles in PubMed/MEDLINE,EMBASE and the Cochra...AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies.METHODS:Articles in PubMed/MEDLINE,EMBASE and the Cochrane database from January 1970 to June 2009,including non-English literature identified in these databases,were searched.Only studies comparing HLA or sub-phenotype matching with mismatching were extracted.The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed.A meta-analysis was performed when at least 3 studies provided data.RESULTS:Sixteen studies met the inclusion criteria.A lower number of HLA mismatches(0-2 vs 3-6) did reduce the incidence of acute rejection(relative risk:0.77,P = 0.03).The degree of HLA mismatching(0-2 vs 3-6) had no significant effect on 1-year [hazard ratio(HR):1.04,P = 0.68] and 5-year(HR:1.09,P = 0.38) graft survival.In sub-phenotype analysis,the degree of HLA-A,B and DR mismatching(0 vs 1-2) had no significant effect on 1-year and 5-year graft survival,either.The HRs and P-values were 0.95,0.71(HLA-A,1-year);1.06,0.60(HLA-A,5-year);0.77,0.16(HLA-B,1-year);1.07,0.56(HLA-DR,1-year);1.18,0.23(HLADR,5-year),respectively.CONCLUSION:The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes.To obtain a short recovery time and minimize rejection post transplantation,HLA matching studies should be considered before the operation.展开更多
基金supported by the National Natural Science Foundation of China(No.50904020)the Fundamental Research Funds for the Central Universities(No.HIT.NSRIF.2012007)
文摘In this paper,6 mm thick 2219-T6 aluminum alloy was joined by means of variable polarity tungsten-arc welding( VP-TIG) and the influence of gradient mismatches on VP-TIG joints is investigated. The average tensile strength of the joints reduces 32%,53% and 59%,when the mismatch of the joint was 0. 635 mm,1. 44 mm,1. 83 mm,respectively.Incomplete penetration,additional bending moment( Ma) and decrease of effective load region area are considered to explain this phenomenon. The fracture location of tensile specimens occurred at the weld zone( WZ) close to partial melt zone( PMZ),corresponding to a sharp decline of microhardness from PMZ to WZ. The original position of fracture is found at weld toe,where incomplete penetration forms due to the introduction of gradient mismatches.
基金supported by the Aviation Science Foundation of China under Grant No. 20112080014
文摘The effect of system mismatches on an adaptive linear constrained generalized sidelobe canceller (LC-GSC) is discussed in this paper. Based on the array gain index, two classic system mismatches, the direction of arrival (DOA) mismatch and the mismatches arising from array disturbance, are studied, respectively. To obtain the effective methods for compensating for the system mismatches, we analyze the performance of the improved LC-GSC with the diagonal loading and additional constraints (such as the directional constraints and derivative constraints). The computer simulations show that the techniques of diagonal loading and additional constraints can effectively compensate for the system mismatches. The loss of array gains can be controlled within 3 dB in the presence of 20% of array disturbances or DOA mismatch when the signal-to-noise ratio is less than 10 dB. The analysis illustrates that the proposed compensation methods are valid and feasible.
基金Project supported by the Natural Science Foundation of Guangdong Province, China (Grant No 021093) and Key-stone Science and Technology Foundation of Guangdong Province, China (Grant No 2KM04502S).
文摘G-A mismatches are non-canonical base pairs that widely occur in native nucleic acids. They have been found to be functionally important in adopting unusual structures. In this paper, G-A mispairing was studied by Raman spectral characterization of Polyadenylic acid (PolyA), Polyguanylic acid (PolyG) and their equimolar mixture in solution of 0.08 mol/L Na^+, pH7.0. The experiment showed the following three results. (1) At the experimental conditions used in the present work, PolyA and G A complexes existed as single-stranded and double-stranded helix of A form, respectively. And PolyG mainly occurred to be anti-parallel quadruplex conformers. (2) The formation of G A complexes, on one hand strengthened parts of base stacking interactions especially for PolyG, leading to Raman hypochromism effect with some corresponding bands shifting, and on the other hand weakened other base stacking interactions especially for PolyA to a certain degree. During this process, the backbone of PolyG underwent a significant change, but PolyA still conserved its main chain conformation. (3) The formation of G A complexes was stabilized by two interbase hydrogen- bond interactions (i.e. N6H2(A)-N3 (G) and N7 (A)--N2H2(G)) and a third hydrogen bond between O2^+ (G) and N6 (A). The third hydrogen bond was responsible for the remarkable changes of PolyG backbone conformation.
文摘Event-related potential (ERP) studies demonstrated that emotional state immediately affects the processing of different linguistic mismatches (e.g., semantic and syntactic mismatches) in sentences. Furthermore, mood has been shown to impact discourse processing. In these studies, a strong expectancy was evoked by a linguistic context. In the present study, a strong expectancy was induced by a visual (non-linguistic) context paired with a sentence. A spatial array was followed by a sentence that matched (□○—The square stands in front of the circle) or mismatched the picture (intra-dimensional mismatch: □○—The square stands behind the circle;extra-dimensional mismatch: □○—The square stands above the circle). The main question was whether mood effects on the processing of visually induced expectancies are similar or different from mood effects on the processing of linguistically induced expectancies. To this aim, we presented conceptual (mis)matches that differed in saliency: intra-dimensional vs. extra-dimensional mismatches which are both reported to elicit an N2b/N400 and P600, reflecting reanalysis. EEG was recorded while participants read for comprehension. Mood (happy vs. sad) was effectively induced by film clips. Neither for N2b/N400 nor for P600, an interaction between mood and match was observed. Thus, in contrast with studies investigating the effects of pure linguistic mismatches (linguistic context paired with unexpected lexical item), mood did not modulate the processing of conceptual mismatches. However, a main effect of match revealed different ERP patterns for the two mismatches. While an increase in N2b/ N400 occurred for the intra-dimensional and extra-dimensional mismatches, a P600 only occurred to the extra-dimensional (more salient) mismatches. This finding is taken as support that being in an emotional state (positive or negative mood) influences processes of reanalysis. That is, when being in an emotional state, a reanalysis (monitoring) process is exclusively triggered by salient mismatches.
基金Supported by the Doctoral Program Foundation of Institutions of Higher Education of China (No.20120111120008)State Key Lab of ASIC & System(Fudan University) (No. 11KF001)Special Fund for Doctoral Program (Hefei University of Technology) (No.2011HGBZ0953)
文摘A correlation-based digital background calibration algorithm for pipelined Analog-to- Digital Converters (ADCs) is presented in this paper. The merit of the calibration algorithm is that the main errors information, which include the capacitor mismatches and residue amplifier distortion, are extracted integrally. A modified 1st pipelined stage is adopted to solve the signal overflow caused by the Pseudo-random Noise (PN) sequences. Behavioral simulation results verify the effectiveness of the algorithm. It improves the Signal-to-Noise-plus-Distortion Ratio (SNDR) and Spurious-Free-Dynamic-Range (SFDR) of the pipelined ADC from 41.8 dB to 78.3 dB and 55.6 dB to 98.6 dB, respectively, which is comparable to the prior arts.
基金supported by a grant-in-aid from the Ministry of Education,Culture,Sports,Science and Technology of Japangrants for Research and Development project of Yokohama City University
文摘It is well known that primates,including humans,hardly recover motor function after spinal cord injury(SCI)when compared with non-primate mammals such as rodents.This limited functional recovery is in part due to a non-permissive environment of the central nervous system(CNS)inhibiting axonal regrowth.
基金Supported by Ministerio de la Produccion de Peru,No.317-PNICP-EC-2014,and No.430-PNICP-PIAP-2014Consejo Nacional de Ciencia Tecnologia e Innovacion Tecnologica,No.196-2015-FONDECYT,No.197-2015-FONDECYT,and No.204-2015-FONDECYT.
文摘BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.
基金Supported by National High Level Hospital Clinical Research Funding,No.2023-NHLHCRF-YYPPLC-TJ-03.
文摘BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.
基金sponsored by BeiGene.Third-party medical writing assistance was provided by Ghina Yaacoub,MSc,of Ashfield MedComms,an Inizio Company,and funded by BeiGene.
文摘Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
文摘The coordinated development of tourism resources and tourism economy is vital improve the quality and efficiency of regional tourism.Taking the ice and snow tourism in Altay region as an example,this study constructed an evaluation indicator system and used the methods of gravity center model,spatial mismatch index model and obstacle degree model to calculate the spatial mismatch index and influencing factors of ice and snow tourism resources and tourism economy in Altay region as a whole and in each county and city.It found in the study period:(i)the ice and snow tourism resources and tourism economy in Altay region was synchronous in the development of time sequence,while the spatial distribution pattern was characterized by regional imbalance;(ii)at the macro scale,the spatial mismatch degree of the ice-snow tourism resource center and the tourism economic center in Altay region was gradually reduced,but they were always separated from the spatial geometric center of Altay region;(iii)at the micro scale,the spatial mismatch index of counties and cities in Altay region was mainly negative mismatch,and the types of spatial mismatch changed in different degrees;(iv)the factors showed certain spatial differentiation characteristics in different counties of Altay region,and there were some differences in the obstacles of different mismatch level areas,and the economic basis was the most frequent obstacle in different mismatch level areas of Altay region.
基金supported in part by the National Natural Science Founda⁃tion of China(NSFC)under Grant Nos.62301148,62341107,and 62261160576by the Natural Science Foundation of Jiangsu Prov⁃ince under Grant No.BK20230824in part by the Key Technologies R&D Program of Jiangsu(Prospective and Key Technologies for Indus⁃try)under Grant Nos.BE2023022 and BE2023022-1.
文摘Extremely large-scale hybrid reconfigurable intelligence surface(XL-HRIS),an improved version of the RIS,can receive the incident signal and enhance communication performance.However,as the RIS size increases,the phase variations of the received signal across the whole array are nonnegligible in the near-field region,and the channel model mismatch,which will decrease the estimation accuracy,must be considered.In this paper,the lower bound(LB)of the estimated parameter is studied and the impacts of the distance and signal-tonoise ratio(SNR)on LB are then evaluated.Moreover,the impacts of the array scale on LB and spectral efficiency(SE)are also studied.Simulation results verify that even in extremely large-scale array systems with infinite SNR,channel model mismatch can still limit estimation accuracy.However,this impact decreases with increasing distance.
文摘The photoluminescence (PL) and Raman spectra of undoped ZnO films deposited directly on Si substrate (sample A),on Si substrate through a SiC buffer layer (sample B),and on a ZnO crystal wafer (sample C) are investigated. There are emission peaks centered at 3.18eV (ultraviolet,UV) and 2.38eV (green) in these sampies. Comparing the Raman spectra and the variation of the PL peak intensities with annealing atmosphere, we conclude that the luminescence of the samples is related to the tensile strain in the ZnO film due to the lattice mismatch between the film and the substrate. In particular, the tensile strain reduces the formation energy of OZn antisite oxygen defects,which generate the green emission center. After annealing in oxygen-rich atmosphere, many OZn defects are generated. Thus, the intensity of green emission in ZnO/Si hetero-structure materials increases due to tensile strain in ZnO films.
基金Supported by Grant from the Xinjiang Uygur Autonomous Region Natural Science Fund,No.201233146-14(partly)
文摘AIM:To investigate gene mutations and DNA mismatch repair(MMR) protein abnormality in Chinese colorectalcarcinoma(CRC) patients and their correlations with clinicopathologic features.METHODS:Clinical and pathological information for 535 patients including 538 tumors was reviewed and recorded.Mutation analyses for exon 2 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was used.Expression of MMR proteins including MHL1,MSH2,MSH6 and PMS2 was evaluated by immunohistochemistry.Correlations of KRAS and BRAF mutation status and the expression status of MMR proteins with age,gender,cancer stage,location,and histology were analyzed.Correlations between KRAS or BRAF mutations and MMR protein expression were also explored.RESULTS:The overall frequencies of KRAS and BRAF mutations were 37.9% and 4.4%,respectively.KRAS mutations were more common in patients ≥ 50 years old(39.8% vs 22% in patients < 50 years old,P < 0.05).The frequencies of BRAF mutants were higher in tumors from females(6.6% vs males 2.8%,P < 0.05),located in the right colon(9.6% vs 2.1% in the left colon,1.8% in the rectum,P < 0.01),with mucinous differentiation(9.8% vs 2.8% without mucinous differentiation,P < 0.01),or being poorly differentiated(9.5% vs 3.4% well/moderately differentiated,P < 0.05).MMR deficiency was strongly associated with proximal location(20.5% in the right colon vs 9.2% in the left colon and 5.1% in the rectum,P < 0.001),early cancer stage(15.0% in stages Ⅰ-Ⅱ vs 7.7% in stages Ⅲ-Ⅳ,P < 0.05),and mucinous differentiation(20.2% vs 9.2% without mucin,P < 0.01).A higher frequency of MLH1/PMS2 loss was found in females(9.2% vs 4.4% in males,P < 0.05),and MSH2/MSH6 loss tended to be seen in younger(<50 years old) patients(12.0% vs 4.0% ≥ 50 years old,P < 0.05).MMR deficient tumors were less likely to have KRAS mutations(18.8% vs 41.7% in MMR proficient tumors,P < 0.05) and tumorswith abnormal MLH1/PMS2 tended to harbor BRAF mutations(15.4% vs 4.2% in MMR proficient tumors,P < 0.05).CONCLUSION:The frequency of sporadic CRCs having BRAF mutation,MLH1 deficiency and MSI in Chinese population may be lower than that in the Western population.
文摘AIM:To analyze the mismatch repair(MMR)status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas.METHODS:We examined the expressions of MMR proteins and ARID1A by immunohistochemistry in consecutive 489 primary gastric adenocarcinomas.The results were further correlated with clinicopathological variables.RESULTS:The loss of any MMR protein expression,indicative of MMR deficiency,was observed in 38cases(7.8%)and was significantly associated with an older age(68.6±9.2 vs 60.4±11.7,P<0.001),a female sex(55.3%vs 31.3%,P=0.004),an antral location(44.7%vs 25.7%,P=0.021),and a differentiated histology(57.9%vs 39.7%,P=0.023).Abnormal ARID1A expression,including reduced or loss of ARID1A expression,was observed in 109 cases(22.3%)and was significantly correlated with lymphatic invasion(80.7%vs 69.5%,P=0.022)and lymph node metastasis(83.5%vs 73.7%,P=0.042).The tumors with abnormal ARID1A expression more frequently indicated MMR deficiency(47.4%vs 20.2%,P<0.001).A multivariate analysis identified abnormal ARID1A expression as an independent poor prognostic factor(HR=1.36,95%CI:1.01-1.84;P=0.040).CONCLUSION:Our observations suggest that the AIRD1A inactivation is associated with lymphatic invasion,lymph node metastasis,poor prognosis,and MMR deficiency in gastric adenocarcinomas.
基金Supported by Siriraj Research Development Fund No.459/2554(EC2)
文摘AIM:To determine the prognostic significance of deficient mismatch repair(d MMR) and BRAF V600 E in Thai sporadic colorectal cancer(CRC) patients.METHODS:We studied a total of 211 out of 405 specimens obtained from newly diagnosed CRC patients between October 1,2006 and December 31,2007 at Siriraj Hospital,Mahidol University.Formalinfixed paraffin-embedded blocks of CRC tissue samples w e re a n a l y ze d fo r d M M R b y d e t e c t i o n o f M M R protein expression loss by immunohistochemistry or microsatellite instability using polymerase chain reaction(PCR)-DHPLC.BRAF V600 E mutational analysis was performed in DNA extracted from the same archival tissues by two-round allele-specific PCR and analyzed by high sensitivity DHPLC.Associations between patient characteristics,MMR and BRAF status with diseasefree survival(DFS) and overall survival(OS) were determined by Kaplan-Meier survival plots and log-rank test together with Cox's proportional hazard regression.RESULTS:d MMR and BRAF V600 E mutations were identified in 31 of 208(14.9%) and 23 of 211(10.9%) tumors,respectively.d MMR was more commonly found in patients with primary colon tumors rather than rectal cancer(20.4% vs 7.6%,P =0.01),but there was no difference in MMR status between the right-sided and left-sided colon tumors(20.8% vs 34.6%,P = 0.24).d MMR was associated with early-stage rather than metastatic disease(17.3% vs 0%,P = 0.015).No clinicopathological features such primary site or tumor differentiation were associated with the BRAF mutation.Six of 31(19.3%) samples with d MMR carried the BRAFmutation,while 17 of 177(9.6%) with proficient MMR(p MMR) harbored the mutation(P = 0.11).Notably,patients with d MMR tumors had significantly superior DFS(HR = 0.30,95%CI:0.15-0.77; P = 0.01) and OS(HR = 0.29,95%CI:0.10-0.84; P = 0.02) compared with patients with p MMR tumors.By contrast,the BRAF V600 E mutation had no prognostic impact on DFS and OS.CONCLUSION:The prevalence of d MMR and BRAF V600 E in Thai sporadic CRC patients was 15% and 11%,respectively.The d MMR phenotype was associated with a favorable outcome.
基金supported by the National Natural Science Foundation of China,No. 30973309
文摘In this experiment, 97 patients with obstructive sleep apnea hypopnea syndrome were divided into three groups (mild, moderate, severe) according to minimum oxygen saturation, and 35 healthy subjects were examined as controls. Cognitive function was determined using the mismatch negativity paradigm and the Montreal Cognitive Assessment. The results revealed that as the disease worsened, the mismatch negativity latency was gradually extended, and the amplitude gradually declined in patients with obstructive sleep apnea hypopnea syndrome. Importantly, mismatch negativity latency in severe patients with a persistent time of minimum oxygen saturation 〈 60 seconds was significantly shorter than that with a persistent time of minimum oxygen saturation 〉 60 seconds. Correlation analysis revealed a negative correlation between minimum oxygen saturation latency and Montreal Cognitive Assessment scores. These findings indicate that intermittent night-time hypoxemia affects mismatch negativity waveforms and Montrea Cognitive Assessment scores. As indicators for detecting the cognitive functional status of obstructive sleep apnea hypopnea syndrome patients, the sensitivity of mismatch negativity is 82.93%, the specificity is 73.33%, the accuracy rate is 81.52%, the positive predictive value is 85.00%, the negative predictive value is 70.21%, the positive likelihood ratio is 3, and the negative likelihood ratio is 0.23. These results indicate that mismatch negativity can be used as an effective tool for diagnosis of cognitive dysfunction in obstructive sleep apnea hypopnea syndrome patients.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39990570).
文摘To develop a quantitative method for methylation analysis of the p16 gene based on mismatch hybridization and chemiluminescence. Methods Genomic DNA was modified by sodium bisulfite to convert all unmethylated but not methylated cytosines to uracil, and subsequently a pair of primer having no CpG sites was designed for amplification target DNA containing methylated or unmethylated CpG sites. The PCR product spanning CpG sites were hybridized with two oligonucleotide probes which perfectly matched the methylated and unmethylated CpG sequences respectively, and the hybrids were detected by chemiluminescent method. The percentage of methylated target sequences could be estimated by calculating the ratio of signals obtained with two probes. Results The percentage of methylation of artificial mixtures DNA showed a linear relation. There was a negative correlation between the methyaltion index with p16 transcriptional mRNA of p16 gene in tumor cell lines. Conclusion Compared with existing methods, this assay is nonisotopic, rapid, simple, and can be widely applied to the study of DNA methylation.
文摘AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies.METHODS:Articles in PubMed/MEDLINE,EMBASE and the Cochrane database from January 1970 to June 2009,including non-English literature identified in these databases,were searched.Only studies comparing HLA or sub-phenotype matching with mismatching were extracted.The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed.A meta-analysis was performed when at least 3 studies provided data.RESULTS:Sixteen studies met the inclusion criteria.A lower number of HLA mismatches(0-2 vs 3-6) did reduce the incidence of acute rejection(relative risk:0.77,P = 0.03).The degree of HLA mismatching(0-2 vs 3-6) had no significant effect on 1-year [hazard ratio(HR):1.04,P = 0.68] and 5-year(HR:1.09,P = 0.38) graft survival.In sub-phenotype analysis,the degree of HLA-A,B and DR mismatching(0 vs 1-2) had no significant effect on 1-year and 5-year graft survival,either.The HRs and P-values were 0.95,0.71(HLA-A,1-year);1.06,0.60(HLA-A,5-year);0.77,0.16(HLA-B,1-year);1.07,0.56(HLA-DR,1-year);1.18,0.23(HLADR,5-year),respectively.CONCLUSION:The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes.To obtain a short recovery time and minimize rejection post transplantation,HLA matching studies should be considered before the operation.