Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

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.

Implications of the mismatch repair-deficient status for the management of colorectal cancers

Although the majority of colorectal cancer(CRC) cases develop through the CIN pathway, approximately 15% of cases are caused by the hypermutation known as microsatellite instability(MSI) that is a consequence of deficient(d) DNA mismatch repair(MMR). d MMR CRCs have distinct phenotypic characteristics compared with microsatellite stable(MSS) tumors. MSI CRC is associated with an earlier stage at diagnosis and improved stage-specific prognosis, although this is controversial in stage IV patients. Current evidence supports the use of adjuvant chemotherapy with fluoropyrimidine plus oxaliplatin for stage III d MMR CRC. The distinctive genomic characterization and expression profiling of d MMR CRC paves the way for tailored immunotherapies. This is supported by recent studies that highlighted the efficacy of immunotherapy in d MMR CRC. Here, we describe the molecular aspects of the MMR system and discuss the associations of MMR-deficient/MSI-H status with clinical management, especially for patients with metastatic CRC.

Constitutional Mismatch Repair-Deficiency Syndrome Is a Rare Cause of Cancer Even in a Highly Consanguineous Population

Biallelic germline mutations in the mismatch repair genes, including MLH1, MSH2, MSH6 or PMS2, lead to a recessive constitutional mismatch repair-deficiency (CMMR-D) syndrome characterized by early onset malignancies in children and young adults. Because consanguinity unmasks autosomal recessive disorders, we hypothesized that the frequency of CMMR-D is inflated in the highly consanguineous population of Saudi Arabia. In this study, 371 pediatric and young adult?patient samples from Saudi Arabia that cover the tumor spectrum of CMMR-D syndrome were analyzed for biallelic germline mutations in the MLH1, MSH2, MSH6 and PMS2 with the use of direct genomic sequencing. However, none of the 371 patients involved in the study was found to have biallelic pathological mutations of MLH1, MSH2, MSH6 or PMS2. This result indicates that CMMR-D is exceptionally rare among pediatric cancer patients and adult early onset cancer patients, even in the highly consanguineous Saudi population. Our findings suggest that larger cohorts will be needed, particularly in outbred populations, to determine the frequency of CMMR-D and that routine screening for this syndrome among cancer patients is not warranted.

Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

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.

Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

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.

Impacts of Model Mismatch and Array Scale on Channel Estimation for XL-HRIS-Aided Systems

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.

一种前后台结合的Pipelined ADC校准技术

针对Pipelined模数转换器(ADC)中采样电容失配和运放增益误差带来的非线性问题,提出了一种前后台结合的Pipelined ADC校准技术。前台校准技术通过对ADC量化结果的余量分析,补偿相应流水级的量化结果,后台校准技术基于伪随机(PN)注入的方式,利用PN的统计特性校准增益误差。本校准技术在系统级建模和RTL级电路设计的基础上,实现了现场可编程门阵列(FPGA)验证并成功流片。测试结果显示,在1 GS/s采样速率下,校准精度为14 bit的Pipelined ADC的有效位数从9.30 bit提高到9.99 bit,信噪比提高约4 dB,无杂散动态范围提高9.5 dB,积分非线性(INL)降低约10 LSB。

数字普惠金融对企业数字化转型的影响——基于A股上市公司的研究

数字普惠金融对企业数字化发挥引导和促转作用。本文将数字普惠金融2013~2023年市级数据与中国上市企业数据进行匹配,深入研究数字普惠金融对企业数字化转型的影响。研究发现:数字普惠金融的发展对企业数字化转型有显著驱动作用,二者之间的非线性影响存在门槛效应,这种作用在非国有企业、小型企业和高科技企业中更为明显。进一步研究二者之间的传导机制,发现数字普惠金融通过3个渠道助力企业数字化转型:缓解融资约束、优化金融错配、加大研发投入。据此,本文提出了数字普惠金融服务实体经济促进企业数字化转型的政策建议。

Effect of Lattice Mismatch on Luminescence of ZnO/Si Hetero-Structure

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.

带Mismatch算子的高阶π演算

主要研究带mismatch的高阶进程演算的公理化问题.首先,建立存在mismatch时高阶进程的开弱高阶互模拟理论,证明了等价关系、同余性等重要性质;其次,沿用线性的方法,构建得到带mismatch的有限进程上的公理系统;最后,基于对开弱高阶互模拟的刻画,证明了该公理系统的完备性定理.该工作为带mismatch的高阶进程上互模拟判定的有效算法的设计与实现,进而为相关的应用建模工作提供了理论借鉴.

G-CSF动员的HLA-Mismatched-BPSC输注联合化疗治疗恶性血液病安全性观察

目的观察G-CSF(粒细胞集落刺激因子)动员的HLA-Mismatched-BPSC(活化HLA错配的外周血造血干细胞)输注联合化疗治疗恶性血液病的安全性。方法 10例恶性血液病患者G-CSF动员的HLA-Mismatched-BPSC输注联合化疗,观察其嵌合度、不良反应及血细胞恢复时间。结果 10例恶性血液病患者于化疗24~48 h后输注G-CSF动员的HLA-MismatchedBPSC,仅1例患者出现短暂嵌合,其余9例未检测出嵌合,干细胞输注后24 h内10例患者均出现发热,经对症处理后均能缓解,4例患者出现一过性皮疹经抗过敏治疗2 d内消退;无肝、肾功能损害、出血及腹泻等GVHD表现。4例自身对照患者血细胞恢复时间较仅接受化疗有缩短倾向。结论 G-CSF动员的HLA-Mismatched-BPSC输注联合化疗,仅1例有短暂嵌合,无GVHD发生及严重不良反应。

媒体关注、投资者情绪与企业资金期限错配

为缓解企业债务“爆雷”背后的资金期限错配,文章以2008—2022年中国A股上市公司为研究样本,分析媒体关注、投资者情绪与企业资金期限错配三者的关系。研究发现:媒体关注能缓解企业资金期限错配,投资者情绪会抑制媒体关注对企业资金期限错配的缓解作用;机制分析表明,媒体关注通过缓解融资约束和抑制管理层短视来降低企业资金期限错配;异质性分析显示,媒体关注对企业资金期限错配的缓解作用在非负面媒体报道、长期借款占比低、非国有以及内部控制质量高的企业中更显著。研究结论为缓解企业资金期限错配提供理论依据和政策参考,有助于降低市场系统性金融风险,更好支撑实体企业高质量发展。

KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients

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.

ARID1A expression in gastric adenocarcinoma:Clinicopathological significance and correlation with DNA mismatch repair status

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.

Deficient DNA mismatch repair is associated with favorable prognosis in Thai patients with sporadic colorectal cancer

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.

Detection of cognitive impairment in patients with obstructive sleep apnea hypopnea syndrome using mismatch negativity

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.

PD-1、PD-L1、MMR蛋白在子宫内膜癌中的表达及与患者临床病理特征的相关性分析

目的探究子宫内膜癌(EC)患者的诊断与预后评价,考虑应用程序性死亡受体-1(PD-1)、程序性死亡受体-配体1(PD-L1)、错配修复(MMR)蛋白的价值。方法研究样本共计62例,均选取于洛阳市第三人民医院2019年1月至2024年3月期间收治的EC患者,对其子宫内膜组织开展免疫组化检测,分析PD-1、PD-L1、MMR蛋白水平的表达,同时探讨PD-1、PD-L1、MMR蛋白水平与患者临床病理特征的相关性情况。结果62例EC患者中,PD-1的阳性表达率为62.90%(39/62)、PD-L1的阳性表达率为66.13%(41/62)、MMR蛋白表达缺失率为69.35%(43/62)。表达情况方面,PD-1在国际妇产科联盟分期、细胞分化程度、淋巴结转移以及子宫肌层浸润方面差异有统计学意义(P<0.05);PD-L1在病理学不同类型、国际妇产科联盟分期、细胞分化程度、淋巴结转移以及子宫肌层浸润方面差异有统计学意义(P<0.05);MMR蛋白在细胞分化程度、肿瘤部位、淋巴结转移以及子宫肌层浸润方面差异有统计学意义(P<0.05)。相关性分析结果显示,PD-1在国际妇产科联盟分期、细胞分化程度、淋巴结转移以及子宫肌层浸润方面呈现出正相关;PD-L1在病理学类型、国际妇产科联盟分期、细胞分化程度、淋巴结转移以及子宫肌层浸润方面呈现出正相关;MMR蛋白在细胞分化程度、肿瘤部位、淋巴结转移以及子宫肌层浸润方面呈现出正相关(P<0.05)。结论EC患者的诊断与预后评价方面,考虑应用PD-1、PD-L1、MMR蛋白的价值较为理想,三者在临床病理特征方面具有较为密切的关系,具有临床参考意义。

A Quantitative DNA Methylation Assay Using Mismatch Hybridization and Chemiluminescence

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.

Impact of human leukocyte antigen mismatching on outcomes of liver transplantation:A meta-analysis

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.

Magnetic resonance diffusion-perfusion mismatch in acute ischemic stroke:An update

The concept of magnetic resonance perfusion-diffusion mismatch(PDM) provides a practical and approximate measure of the tissue at risk and has been increasingly applied for the evaluation of hyperacute and acute stroke in animals and patients.Recent studies demonstrated that PDM does not optimally define the ischemic penumbra;because early abnormality on diffusion-weighted imaging overestimates the infarct core by including part of the penumbra,and the abnormality on perfusion weighted imaging overestimates the penumbra by including regions of benign oligemia.To overcome these limitations,many efforts have been made to optimize conventional PDM.Various alternatives beyond the PDM concept are under investigation in order to better define the penumbra.The PDM theory has been applied in ischemic stroke for at least three purposes:to be used as a practical selection tool for stroke treatment;to test the hypothesis that patients with PDM pattern will benefit from treatment,while those without mismatch pattern will not;to be a surrogate measure for stroke outcome.The main patterns of PDM and its relation with clinical outcomes were also briefly reviewed.The conclusion was that patients with PDM documented more reperfusion,reduced infarct growth and better clinical outcomes compared to patients without PDM,but it was not yet clear that thrombolytic therapy is beneficial when patients were selected on PDM.Studies based on a larger cohort are currently under investigation to further validate the PDM hypothesis.