Pregnancy Outcomes for Day 5 Versus Day 6 Single Frozen-thawed Blastocyst Transfer with Different Qualities of Embryos: A Large Matched-cohort Study

Objective This study aimed to determine whether the day of blastocyst expansion affects pregnancy outcomes in frozen-thawed blastocyst transfer(FBT)cycles.Methods A retrospective match-cohort study was conducted.Patients who underwent blastocyst transfer in frozen-thawed cycles at day 5 or 6 were matched for potential confounding factors.A total of 2207 matched pairs of FBT cycles were included from January 2016 to December 2019 in our Reproductive Medicine Center.Results The clinical pregnancy rate(CPR)and live birth rate(LBR)were significantly increased in day 5 blastocyst transfers when compared to day 6 blastocyst transfers,in terms of the same embryo quality.For FBT cycles with good-quality embryo,the CPR at day 5 and 6 was 61.30%and 57.56%,respectively(P=0.045),and the LBR was 44.79%and 36.16%,respectively(P<0.001).For FBT cycles with poor-quality embryo,the CPR at day 5 and 6 was 48.61%and 40.89%,respectively(P=0.006),and the LBR was 31.71%and 25.74%,respectively(P=0.019).The CPR for FBT cycles with good-quality embryo was statistically higher at day 6 than that at day 5 with poor-quality embryo transferred(57.56%vs.48.61%,P=0.001).Maternal age,anti-Müllerian hormone(AMH),endometrial thickness,embryo quality,and the day of blastocyst expansion were independently correlated with the CPR and LBR.The FBT cycles at day 5 had significantly higher CPR(adjusted odds ratio[OR]=1.246,95%confidence intervals[CI]:1.097–1.415,P=0.001)and LBR(adjusted OR=1.435,95%CI:1.258–1.637,P<0.001)than those at day 6.Conclusion The embryo quality is the primary indicator for FBT cycles.Day 5 blastocysts should be preferred when the quality of embryo at day 5 is the same as that at day 6.

两种圈套器改良牵引法辅助内镜黏膜下剥离术治疗上消化道早癌和黏膜下肿瘤的临床对比研究

目的研究体外圈套器改良牵引辅助技术在内镜黏膜下剥离术(ESD)治疗上消化道早癌和黏膜下肿瘤中的应用价值,并对比两种圈套器牵引法的应用效果。方法回顾性分析该院接受ESD治疗的上消化道早癌和黏膜下肿瘤患者72例,A组为传统ESD方法治疗组,B组为粗圈套器圈套牵引组,C组为细圈套器圈套牵引组。比较3组病变直径、手术平均时间、止血夹脱离次数、黏膜下补充注射量、一次完整切除率、并发症和随访情况。结果72例患者均成功完成ESD术,3组病灶直径、术中明显出血和迟发性出血比较,差异均无统计学意义(P>0.05);C组手术平均时间和黏膜下补充注射量明显少于A组,两组比较,差异有统计学意义(P<0.05);C组(100.00%)一次完整切除率高于B组和A组,3组比较,差异有统计学意义(P<0.05);C组组织夹脱离次数少于B组,两组比较,差异有统计学意义(P<0.05)。结论改良圈套器牵引辅助技术能明显缩短操作时间,减少术中黏膜下补充注射量,且具有牵引方向可调节的优点。使用体外细圈套器辅助牵引法,组织夹不易脱离,一次完整切除率高,特别是在上消化道困难ESD术中应用更具优势。

人胸膜间皮瘤UGTA17基因序列分析

以胸膜间皮瘤和非胸膜间皮瘤病理组织为研究对象,分析UGT1A7基因突变与胸膜间皮瘤发生的关系。对楚雄彝族自治州人民医院50例胸膜间皮瘤患者病理组织及7例非胸膜间皮瘤患者病理组织进行UGT1A7基因片段分离、测序,并将测序结果与正常人UGT1A7基因参考系列进行比对。结果显示,4例胸膜间皮瘤患者的UGT1A7基因片段发生了突变,病例XL17、XL20、XL41都在UGT1A7基因234676872位点(扩增片段401位点)发生碱基突变,碱基C突变成碱基T;病例XL21在UGT1A7基因23467979位点(扩增片段病例508位点)发生碱基突变,碱基A突变成碱基C,总突变率为8.00%。非胸膜间皮瘤与正常参考序列比对,Z2在401位点上的的碱基C突变为T,突变率为14.29%。以上研究说明,胸膜间皮瘤的发生与UGTA1A7基因突变有关。

Effect of sevoflurane preconditioning on astrocytic dynamics and neural network formation after cerebral ischemia and reperfusion in rats

Astrocytes, the major component of blood-brain barriers, have presented paradoxical profiles after cerebral ischemia and reperfusion in vivo and in vitro. Our previous study showed that sevoflurane preconditioning improved the integrity of blood-brain barriers after ischemia and reperfusion injury in rats. This led us to investigate the effects of sevoflurane preconditioning on the astrocytic dynamics in ischemia and reperfusion rats, in order to explore astrocytic cell-based mechanisms of sevoflurane preconditioning. In the present study, 2,3,5-triphenyltetrazolium chloride staining and Garcia behavioral scores were utilized to evaluate cerebral infarction and neurological outcome from day 1 to day 3 after transient middle cerebral artery occlusion surgery. Using immunofluorescent staining, we found that sevoflurane preconditioning substantially promoted the astrocytic activation and migration from the penumbra to the infarct with microglial activation from day 3 after middle cerebral artery occlusion. The formation of astrocytic scaffolds facilitated neuroblasts migrating from the subventricular zone to the lesion sites on day 14 after injury. Neural networks increased in the infarct of sevoflurane preconditioned rats, consistent with decreased infarct volume and improved neurological scores after ischemia and reperfusion injury. These findings demonstrate that sevoflurane preconditioning confers neuroprotection, not only by accelerating astrocytic spatial and temporal dynamics, but also providing astrocytic scaffolds for neuroblasts migration to ischemic regions, which facilitates neural reconstruction after brain ischemia.

Noninherited Factors in Fetal Congenital Heart Diseases Based on Bayesian Network:A Large Multicenter Study

Background:Current studies have confirmed that fetal congenital heart diseases(CHDs)are caused by various factors.However,the quantitative risk of CHD is not clear given the combined effects of multiple factors.Objective:This cross-sectional study aimed to detect associated factors of fetal CHD using a Bayesian network in a large sample and quantitatively analyze relative risk ratios(RRs).Methods:Pregnant women who underwent fetal echocardiography(N=16,086 including 3,312 with CHD fetuses)were analyzed.Twenty-six maternal and fetal factors were obtained.A Bayesian network is constructed based on all variables through structural learning and parameter learning methods to find the environmental factors that directly and indirectly associated with outcome,and the probability of fetal CHD in the two groups is predicted through a junction tree reasoning algorithm,so as to obtain RR for fetal CHD under different exposure factor combinations.Taking into account the effect of gestational week on the accuracy of model prediction,we conducted sensitivity analysis on gestational week groups.Results:The single-factor analysis showed that the RRs for the numbers of births,spontaneous abortions,and parental smoking were 1.50,1.38,and 1.11(P<0.001),respectively.The risk gradually increased with the synergistic effect of ranging from one to more environmental factors above.The risk was higher among subjects with five synergistic factors,including the number of births,upper respiratory tract infection during early pregnancy,anemia,and mental stress as well as a history of spontaneous abortions or parental smoking,than in those with less than 5 factors(RR=2.62 or 2.28,P<0.001).This result was consistent across the participants grouped by GWs.Conclusion:We identified six factors that were directly associated with fetal CHD.A higher number of these factors led to a higher risk of CHD.These findings suggest that it is important to strengthen healthcare and prenatal counseling for women with these factors.

人胸膜间皮瘤ALDH3B1基因序列分析

通过人胸膜间皮瘤DNA从头测序,发现ALDH3B1基因突变与人胸膜间皮瘤发生发展有一定的关联。通过PCR扩增,得到52例人胸膜间皮瘤、11例人非胸膜间皮瘤样本的ALDH3B1基因片段,利用一代测序技术对人胸膜间皮瘤ALDH3B1基因突变进行验证。ALDH3B1基因片段系列比对结果显示:①与非胸膜间皮瘤患者相比,人胸膜间皮瘤患者ALDH3B1基因突变位点较多,有9个基因替换位点,一个基因颠换位点,3个基因片段严重缺失。②突变率较高的位点有:67789454 bp位点的碱基发生G-A替换,突变率为12.96%;67789380 bp位点的碱基发生G-A替换,突变率为9.43%;67789589 bp位点的碱基发生G-A替换,突变率为7.69%;67789407 bp位点的碱基发生C-T替换,突变率为7.55%。③突变位点较多的病例是XL1、XL36、XL47和XLZCH,它们各有四个突变位点;Z17例非胸膜间皮瘤患者有三个突变位点,且有基因片段严重缺失。④XL44ZL与XL44是同一病例的癌旁组织与癌组织,它们在67789454 bp位点的碱基发生发了G-A替换,其他突变未发生。⑤考查位点67789292 bp没有发生基因突变。结果表明,人胸膜间皮瘤的发生发展与ALDH3B1基因突变有关,但ALDH3B1基因是否能充当人胸膜间皮瘤的生物标志物仍需进一步扩大样本验证。

ABCB9 polymorphism rs61955196 is associated with schizophrenia in a Chinese Han population

BACKGROUND Schizophrenia(SCZ)is a complex disease which can be affected by both genetic and environmental factors.Prenatal famine exposure may cause changes in DNA methylation levels of genes.Meanwhile,maternal nutrition during pregnancy is a pivotal environmental factor in the development of SCZ.DNA methylation may be an intermediate factor mediating exposure to famine during pregnancy and SCZ,and DNA methylation quantitative trait loci might serve as a promising tool for linking SCZ and prenatal famine.AIM To analyze the association between prenatal famine exposure and SCZ risk in Northeast Han Chinese through analysis of DNA methylation related loci.METHODS A total of 954 Han Chinese from Northeast China were recruited,including 443 patients with SCZ and 511 healthy controls.The participants were further divided into famine(born in 1960-1962)and non-famine(born in 1963-1965)groups to investigate the effect of prenatal famine exposure.Four single-nucleotide polymorphisms(SNPs)selected according to the relevant literature were genotyped,namely,rs11917047 in PTPRG,rs2239681 in IGF2,rs3842756 in INSIGF,and rs61955196 in ABCB9.DNA were extracted from peripheral blood samples,and the genotypes of these SNP loci were detected using the improved Multiple Ligase Detection Reaction multiple SNP typing technique.The associations of the DNA methylation related SNPs with SCZ risk and prenatal famine,and their interactions were analyzed using logistic regression analysis and generalized multifactor dimensionality reduction(GMDR)software.RESULTS Based on the sequencing data,genotype distributions and allele frequencies of the four selected SNPs were determined.All genotype frequencies of the four SNPs in the healthy control group were tested for deviation from Hardy-Weinberg equilibrium(P>0.05).Logistic regression analysis showed that rs61955196 was significantly associated with SCZ risk in the log-additive model[odds ratio(OR):1.22;95%confidence interval(CI):1.01-1.48;P=0.040].We also found that the rs61955196 allele was related with an enhanced risk of SCZ(G>C,OR:1.22;95%CI:1.01-1.47;P=0.042).However,no associations were observed between rs11917047,rs2239681,or rs3842756 and SCZ risk.Under the optimal genetic model,no significant association of famine with the four SNPs was seen.Though the gene–gene interactions between rs2239681 and rs61955196 were found in GMDR analysis,none of the gene-gene interactions and gene-famine interactions were associated with the risk of SCZ.CONCLUSION Our study suggested that rs61955196 in ABCB9 is associated with SCZ susceptibility in Northeast Han Chinese,providing insight into genetic effects on SCZ.

Diploid species phylogeny and evolutionary reticulation indicate early radiation of Ephedra in the Tethys coast

Reconstructing a robust species phylogeny and disentangling the evolutionary and biogeographic history of the gymnosperm genus Ephedra,which has a large genome and rich polyploids,remain a big challenge.Here we reconstructed a transcriptome-based phylogeny of 19 diploid Ephedra species,and explored evolutionary reticulations in this genus represented by 50 diploid and polyploid species,using four low-copy nuclear and nine plastid genes.The diploid species phylogeny indicates that the Mediterranean species diverged first,and the remaining species split into three clades,including the American species(Clade A),E.rhytidosperma,and all other Asian species(Clade B).The single-gene trees placed E.rhytidosperma sister to Clade A,Clade B,or Clades A+B in similar proportions,suggesting that radiation and gene flow likely occurred in the early evolution of Ephedra.In addition,reticulate evolution occurred not only among the deep nodes,but also in the recently evolved South American species,which further caused difficulty in phylogenetic reconstruction.Moreover,we found that allopolyploid speciation was pervasive in Ephedra.Our study also suggests that Ephedra very likely originated in the Tethys coast during the late Cretaceous,and the South American Ephedra species have a single origin by dispersal from Mexico or North America.

Safety and Efficacy of Physical Thermal Ablation Combined Sorafenib for Hepatocellular Carcinoma:A Meta-analysis

Background and Aims:To compare the efficacy and safety of physical thermal ablation(PTA),including radiofrequency ablation(RFA)and microwave ablation(MWA),combined with sorafenib and physical thermal ablation alone for the control and treatment of hepatocellular carcinoma(HCC)according to the available literature.Methods:Comprehensive searches were performed on PubMed,Embase,CNKI,the Cochrane Library,China Biomedical Literature Database(known as CBM),Weipu Journal,and Wanfang Database.Meta-analysis was performed using Revman 5.3 software.Results:A total of 15 studies,consisting of 2,227 HCC patients,were selected and included in this meta-analysis.Compared with the RFA-alone group,the patients in the RFA+sorafenib group had longer 1-,2-,and 3-year overall survival(all p<0.05),better overall efficacy(p<0.0001),longer radiofrequency interval(p<0.001),and lower 2-year recurrence rate(p=0.02).The 1-year overall survival(p=0.003)and overall efficacy(p=0.002)of the MWA+sorafenib group were also higher than those of the MWA-alone group.The incidences of adverse reactions in the RFA+sorafenib group,such as hand-foot skin reactions(p<0.001),diarrhea and constipation(p=0.0001),hypertension(p=0.009),and alopecia(p<0.001),were significantly higher than those in the RFA-alone group.Conclusions:RFA or MWA combined with sorafenib has produced a better therapeutic effect on HCC than physical thermal ablation alone;however,adverse reactions have been obvious.It is necessary to evaluate the safety of combination therapy,and pay close attention to the adverse reactions that develop in patients.

New design of sense amplifier for EEPROM memory

We present a new sense amplifier circuit for EEPROM memory. The topology of the sense amplifier uses a voltage sensing method,having low cost and low power consumption as well as high reliability. The sense amplifier was implemented in an EEPROM realized with an SMIC 0.35-μm 2P3M CMOS embedded EEPROM process. Under the condition that the power supply is 3.3 V,simulation results showed that the charge time is 35 ns in the proposed sense amplifier,and that the maximum average current consumption during the read period is 40 μA. The novel topology allows the circuit to function with power supplies as low as 1.4 V. The sense amplifier has been implemented in 2-kb EEPROM memory for RFID tag IC applications,and has a silicon area of only 240 μm2.

Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han population of Northern China？

Papillary thyroid carcinoma （PTC） is one of the most common tumors of the thyroid gland. The common risk factors of PTC include ionizing radiation, positive family history, and thyroid nodular disease. PTC was identified in Europeans by conducting a genome-wide association study, and a strong association signal with PTC was observed in rs944289 and NKX2-1 （located at the 14q13.3 locus）, which was probably the genetic risk factor of PTC. This study aimed to examine the association of this gene with PTC in Chinese. A total of 354 patients with PTC and 360 healthy control subjects from the Han population of Northern China were recruited in the study. These individuals were genotyped to determine rs12589672, rs12894724, rs2076751, and rs944289. The association of rs944289 with PTC was obtained （C vs. T, P= 0.027, OR= 1.264, 95% CI = 1.026-1.557; and C/C-C/T vs. T/T, P= 0.034, OR= 1.474, 95% CI = 1.028-2.112）. Conducting a subgroup analysis, we found a marginal difference in the allele frequency distribution of rs944289 （adjusted P = 0.062） between the patients with PTC and multi-nodular goiter and the control subjects. We also observed an interaction （P= 0.029; OR = 2.578, 95% CI=1.104-6.023） between rs944289 and diabetes in patients with PTC. In conclusion, rs944289 was associated with an increased risk of PTC in the Han population of Northern China, but no clear association was observed in either of the tag single nucleotide polymorphisms of NKX2-1.

Genetic association between the polymorphism of cytosolicPLA2 gene family and schizophrenia

Abnormal phospholipid metabolism in the brain plays an important role in neuropsychiatric diseases.Phospholipase A2(PLA2)is a crucial element for normal neuro-physiological function.This study aims to investi-gate the genetic association between the polymorphism of cytosolic phospholipase A2(cPLA2)family genes and schizophrenia among Han Chinese in the northern part of China.The polymerase chain reaction-based ligase detec-tion reaction(PCR-LDR)was applied to detect the genotype ten single nucleotide polymorphisms(SNPs)of cPLA2 family genes among 201 pedigrees consisting of fathers,mothers and affected offsprings with schizophre-nia.The pedigrees were collected from 2000 to 2006.Haplotype relative risk(HRR)test,transmission disequili-brium test(TDT),haplotype transmission analysis and multiple locus analysis were conducted to analyze the genotyping data.The genotypic frequency of cPLA2 gene did not deviate from Hardy-Weinberg equilibrium either in case or control group.HRR and TDT showed that the ten SNPs were not associated with schizophrenia(P>0.05).Analysis for haplotype transmission showed that no haplotype system was associated with schizophrenia(P>0.05).The conditioning on allele(COA)and conditioning on gene(COG)tests showed disease associations with the haplotype of rs2162886-rs1668589,rs891014-rs1668589 and rs2307279-rs7542180(χ2=6.913,P=0.032;χ2=8.393,P=0.015;χ2=8.447,P=0.038).Our data suggest that many loci in the cPLA2 family genes may be associated with schizophrenia.