Maceral evolution of lacustrine shale and its effects on the development of organic pores during low mature to high mature stage:A case study from the Qingshankou Formation in northern Songliao Basin,northeast China

Organic matter(OM)hosted pores are crucial for the storage and migration of petroleum in shale reservoirs.Thermal maturity and macerals type are important factors controlling the development of pores therein.In this study,six lacustrine shale samples with different thermal maturities from the first member of the Qingshankou Formation in the Songliao Basin,of which vitrinite reflectance(R_(o))ranging from 0.58% to 1.43%,were selected for a comparative analysis.Scanning electron microscopy(SEM)and reflected light microscopy were combined to investigate the development of organic pores in different macerals during thermal maturation.The results show that alginite and liptodetrinite are the dominant primary macerals,followed by bituminite.Only a few primary organic pores developed in the alginite at the lowest maturity(R_(o)=0.58%).As a result of petroleum generation,oil-prone macerals began to transform to initial-oil solid bitumen at the early oil window(R_(o)=0.73%)and shrinkage cracks were observed.Initial-oil solid bitumen cracked to oil,gas and post-oil bitumen by primary cracking(R_(o)=0.98%).Moreover,solid bitumen(SB)was found to be the dominant OM when R_(o)>0.98%,which indicates that SB is the product of oil-prone macerals transformation.Many secondary bubble pores were observed on SB,which formed by gas release,while devolatilization cracks developed on migrated SB.Additionally,at the late oil window(Ro?1.16%),migrated SB filled the interparticle pore spaces.With further increase in temperature,the liquid oil underwent secondary cracking into pyrobitumen and gas,and spongy pores developed on the pyrobitumen at higher levels of maturity(Ro=1.43%),which formed when pyrobitumen cracked into gas.Vitrinite and inertinite are stable without any visible pores over the range of maturities,verifying their low petroleum generation potential.In addition,it was concluded that clay minerals could have a catalytic effect on the petroleum generation,which may explain why organicclay mixtures had more abundant pores than single OM particles.However,after R_(o)>0.98%,authigenic minerals occupied the organic pore spaces on the organic-clay mixtures,resulting in fewer pores compared to those observed in samples at the early to peak oil window.

Large animal models of cardiac ischemia-reperfusion injury:Where are we now?

Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation.Nonetheless,current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models,which are not transferable or reproducible in large animal models due to different factors such as:(i)complex and varied features of human ischemic cardiac disease(ICD),which are challenging to mimic in animal models,(ii)significant differences in surgical techniques applied,and(iii)differences in cardiovascular anatomy and physiology between small versus large animals.This article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury(IRI),as well as the different methods used to induce and assess IRI,and the obstacles faced in using large animals for translational research in the settings of cardiac IR.

Galectin-14 promotes hepatocellular carcinoma tumor growth via enhancing heparan sulfate proteoglycan modification

Hepatocellular carcinoma(HCC)is a highly heterogeneous malignancy and lacks effective treatment.Bulk-sequencing of different gene transcripts by comparing HCC tissues and adjacent normal tissues provides some clues for investigating the mechanisms or identifying potential targets for tumor progression.However,genes that are exclusively expressed in a subpopulation of HCC may not be enriched or detected through such a screening.In the current study,we performed a single cell-clone-based screening and identified galectin-14 as an essential molecule in the regulation of tumor growth.The aberrant expression of galectin-14 was significantly associated with a poor overall survival of liver cancer patients with database analysis.Knocking down galectin-14 inhibited the proliferation of tumor growth,whereas overexpressing galectin-14 promoted tumor growth in vivo.Non-targeted metabolomics analysis indicated that knocking down galectin-14 decreased glycometabolism;specifically that glycoside synthesis was significantly changed.Further study found that galectin-14 promoted the expression of cell surface heparan sulfate proteoglycans(HSPGs)that functioned as co-receptors,thereby increasing the responsiveness of HCC cells to growth factors,such as epidermal growth factor and transforming growth factor-alpha.In conclusion,the current study identifies a novel HCC-specific molecule galectin-14,which increases the expression of cell surface HSPGs and the uptake of growth factors to promote HCC cell proliferation.

Endocrine-Disrupting Chemicals: Possible Genesis of Ovarian Tumors

Background: Prolonged exposure to environmental toxicants like endocrine-disrupting chemicals has been linked to several ovarian pathologies. Exposure to endocrine-disrupting chemicals may start at any time of life from the fetal stage to adulthood resulting in various health complications The purpose of our study is to compare the concentration levels and association of benzopyrene, bisphenol A and genistein in patients with ovarian tumors and normal control group. We also sort to evaluate the predictive performance of benzopyrene, bisphenol A and genistein in patients with ovarian tumors. Methods: A case-control study was conducted for randomly selected participants involving 30 patients and 30 controls. 30 patients with radiologically diagnosed and histopathological confirmed ovarian tumors were included in the study between January 2022 and December 2022. Urine samples from each group were analyzed using liquid chromatography-mass spectrometry. Descriptive analysis for normally distributed continuous variables was done accordingly. Concentration levels of endocrine-disrupting chemicals were assessed using the Mann-Whitney test. The association of endocrine-disrupting chemicals with pathological ovarian tumors was analyzed using binary logistic regression. Evaluation of the diagnostic performance of endocrine-disrupting chemicals was analyzed using the ROC curve. Results: Overall, patients were significantly (P = 0.000) older than the healthy controls. Mean years (SD) were 36.7 (7.90) and 28.8 years (4.89) for patients and normal women respectively. Endometriomas had the highest incidence of 50%. The level of benzopyrene and bisphenol A in patients was significantly higher than those in the control group, while the level of genistein was significantly higher in normal controls. Benzopyrene and bisphenol A were significantly associated with ovarian cysts, and the incidence of pathological ovarian cysts was positively correlated to these EDCs, with OR value 64.79 (P = 0.005) for benzopyrene and 9.609 (P = 0.001) for bisphenol A. Genistein was significantly negatively correlated with the incidence of pathological ovarian tumors, with OR value of 0.153 (P = 0.007). Diagnostic performance on the AUC for benzopyrene, bisphenol A and genistein&l.

Prediction model of in-hospital mortality in elderly patients with acute heart failure based on retrospective study

Objectives The aim of this study was to develop a clinical risk model that is predictive of in-hospital mortality in elderly patients hos- pitalized with acute heart failure （AHF）. Methods 2486 patients who were 60 years and older from intensive care units of Cardiology De- partment in the hospital were analyzed. Independent risk factors for in-hospital mortality were obtained by binary logistic regression and then used to establish the risk prediction score system （RPSS）. The area under the curve （AUC） of receiver operator characteristic and C-statistic test were adopted to assess the performance of RPSS and to compare with previous get with the guidelines-heart failure （GWTG-HF）. Re- sults By binary logistic regression analysis, heart rate （OR： 1.043, 95% CI： 1.030-1.057, P 〈 0.001）, left ventricular ejection fraction （OR： 0.918, 95% CI： 0.833~）.966, P 〈 0.001）, pH value （OR： 0.001, 95% CI： 0.000-0.002, P 〈 0.001）, renal dysfunction （OR： 0.120, 95% CI： 0.066M）.220, P 〈 0.001） and NT-pro BNP （OR： 3.463, 95% CI： 1.870-6.413, P 〈 0.001） were independent risk factors of in-hospital mortal- ity for elderly AHF patients. Additionally, RPSS, which was composed of all the above-mentioned parameters, provided a better risk predic- tion than GWTG-THF （AUC： 0.873 vs. 0.818, P = 0.016）. Conclusions Our risk prediction model, RPSS, provided a good prediction for in-hospital mortality in elderly patients with A/IF.

Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis

Objective： A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase （PI3K） and mitogen-activated protein kinase （MAPK） pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI） treatment of non-small cell lung cancer （NSCLC） patients. Methods： Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios （ORs） for objective response rate （ORR） and hazard ratios （HRs） for progression-free survival （PFS） and overall survival （OS） were calculated. Results： Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval （CI）, 0.13-0.35], shorter PFS （HR =1.56; 95% CI, 1.27-1.92）, and shorter OS （HR =1.59; 95% CI, 1.33-1.91） in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS （HR =1.83; 95% CI, 1.05-3.20）, showed poor ORR （OK =0.70; 95% CI, 0.22-2.18）, and shorter PFS （HR = 1.79; 95% CI, 0.91-3.53） in NSCLC patients treated with EGFR-TKIs. Conclusion： K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR- TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.

In vivo genome editing thrives with diversified CRISPR technologies

Prokaryotic type II adaptive immune systems have been developed into the versatile CRISPR technology, which has been widely applied in site- specific genome editing and has revolutionized biomedical research due to its superior efficiency and flexibility. Recent studies have greatly diversified CRISPR technologies by coupling it with various DNA repair mechanisms and targeting strategies. These new advances have significantly expanded the generation of genetically modified animal models, either by including species in which targeted genetic modification could not be achieved previously, or through introducing complex genetic modifications that take multiple steps and cost years to achieve using traditional methods. Herein, we review the recent developments and applications of CRISPR-based technology in generating various animal models, and discuss the everlasting impact of this new progress on biomedical research.

Relationship of serum polyunsaturated fatty acids with cytokines in colorectal cancer

AIM: To investigate the relationship of serum levels of polyunsaturated fatty acid(PUFA) with kinds of cytokines in colorectal cancer(CRC).METHODS: Serum samples of 100 CRC patients were collected. The concentration of total n-3 PUFA which included C18:3 n-3, C20:5 n-3, C22:5 n-3, C22:6 n-3 and the total n-6 PUFA included C18:2 n-6, C18:3 n-6, C20:3 n-6, C20:4 n-6, and C22:5 n-6 were detected onGC-2010 Plus Gas Chromatograph with a Omegawax TM 250 column. Cytokines were detected by Mag Plex TM-C microspheres. P values for the trend were estimated by creating a continuous variable using the median value within quartiles.RESULTS: Interleukin-6(IL-6) showed significantly positive association with the C20:4 n-6(P for trend = 0.004). Interferon gamma(IFN-γ) showed significant positive association with the C22:5 n-3(P for trend = 0.035). IL-8 and matrix metalloproteinase-9(MMP-9) showed significant inverse association with the C22:6 n-3(P for trend = 0.049, and 0.021). MMP-2 showed significant inverse association with the C20:5 n-3(P for trend = 0.008). MMP-7 showed significantly positive association with the ratio of n-6 PUFA and n-3 PUFA(P for trend = 0.008). MMP-7 also showed significantly inverse association with the ratio of C20:4 n-6 and(n-6 PUFA + n-3 PUFA)(P for trend = 0.024). IL-10(P for trend = 0.023) and IL-6(P for trend = 0.036) showed significantly positive association with the ratio of C20:4 n-6 and C20:5 n-3.CONCLUSION: Our data suggested that serum levels of PUFA is related to the inflammation of CRC, and also play different role in regulation of immune response.

Thermal maturity evaluation using Raman spectroscopy for oil shale samples of USA:comparisons with vitrinite reflectance and pyrolysis methods

Thermal maturity is commonly assessed by various geochemical screening methods(e.g.,pyrolysis and organic petrology).In this contribution,we attempt to establish an alternative approach to estimating thermal maturity with Raman spectroscopy,using 24 North American oil shale samples with thermal maturity data generated by vitrinite reflectance(VRo%)and pyrolysis(Tmax)-based maturity calculation(VRe%).The representative shale samples are from the Haynesville(East Texas),Woodford(West Texas),Eagle Ford and Pearsall(South Texas)Formations,as well as Gothic,Mancos,and Niobrara Formation shales(all from Colorado).The Raman spectra of disordered carbonaceous matter(D1 and G bands separation)of these samples were directly obtained from the rock chips without prior sample preparation.Using the Gaussian and Lorentzian distribution approach,thermal maturities from VR were correlated with carbon G and D1.We found that the Raman band separation(RBS)displayed a better correlation for equivalent VRe%than vitrinite reflectance VRo%.The RBS(D1–G)distance versus total organic carbon,free hydrocarbons from thermal extraction(S1),and the remaining hydrocarbon generating potential(S2)indicate that the RBS(D1–G)distance is also related to kerogen type.Data presented here from three methods of maturity determination of shale demonstrate that Raman spectroscopy is a quick and valid approach to thermal maturity assessment.

Prediction of early-stage hepatocellular carcinoma using Onco Scan chromosomal copy number aberration data

AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient prognosis.METHODS One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded(FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosinstained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix Onco Scan platform to assess CNAs and loss of heterozygosity(LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage Ⅰ/Ⅱ HCC were enrolled to analyze gene expression and to correlate findings with the Onco Scan data.RESULTS Copy number amplifications occurred at chromosomes 1 q21.1-q44 and 8 q12.3-24.3 and deletions were found at 4 q13.1-q35.2, 8 p 23.2-21.1, 16 q23.3-24.3, and 17 p13.3-12, while LOH commonly occurred at 1 p32.3, 3 p21.31, 8 p23.2-21.1, 16 q22.1-24.3, and 17 p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change(≥ 60%) was an independent factor for worse prognosis in early-stage HCC(P = 0.031). Among the 875 genes in the Onco Scan Gene Chip, six were independent predictors of worse disease-free survival, of which three were amplified(MYC, ELAC2, and SYK) and three were deleted(GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs(P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes.CONCLUSION Patients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.

Genetic variations in the SMAD4 gene and gastric cancer susceptibility

AIM:To explore the association between mothers against decapentaplegic homolog 4 (SMAD4) gene polymorphisms and gastric cancer risk.METHODS:Five tagging single nucleotide polymor-phisms (tSNPs) in the SMAD4 gene were selected and genotyped in 322 gastric cancer cases and 351 cancerfree controls in a Chinese population by using the polymerase chain reactionrestriction fragment length polymorphism method.Immunohistochemistry was used to examine SMAD4 protein expression in 10 normal gastric tissues adjacent to tumors.RESULTS:In the single-locus analysis,two significantly decreased risk polymorphisms for gastric cancer were observed:the SNP3 rs17663887 TC genotype (adjusted odds ratio=0.38,95% confidence interval:0.21-0.71),compared with the wild-type TT genotype and the SNP5 rs12456284 GG genotype (0.31,0.16-0.60),and with the wild-type AA genotype.In the combined analyses of these two tSNPs,the combined genotypes with 2-3 protective alleles (SNP3 C and SNP5 G allele) had a significantly decreased risk of gastric cancer (0.28,0.16-0.49) than those with 0-1 protective allele.Furthermore,individuals with 0-1 protective allele had significantly decreased SMAD4 protein expression levels in the norma tissues adjacent to tumors than those with 2-3 protective alleles (P=0.025).CONCLUSION:These results suggest that genetic variants in the SMAD4 gene play a protective role in gastric cancer in a Chinese population.

Identification of speckle-type POZ protein somatic mutations in African American prostate cancer

The speckle-type POZ protein （SPOP） is a tumor suppressor in prostate cancer （PCa）. SPOP somatic mutations have been reported in up to 15% of PCa of those of European descent. However, the genetic roles of SPOP in African American （AA）-PCa are currently unknown. We sequenced the SPOP gene to identify somatic mutations in 49 AA prostate tumors and identified three missense mutations （p.Y87C, p.F102S, and p.G111E） in five AA prostate tumors （10%） and one synonymous variant （p.11061） in one tumor. Intriguingly, all of mutations and variants clustered in exon six, and all of the mutations altered conserved amino acids. Moreover, two mutations （p.F102S and p.G111E） have only been identified in AA-PCa to date. Quantitative real-time polymerase chain reaction analysis showed a lower level of SPOP expression in tumors carrying SPOP mutations than their matched normal prostate tissues. In addition, SPOP mutations and novel variants were detected in 5 of 27 aggressive PCa and one of 22 less aggressive PCa （P 〈 0.05）. Further studies with increased sample size are needed to validate the clinicopathological significance of these SPOP mutations in AA-PCa.

An optimized procedure for plant recovery from somatic embryos significantly facilitates the genetic improvement of Vitis

Plant regeneration from grapevine(Vitis spp.)via somatic embryogenesis typically is poor.Recovery of plants from Vitis rotundifolia Michx.(muscadine grape)is particularly problematic due to extremely low efficiency,including extended culture durations required for embryo–plant conversion.Poor plant recovery is an obstacle to the selection of improved genetically modified lines.Somatic embryos(SEs)of V.rotundifolia cultivar Delicious(Del-HS)and Vitis vinifera L cultivar Thompson Seedless(TS)were used to identify culture media and conditions that promoted embryo differentiation and plant conversion;this resulted in a two-step culture system.In comparative culture experiments,C2D medium containing 6%sucrose was the most effective,among four distinct formulae tested,for inducing precocious SE germination and cell differentiation.This medium,further supplemented with 4 mM 6-benzylaminopurine(C2D4B),was subsequently determined to enhance post-germinative growth of SE.MS medium supplemented with 0.5 mM 1-naphthaleneacetic acid(MSN)was then utilized to stimulate root and shoot growth of germinated SE.An average of 35%and 80%‘Del-HS’and‘TS’SE,respectively,developed into plants.All plants developed robust root and shoot systems and exhibited excellent survival following transfer to soil.Over 150 plants of‘Del-HS’were regenerated and established within 2.5 months,which is a dramatic reduction from the 6-to 12-month time period previously required.Similarly,88‘TS’plant lines were obtained within the same time period.Subsequently,seven out of eight Vitis cultivars exhibited significantly increased plant conversion percentages,demonstrating broad application of the two-step culture system to produce the large numbers of independent plant lines needed for selection of desired traits.

Optimal concentration of mesenchymal stem cells for fracture healing in a rat model with long bone fracture

BACKGROUND There is still no consensus on which concentration of mesenchymal stem cells(MSCs)to use for promoting fracture healing in a rat model of long bone fracture.AIM To assess the optimal concentration of MSCs for promoting fracture healing in a rat model.METHODS Wistar rats were divided into four groups according to MSC concentrations:Normal saline(C),2.5×10^(6)(L),5.0×10^(6)(M),and 10.0×10^(6)(H)groups.The MSCs were injected directly into the fracture site.The rats were sacrificed at 2 and 6 wk post-fracture.New bone formation[bone volume(BV)and percentage BV(PBV)]was evaluated using micro-computed tomography(CT).Histological analysis was performed to evaluate fracture healing score.The protein expression of factors related to MSC migration[stromal cell-derived factor 1(SDF-1),transforming growth factor-beta 1(TGF-β1)]and angiogenesis[vascular endothelial growth factor(VEGF)]was evaluated using western blot analysis.The expression of cytokines associated with osteogenesis[bone morphogenetic protein-2(BMP-2),TGF-β1 and VEGF]was evaluated using real-time polymerase chain reaction.RESULTS Micro-CT showed that BV and PBV was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture(P=0.040,P=0.009;P=0.004,P=0.001,respectively).Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture(P=0.018,P=0.010;P=0.032,P=0.050,respectively).At 2 wk post fracture,SDF-1,TGF-β1 and VEGF expression were significantly higher in groups M and H than in group L(P=0.031,P=0.014;P<0.001,P<0.001;P=0.025,P<0.001,respectively).BMP-2 and VEGF expression were significantly higher in groups M and H than in group C at 6 wk postfracture(P=0.037,P=0.038;P=0.021,P=0.010).Compared to group L,TGF-β1 expression was significantly higher in groups H(P=0.016).There were no significant differences in expression levels of chemokines related to MSC migration,angiogenesis and cytokines associated with osteogenesis between M and H groups at 2 and 6 wk post-fracture.CONCLUSION The administration of at least 5.0×10^(6)MSCs was optimal to promote fracture healing in a rat model of long bone fractures.

Insulin exerts direct, IGF-1 independent actions in growth plate chondrocytes

Insufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of insulin signaling in the growth plate. Insulin treatment of embryonic metatarsal bones from wild-type mice increased chondrocyte proliferation. Mice lacking insulin receptor （IR） selectively in chondrocytes （CartIR-/-） had no discernable differences in total femoral length compared to control littermates. However, CartIR-/- mice exhibited an increase in chondrocyte numbers in the growth plate than that of the controls. Chondrocytes lacking IR had elevated insulin-like growth factor （IGF）-IR mRNA and protein levels. Subsequently, IGF-1 induced phosphorylafion of Akt and ERK was enhanced, while this action was eliminated when the cells were treated with IGF-1R inhibitor Picropodophyllin. Deletion of the IR impaired chondrogenic differentiation, and the effect could not be restored by treatment of insulin, but partially rescued by IGF-1 treatment. Intriguingly, the size of hypertrophic chondrocytes was smaller in CartIR-/- mice when compared with that of the control littermates, which was associated with upregnlation of tuberous sclerosis complex 2 （TSC2）. These results suggest that deletion of the IR in chondrocytes sensitizes IGF-1R signaling and action, IR and IGF-1R coordinate to regulate the proliferation, differentiation and hypertrophy of growth plate chondrocytes.

复发性自然流产妇女血中膜联蛋白A5水平降低及膜联蛋白A5抗凝活性抵抗

Objective: We investigated whether levels of annexin A5,evidence for resistance to annexin A5 activity, and levels antiannexin A5 antibodies might be altered in women with a history of recurrent spontaneous pregnancy losses. Study design: These annexin A5 parameters were assayed in 70 nonpregnant women with a history of ≥3 recurrent spontaneous pregnancy losses (cases) and 50 women without adverse pregnancy history (control subjects). Results: Cases had significantly lower plasma annexin A5 levels than control subjects (median, 4.7 ng/mL [range, 0.3-40.4 ng/mL] vs 6.7 ng/mL [range, 0.7-56.0]; P = .01), significantly reduced anticoagulant ratios (188%[range, 119%-279%] vs 238%[range, 159%-286%]; P < .0001), and reduced binding of annexin A5 to phospholipid (6.3 ng/aliquot phospholipid [range, 1.5-16.4 ng/aliquot phospholipid] vs 9.7 ng/aliquot phospholipid (range, 3.5-17.0 ng/aliquot phospholipid]; P = .0002). There were no significant differences in anti-annexin A5 antibody levels. Conclusion: Reduction of annexin A5 and interference with its anticoagulant and binding activities are associated significantly with a history of recurrent spontaneous pregnancy losses. These data support the concept of a significant role for annexin A5 in the maintenance of pregnancy.

Heme status affects human hepatic messenger RNA and microRNA expression

AIM:To assess effects of heme on messenger RNA(mRNA) and microRNA(miRNA) profiles of liver cells derived from humans.METHODS:We exposed human hepatoma cell line Huh-7 cells to excess iron protoporphyrin(heme)(10 μmol/L) or induced heme deficiency by addition of 4,6-dioxoheptanoic acid(500 μmol/L),a potent inhibitor of aminolevulinic acid dehydratase,for 6 h or 24 h.We harvested total RNA from the cells and performed both mRNA and miRNA array analyses,with use of Affymetrix chips,reagents,and instruments(human genome U133 plus 2.0 and miRNA 2.0 arrays).We assessed changes and their significance and interrelationships with Target Scan,Pathway Studios,and Ingenuity software.RESULTS:Changes in mRNA levels were most numerous and striking at 6 h after heme treatment but were similar and still numerous at 24 h.After 6 h of heme exposure,the increase in heme oxygenase 1 gene expression was 60-fold by mRNA and 88-fold by quantitative reverse transcription-polymerase chain reaction.We found striking changes,especially up-regulation by heme of nuclear erythroid-2 related factor-mediated oxidative stress responses,protein ubiquitination,glucocorticoid signaling,P53 signaling,and changes in RNAs that regulate intermediary metabolism.Fewer mRNAs were down-regulated by heme,and the fold decreases were less exuberant than were the increases.Notable decreases after 24 h of heme exposure were patatin-like phospholipase domain-containing protein 3(-6.5-fold),neuronal PAS domain protein 2(-1.93-fold),and protoporphyrinogen oxidase(-1.7-fold).CONCLUSION:Heme excess exhibits several toxic effects on liver and kidney,which deserve study in humans and in animal models of the human porphyrias or other disorders.

Elderly patients are doing better with PCI during ST segment elevation myocardial infarction

Elderly patients constitute a growing part of the ST segment elevation myocardial infarction (STEMI) population. By nature of their co-morbid conditions and other factors, elderly patients have a higher absolute rate of mortality and risk of complications from STEMI.

Rapid progression of atherosclerosis in a patient with acute coronary syndrome and ANCA-associated vasculitis:split or confluence?

A59-year-old female patient was admitted to our hospital on 9 March 2021,due to recurrent chest pain.She underwent percutaneous coronary intervention,with a focus on the proximal segment of the left anterior descending(LAD)artery,six months prior to admission.The patient had a long-term history of hyperlipidaemia and obstructive sleep apnoea syndrome(OSAS).She also had rheumatoid arthritis and ANCA-associated vasculitis that lasted for more than 10 years and a 9-year history of concomitant hypertension.She was on long-term oral leflunomide and intermittent oral prednisone.The patient underwent a computed tomography angiogram(CTA)six years ago(2015),which showed minor atherosclerotic plaque build-up in the LAD artery and the right coronary artery(RCA)(Figure 1).