硫利达嗪通过调控miR-3174表达对肝癌Huh-7细胞增殖、迁移和侵袭的影响

目的 探讨硫利达嗪对肝癌Huh-7细胞生物行为的影响和机制。方法肝癌Huh-7细胞分为对照组及硫利达嗪低、中、高浓度组。转染miR-3174模拟物及其阴性对照、miR-3174抑制物及其阴性对照至Huh-7细胞,并用硫利达嗪处理miR-3174模拟物。CCK-8法和平板克隆实验检测硫利达嗪对Huh-7细胞增殖的影响;划痕愈合实验和Transwell实验检测硫利达嗪对Huh-7细胞迁移和侵袭的影响;实时荧光定量PCR检测硫利达嗪对Huh-7细胞中miR-3174表达的影响。蛋白质印迹法检测E-钙黏蛋白(E-cadherin)和N-钙黏蛋白(N-cadherin)的表达。并通过上述方法检测干扰miR-3174表达或上调miR-3174联合硫利达嗪对Huh-7细胞生物行为的影响。结果硫利达嗪处理和干扰miR-3174表达后Huh-7细胞中miR-3174表达降低,增殖、迁移和侵袭能力及N-cadherin蛋白表达降低,E-cadherin蛋白表达升高(P <0.05)。上调miR-3174表达可减弱硫利达嗪处理对Huh-7细胞恶性生物学行为的影响。结论 硫利达嗪通过下调miR-3174表达可抑制肝癌Huh-7细胞增殖、迁移和侵袭。

疏肝降脂汤联合门冬氨酸-鸟氨酸治疗病毒性肝炎后脂肪肝的临床效果

目的探讨中药疏肝降脂汤联合门冬氨酸-鸟氨酸(LOLA)治疗病毒性肝炎后脂肪肝的临床疗效及应用价值。方法纳入2018年10月至2020年10月在河北省胸科医院诊治的病毒性肝炎后脂肪肝患者为研究对象,随机分为对照组和试验组。对照组给予LOLA治疗,试验组在对照组治疗的基础上给予疏肝降脂汤治疗,观察比较两组治疗前后肝功能、血脂及免疫功能变化情况。结果研究共纳入患者144例,对照组和试验组各72例。治疗后试验组总有效率为93.06%,显著高于对照组的79.17%(P<0.05)。治疗后,两组血清中丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素、直接胆红素、谷氨酰转肽酶、总胆固醇、低密度脂蛋白胆固醇、甘油三酯显著降低(P<0.05),且试验组低于对照组(P<0.05)。两组高密度脂蛋白胆固醇值与CD4+T淋巴细胞比例高于治疗前(P<0.05),试验组高于对照组(P<0.05),但CD8+T淋巴细胞比例变化差异无统计学意义(P>0.05)。试验组脂肪肝超声分级优于对照组(P<0.05)。结论疏肝降脂汤联合门冬氨酸-鸟氨酸可改善病毒性肝炎后脂肪肝患者的免疫功能,提高患者肝功能,平衡血脂水平,持续改善患者的预后。

Value of combining the serum D-lactate, diamine oxidase, and endotoxin levels to predict gut-derived infections in cancer patients

Objective:This is a retrospective observational cohort study.The objective of this retrospective observational cohort study was to evaluate the value of the combined serum D-lactic acid,diamine oxidase(DAO),and endotoxin levels to predict intestinal barrier impairment and gut-derived infection(GDI)in cancer patients.Methods:Cancer patients receiving chemotherapy or palliative care treatment at our hospital were enrolled in the study.The serum concentrations of DAO,D-lactic acid,and endotoxin were determined using the intestinal barrier function biochemical index analysis system.The patients'infection information came from the hospital's Medicom Prescription Automatic Screening System and themedical records.Three hundred fifty-three cancer patients were included in the study(53.8%female,73.7%cancer stage IV,27.8%had bowel obstruction).Results:The total incidence of GDI was 33.4%(118/353).The median length of hospital stay was 16 days for patients with GDI,compared with 7 days for patients without GDI(P<0.001).The media hospitalization costs were¥27,362.35 for patients with GDI compared with¥11,614.08 for patients without GDI(P<0.001).The serum concentrations of DAO,D-lactic acid,and endotoxin were significantly higher in patients with GDI.As malignant bowel obstruction(MBO)worsened,the concentrations of DAO,D-lactic acid,and endotoxin increased.Multivariate logistic regression models revealed that the DAO,endotoxin,IL-6,and C-reactive protein levels were significantly associated with an increased risk of GDI.In addition,we also found a fivefold increased risk of infection in patients withMBO compared with those without bowel obstruction(OR=6.210,P<0.001).All of the areas under the receiver operating characteristic curve(AUCs)for DAO,D-lactate,and endotoxin to predict GDI were<0.7(AUC=0.648,P<0.001;AUC=0.624,P<0.01;AUC=0.620,P<0.01,respectively).However,when the parameters were combined(DAO+D-lactate+endotoxin),the predictive power increased significantly(AUC=0.797,P<0.001).Moreover,combining these intestinal barrier indicators and the presence of MBO had better power to predict GDI than either alone(AUC=0.837,P<0.001).Conclusions:Combining the serum DAO,D-lactic acid,and endotoxin levels was a better predictor of GDI than any of the indicators alone,and combining these with the diagnosis of MBO could further improve the efficacy for predicting GDI.

来曲唑联合高脂膳食诱导PCOS-IR大鼠模型复制时间及其内分泌、代谢改变的实验研究

目的研究多囊卵巢综合征胰岛素抵抗(PCOS-IR)大鼠理想模型复制时间及其内分泌、代谢等病理改变。方法对照组大鼠予普通饲料,每日灌胃羧甲基纤维素钠溶液;模型组大鼠予高脂饲料,每日灌胃来曲唑加羧甲基纤维素钠溶液。根据喂养时间,每组在第21、24、27及30天处死6只。观察两组大鼠的体重、卵巢体积和组织学变化、内分泌与代谢指标。检测大鼠空腹血糖(FBG),ELISA法检测大鼠性激素水平、甘油三酯(TG)及空腹胰岛素(FINS);计算卵巢指数、促卵泡激素(FSH)/黄体生成素(LH)比值及胰岛素抵抗指数(HOMA-IR)等。结果模型组各时间点大鼠体重均高于对照组(P<0.05),其中第27和30天大鼠体重及Lee’s指数均高于第21天(P<0.05)。肉眼可见模型组大鼠卵巢体积增大(P<0.05),卵巢表面可见较多密集的透明囊状扩张卵泡,镜下卵巢呈多囊样改变;模型组第30天大鼠的卵巢体积大于第21天(P<0.05)。模型组各时间点大鼠血清TG、FSH/LH比值、T水平较对照组升高(P<0.05);模型组第27和30天大鼠血清FINS及HOMAIR较同时间点对照组升高(P<0.05)。结论来曲唑联合高脂膳食连续喂养27 d可成功复制符合PCOS-IR病理特征及内分泌、代谢紊乱的大鼠模型。

Trends in research related to high myopia from 2010 to 2019:a bibliometric and knowledge mapping analysis

AIM:To evaluate the global trends in and explore hotspots of high myopia(HM)research.METHODS:This bibliometric analysis was used to reveal the publication trends in HM research field based on the Web of Science Core Collection(WoSCC).VOSviewer version 1.6.13 software was used to analyze the data and construct a knowledge map including the yearly publication number,journals,countries,international collaborations,authors,research hotspots,and intellectual base in HM.RESULTS:The search engine found 3544 peer-reviewed publications on HM between 2010 and 2019,and the yearly research output substantially elevated over the past decade.China is the top publishing country,and Sun Yatsen University was the most active academic institution.Jonas JB is the top publishing scientist,and Investigative Ophthalmology and Visual Science(IOVS)was the most productive journal.The highest cited references mainly focused on epidemiology and management.The keywords formed 6 clusters:1)refractive surgery;2)etiology and clinical characteristics;3)the mechanism of eye growth;4)management for myopic maculopathy;5)vitrectomy surgical treatment;6)myopia-associated glaucoma-like optic neuropathy.CONCLUSION:The evaluation of development trends based on the data extracted from WoSCC can provide valuable information and guidance for ophthalmologists and public health researchers to improve management procedures in HM field.

Optimization of axial symmetrical FGM under the transient-state temperate field

A numerical procedure for analyzing the temperature distribution in a hollow axisymmetric cylinder, made of functionally gradient material （FGM）, was investigated. Based on the thermal elasticity theory and the arbitrary difference precise integration （ADPI） method, temperature distribution through the FGM cylinder in the ring section under a transient-state temperature field was developed and presented. A genetic algorithm （GA） was applied to the thermal stress optimal design of an FGM hollow cylinder, and as a result, the minimum thermal stress distribution in the FGM cylinder was obtained. A corresponding numerical procedure regarding to a ceramic-metal FGM cylinder was perforrned. and the comnutational results were discussed.

Influence of genetic polymorphisms in drug metabolism enzymes and transporters on pharmacokinetics of different fluvastatin formulations

OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release(ER) 80 mg tablet and an immediate-release(IR) 40 mg capsule in terms of drug metabolism enzyme and transporter ge.netic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study,ef.fects of BCRP,SLCO1B1,MDR1,CYP2C9,and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using highperformance liquid chromatography-tandem mass spectrometry.RESULTS The SLCO1 B1 T521 C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1 B1 T521 C genotype correlated with the AUC_(0-24) of repeat doses(P=0.01).The CYP2C9*3 genotype correlated with the AUC_(0-24) after the first dose IR40 mg capsule(P<0.05);however,the difference between CYP2C9*1/*1 and CYP2 C9*1/*3 was not statistically significant after repeated doses.CONCLUSION The effect of SLCO1B1T521C on fluvas.tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.

Comparison of involved-field intensity-modulated radiotherapy combined with S-1 vs radiotherapy alone for elderly patients with esophageal cancer

BACKGROUND It is estimated that about 30%of esophageal cancer(EC)patients are over 70 years old.Therefore,there is less evidence on the diagnosis and management of elderly EC patients.It is important to explore how elderly EC patients benefit from radical radiochemotherapy regimens,including the target area of radiotherapy(RT),radiation dose and fraction,and choice of chemotherapy drugs.AIM To compare the efficacy of involved-field intensity-modulated RT(IF-IMRT)combined with S-1 vs RT alone in the treatment of elderly EC patients in terms of safety,short-term response,and survival.METHODS Thirty-four EC patients aged>70 years were prospectively enrolled between December 2017 and December 2019.Based on the random number table,they were divided into an IF-IMRT+S-1 group and an IF-IMRT alone group,with 17 patients in each group.All patients were treated with IF-IMRT at a dose of 50.4-56 Gy in 28-30 fractions(1.8-2 Gy/fraction,5 fractions/wk).Oral S-1 was administered concomitantly in the IF-IMRT+S-1 group for 14 consecutive days,and a second cycle was started 7 d after drug withdrawal.After RT,4 cycles of S-1 treatment were offered as the consolidation chemotherapy.The safety,short-term response,and survival were observed after the treatment.RESULTS As of April 2022,these 34 patients had been followed up for 15.2-32.5 mo,with a median follow-up period of 24.5 mo.Complete efficacy indicators were obtained from all the patients.The objective response rate was 88.2%vs 76.5%,respectively,in the IF-IMRT+S-1 group and the RT alone group,where as the disease control rate was 100%vs 82.4%,respectively.The incidence of adverse events including grade 1-2 fatigue,granulocytopenia,thrombocytopenia,anemia,radiation esophagitis,radiation-induced skin injury,and radiation-induced lung injury was not significantly different between these two groups,so was the incidence of the grade 3 radiation esophagitis(0%vs 5.7%).The rate of progressive disease(PD)was 52.9%(n=9)in the IF-IMRT+S-1 group and 64.7%(n=11)in the RT alone group.The median progression-free survival(PFS)was 23.4 mo vs 16.3 mo,and the 2-year PFS rate was 42%vs 41.2%.The median overall survival(OS)was 27.0 mo vs 23.0 mo,and the 2-year OS rate was 58.8%vs 47.1%.Multivariate analysis showed that age was a significant prognostic factor(P=0.0019);patients aged<75 years had a significant survival advantage over patients aged≥75 years.The locations of EC also affected the prognosis.In the IFIMRT+S-1 group,the number of chemotherapy cycles was a significant prognostic factor(P=0.0125),and the risk of PD was significantly lower in EC patients who had received 6 cycles of chemotherapy than those who had received 2-5 cycles of chemotherapy.CONCLUSION Compared with IF-IMRT alone,IF-IMRT+S-1 shows the benefits of preventing PD and prolonging survival without increasing adverse reactions.Therefore,this concurrent radiochemotherapy deserves clinical application.

A diagnosis model of parental care:How parents optimize their provisioning strategy in brood reduction?

Altricial birds often display biased preferences in providing parental care for their dependent offspring,especially during food shortages.During this process,such inflexible rules may result in provisioning errors.To demonstrate how parents optimize their provisioning strategies,we proposed a“diagnosis model”of parental care to posit that parents will undergo a diagnosis procedure to test whether selecting against some particular offspring based on phenotype is an optimal strategy.We tested this model in an asynchronous hatching bird,the Azure-winged Magpie Cyanopica cyanus,based on 10 years of data about demography and parental provisioning behaviors.Given their higher daily survival rates,core offspring(those hatched on the first day)merits an investment priority compared with their marginal brood mates(those hatched on later days).However,a marginal offspring also merited a priority if it displayed greater weight gain than the expected value at the early post-hatching days.Parents could detect such a marginal offspring via a diagnosis strategy,in which they provisioned the brood at the diagnosis stage by delivering food to every nestling that begged,then biased food toward high-value nestlings at the subsequent decision stage by making a negative response to the begging of low-value nestlings.In this provisioning strategy,the growth performance of a nestling became a more reliable indicator of its investment value than its hatching order or competitive ability.Our findings provide evidence for this“diagnosis model of parental care”wherein parents use a diagnosis method to optimize their provisioning strategy in brood reduction.

Fitness consequences of divorce in the azure-winged magpie depends on the breeding experience of a new mate

Sexual conflict in producing and raising offspring is a critical issue in evolutionary ecology research.Individual experience affects their breeding performance,as measured by such traits of provisioning of offspring and engagement in extra-pair copulations,and may cause an imbalance in sexual conflict.Thus,divorce is hypothesized to occur within aged social pairs,irrespective of current reproductive success.This concept was explored in the azure-winged magpie Cyanopica cyanus by investigating the divorce of a social pair and its relationship to their changes in breeding performance with prior experience.Females engaging in extra-pair copulation may intensify sexual conflicts and may be the main reason for divorce.Once divorced,females repairing with an inexperienced male realized higher reproductive success than that repairing with an experienced male;males repairing with an experienced female realized higher reproductive success than that repairing with an inexperienced female.This finding indicates that the fitness consequence of divorce depends on the breeding experience of new mates.Divorced females can obtain more extra-pair copulations,whereas divorced males cannot,when they repair with inexperienced breeders.Divorced females provisioned a brood at lower rates than inexperienced females whereas divorced males had no such difference.It appears that divorced females can obtain an advantage in sexual conflicts with inexperienced mates in future reproduction.Consequently,females are probably more active than males in divorcing their aged mates so as to select an inexperienced male as a new mate.Azure-winged magpies thus provide novel insights into the implicaticns of sexual conflict in birds.

In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks

Short DNA represents an important class of bioma-cromolecules that arewidely applied in gene therapy,editing,and modulation.However,the development of simple and reliable methods for their intracellular delivery remains a challenge.Herein,we describe that seven water-soluble,homogeneous supramole-cular organic frameworks(SOFs)with a well-defined pore size and high stability in water that can accom-plish in situ inclusion of single-stranded(ss)and double-stranded(ds)DNA(21,23,and 58 nt)and effective intracellular delivery(including two non-cancerous and six cancerous cell lines).

High Ductility and Toughness of a Micro-duplex Medium-Mn Steel in a Large Temperature Range from—196 ℃ to 200 ℃

A medium-Mn steel （0.2C5Mn） was processed by intercritical annealing at different temperatures （625 ℃ and 650 ℃ ）. An ultrafine-grained micro-duplex structure consisting of alternating austenite and ferrite laths was de- veloped by austenite reverse transformation （ART） during intercritical annealing after forging and hot rolling. Ultra- high ductility with a total elongation higher than 30% was achieved in the temperature range from -196 ℃ to 200 ℃, and high impact toughness no less than 200 J at -40 ℃ was obtained. Based on the analysis of microstructure and mechanical properties, it was found that the enhanced ductility was determined by the phase transformation effect of austenite （TRIP effect）, while the delayed ductile to brittle transition was controlled by austenite stability.

Parental dependence on the nest's spatial cues in offspring recognition decreases with nestling growth in the azure-winged magpie

In altricial birds,to address which cues are used by parents to recognize their offspring,and when they switch between cues during reproduction,it has not been well determined.In this study,we address this questi on in a Tibetan populatio n of the azure-winged magpie Cyanopica cyan us f by examining the dependence of parents on a nest's spatial position in offspring recognition.During the egg and nestling phases,azure-winged magpie nests were translocated to new positions across various distances from their original site,and parental responses to the translocated nests were investigated.Our findings show that a nesfs spatial position is not connected with the survival of its young,but might be used as a cue in parental offspring recognition.When nests are translocated to a new position within a certain distance,parents could recognize their nests and returned to resume their parenting behaviors.Parental dependence on the nest's spatial position in offspring recognition is higher during the egg phase than during the nestling phase,and it decreases with the growth of nestlings.After nestlings reach a certain age,the nest's spatial position was no longer used by pare nts as the single cue for offspring recog nition.These findings suggest that azure-winged magpies switch their cues in offspring recog nition during the differe nt stages of reproduction.After parent-offspring communication has been established,the offspring's phenotypic traits may become a more reliable cue than the nests spatial position in offspring recognition.

Fecal consumption by adults of altricial birds in relation to the temporal change in nestling gut microbiota

Nest sanitation behavior of altricial birds has been selected to reduce the exposure of young to pathogens,parasites,or predators,and thus to maintain the health and safety of nestlings(Guigueno and Sealy 2012).During the process of nest sanitation,caregivers either carry away the fecal sacs of nestlings or directly eat them.Given that adults endure higher risk of being infected by pathogens during fecal consumption(Potti et al.2007),it remains a puzzle about why adults consume the nestling feces when they can transport them.Several hypotheses have been proposed to explain the fecal consumption behavior of altricial birds,including the nutrition hypothesis(Gliick 1988),economic hypothesis(Hurd et al.1991),and predation hypothesis(Ibanez-Alamo et al.2013).