BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,an...BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver organs.AIM To develop a model for predicting prognosis after LT in patients with HCC.METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated.The expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer.The best cutoff value of biomarkers was determined using the Youden index.Cox regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest method.We evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the nomograms.RESULTS The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after LT.The nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou criteria.The calibration curve analyses indicated a good fit.The survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical practicability.CONCLUSION The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after LT.It can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.展开更多
Objective:To explore the application and effect evaluation of the integrated“5A and 3+3”management model in ensuring safe medication use for chemotherapy patients.Methods:A total of 100 intravenous chemotherapy pati...Objective:To explore the application and effect evaluation of the integrated“5A and 3+3”management model in ensuring safe medication use for chemotherapy patients.Methods:A total of 100 intravenous chemotherapy patients admitted to the oncology department of Shaanxi Provincial People’s Hospital were randomly divided into two groups using a random number list method.Both groups received conventional nursing management during chemotherapy,while the study group additionally received the integrated“5A and 3+3”safety management model.The nursing intervention effects between the two groups were compared.Results:After the intervention,the study group showed higher levels of self-management ability,compliance,and nursing satisfaction compared to the control group.The overall incidence of adverse events during hospitalization was lower in the study group,with statistically significant differences(P<0.05).The knowledge scores of medical staff in the study group,related to the prevention and treatment of chemotherapy drug side effects,daily symptom management,and daily life management,were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion:Implementing the integrated“5A and 3+3”model in the safe medication management of intravenous chemotherapy patients can effectively enhance patients’self-management abilities and compliance,improve medical staff’s ability to safely administer chemotherapy drugs,reduce adverse events caused by chemotherapy,and increase patient satisfaction.展开更多
Polyploid plants typically display advantages on some agronomically important traits over their diploid counterparts.Extensive studies have shown genetic,transcriptomic,and epigenetic dynamics upon polyploidization in...Polyploid plants typically display advantages on some agronomically important traits over their diploid counterparts.Extensive studies have shown genetic,transcriptomic,and epigenetic dynamics upon polyploidization in multiple plant species.However,few studies have unveiled those alternations imposed only by ploidy level,without any interference from heterozygosity.Cultivated potato is highly heterozygous.Thus,in this study,we developed two homozygous autotetraploid lines and one homozygous diploid line in parallel from a homozygous diploid potato.We confirmed their ploidy levels using chloroplast counting and karyotyping.Oligo-FISH and genome re-sequencing validated that these potato lines are nearly homozygous.We investigated variations in phenotypes,transcription,and histone modifications between two ploidies.Both autotetraploid lines produced larger but fewer tubers than the diploid line.Interestingly,each autotetraploid line displayed ploidy-related differential expression for various genes.We also discovered a genomewide enrichment of H3K27ac in genic regions upon whole-genome doubling(WGD).However,such enrichment was not associated with the differential gene expression between two ploidies.The tetraploid lines may exhibit better resistance to cold-induced sweetening(CIS)than the diploid line in tubers,potentially regulated through the expression of CIS-related key genes,which seems to be associated with the levels of H3K4me3 in cold-stored tubers.These findings will help to understand the impacts of autotetraploidization on dynamics of phenotypes,transcription,and histone modifications,as well as on CIS-related genes in response to cold storage.展开更多
Diabetes is a pervasive and serious global health issue.According to the International Diabetes Federation report,463 million adults worldwide were living with diabetes in 2019,and this number is projected to reach 70...Diabetes is a pervasive and serious global health issue.According to the International Diabetes Federation report,463 million adults worldwide were living with diabetes in 2019,and this number is projected to reach 700 million in 2045^([1]).展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related death worldwide.Serum biomarkers play an important role in the early diagnosis and prognosis of HCC.Because a certain percentage of ...BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related death worldwide.Serum biomarkers play an important role in the early diagnosis and prognosis of HCC.Because a certain percentage of HCC patients are negative for alpha-fetoprotein(AFP),the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC.AIM To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers.METHODS A total of 180 HCC patients were enrolled in this study.The expression levels of GP73,des-γ-carboxyprothrombin(DCP),CK18-M65,and CK18-M30 were detected by a fully automated chemiluminescence analyser.The variables were selected by logistic regression analysis.Several models were constructed using stepwise backward logistic regression.The performance of the models was compared using the C statistic,integrated discrimination improvement,net reclassification improvement,and calibration curves.The clinical utility of the nomogram was assessed using decision curve analysis(DCA).RESULTS The results showed that the expression levels of GP73,DCP,CK18-M65,and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls(P<0.001).Multivariate logistic regression analysis revealed that GP73,DCP,and CK18-M65 were independent factors for diagnosing AFP-negative HCC.By comparing the diagnostic performance of multiple models,we included GP73 and CK18-M65 as the model variables,and the model had good discrimination ability(area under the curve=0.946)and good goodness of fit.The DCA curves indicated the good clinical utility of the nomogram.CONCLUSION Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC.The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.展开更多
Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the...Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the ameliorative effects of salidroside on homocysteine (Hcy)-induced cell senescence in human umbilical vein endothelial cells (HUVECs) that were mediated via inhibition of Krüppel-like factor 4 (KLF4). An endothelial cell senescence model was induced by Hcy. The cell viability, activities of telomerase and lactate dehydrogenase (LDH), and the level of reactive oxygen species were determined using commercial kits. The expression levels of KLF4, p53 and p21 were determined via western blot analysis, whereas the mRNA expression levels of KLF4 were detected by reverse transcription-quantitative PCR. Small interfering RNA-mediated knockdown of KLF4 was found to reverse Hcy-induced cell senescence. Hcy treatment led to an accelerated cell senescence, as evidenced by decreases in both cell viability and telomerase activity, whereas increases were noted in the leakage of LDH and the level of reactive oxygen species, in addition to an up-regulation of the protein levels of p53 and p21, and up-regulation of KLF4 at both the mRNA and protein level. Treatment with salidroside ameliorated Hcy-induced cell senescence in a dose-dependent manner. Taken together, these results suggested that Hcy may induce cell senescence through upregulation of KLF4, and this may be reversed by treatment with salidroside. Therefore, salidroside was shown to inhibit Hcy-induced cell senescence through KLF4 inhibition.展开更多
In this paper, to solve the problems of low water absorption and weak pressure bearing capacity of current plugging materials, acrylic acid (AA), acrylamide (AM), and sodium allyl sulfonate (SAS) are used as monomers,...In this paper, to solve the problems of low water absorption and weak pressure bearing capacity of current plugging materials, acrylic acid (AA), acrylamide (AM), and sodium allyl sulfonate (SAS) are used as monomers, and soluble starch is used as grafting. Material, the use of free radical aqueous solution method to synthesize the plugging agent SWL-1 with good water absorption and strong salt resistance. The monomer ratio is set as n (AA):n (AM):n (SAS) = 5:2:1, the experimental synthesis temperature is 70°C, and the orthogonal experiment is used to determine the experimental synthesis conditions as AA neutralization degree 80%, The amount of initiator is 0.60%, the amount of crosslinking agent is 0.50%, the ratio of monomer to starch is 7:1, and the amount of calcium carbonate is 13%. The comprehensive evaluation of the performance of the plugging agent SWL-1 shows that the water absorption performance at 60°C is the best 268.78 g/g, and the water absorption performance in 8% NaCl, 0.9% CaCl<sub>2</sub> and composite brine is 21.5 g/g, 12.5 g/g and 24.9 g/g, indicating good resistance to sodium and calcium, the water retention rate is still higher than 30% after 15 days at 160°C. The sand bed plugging test found that the maximum pressure of SWL-1 was 7 MPa, and the crack plugging test found that when the crack width was 1 mm, 2 mm, and 3 mm, the maximum compressive strength of SWL-1 was 10 MPa. The acid solubility test showed that the maximum pressure was 10 MPa. The highest rate is 86.38%.展开更多
Roadways excavated through a coal seam can exert an adverse effect on roadway stability. To investigate the effects of in-situ stress on roadway stability, numerical models were built and high horizontal stresses at v...Roadways excavated through a coal seam can exert an adverse effect on roadway stability. To investigate the effects of in-situ stress on roadway stability, numerical models were built and high horizontal stresses at varying orientations were applied. The results indicate that stress concentrations, roadway deformation and failure increase in magnitude and extent as the excavation angle with respect to the maximum horizontal stress increases. In addition, the stress adjacent to the coal-rock interface sharply varies in space and evolves with time; coal is much more vulnerable to deformation and failure than rock.The results provide insights into the layout of roadways excavated through a coal seam. Roadways should be designed parallel or at a narrow angle to the maximum horizontal stress. The concentrated stress at the top corner of the face-end should be reduced in advance, and the coal seam should be reinforced immediately after excavation.展开更多
Objective To better understand the pathological causes of bone loss in a space environment, including microgravity, ionizing radiation, and ultradian rhythms.Methods Sprague Dawley (SD) rats were randomly divided in...Objective To better understand the pathological causes of bone loss in a space environment, including microgravity, ionizing radiation, and ultradian rhythms.Methods Sprague Dawley (SD) rats were randomly divided into a baseline group, a control group, a hindlimb suspension group, a radiation group, a ultradian rhythms group and a combined-three-factor group. After four weeks of hindlimb suspension followed by X-ray exposure and/or ultradian rhythms, biomechanical properties, bone mineral density, histological analysis, microstructure parameters, and bone turnover markers were detected to evaluate bone loss in hindlimbs of rats.Results Simulated microgravity or combined-three factors treatment led to a significant decrease in the biomechanical properties of bones, reduction in bone mineral density, and deterioration of trabecular parameters. Ionizing radiation exposure also showed adverse impact while ultradian rhythms had no significant effect on these outcomes. Decrease in the concentration of the turnover markers bone alkaline phosphatase (bALP), osteocalcin (OCN), and tartrate-resistant acid phosphatase-5b (TRAP-Sb) in serum was in line with the changes in trabecular parameters.Conclusion Simulated microgravity is the main contributor of bone loss. Radiation also results in deleterious effects but ultradian rhythms has no significant effect. Combined-three factors treatment do not exacerbate bone loss when compared to simulated microgravity treatment alone.展开更多
Nonhuman primates are closest to humans in terms of lineage, and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans. Therefore, nonhuman primates c...Nonhuman primates are closest to humans in terms of lineage, and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans. Therefore, nonhuman primates could be utilized to simulate the process of ischemic stroke in the human. Few studies, however, have reported the use of endovascular technology to establish a rhesus monkey stroke model. In the present study, seven adult, male, rhesus monkeys were selected and, following anesthesia, a microcatheter was inserted into one side of the middle cerebral artery via the femoral artery to block blood flow, thereby resulting in middle cerebral artery occlusion. After 2 hours, the microcatheter was withdrawn to restore the middle cerebral artery blood flow and to establish ischemia/reperfusion. Results from angiography and magnetic resonance angiography confirmed occlusion and reopening of the middle cerebral artery. Magnetic resonance imaging revealed the existence of ischemic brain lesions, and neurological examination showed sustained functional deficits following surgery. The rhesus monkey middle cerebral artery ischemia/reperfusion models established by microcatheter embolization had the advantage of non-craniotomy invasion and reproducibility. The scope and degree of ischemic damage using this model was controllable. Therefore, this nonhuman primate model is an ideal model for cerebral ischemia and reperfusion.展开更多
Several animal models of migraine have been established, and those based on trigeminovascular system activation are widely accepted. How- ever, most of these models have been established on lower animals, such as rode...Several animal models of migraine have been established, and those based on trigeminovascular system activation are widely accepted. How- ever, most of these models have been established on lower animals, such as rodents, and involve only a single administration of a noxious stimulus. In this study, an inflammatory soup (10 μL), consisting of prostaglandin E2 (0.2 mM), serotonin (2 mM), bradykinin (2 raM) and histamine (2 raM), was injected into the dura mater of conscious rhesus monkeys through an indwelling catheter. The infusion started on day 8 and was repeated every 3 days, for a total of six administrations, to induce neurogenic inflammation. We performed behavioral assessments and measured the expression of the oncogene c-fos, neuronal nitric oxide synthase (nNOS) and calcitonin gene related peptide (CGRP) ill the trigeminal system and in multiple brain regions involved in pain processing by immunohistochemical staining. Compared with monkeys in the control group, three of the four animals in the inflammatory soup group displayed decreased motor behaviors, and two showed increased ipsilateral nose and mouth secretions during the stimulus period. Higher expression levels of c-fos, nNOS and CGRP were found in various brain areas of experimental animals compared with controls, including the trigeminal nucleus caudalis, thalamus, hypothalamus, midbrain, pons and other areas involved in pain perception. These results suggest that repeated inflammatory soup stimulation of the dura activates the trigeminovascular system and produces migraine-like pathological changes and abnormal behaviors in conscious rhesus monkeys.展开更多
Lauraceae includes the genus Phoebe,and the family is linked to the evolution of magnoliids.We sequenced the genome of Phoebe bournei Nanmu.The assembled genome size was 989.19 Mb,with a contig N50 value of 2.05 Mb.A ...Lauraceae includes the genus Phoebe,and the family is linked to the evolution of magnoliids.We sequenced the genome of Phoebe bournei Nanmu.The assembled genome size was 989.19 Mb,with a contig N50 value of 2.05 Mb.A total of 28,198 protein-coding genes were annotated in P.bournei.Whole-genome duplication(WGD)analysis showed that Lauraceae has experienced two WGD events;the older WGD event occurred just before the divergence of Lauraceae and Magnoliales,and the more recent WGD was shared by all lineages of Lauraceae.The phylogenetic tree showed that magnoliids form a sister clade to monocots and eudicots.We also identified 63 MADS-box genes,including AGL12-like genes that may be related to the regulation of P.bournei roots and FIN219-like genes encoding GH3 proteins,which are involved in photomorphogenesis.SAUR50-like genes involved in light signal-mediated pedicel or stem development were also identified.Four ATMYB46-and three PtrEPSP-homologous genes related to lignin biosynthesis were identified.These genes may be associated with the formation of straight trunks in P.bournei.Overall,the P.bournei reference genome provides insight into the origin,evolution,and diversification of Phoebe and other magnoliids.展开更多
Water security is under threat worldwide from climate change. A warming climate would accelerate evaporationand cryosphere melting, leading to reduced water availability and unpredictable water supply. However, thewat...Water security is under threat worldwide from climate change. A warming climate would accelerate evaporationand cryosphere melting, leading to reduced water availability and unpredictable water supply. However, thewater crisis in the Northern Slope of Tianshan Mountains(NSTM) faces dual challenges because water demandsforfast-growing urban areas have put heavy pressure on water resources. The mountain-oasis-desert system featuresglacier-fed rivers that sustain intensive water use in the oasis and end in the desert as fragile terminal lakes.The complex balance between water conservation and economic development is subtle. This paper investigateschanges in hydroclimatic variables and water security-related issues on the NSTM. The spatiotemporal variationsin glaciers, climatic variables, rivers, lakes and reservoirs, groundwater, surface water, human water use, andstreamflow were analyzed for the past four decades. The results show that temperature in the NSTM exhibitedan apparent upward trend with a more significant warming rate in the higher altitude regions. Glacier massloss and shrinkage was strong. The average annual streamflow increased from 1980-1989 to 2006–2011 at mosthydrological stations. The monthly dynamics of surface water area showed notable variability at both inter-annual and seasonal scales, revealing the impacts of both natural and anthropogenic drivers on surface wateravailability in the region. The terrestrial water storage anomaly showed a decreasing trend, which might berelated to groundwater pumping for irrigation. Human water use for agriculture and industry grew with theincrease in cultivated land area and gross domestic product (GDP). The increased agricultural water use wasstrongly associated with the expansion of oases. It is unclear whether water availability would remain high underfuture climatic and hydrological uncertainties, posing challenges to water management. In the context of rapidurban growth and climate change, balancing water for humans and nature is vital in achieving the SustainableDevelopment Goals (SDGs) in NSTM. This study provides a baseline understanding of the interplay among water,climate change, and socio-economic development in NSTM. It would also shed light on wise water managementunder environmental changes for other rapidly developing mountain-oasis-desert systems worldwide.展开更多
BACKGROUND Serum small extracellular vesicles(sEVs)and their small RNA(sRNA)cargoes could be promising biomarkers for the diagnosis of liver injury.However,the dynamic changes in serum sEVs and their sRNA components d...BACKGROUND Serum small extracellular vesicles(sEVs)and their small RNA(sRNA)cargoes could be promising biomarkers for the diagnosis of liver injury.However,the dynamic changes in serum sEVs and their sRNA components during liver injury have not been well characterized.Given that hepatic macrophages can quickly clear intravenously injected sEVs,the effect of liver injury-related serum sEVs on hepatic macrophages deserves to be explored.AIM To identify the characteristics of serum sEVs and the sRNAs during liver injury and explore their effects on hepatic macrophages.METHODS To identify serum sEV biomarkers for liver injury,we established a CCL4-induced mouse liver injury model in C57BL/6 mice to simulate acute liver injury(ALI),chronic liver injury(CLI)and recovery.Serum sEVs were obtained and characterized by transmission electron microscopy and nanoparticle tracking analysis.Serum sEV sRNAs were profiled by sRNA sequencing.Differentially expressed microRNAs(miRNAs)were compared to mouse liver-enriched miRNAs and previously reported circulating miRNAs related to human liver diseases.The biological significance was evaluated by Ingenuity Pathway Analysis of altered sEV miRNAs and conditioned cultures of ALI serum sEVs with primary hepatic macrophages.RESULTS We found that both ALI and CLI changed the concentration and morphology of serum sEVs.The proportion of serum sEV miRNAs increased upon liver injury,with the liver as the primary contributor.The altered serum sEV miRNAs based on mouse studies were consistent with human liver disease-related circulating miRNAs.We established serum sEV miRNA signatures for ALI and CLI and a panel of miRNAs(miR-122-5p,miR-192-5p,and miR-22-3p)as a common marker for liver injury.The differential serum sEV miRNAs in ALI contributed mainly to liver steatosis and inflammation,while those in CLI contributed primarily to hepatocellular carcinoma and hyperplasia.ALI serum sEVs decreased both CD86 and CD206 expression in monocyte-derived macrophages but increased CD206 expression in resident macrophages in vitro.CONCLUSION Serum sEVs acquired different concentrations,sizes,morphologies and sRNA contents upon liver injury and could change the phenotype of liver macrophages.Serum sEVs therefore have good diagnostic and therapeutic potential for liver injury.展开更多
连接顺序选择是查询优化领域中极具挑战性的研究方向,对于数据库管理系统获得良好的查询性能至关重要.然而,传统优化方法和现有智能优化方法均存在着不足,如规划时间过长、容易得到质量较差的连接计划、编码未考虑结构特征、依赖基数估...连接顺序选择是查询优化领域中极具挑战性的研究方向,对于数据库管理系统获得良好的查询性能至关重要.然而,传统优化方法和现有智能优化方法均存在着不足,如规划时间过长、容易得到质量较差的连接计划、编码未考虑结构特征、依赖基数估计和代价估计使得连接计划无法反映真实的执行时间等.针对上述问题,提出了一种新型基于异步Dueling DQN(Deep Q-network)和计划时间预测网络的连接优化器:ADP-Join(Asynchronous Dueling DQN and Plan Latency Prediction Network for Join Order Selection).ADP-Join集成了一种新的编码方法,能够区分不同结构的连接计划.ADP-Join设计了计划时间预测网络PLN(Plan Latency Prediction Network)来改善现有基于强化学习优化器的奖励机制.再者,提出异步更新机制改进Dueling DQN模型来提升训练性能和减少训练时间.大量的实验结果表明,在TPC-H和JOB真实数据集上ADP-Join的性能优于现有的智能优化器.展开更多
BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and...BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.展开更多
基金Supported by the National Natural Science Foundation of China,No.81372595 and No.81972696.
文摘BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver organs.AIM To develop a model for predicting prognosis after LT in patients with HCC.METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated.The expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer.The best cutoff value of biomarkers was determined using the Youden index.Cox regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest method.We evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the nomograms.RESULTS The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after LT.The nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou criteria.The calibration curve analyses indicated a good fit.The survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical practicability.CONCLUSION The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after LT.It can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.
文摘Objective:To explore the application and effect evaluation of the integrated“5A and 3+3”management model in ensuring safe medication use for chemotherapy patients.Methods:A total of 100 intravenous chemotherapy patients admitted to the oncology department of Shaanxi Provincial People’s Hospital were randomly divided into two groups using a random number list method.Both groups received conventional nursing management during chemotherapy,while the study group additionally received the integrated“5A and 3+3”safety management model.The nursing intervention effects between the two groups were compared.Results:After the intervention,the study group showed higher levels of self-management ability,compliance,and nursing satisfaction compared to the control group.The overall incidence of adverse events during hospitalization was lower in the study group,with statistically significant differences(P<0.05).The knowledge scores of medical staff in the study group,related to the prevention and treatment of chemotherapy drug side effects,daily symptom management,and daily life management,were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion:Implementing the integrated“5A and 3+3”model in the safe medication management of intravenous chemotherapy patients can effectively enhance patients’self-management abilities and compliance,improve medical staff’s ability to safely administer chemotherapy drugs,reduce adverse events caused by chemotherapy,and increase patient satisfaction.
基金supported by grants from the National Natural Science Foundation of China(31900386 to Z.Z.)Sichuan Science and Technology Program(2021YFH0025 to Z.Z.and 2021YFYZ0019 to B.Z.and Z.Z.)+1 种基金State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China at Sichuan Agricultural University(SKL-KF202205 to B.Z.)State Key Laboratory of Crop Biology Open Fund(2020KF01 to B.Z.)。
文摘Polyploid plants typically display advantages on some agronomically important traits over their diploid counterparts.Extensive studies have shown genetic,transcriptomic,and epigenetic dynamics upon polyploidization in multiple plant species.However,few studies have unveiled those alternations imposed only by ploidy level,without any interference from heterozygosity.Cultivated potato is highly heterozygous.Thus,in this study,we developed two homozygous autotetraploid lines and one homozygous diploid line in parallel from a homozygous diploid potato.We confirmed their ploidy levels using chloroplast counting and karyotyping.Oligo-FISH and genome re-sequencing validated that these potato lines are nearly homozygous.We investigated variations in phenotypes,transcription,and histone modifications between two ploidies.Both autotetraploid lines produced larger but fewer tubers than the diploid line.Interestingly,each autotetraploid line displayed ploidy-related differential expression for various genes.We also discovered a genomewide enrichment of H3K27ac in genic regions upon whole-genome doubling(WGD).However,such enrichment was not associated with the differential gene expression between two ploidies.The tetraploid lines may exhibit better resistance to cold-induced sweetening(CIS)than the diploid line in tubers,potentially regulated through the expression of CIS-related key genes,which seems to be associated with the levels of H3K4me3 in cold-stored tubers.These findings will help to understand the impacts of autotetraploidization on dynamics of phenotypes,transcription,and histone modifications,as well as on CIS-related genes in response to cold storage.
基金The Central Universities,Lanzhou University,China [lzujbky-2021-ey07]the innovative talent project of Lanzhou city[Lanzhou science and technology bureau, 2022-RC-42 to BL]Gansu Province Young Doctoral Fund Project [2021QB005]
文摘Diabetes is a pervasive and serious global health issue.According to the International Diabetes Federation report,463 million adults worldwide were living with diabetes in 2019,and this number is projected to reach 700 million in 2045^([1]).
基金Supported by National Natural Science Foundation of China,No.81972696.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related death worldwide.Serum biomarkers play an important role in the early diagnosis and prognosis of HCC.Because a certain percentage of HCC patients are negative for alpha-fetoprotein(AFP),the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC.AIM To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers.METHODS A total of 180 HCC patients were enrolled in this study.The expression levels of GP73,des-γ-carboxyprothrombin(DCP),CK18-M65,and CK18-M30 were detected by a fully automated chemiluminescence analyser.The variables were selected by logistic regression analysis.Several models were constructed using stepwise backward logistic regression.The performance of the models was compared using the C statistic,integrated discrimination improvement,net reclassification improvement,and calibration curves.The clinical utility of the nomogram was assessed using decision curve analysis(DCA).RESULTS The results showed that the expression levels of GP73,DCP,CK18-M65,and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls(P<0.001).Multivariate logistic regression analysis revealed that GP73,DCP,and CK18-M65 were independent factors for diagnosing AFP-negative HCC.By comparing the diagnostic performance of multiple models,we included GP73 and CK18-M65 as the model variables,and the model had good discrimination ability(area under the curve=0.946)and good goodness of fit.The DCA curves indicated the good clinical utility of the nomogram.CONCLUSION Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC.The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.
文摘Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the ameliorative effects of salidroside on homocysteine (Hcy)-induced cell senescence in human umbilical vein endothelial cells (HUVECs) that were mediated via inhibition of Krüppel-like factor 4 (KLF4). An endothelial cell senescence model was induced by Hcy. The cell viability, activities of telomerase and lactate dehydrogenase (LDH), and the level of reactive oxygen species were determined using commercial kits. The expression levels of KLF4, p53 and p21 were determined via western blot analysis, whereas the mRNA expression levels of KLF4 were detected by reverse transcription-quantitative PCR. Small interfering RNA-mediated knockdown of KLF4 was found to reverse Hcy-induced cell senescence. Hcy treatment led to an accelerated cell senescence, as evidenced by decreases in both cell viability and telomerase activity, whereas increases were noted in the leakage of LDH and the level of reactive oxygen species, in addition to an up-regulation of the protein levels of p53 and p21, and up-regulation of KLF4 at both the mRNA and protein level. Treatment with salidroside ameliorated Hcy-induced cell senescence in a dose-dependent manner. Taken together, these results suggested that Hcy may induce cell senescence through upregulation of KLF4, and this may be reversed by treatment with salidroside. Therefore, salidroside was shown to inhibit Hcy-induced cell senescence through KLF4 inhibition.
文摘In this paper, to solve the problems of low water absorption and weak pressure bearing capacity of current plugging materials, acrylic acid (AA), acrylamide (AM), and sodium allyl sulfonate (SAS) are used as monomers, and soluble starch is used as grafting. Material, the use of free radical aqueous solution method to synthesize the plugging agent SWL-1 with good water absorption and strong salt resistance. The monomer ratio is set as n (AA):n (AM):n (SAS) = 5:2:1, the experimental synthesis temperature is 70°C, and the orthogonal experiment is used to determine the experimental synthesis conditions as AA neutralization degree 80%, The amount of initiator is 0.60%, the amount of crosslinking agent is 0.50%, the ratio of monomer to starch is 7:1, and the amount of calcium carbonate is 13%. The comprehensive evaluation of the performance of the plugging agent SWL-1 shows that the water absorption performance at 60°C is the best 268.78 g/g, and the water absorption performance in 8% NaCl, 0.9% CaCl<sub>2</sub> and composite brine is 21.5 g/g, 12.5 g/g and 24.9 g/g, indicating good resistance to sodium and calcium, the water retention rate is still higher than 30% after 15 days at 160°C. The sand bed plugging test found that the maximum pressure of SWL-1 was 7 MPa, and the crack plugging test found that when the crack width was 1 mm, 2 mm, and 3 mm, the maximum compressive strength of SWL-1 was 10 MPa. The acid solubility test showed that the maximum pressure was 10 MPa. The highest rate is 86.38%.
基金provided by the Fundamental Research Funds for the Central Universities(No.2014QNA02)the Program for Changjiang Scholars and Innovative Research Team in University(No.IRT13098)+3 种基金the National Basic Research Program of China(No.2011CB201205)the National Natural Science Foundation of China(No.51404261)the Natural Science Foundation of Jiangsu Province(No.BK20140196)China PostdoctoralScience Foundation funded project(No.2014M551057)
文摘Roadways excavated through a coal seam can exert an adverse effect on roadway stability. To investigate the effects of in-situ stress on roadway stability, numerical models were built and high horizontal stresses at varying orientations were applied. The results indicate that stress concentrations, roadway deformation and failure increase in magnitude and extent as the excavation angle with respect to the maximum horizontal stress increases. In addition, the stress adjacent to the coal-rock interface sharply varies in space and evolves with time; coal is much more vulnerable to deformation and failure than rock.The results provide insights into the layout of roadways excavated through a coal seam. Roadways should be designed parallel or at a narrow angle to the maximum horizontal stress. The concentrated stress at the top corner of the face-end should be reduced in advance, and the coal seam should be reinforced immediately after excavation.
基金supported by the International Science&Technology Cooperation Program of China[No.2015DFR30940]the Science and Technology Research Project of Gansu Province[No.145RTSA012 and No.17JR5RA307]
文摘Objective To better understand the pathological causes of bone loss in a space environment, including microgravity, ionizing radiation, and ultradian rhythms.Methods Sprague Dawley (SD) rats were randomly divided into a baseline group, a control group, a hindlimb suspension group, a radiation group, a ultradian rhythms group and a combined-three-factor group. After four weeks of hindlimb suspension followed by X-ray exposure and/or ultradian rhythms, biomechanical properties, bone mineral density, histological analysis, microstructure parameters, and bone turnover markers were detected to evaluate bone loss in hindlimbs of rats.Results Simulated microgravity or combined-three factors treatment led to a significant decrease in the biomechanical properties of bones, reduction in bone mineral density, and deterioration of trabecular parameters. Ionizing radiation exposure also showed adverse impact while ultradian rhythms had no significant effect on these outcomes. Decrease in the concentration of the turnover markers bone alkaline phosphatase (bALP), osteocalcin (OCN), and tartrate-resistant acid phosphatase-5b (TRAP-Sb) in serum was in line with the changes in trabecular parameters.Conclusion Simulated microgravity is the main contributor of bone loss. Radiation also results in deleterious effects but ultradian rhythms has no significant effect. Combined-three factors treatment do not exacerbate bone loss when compared to simulated microgravity treatment alone.
基金the National High Technology Program of China,No.2006AA02A117
文摘Nonhuman primates are closest to humans in terms of lineage, and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans. Therefore, nonhuman primates could be utilized to simulate the process of ischemic stroke in the human. Few studies, however, have reported the use of endovascular technology to establish a rhesus monkey stroke model. In the present study, seven adult, male, rhesus monkeys were selected and, following anesthesia, a microcatheter was inserted into one side of the middle cerebral artery via the femoral artery to block blood flow, thereby resulting in middle cerebral artery occlusion. After 2 hours, the microcatheter was withdrawn to restore the middle cerebral artery blood flow and to establish ischemia/reperfusion. Results from angiography and magnetic resonance angiography confirmed occlusion and reopening of the middle cerebral artery. Magnetic resonance imaging revealed the existence of ischemic brain lesions, and neurological examination showed sustained functional deficits following surgery. The rhesus monkey middle cerebral artery ischemia/reperfusion models established by microcatheter embolization had the advantage of non-craniotomy invasion and reproducibility. The scope and degree of ischemic damage using this model was controllable. Therefore, this nonhuman primate model is an ideal model for cerebral ischemia and reperfusion.
基金supported by the National Natural Science Foundation of China,No.81500959(to NC)
文摘Several animal models of migraine have been established, and those based on trigeminovascular system activation are widely accepted. How- ever, most of these models have been established on lower animals, such as rodents, and involve only a single administration of a noxious stimulus. In this study, an inflammatory soup (10 μL), consisting of prostaglandin E2 (0.2 mM), serotonin (2 mM), bradykinin (2 raM) and histamine (2 raM), was injected into the dura mater of conscious rhesus monkeys through an indwelling catheter. The infusion started on day 8 and was repeated every 3 days, for a total of six administrations, to induce neurogenic inflammation. We performed behavioral assessments and measured the expression of the oncogene c-fos, neuronal nitric oxide synthase (nNOS) and calcitonin gene related peptide (CGRP) ill the trigeminal system and in multiple brain regions involved in pain processing by immunohistochemical staining. Compared with monkeys in the control group, three of the four animals in the inflammatory soup group displayed decreased motor behaviors, and two showed increased ipsilateral nose and mouth secretions during the stimulus period. Higher expression levels of c-fos, nNOS and CGRP were found in various brain areas of experimental animals compared with controls, including the trigeminal nucleus caudalis, thalamus, hypothalamus, midbrain, pons and other areas involved in pain perception. These results suggest that repeated inflammatory soup stimulation of the dura activates the trigeminovascular system and produces migraine-like pathological changes and abnormal behaviors in conscious rhesus monkeys.
基金funded by the Project of Forestry Peak Discipline at Fujian Agriculture and Forestry University,China(118/712018007)the Science and Technology Innovation Special Fund at Fujian Agriculture and Forestry University(118/KF2015088)the 6th Project of Forest Seeding Breaking in Fujian Province([2–19]357).
文摘Lauraceae includes the genus Phoebe,and the family is linked to the evolution of magnoliids.We sequenced the genome of Phoebe bournei Nanmu.The assembled genome size was 989.19 Mb,with a contig N50 value of 2.05 Mb.A total of 28,198 protein-coding genes were annotated in P.bournei.Whole-genome duplication(WGD)analysis showed that Lauraceae has experienced two WGD events;the older WGD event occurred just before the divergence of Lauraceae and Magnoliales,and the more recent WGD was shared by all lineages of Lauraceae.The phylogenetic tree showed that magnoliids form a sister clade to monocots and eudicots.We also identified 63 MADS-box genes,including AGL12-like genes that may be related to the regulation of P.bournei roots and FIN219-like genes encoding GH3 proteins,which are involved in photomorphogenesis.SAUR50-like genes involved in light signal-mediated pedicel or stem development were also identified.Four ATMYB46-and three PtrEPSP-homologous genes related to lignin biosynthesis were identified.These genes may be associated with the formation of straight trunks in P.bournei.Overall,the P.bournei reference genome provides insight into the origin,evolution,and diversification of Phoebe and other magnoliids.
基金This work is supported by the Third Xinjiang Scientific Expedition Program(Grant No.2021xjkk0800).Thanks to Professor Lu Zhang for his valuable comments.
文摘Water security is under threat worldwide from climate change. A warming climate would accelerate evaporationand cryosphere melting, leading to reduced water availability and unpredictable water supply. However, thewater crisis in the Northern Slope of Tianshan Mountains(NSTM) faces dual challenges because water demandsforfast-growing urban areas have put heavy pressure on water resources. The mountain-oasis-desert system featuresglacier-fed rivers that sustain intensive water use in the oasis and end in the desert as fragile terminal lakes.The complex balance between water conservation and economic development is subtle. This paper investigateschanges in hydroclimatic variables and water security-related issues on the NSTM. The spatiotemporal variationsin glaciers, climatic variables, rivers, lakes and reservoirs, groundwater, surface water, human water use, andstreamflow were analyzed for the past four decades. The results show that temperature in the NSTM exhibitedan apparent upward trend with a more significant warming rate in the higher altitude regions. Glacier massloss and shrinkage was strong. The average annual streamflow increased from 1980-1989 to 2006–2011 at mosthydrological stations. The monthly dynamics of surface water area showed notable variability at both inter-annual and seasonal scales, revealing the impacts of both natural and anthropogenic drivers on surface wateravailability in the region. The terrestrial water storage anomaly showed a decreasing trend, which might berelated to groundwater pumping for irrigation. Human water use for agriculture and industry grew with theincrease in cultivated land area and gross domestic product (GDP). The increased agricultural water use wasstrongly associated with the expansion of oases. It is unclear whether water availability would remain high underfuture climatic and hydrological uncertainties, posing challenges to water management. In the context of rapidurban growth and climate change, balancing water for humans and nature is vital in achieving the SustainableDevelopment Goals (SDGs) in NSTM. This study provides a baseline understanding of the interplay among water,climate change, and socio-economic development in NSTM. It would also shed light on wise water managementunder environmental changes for other rapidly developing mountain-oasis-desert systems worldwide.
文摘BACKGROUND Serum small extracellular vesicles(sEVs)and their small RNA(sRNA)cargoes could be promising biomarkers for the diagnosis of liver injury.However,the dynamic changes in serum sEVs and their sRNA components during liver injury have not been well characterized.Given that hepatic macrophages can quickly clear intravenously injected sEVs,the effect of liver injury-related serum sEVs on hepatic macrophages deserves to be explored.AIM To identify the characteristics of serum sEVs and the sRNAs during liver injury and explore their effects on hepatic macrophages.METHODS To identify serum sEV biomarkers for liver injury,we established a CCL4-induced mouse liver injury model in C57BL/6 mice to simulate acute liver injury(ALI),chronic liver injury(CLI)and recovery.Serum sEVs were obtained and characterized by transmission electron microscopy and nanoparticle tracking analysis.Serum sEV sRNAs were profiled by sRNA sequencing.Differentially expressed microRNAs(miRNAs)were compared to mouse liver-enriched miRNAs and previously reported circulating miRNAs related to human liver diseases.The biological significance was evaluated by Ingenuity Pathway Analysis of altered sEV miRNAs and conditioned cultures of ALI serum sEVs with primary hepatic macrophages.RESULTS We found that both ALI and CLI changed the concentration and morphology of serum sEVs.The proportion of serum sEV miRNAs increased upon liver injury,with the liver as the primary contributor.The altered serum sEV miRNAs based on mouse studies were consistent with human liver disease-related circulating miRNAs.We established serum sEV miRNA signatures for ALI and CLI and a panel of miRNAs(miR-122-5p,miR-192-5p,and miR-22-3p)as a common marker for liver injury.The differential serum sEV miRNAs in ALI contributed mainly to liver steatosis and inflammation,while those in CLI contributed primarily to hepatocellular carcinoma and hyperplasia.ALI serum sEVs decreased both CD86 and CD206 expression in monocyte-derived macrophages but increased CD206 expression in resident macrophages in vitro.CONCLUSION Serum sEVs acquired different concentrations,sizes,morphologies and sRNA contents upon liver injury and could change the phenotype of liver macrophages.Serum sEVs therefore have good diagnostic and therapeutic potential for liver injury.
文摘连接顺序选择是查询优化领域中极具挑战性的研究方向,对于数据库管理系统获得良好的查询性能至关重要.然而,传统优化方法和现有智能优化方法均存在着不足,如规划时间过长、容易得到质量较差的连接计划、编码未考虑结构特征、依赖基数估计和代价估计使得连接计划无法反映真实的执行时间等.针对上述问题,提出了一种新型基于异步Dueling DQN(Deep Q-network)和计划时间预测网络的连接优化器:ADP-Join(Asynchronous Dueling DQN and Plan Latency Prediction Network for Join Order Selection).ADP-Join集成了一种新的编码方法,能够区分不同结构的连接计划.ADP-Join设计了计划时间预测网络PLN(Plan Latency Prediction Network)来改善现有基于强化学习优化器的奖励机制.再者,提出异步更新机制改进Dueling DQN模型来提升训练性能和减少训练时间.大量的实验结果表明,在TPC-H和JOB真实数据集上ADP-Join的性能优于现有的智能优化器.
基金supported by a grant from Surface Project of Natural Science Foundation of Fujian Province(2008J0075)
文摘BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.