[Guidelines for Diagnosis and Treatment of Pancreatic Cystic Neoplasms Based on Radiology].

As the detection rate of pancreatic cystic neoplasms (PCN) increases,recommendations or guidelines for the diagnosis and treatment of PCN have been released from professional organizations.From the perspective of radiology,we compared seven guidelines in terms of general introduction,preoperative monitoring methods and strategies,stratification of risk factors,surgical indications,and postoperative follow-ups,aiming to provide references for the evaluation of images and the formulation of individualized approach for the treatment of PCN.

Long non-coding RNA CASC7 is associated with the pathogenesis of heart failure via modulating the expression of miR-30c.

MiRNAs can be used as promising diagnostic biomarkers of heart failure, while lncRNAs act as competing endogenous RNAs of miRNAs. In this study, we collected peripheral blood monocytes from subjects with or without HF to explore the association between certain lncRNAs, miRNAs and HF. Heart failure patients with preserved or reduced ejection fraction were recruited for investigation. ROC analysis was carried out to evaluate the diagnostic values of certain miRNAs and lncRNAs in HF. Luciferase assays were used to study the regulatory relationship between above miRNAs and lncRNAs. LncRNA overexpression was used to explore the effect of certain miRNAs in H9C2 cells. Expression of miR-30c was significantly decreased in the plasma and peripheral blood monocytes of patients suffering from heart failure, especially in these with reduced ejection fraction. On the contrary, the expression of lncRNA-CASC7 was remarkably increased in the plasma and peripheral blood monocytes of patients suffering from heart failure. Both miR-30c and lncRNA-CASC7 expression showed a promising efficiency as diagnostic biomarkers of heart failure. Luciferase assays indicated that miR-30c played an inhibitory role in lncRNA-CASC7 and IL-11 mRNA expression. Moreover, the overexpression of lncRNA-CASC7 suppressed the expression of miR-30c while evidently increasing the expression of IL-11 mRNA and protein in H9C2 cells. This study clarified the relationship among miR-30c, lncRNA-CASC7 and IL-11 expression and the risk of heart failure and showed that lncRNA-CASC7 is potentially involved in the pathogenesis of HF via modulating the expression of miR-30c.

LncRNA TUG1 mediates ischemic myocardial injury by targeting miR-132-3p/HDAC3 axis.

Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). In this study, we explored the functional significance and molecular mechanisms of TUG1/miR-132-3p axis in ischemia-challenged cardiomyocytes. In primary cardiomyocytes challenged with H2O2, expressions of miR-132-3p, TUG1, and other target proteins were measured by RT quantitative PCR or Western blot analysis; cell viability by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay; apoptosis by annexin V and propidium iodide staining; the abundance of acetylated H3K9 or histone deacetylase 3 (HDAC3) within the promoter of target genes by chromatin immunoprecipitation; the direct interaction between miR-132-3p and HDAC3 or TUG1 by luciferase reporter assay. The biological significance of miR-132-3p, TUG1, and HDAC3 was assessed using miR-132-3p mimic, siRNA-targeting TUG1 and HDAC3 inhibitor RGF966, respectively, in H2O2-challenged cells in vitro or ischemia-reperfusion (I/R)-induced AMI in vivo. miR-132-3p was downregulated, whereas TUG1 upregulated in H2O2-challenged cardiomyocytes. Overexpressing miR-132-3p or knocking down TUG1 significantly improved viability, inhibited apoptosis, and reduced ROS production in H2O2-stressed cardiomyocytes in vitro and alleviated I/R-induced AMI in vivo. Mechanistically, TUG1 sponged miR-132-3p and upregulated HDAC3, which reduced the acetylation of H3K9 and epigenetically inhibited expressions of antioxidative genes, including Bcl-xL, Prdx2, and Hsp70. The TUG1/miR-132-3p/HDAC3 axis critically regulates ROS production and the pathogenic development of AMI. Targeting TUG1, upregulating miR-132-3p, or inhibiting HDAC3 may benefit AMI treatment.NEW & NOTEWORTHY Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). However, the underlying mechanisms remain elusive. In the present study, we reported for the first time that H2O2 or ischemia-reperfusion-induced TUG1, by sponging microRNA 132-3p, activated histone deacetylase 3, which in turn targeted multiple protective genes, stimulated intracellular ROS accumulation, and aggravated the injury of AMI. Our findings might provide some insight to seek new targets for AMI treatment.

Research on the Accumulation Effect of Pension Income and Payments Caused by Progressive Retirement Age Postponement Policy in China.

A retirement age postponement policy will not only increase pension income but also reduce pension payments, which will cause an accumulation effect on the size of the pension fund and relieve the intensifying pressure on pension payments. Based on the analysis of historical data in order to predict the population and pension scale in China, this research shows that the working-age population will gradually decrease, the supply of labor will decrease, and the demographic dividend will gradually disappear between 2018 and 2055 if the current retirement policy remains unrevised. According to three different retirement age postponement policy options, we establish that there are significant accumulation effects that can alleviate the pressure on pension funds. Among these policies, the postpone retirement policy option, which is based on the working period, is more conducive to a smoother policy implementation effect in the long term.

Negative Pressure Induced Droplet Generation in a Microfluidic Flow-Focusing Device.

We introduce an effective method to actively induce droplet generation using negative pressure. Droplets can be generated on demand using a series of periodic negative pressure pulses. Fluidic network models were developed using the analogy to electric networks to relate the pressure conditions for different flow regimes. Experimental results show that the droplet volume is correlated to the pressure ratio with a power law of 1.3. Using a pulsed negative pressure at the outlet, we are able to produce droplets in demand and with a volume proportional to the pulse width.

Comparative Experimental Study of Fixed Temperature and Fixed Heat Flux Boundary Conditions in Turbulent Thermal Convection.

We report the first experimental study of the influences of the thermal boundary condition on turbulent thermal convection. Two configurations were examined: one had a constant heat flux at the bottom boundary and a constant temperature at the top (CFCT cell); the other had constant temperatures at both boundaries (CTCT cell). In addition to producing different temperature stability in the boundary layers, the differences in the boundary condition lead to rather unexpected changes in the flow dynamics. It is found that, surprisingly, reversals of the large-scale circulation occur more frequently in the CTCT cell than in the CFCT cell, despite the fact that in the former its flow strength is on average 9% larger than that in the latter. Our results not only show which aspects of the thermal boundary condition are important in thermal turbulence, but also reveal that, counterintuitively, the stability of the flow is not directly coupled to its strength.

Physiologically based pharmacokinetic modeling to predict the pharmacokinetics of codeine in different CYP2D6 phenotypes.

Objectives: Codeine, a prodrug used as an opioid agonist, is metabolized to the active product morphine by CYP2D6. This study aimed to establish physiologically based pharmacokinetic (PBPK) models of codeine and morphine and explore the influence of CYP2D6 genetic polymorphisms on the pharmacokinetics of codeine and morphine. Methods: An initial PBPK modeling of codeine in healthy adults was established using PK-Sim® software and subsequently extrapolated to CYP2D6 phenotype-related PBPK modeling based on the turnover frequency (Kcat) of CYP2D6 for different phenotype populations (UM, EM, IM, and PM). The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between the predicted and observed values of the pharmacokinetic parameters to evaluate the accuracy of PBPK modeling. The validated models were then used to support dose safety for different CYP2D6 phenotypes. Results: The developed and validated CYP2D6 phenotype-related PBPK model successfully predicted codeine and morphine dispositions in different CYP2D6 phenotypes. Compared with EMs, the predicted AUC0-∞ value of morphine was 98.6% lower in PMs, 60.84% lower in IMs, and 73.43% higher in UMs. Morphine plasma exposure in IMs administered 80 mg of codeine was roughly comparable to that in EMs administered 30 mg of codeine. CYP2D6 UMs may start dose titration to achieve an optimal individual regimen and avoid a single dose of over 20 mg. Codeine should not be used in PMs for pain relief, considering its insufficient efficacy. Conclusion: PBPK modeling can be applied to explore the dosing safety of codeine and can be helpful in predicting the effect of CYP2D6 genetic polymorphisms on drug-drug interactions (DDIs) with codeine in the future.

Bibliometrics and knowledge mapping of the pathogenesis of hepatic encephalopathy in patients with liver cirrhosis.

Background: Hepatic encephalopathy is a common and serious complication of decompensated cirrhosis. It can considerably contribute to economic burden and impaired quality of life. However, its pathogenesis remains unclear. Method: In this study, we aimed to visually analyse the research status and development trends in hepatic encephalopathy pathogenesis using bibliometrics and knowledge mapping. Information regarding publications between 1978 and 2022 were obtained from the Web of Science Core Collection. CiteSpace was used to analyse and present data by year, author, institution, country, journal, reference, and keyword. Results: A total of 1578 publications on hepatic encephalopathy pathogenesis in patients with cirrhosis were retrieved from Web of Science Core Collection. A gradual increasing trend in annual publications has occurred. The collaborative network analysis results suggest the United States of America, the University of London, and Bajaj, Jasmohan S as the most influential country, institution, and author, respectively, in this research field. Notably, China appeariiuis to be the most promising country. Research on 'hepatology' garners the most significant papers in the field. Combined with reference co-citation and keyword co-occurrence analyses, we found that ammonia metabolism, gut microbiota, sarcopenia, and trace elements will become future research frontiers that are likely to be explored for a considerable length of time. Conclusion: Future research directions in HE pathogenesis may target modulating the ammonia metabolism, the gut microbiota, sarcopenia, and trace elements.

Visual Analysis of Hot Topics and Trends in Nutrition for Decompensated Cirrhosis Between 1994 and 2024.

OBJECTIVE: An updated summary of the research profile of nutrition for the last 30 years for decompensated cirrhosis is lacking. This study aimed to explore the literature on nutrition for decompensated cirrhosis, draw a visual network map to investigate the research trends, and provide suggestions for future research. The Web of Science database retrieves the literature on nutrition for decompensated cirrhosis between 1994 and 2024. METHODS: We used the cooperative, co-occurrence, and co-citation networks in the CiteSpace knowledge graph analysis tool to explore and visualize the relevant countries, institutions, authors, co-cited journals, keywords, and co-cited references. RESULTS: We identified 741 articles on nutrition for decompensated cirrhosis. The number of publications and research interests has generally increased. The USA contributed the largest number of publications and had the highest centrality. The University of London ranked first in the number of articles issued, followed by the University of Alberta and Mayo Clinic. TANDON P, a "core strength" researcher, is a central hub in the collaborative network. Of the cited journals, HEPATOLOGY had the highest output (540, 15.3%). CONCLUSIONS: Over the past three decades, the focus of research on nutrition in decompensated cirrhosis has shifted from "hepatic encephalopathy, intestinal failure, metabolic syndrome, and alcoholic hepatitis" to "sarcopenia and nutritional assessment." In the future, nutritional interventions for sarcopenia should be based on a multimodal approach to address various causative factors. Its targeted treatment is an emerging area that warrants further in-depth research.

Elastic energy flux by flexible polymers in fluid turbulence.

We present a study of the energy transfer in the bulk of a turbulent flow with dilute long-chain polymer additives. Based on prior work by Tabor and de Gennes [Europhys. Lett. 2, 519 (1986); Physica (Amsterdam) 140A, 9 (1986)], we propose a theory on the energy flux into the elastic degrees of freedom of the polymer chains. This elastic energy flux, which increases as the length scale decreases, gradually reduces the energy transferred to smaller scales through turbulence cascade and hence suppresses small scale fluctuations. The balance of the elastic energy flux and the turbulence energy cascade gives an elastic length scale, which describes the effect of polymer elasticity on turbulence in the inertial range. Predictions of this new "energy flux balance theory" agree excellently with our experimental results.

Palladium-catalyzed synthesis and anti-AD biological activity evaluation of N-aryl-debenzeyldonepezil analogues.

A series of novel N-aryl-debenzeyldonepezil derivatives (1-26) were designed and synthesized as cholinesterase inhibitors by the modification of anti-Alzheimer's disease drug donepezil, using Palladium catalyzed Buchwald-Hartwig cross-coupling reaction as a key chemical synthesis strategy. In vitro cholinesterase inhibition studies demonstrated that the majority of synthesized compounds exhibited high selective inhibition of AChE. Among them, analogue 13 possessing a quinoline functional group showed the most potent AChE inhibition effect and significant neuroprotective effect against H2O2-induced injury in SH-SY5Y cells. Furthermore, Compound 13 did not show significant cytotoxicity on SH-SY5Y. These results suggest that 13 is a potential multifunctional active molecule for treating Alzheimer's disease.

Research Models in Dentine Development and Regeneration.

Dentine is a major component of teeth and is responsible for many of their functions, such as mastication and neural sensation/transduction. Over the past decades, numerous studies have focused on dentine development and regeneration using a variety of research models, including in vivo, ex vivo and in vitro models. In vivo animal models play a crucial role in the exploration of biochemical factors that are involved in dentine development, whereas ex vivo and in vitro models contribute mainly to the identification of biophysical factors in dentine regeneration, of which mechanical force is most critical. In the present review, research models involved in studies related to dentine development and regeneration were screened from publications released in recent years and summarised comprehensively, particularly in vivo animal models including prokaryotic microinjection, Cre/LoxP, CRISPR/Cas9, ZFN and TALEN, and scaffold-based in vitro and ex vivo models. The latter were further divided by the interactive forces. Summarising these research models will not only benefit the development of future dentine-related studies but also provide hints regarding the evolution of novel dentine regeneration strategies.

A family-based association study of DIO2 and children mental retardation in the Qinba region of China.

Deiodinase enzyme II (DIO2) has an important role in individuals' thyroid hormones' level, the development of central and peripheral nervous systems and characterized by mental retardation (MR). The DIO2 gene was genotyped by using five haplotype-tagging single-nucleotide polymorphisms (SNPs) in 157 Chinese MR high-density family pedigrees, including 452 nuclear families and >1460 persons. The single marker and haplotype analyses were performed by Family-based Association Tests (FBAT). Three SNPs had P-values <0.05 in at least one inherited model survived with the correction. Several haplotypes composed of these SNPs were also associated with MR. The in silico analyses identified that one of the SNPs, rs1388378, may be a functional SNP. However, further in vitro studies of this SNP should be considered in elucidating its effect on gene expression and the possible role in MR susceptibility.

[Integrated pharmacokinetic study of multiple effective components of tea polyphenols and its correlation with anti-free radical pharmacodynamics in rats].

LC-MS/MS method was used to simultaneously determine anti-oxidative active catechins EGCG, ECG, EGC and EC in plasma of rats treated with tea polyphenols (TP). The integrated plasma concentration (C') of TP was calculated by means of self-defined weighing coefficient based on percent AUC of individual components, thereby assessing integrated pharmacokinetic (PK) parameters of TP via log C'-T curve. The anti-free radical effects of TP were estimated using inhibitory rate of drug-containing serum collected at different times from rats against in vitro lipid peroxidation of mouse liver homogenate. The obtained E-T curves were used to calculate anti-free radical pharmacodynamic (PD) parameters of TP. E-logC and E-log C' plots and linear regression were carried out in order to obtain the correlation coefficient (R2). The results indicated that the log C'-T curves of TP, which could be best described by three-compartment model, corresponded to elimination rule of iv administration of drugs. The integrated PK parameters showed that TP was distributed in body rapidly and widely, and eliminated from deep compartment slowly. From comparison of R2 values and consistence of C'-T course and E-T course, it was evident that TP integrated PK behaviors correlated much better with its PD behaviors than individual active components, and thus demonstrated that integrated PK parameters could characterize to maximal extent holistic disposition of Chinese herbal drugs and reflect residence properties of holistic effective substances in biological body.

Risk factors for repeated recurrence of cerebral aneurysms treated with endovascular embolization.

Purpose: To explore the risk factors of recurrence after second endovascular embolization of recurrent aneurysms and the characteristics of recurrent refractory aneurysms to help clinical decision-making. Materials and methods: Forty-nine patients with recurrent aneurysms who underwent repeated embolization were retrospectively enrolled and divided into the recurrent and non-recurrent group. The risk factors of recurrence, complications and follow-up results of repeated embolization, and characteristics of recurrent refractory aneurysms were analyzed. Results: Among the 49 patients with the second embolization, 5 were lost to follow-up, 9 recurred, and 35 did not. Univariate analysis showed that aneurysm size (P = 0.022), aneurysm classification (P = 0.014), and Raymond-Roy grade after the second embolization (P = 0.001) were statistically different between the two groups. Multivariate analysis demonstrated the Raymond-Roy grade as an independent risk factor for the recurrence of aneurysms after the second embolization (P = 0.042). The complication rate after the second embolization was 4%. There were five recurrent refractory aneurysms with an average aneurysm size of 23.17 ± 10.45 mm, including three giant aneurysms and two large aneurysms. To achieve complete or near-complete embolization of the recurrent refractory aneurysms, multiple treatment approaches were needed with multiple stents or flow diverting devices. Conclusion: Aneurysm occlusion status after the second embolization is an independent risk factor for the recurrence of intracranial aneurysms. Compared with near-complete occlusion, complete occlusion can significantly reduce the risk of recurrence after second embolization. In order to achieve complete or near-complete occlusion, recurrent refractory aneurysms need multiple treatments with the use of multiple stents or flow diverting devices.

[Impaired glucose metabolism in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the prevalence of impaired glucose-insulin metabolism in obstructive sleep apnea hypopnea syndrome (OSAHS); to examine the relation between severity of OSAHS and impaired glucose metabolism; and to evaluate the effectiveness of continuous positive airway pressure (CPAP) on impaired glucose metabolism. METHODS: A total of 214 patients who were free of diabetes at baseline underwent both nocturnal polysomnography (PSG), and 2-h oral glucose-tolerance test, insulin and hemoglobin A1c test. CPAP treatment for glucose-insulin metabolism (+) was given to OSAHS group after informed consent had been obtained. RESULTS: Eighty-eight patients and 17 patients with impaired glucose-insulin metabolism were found in OSAHS group and the control group respectively. Impaired glucose-insulin metabolism was present in 54.3% of OSAHS group and 32.7% of control group. Logistic regression analysis showed a significant positive correlation with OSAHS (AHI ≥ 10 times/h) and impaired glucose-insulin metabolism in all patients (OR = 2.440, 95%CI 1.201 - 4.958). Plasma glucose level changes had no significant differences between before and after CPAP treatment (P > 0.05). CONCLUSION: OSAHS is associated with a high frequency of impaired glucose metabolism. The relationship between OSAHS and impaired glucose metabolism is independent of obesity. Longest apnea time (LAT) and AHI are important contributors to impaired glucose metabolism in OSAHS patients. Short-term CPAP therapy has no significant improvement on glucose metabolism in patients with OSAHS.

[Pharmacokinetics and metabolic disposition of exogenous phosphocreatine in rats].

This article is report the study of the pharmacokinetics and metabolic disposition of exogenous phosphocreatine (PCr) in rats by means of an ion-pair HPLC-UV assay. PCr and its metabolite creatine (Cr) and related-ATP in rat plasma and red blood cell (RBC) were simultaneously determined. A blank plasma and RBC were initially run for baseline subtraction. Plasma and RBC samples were deproteinized with 6% PCA prior to HPLC. Following i.v. administration of PCr 500 mg x kg(-1) and 1 000 mg x kg(-1) the C-T curve could be described by the two-compartment model with t1/2beta 22.5-23.3 min, V(d) 0.956 4-0.978 6 L x kg(-1), CL 0.029 L. kg(-1) x min(-1). The Cr as PCr degraded product appeared as early as 2 min post i.v. dosing with t(max) 20 min, t1/2kappa (m) 40.6-42.7 min and f(m) 60%-76%. After po administration of PCr, the parent drug in plasma was undetectable, but the metabolite Cr was detected with t(max) 65-95 min, t1/2kappa (m) 56.0-57.7 min, metabolite-based bioavailability F(m) 55.02%-62.31%. PCr i.v. administration resulted in significant elevation of ATP level in RBC but not in plasma, the related-ATP in RBC was characterized by t(max) 68-83 min, t1/2kappa 49-52 min. In RBC no exogenous PCr was found but Cr was detected following i.v. administration of PCr, with the t(max) 120 min and t1/2k (m) 70 min for Cr. The above results indicate that PCr eliminates and bio-transforms in body very rapidly; K > K(m) confers ERL, instead of FRL, type upon the metabolic disposition of Cr. Following po administration of PCr, the degraded product Cr is absorbed but not the parent drug PCr. The formed Cr can be accounted for by most of i.v. and po PCr. Intravenous dosing leads apparently increased and sustained Cr and related-ATP concentration in RBC.

Experimental observation of the elastic range scaling in turbulent flow with polymer additives.

A minute amount of long-chain flexible polymer dissolved in a turbulent flow can drastically change flow properties, such as reducing the drag and enhancing mixing. One fundamental riddle is how these polymer additives interact with the eddies of different spatial scales existing in the turbulent flow and, in turn, alter the turbulence energy transfer. Here, we show how turbulent kinetic energy is transferred through different scales in the presence of the polymer additives. In particular, we observed experimentally the emerging of a previously unidentified scaling range, referred to as the elastic range, where increasing amount of energy is transferred by the elasticity of the polymers. In addition, the existence of the elastic range prescribes the scaling of high-order velocity statistics. Our findings have important implications to many turbulence systems, such as turbulence in plasmas or superfluids where interaction between turbulent eddies and other nonlinear physical mechanisms are often involved.

Exosomal LINC00174 derived from vascular endothelial cells attenuates myocardial I/R injury via p53-mediated autophagy and apoptosis.

In this study, we aim to investigate the regulation of specific long non-coding RNAs (lncRNAs) on the progression of ischemia/reperfusion (I/R) injury. We identified and characterized the exosomes derived from mouse primary aortic endothelial cells. Subsequently, we found that these exosomes expressed typical exosomal markers and high levels of LINC00174, which significantly ameliorated I/R-induced myocardial damage and suppressed the apoptosis, vacuolation, and autophagy of myocardial cells. Mechanistic approaches revealed that LINC00174 directly interacted with SRSF1 to suppress the expression of p53, thus restraining the transcription of myocardin and repressing the activation of the Akt/AMPK pathway that was crucial for autophagy initiation in I/R-induced myocardial damage. Moreover, this molecular mechanism was verified by in vivo study. In summary, exosomal LINC00174 generated from vascular endothelial cells repressed p53-mediated autophagy and apoptosis to mitigate I/R-induced myocardial damage, suggesting that targeting LINC00174 may be a novel strategy to treat I/R-induced myocardial infarction.

Flow reversals in thermally driven turbulence.

We analyze the reversals of the large-scale flow in Rayleigh-Bénard convection both through particle image velocimetry flow visualization and direct numerical simulations of the underlying Boussinesq equations in a (quasi-) two-dimensional, rectangular geometry of aspect ratio 1. For medium Prandtl number there is a diagonal large-scale convection roll and two smaller secondary rolls in the two remaining corners diagonally opposing each other. These corner-flow rolls play a crucial role for the large-scale wind reversal: They grow in kinetic energy and thus also in size thanks to plume detachments from the boundary layers up to the time that they take over the main, large-scale diagonal flow, thus leading to reversal. The Rayleigh vs Prandtl number space is mapped out. The occurrence of reversals sensitively depends on these parameters.