The Moon provides a unique environment for investigating nearby astrophysical events such as supernovae.Lunar samples retain valuable information from these events,via detectable long-lived“fingerprint”radionuclides...The Moon provides a unique environment for investigating nearby astrophysical events such as supernovae.Lunar samples retain valuable information from these events,via detectable long-lived“fingerprint”radionuclides such as^(60)Fe.In this work,we stepped up the development of an accelerator mass spectrometry(AMS)method for detecting^(60)Fe using the HI-13tandem accelerator at the China Institute of Atomic Energy(CIAE).Since interferences could not be sufficiently removed solely with the existing magnetic systems of the tandem accelerator and the following Q3D magnetic spectrograph,a Wien filter with a maximum voltage of±60 kV and a maximum magnetic field of 0.3 T was installed after the accelerator magnetic systems to lower the detection background for the low abundance nuclide^(60)Fe.A 1μm thick Si_(3)N_(4) foil was installed in front of the Q3D as an energy degrader.For particle detection,a multi-anode gas ionization chamber was mounted at the center of the focal plane of the spectrograph.Finally,an^(60)Fe sample with an abundance of 1.125×10^(-10)was used to test the new AMS system.These results indicate that^(60)Fe can be clearly distinguished from the isobar^(60)Ni.The sensitivity was assessed to be better than 4.3×10^(-14)based on blank sample measurements lasting 5.8 h,and the sensitivity could,in principle,be expected to be approximately 2.5×10^(-15)when the data were accumulated for 100 h,which is feasible for future lunar sample measurements because the main contaminants were sufficiently separated.展开更多
Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphism...Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.展开更多
BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged.AIM To assess the prognostic significance of preoperative inflammatory biomark...BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged.AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma(dCCA)who underwent pancreat-oduodenectomy(PD).METHODS This single-center study included 216 patients with dCCA after PD between January 1,2011,and December 31,2022.The individuals were categorized into two sets based on their systemic inflammatory response index(SIRI)levels:A low SIRI group(SIRI<1.5,n=123)and a high SIRI group(SIRI≥1.5,n=93).Inflam-matory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves.Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival(OS)and recurrence-free survival(RFS).RESULTS The study included a total of 216 patients,with 58.3%being male and a mean age of 65.6±9.6 years.123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA.SIRI had an area under the curve value of 0.674 for diagnosing dCCA,showing better performance than other inflammatory biomarkers.Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD,leading to lower OS[hazard ratios(HR)=1.868,P=0.006]and RFS(HR=0.949,P<0.001).Additionally,survival analysis indicated a significantly better prognosis for patients in the low SIRI group(P<0.001).CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.展开更多
BACKGROUND Inflammatory bowel disease(IBD) is characterized by chronic and non-specific inflammation of the intestinal mucosa and mainly includes ulcerative colitis and Crohn’s disease.AIM To explore the beneficial...BACKGROUND Inflammatory bowel disease(IBD) is characterized by chronic and non-specific inflammation of the intestinal mucosa and mainly includes ulcerative colitis and Crohn’s disease.AIM To explore the beneficial effect of Toxo ROP16Ⅰ/Ⅲ-induced M2 phynotype macrophages in homeostasis of IBDs through downregulation of M1 inflammatory cells.METHODS RAW264.7 macrophages stimulated by lipopolysaccharide(LPS)(M1 cells) were co-cultured with Caco-2 cells as an inflammatory model of IBD in vitro.The expression of Toxo ROP16Ⅰ/Ⅲ was observed in RAW264.7 macrophages that were transfected with p EGFP-rop16Ⅰ/Ⅲ.The phenotypes of M2 and M1 macrophage cells were assessed by quantitative real-time reverse transcriptase polymerase chain reaction and the expression of tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,transforming growth factor(TGF)-β1,IL-10,inducible nitric oxide synthase(i NOS),and arginase-1(Arg-1) was detected.The expression of i NOS,Arg-1,signal transducer and activator of transcription 3(Stat3),p-Stat3,Stat6,pStat6,programmed death ligand-2(PD-L2),caspase-3,-8,and-9 was analyzed by Western blotting,and Griess assays were performed to detect nitric oxide(NO).TNF-α,IL-1β,IL-6,TGF-β1,and IL-10 expression in the supernatants was detected by enzyme-linked immunosorbent assay,and Caco-2 cell apoptosis was determined by flow cytometry after mixing M1 cells with M2 cells in a Caco-2 cell co-culture system.RESULTS M1 cells exhibited significantly increased production of i NOS,NO,TNF-α,IL-1β,and IL-6,while Toxo ROP16Ⅰ/Ⅲ induced macrophage bias to M2 cells in vitro,showing increased expression of Arg-1,IL-10 and TGF-β1 and elevated production of p-Stat3 and p-Stat6.The mixed M1 and M2 cell culture induced by Toxo ROP16 Ⅰ/Ⅲ exhibited decreased production of NO and i NOS and upregulated expression of Arg-1 and PD-L2.Accordingly,Caco-2 cells became apoptotic,and apoptosis-associated proteins such as caspase-3,-8 and-9 were dampened during co-culture of M1 and M2 cells.Flow cytometry analysis showed that co-culture of M1 cells with Caco-2 cells facilitated the apoptosis of Caco-2 cells,but co-culture of M1 and M2 cells alleviated Caco-2 cell apoptosis.CONCLUSION Toxo ROP16 Ⅰ/Ⅲ-induced M2 macrophages inhibited apoptosis of Caco-2 cells caused by M1 macrophages.This finding may help gain a better understanding of the underlying mechanism and represent a promising therapeutic strategy for IBDs.展开更多
OBJeCTIve:To assess the efifcacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis. DATA ReTRIvAL: We searched the main databases for eligible trials including Me...OBJeCTIve:To assess the efifcacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis. DATA ReTRIvAL: We searched the main databases for eligible trials including Medline (from 1966 to June 2014), Embase (from 1980 to June 2014), Cochrane Library (Issue 6, 2014), Chinese National Knowledge Infrastructure (from 1995 to June 2014), Current Controlled Trials (http://controlled-trials.com), Clinical Trials.gov (http://clinicaltrials.gov), and Chinese Clinical Trial Registry (http://www.chictr.org). All studies regarding prevention and treatment of symptomatic intracranial arterial stenosis by cilostazol were collected. The Mesh or text keywords were the En-glish words: “cilostazol, phosphodiesterase 3 inhibitor, atherosclerosis, and ischemic stroke.” No restrictions were put on publications or publication language. SeLeCTION CRITeRIA:Grade A or B randomized controlled trials were selected according to the quality of evaluation criteria from the Cochrane Collaboration, in which cilostazol and aspi-rin were used to evaluate the effects of cilostazol in the treatment of patients with symptomatic intracranial artery stenosis. The quality of study methodology was evaluated based on criteria de-scribed in Cochrane Reviewer’s Handbook 5.0.1. RevMan 5.2 software was used for data analysis. MAIN OUTCOMe MeASUReS: Clinical efifcacy and safety of cilostazol in stopping progression and promoting regression of symptomatic intracranial artery stenosis were measured by magnet-ic resonance angiography and transcranial Doppler. ReSULTS:Two randomized controlled trials with a total of 203 patients were included in this study. The results showed that while cilostazol was associated with a significantly reduced progression of intracranial artery stenosis (OR = 0.21, 95%CI: 0.09–0.47,P 〈 0.01), it had no beneifcial effect on symptom regression (OR = 1.42, 95%CI: 0.80–2.51,P = 0.24). During the follow-up period, although some adverse effects developed, including headache, gastrointestinal disturbance, and dizziness, incidences of bleeding were lower than in aspirin-treated patients. CONCLUSION:Cilostazol may prevent the progression of symptomatic intracranial artery ste-nosis, which could reduce the incidence of ischemic stroke.展开更多
Ophiocordyceps sinensis and Cordyceps militaris both contain many bioactive compounds that confer potential therapeutic benefits. This review discusses the possible use of cultivated C. militaris as an effective subst...Ophiocordyceps sinensis and Cordyceps militaris both contain many bioactive compounds that confer potential therapeutic benefits. This review discusses the possible use of cultivated C. militaris as an effective substitute for native O. sinensis in the face of ever-increasing prices of O. sinensis because of its short supply. On the one hand, cultivated C. militaris contains higher levels of cordycepin when compared with that of wild-type O. sinensis and cultivation of C. militaris has been shown to be capable of reducing the risk of heavy metal contamination. On the other hand, there is a paucity of robust in vivo studies and randomized controlled tests comparing the pharmacology and use of C. militaris and O. sinensis. For extraction of cordycepin as western-style tablets, the use of cultivated C. militaris rather than O. sinensis represents the most appropriate future approach. For many other purposes, comparative pharmacology and clinical trials are in urgent needs.展开更多
BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unkno...BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unknown.AIM To study the relationship between VDR,Jmjd3 and H3K27me3 in patients with active UC.METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study.The patients with active UC were divided into groups according to mild(n=29),moderate(n=32)and severe(n=29)disease activity based on the modified Mayo score.Vitamin D levels were measured by radioimmunoassay.Colonic mucosal tissues from UC patients and controls were collected by colonoscopy.The expression of VDR,Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining.RESULTS Patients with active UC had lower levels of serum vitamin D(13.7±2.8 ng/mL,P<0.001)than the controls(16.2±2.5 ng/mL).In the UC cohort,serum vitamin D level was negatively correlated with disease activity(r=-0.323,P=0.001).VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues(P<0.001)and negatively correlated with disease activity(r=-0.868,P<0.001).Similar results for VDR expression were noted in the most serious lesion(defined as UC diseased)and 20 cm proximal to the anus(defined as UC normal)(P<0.05).Simultaneously,Jmjd3 expression significantly increased in UC patients(P<0.001),but no difference was found between the different sites in UC patients.H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues(P<0.001),but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients(P<0.05).Jmjd3 Level was negatively correlated with the level of VDR(r=-0.342,P=0.002)and H3K27me3(r=-0.341,P=0.002),while VDR level was positively correlated with H3K27me3(r=0.473,P<0.001).CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC.Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.展开更多
Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipi...Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC(recurrence HR = 0.306, P = 0.011;mortality HR = 0.325, P = 0.031).Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.展开更多
Background:To analyze the medication and methods of ancient traditional Chinese medicine for the prevention of plague and seasonal pathogen in order to reduce the spread of infectious diseases such as flu and protect ...Background:To analyze the medication and methods of ancient traditional Chinese medicine for the prevention of plague and seasonal pathogen in order to reduce the spread of infectious diseases such as flu and protect the susceptible people.Methods:Search the medication and the methods for preventing plague and seasonal pathogen in the Chinese Medical Code,classify and summarize the methods,perform frequency analysis and efficacy cluster analysis on Chinese medicines of involved medicines.Results:The methods of preventing ancient plague were as follows:burning and fumigating Chinese medicines,medicating nostrils,wearing bags filled with Chinese medicines,oral Chinese medicines and applying medicines to skin.The 3 main ways for drugs to work were external medication,nostril inhalation,and internal absorption.The Chinese medicines for preventing plague are mostly warm in nature and pungent in flavour,belonging to the spleen,stomach,liver,lung meridian.The 3 categories of drugs obtained by cluster analysis are C1:drugs for facilitating lung,relieving exterior and dissipating cold,such as Cangzhu(Atractylodis rhizoma)-Qianghuo(Notopterygh rhizoma et radix)-Xixin(Asari radix et rhizoma)-Baizhi(Angelicae dahuricae radix)-Fangfeng(Saposhnikoviae radix)-Zaojiao(Gleditsiae sinensis fructus);C2:drugs for promoting blood circulation and removing blood stasis,such as Xionghuang(Realgar)-Zhusha(Cinnabaris)-Dahuang(Rhei radix rhizoma)-Chuanxiong(Chuanxiong rhizoma)-Jiegeng(Platycodonis radix);C3:drugs for replenishing Qi(it is the most basic element that constitutes human body and maintains life activities in traditional Chinese medicine)and tonifying the spleen,such as Gancao(Glycyrrhizae radix et rhizoma)-Dazao(Jujubae fructus)-Ganjiang(Zingiberis rhizoma)-Rougui(Cinnamomi cortex)-Gansong(Nardostachyos radix et rhizoma)-Chenpi(Citri reticulatae pericarpium)-Baizhu(Atractylodis macrocephalae rhizoma).Conclusion:Through analysis the medication and methods of ancient traditional Chinese medicine for the prevention of plague,we can provide reference for modern research from the original plague prevention methods,and make an important contribution to the use of traditional Chinese medicine in the prevention and treatment of epidemic infectious diseases in modern clinic.展开更多
As an essential transcriptional activator,PDX1 plays a crucial role in pancreatic development andβ-cell function.Mutations in the PDX1 gene may lead to type 4 maturityonset diabetes of the young(MODY4)and neonatal di...As an essential transcriptional activator,PDX1 plays a crucial role in pancreatic development andβ-cell function.Mutations in the PDX1 gene may lead to type 4 maturityonset diabetes of the young(MODY4)and neonatal diabetes mellitus.However,the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models.In this study,three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology,all of which succumbed shortly postpartum,exhibiting pancreatic agenesis.Notably,one tri-allelic PDX1-mutant cynomolgus macaque(designated as M4)developed a pancreas,whereas the two monoallelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation.RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions,indicating developmental delay and PDX1haploinsufficiency.A marked change in m6A methylation was identified in the M4 pancreas,confirmed through cultured PDX1-mutantisletorganoids.Notably,overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids.This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.展开更多
Background: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted t...Background: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS. Methods: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation. The intracellular calcium concentration and ROS level were measured using flow cytometry, and the gene expressions of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), encoding sarcoplasmic reticulum Ca2+-ATPase 2a, encoding sodium-calcium exchanger (NCX), andp47phox encoding a subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were examined using real-time quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Results: We found that the calcium accumulation and ROS generation in the coronary artery smooth muscle cells isolated from either the ischemic or the nonischemic part of the CAL coronary artery vessel were significantly increased irrespective of blood supply (all P 〈 0.01 ). Moreover, these were accompanied by the increased expressions of NCX and p47phox, the decreased expression of S ERCA2a, and the increased amount of phosphorylated forms of p47phox in NADPH oxidase (all P 〈 0.05). Conclusions: Our results demonstrated that the disordered calcium clearance and the increased ROS generation occurred in the coronary artery smooth muscle cells in rats with chronic HF produced by ligation of the left anterior descending coronary artery (CAL), and which was found to be disassociated from blood supply, and the increased generation of ROS in the ceils was found to make concomitancy to the increased activity of NADPH oxidase in cytoplasm.展开更多
Background: Spinal muscular atrophy (SMA) is caused by homozygous deletion or compound heterozygous mutation of survival motor neuron gene 1 (SMN1), which is the key to diagnose SMA. The study was to establish and eva...Background: Spinal muscular atrophy (SMA) is caused by homozygous deletion or compound heterozygous mutation of survival motor neuron gene 1 (SMN1), which is the key to diagnose SMA. The study was to establish and evaluate a new diagnostic method for SMA. Methods: A total of 1494 children suspected with SMA were enrolled in this study. Traditional strategy, including multiplexed ligation-dependent probe amplification (MLPA) and TA cloning, was used in 1364 suspected SMA children from 2003 to 2014, and the 130 suspected SMA children were tested by a new strategy from 2015 to 2016, who were also verified by MLPA combined with TA cloning. The SMN1 and SMN2 were simultaneously amplified by polymerase chain reaction using the same primers. Mutation Surveyor software was used to detect and quantify the SMN1 variants by calculating allelic proportions in Sanger sequencing. Finally, turnaround time and cost of these two strategies were compared. Results: Among 1364 suspected SMA children, 576 children had SMN1 homozygous deletion and 27 children had SMN1 compound heterozygous mutation. Among the 130 cases, 59 had SMN1 homozygous deletion and 8 had heterozygous deletion: the SMN1-specific peak proportion on exon 7 was 34.6 ± 1.0% and 25.5 ± 0.5%, representing SMN1:SMN2 to be 1:2 and 1:3, respectively. Moreover, five variations, including p.Ser8Lysfs *23 (in two cases), p.Leu228*, p.Pro218Hisfs *26, p.Ser143Phefs*5, and p.Tyr276His, were detected in 6/8 cases with heterozygous deletion, the mutant allele proportion was 31.9%, 23.9%, 37.6%, 32.8%, 24.5%, and 23.6%, which was similar to that of the SMN1-specific site on exon 7, suggesting that those subtle mutations were located in SMN1. All these results were consistent with MLPA and TA cloning. The turnaround times of two strategies were 7.5 h and 266.5 h, respectively. Cost of a new strategy was only 28.5% of the traditional strategy. Conclusion: Sanger sequencing combined with Mutation Surveyor analysis has potential application in SMA diagnosis.展开更多
Many MXenes are efficient catalysts for MgH_(2)hydrogen storage material.Nevertheless,the synthesis of MXenes should consume a large amount of corrosive HF to etch out the Al layers from the transition metal aluminum ...Many MXenes are efficient catalysts for MgH_(2)hydrogen storage material.Nevertheless,the synthesis of MXenes should consume a large amount of corrosive HF to etch out the Al layers from the transition metal aluminum carbides or nitrides(MAX) phases,which is environmentally unfriendly.In this work,Ti_(3)AlCN MAX without HFetching was employed directly to observably enhance the kinetics and the cycling stability of MgH_(2).With addition of10 wt% Ti_(3)AlCN,the onset dehydrogenation temperature of MgH2 was dropped from 320 to 205℃,and the rehydrogenation of MgH2 under 6 MPa H2 began at as low as50℃.Furthermore,at 300℃,it could provide 6.2 wt% of hydrogen in 10 min.Upon cycling,the composite underwent an activation process during the initial 40 cycles,with the reversible capacity increased from 4.7 wt% to 6.5 wt%.After that,the capacity showed almost no attenuation for up to 100 cycles.The enhancing effect of Ti_(3)AICN on MgH_(2) was comparable to many MXenes.It was demonstrated that Ti_(3)AICN did not destabilize MgH_(2) but acted as an efficient catalyst for MgH_(2).Ti_(3)AICN was observed to be the active sites for the nucleation and growth of MgH_(2)and might also help in dissociation and recombination of hydrogen molecules.Such two factors are believed to contribute to the improvement of MgH_(2).This study not only provides a promising strategy for improving the hydrogen storage performances of MgH_(2) by using noncorrosive MAX materials,but also adds evidence of nucleation and growth of MgH_(2) on a catalyst.展开更多
Background:Little is known about the risk factors for sudden cardiac death (SCD) in the overall hospitalized cardiac department population.This study was conducted to investigate the risk factors and develop a predict...Background:Little is known about the risk factors for sudden cardiac death (SCD) in the overall hospitalized cardiac department population.This study was conducted to investigate the risk factors and develop a predictive model for SCD in a hospitalized cardiac department population.Methods:We conducted a retrospective study of patients admitted to the cardiac department of the First Affiliated Hospital of Xinjiang Medical University from June 2015 to February 2017.We collected the clinical data from medical records.Multiple stepwise logistic regression analysis was carried out to confirm the risk factors for SCD and develop a predictive risk model.The risk score was assessed by the area under receiver operating characteristic (AUROC) curve and the Hosmer-Lemeshow goodness-of-fit test.Results:A total of 262 patients with SCD and 4485 controls were enrolled in our study.Logistic regression modeling identified eight significant risk factors for in-hospital SCD:age,main admitting diagnosis,diabetes,corrected QT interval,QRS duration,ventricular premature beat burden,left ventricular ejection fraction,and estimated glomerular filtration rate.A predictive risk score including these variables showed an AUROC curve of 0.774 (95% confidence interval:0.744–0.805).The Hosmer-Lemeshow goodness-of-fit test showed the chi-square value was 2.527 (P= 0.640).The incidence of in-hospital SCD was 1.3%,4.1%,and 18.6% for scores of 0 to 2,3 to 5 and ≥6,respectively (P<0.001).Conclusions:Age,main admitting diagnosis,diabetes,QTc interval,QRS duration,ventricular premature beat burden,left ventricular ejection fraction,and estimated glomerular filtration rate are factors related to in-hospital SCD in a hospitalized cardiac department population.We developed a predictive risk score including these factors that could identify patients who are predisposed to in-hospital SCD.展开更多
Rare earth(La,Pr,Sm,Ce and Yb)-doped porous In_(2)O_(3) nanosheets are prepared by a solvothermal method.The effect of rare earth elements on the structure,morphologies and gas-sensing performance of In_(2)O_(3) nanos...Rare earth(La,Pr,Sm,Ce and Yb)-doped porous In_(2)O_(3) nanosheets are prepared by a solvothermal method.The effect of rare earth elements on the structure,morphologies and gas-sensing performance of In_(2)O_(3) nanosheets is systematically investigated.The mixed phase composed of c-In_(2)O_(3) and rh-In_(2)O_(3) can be transformed into rh-In_(2)O_(3) by doping with rare earth elements.After doping with rare earth elements,the morphology can be changed from compact nanosheets to porous sheets.Compared with pure In_(2)O_(3) and La,Pr,Sm,Ce-doped porous In_(2)O_(3) nanosheets,Yb-doped In_(2)O_(3) nanosheets present the best gas-sensing performance.Among 3%-10%Yb-doped samples,6%Yb-doped In_(2)O_(3) porous nanosheets exhibit the optimal gas-sensing performance to 5×10^(-6)-750×10^(-6) acetone,giving a high response of 15.3 toward 50×10^(-6) acetone and fast response/recovery time at the operating temperature of 220℃.Moreover,6% Yb-doped porous In_(2)O_(3) nanosheet sensor also exhibits excellent selectivity and stability,indicating its potential in the nextgeneration gas sensor.展开更多
Background:The ongoing transmission of the Middle East respiratory syndrome coronavirus(MERS-CoV)in the Middle East and its expansion to other regions are raising concerns of a potential pandemic.An in-depth analysis ...Background:The ongoing transmission of the Middle East respiratory syndrome coronavirus(MERS-CoV)in the Middle East and its expansion to other regions are raising concerns of a potential pandemic.An in-depth analysis about both population and molecular epidemiology of this pathogen is needed.Methods:MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports,supplemented by other reliable sources.Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models,respectively.Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV.Results:A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7%(95%Cl:30.9-34.6%).Saudi Arabia accounted for 83.6%of the cases.Age of>65 years old,underlying conditions and>5 days delay in diagnosis were independent risk factors for death.However,a history of animal contact was associated with a higher risk(adjusted OR=297,95%Cl:1」0-7.98)among female cases<65 years but with a lower risk(adjusted OR=0.31,95%Cl:0.18-0.51)among male cases>65 years old.Diffusion of the disease was fastest from its origin in Saudi Arabia to the east,and was primarily driven by the transportation network.The most recent subclade C5.1(since 2013)was associated with non-synonymous mutations and a higher mortality rate.Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV.Conclusions:MERS-CoV remains primarily locally transmitted in the Middle East,with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases.Animal contact is associated with a higher risk of death,but the association differs by age and sex.Transportation network is the leading driver for the spatial diffusion ofthe disease.These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic.展开更多
Quercetin (QE) and resveratrol (RSV) are powerful antioxidants with the potential to protect the testes against ischemia/reperfusion (I/R) injury. We compared their effects in testicular torsion/detorsion (T/D...Quercetin (QE) and resveratrol (RSV) are powerful antioxidants with the potential to protect the testes against ischemia/reperfusion (I/R) injury. We compared their effects in testicular torsion/detorsion (T/D) in adult rats. Twenty-four male Wistar rats were divided into four groups: sham (group A), T/D (group B), T/D treated with QE (group C), and T/D treated with RSV (group D). QE (20 mg kg-1) and RSV (20 mg kg-1) were injected intra-peritoneally at 60 min of torsion. After 90 rain of surgically induced torsion, the testicular cord was restored to its anatomical position. Twenty-four hour after torsion, blood and tissue samples were obtained for further examination. Testicular tissue malondialdehyde (MDA) and nitric oxide (NO) levels and serum total oxidant status (TOS) were higher in group B than in group A (P 〈 0.05). Group A had higher serum total antioxidant status (TAS) than group B. (P 〈 0.05) QE and RSV significantly lowered MDA, NO, and TOS levels and TAS consumption (P 〈 0.05). QE reduced the MDA and TOS levels more than RSV (P〈 0.05), but their effects on NO reduction and TAS consumption were similar (P〉 0.05). Group A had normal testicular architecture (grade 1). Groups C (mean grade 2.60) and D (mean grade 3.00) had lower testicular injury grades than group B (mean grade 3.45) (P 〈 0.05). Group C had lower testicular injury grade than group D (P 〈 0.05). Treatment with QE and RSV protects against I/R injury after testicular T/D. QE may exhibit better function than RSV at the doses tested in this study.展开更多
Coronavirus disease 2019(COVID-19)is a challenging health crisis and has strained medical capacities worldwide.The clustering of cases in families is a characteristic trait of COVID-19.E Many patients are admitted wit...Coronavirus disease 2019(COVID-19)is a challenging health crisis and has strained medical capacities worldwide.The clustering of cases in families is a characteristic trait of COVID-19.E Many patients are admitted with family members also infected with the causative virus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Here,we describe companion of family members with COVID-19 and its potential benefit for the treatment of the disease.展开更多
The Omicron variant of the severe acute respiratory syndrome coronavirus 2(SARS‑CoV‑2)infected a substantial proportion of Chinese population,and understanding the factors underlying the severity of the disease and fa...The Omicron variant of the severe acute respiratory syndrome coronavirus 2(SARS‑CoV‑2)infected a substantial proportion of Chinese population,and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment.We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles,plus viral,bacterial,and fungal content,as well as virulence factors and examined their relationships to 28-day mortality were examined.In addition,the bronchoalveolar lavage fluid(BALF)samples from invasive ventilated hospital/community-acquired pneumonia patients(HAP/CAP)sampled in 2019 were included for comparison.Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages,with no difference in 28-day mortality between them.Compared to HAP/CAP cohort,invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract;and in the COVID-19 non-survivors,we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane,higher abundance of opportunistic pathogens including bacterial Alloprevotella,Caulobacter,Escherichia-Shigella,Ralstonia and fungal Aspergillus sydowii and Penicillium rubens.Correlational analysis further revealed significant associations between host immune responses and microbial compositions,besides synergy within viral,bacterial,and fungal pathogens.Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients,providing the basis for future clinical treatment and reduction of fatality.展开更多
基金supported by the National Natural Science Foundation of China(Nos.12125509,12222514,11961141003,and 12005304)National Key Research and Development Project(No.2022YFA1602301)+1 种基金CAST Young Talent Support Planthe CNNC Science Fund for Talented Young Scholars Continuous support for basic scientific research projects。
文摘The Moon provides a unique environment for investigating nearby astrophysical events such as supernovae.Lunar samples retain valuable information from these events,via detectable long-lived“fingerprint”radionuclides such as^(60)Fe.In this work,we stepped up the development of an accelerator mass spectrometry(AMS)method for detecting^(60)Fe using the HI-13tandem accelerator at the China Institute of Atomic Energy(CIAE).Since interferences could not be sufficiently removed solely with the existing magnetic systems of the tandem accelerator and the following Q3D magnetic spectrograph,a Wien filter with a maximum voltage of±60 kV and a maximum magnetic field of 0.3 T was installed after the accelerator magnetic systems to lower the detection background for the low abundance nuclide^(60)Fe.A 1μm thick Si_(3)N_(4) foil was installed in front of the Q3D as an energy degrader.For particle detection,a multi-anode gas ionization chamber was mounted at the center of the focal plane of the spectrograph.Finally,an^(60)Fe sample with an abundance of 1.125×10^(-10)was used to test the new AMS system.These results indicate that^(60)Fe can be clearly distinguished from the isobar^(60)Ni.The sensitivity was assessed to be better than 4.3×10^(-14)based on blank sample measurements lasting 5.8 h,and the sensitivity could,in principle,be expected to be approximately 2.5×10^(-15)when the data were accumulated for 100 h,which is feasible for future lunar sample measurements because the main contaminants were sufficiently separated.
基金supported by the General Project of Henan Natural Science Foundation(No.232300420034)the National Natural Science Foundation of China for the Youth(No.81600555)the General Project of China Postdoctoral Science Foundation(No.2018M640684)。
文摘Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.
文摘BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged.AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma(dCCA)who underwent pancreat-oduodenectomy(PD).METHODS This single-center study included 216 patients with dCCA after PD between January 1,2011,and December 31,2022.The individuals were categorized into two sets based on their systemic inflammatory response index(SIRI)levels:A low SIRI group(SIRI<1.5,n=123)and a high SIRI group(SIRI≥1.5,n=93).Inflam-matory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves.Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival(OS)and recurrence-free survival(RFS).RESULTS The study included a total of 216 patients,with 58.3%being male and a mean age of 65.6±9.6 years.123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA.SIRI had an area under the curve value of 0.674 for diagnosing dCCA,showing better performance than other inflammatory biomarkers.Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD,leading to lower OS[hazard ratios(HR)=1.868,P=0.006]and RFS(HR=0.949,P<0.001).Additionally,survival analysis indicated a significantly better prognosis for patients in the low SIRI group(P<0.001).CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.
基金Supported by the National Natural Science Foundation of China,No.81471983the Key Research and Development Plan Project of Anhui Province,Department of Science and Technology 2019,No.201904a07020043+1 种基金the Key Project of Natural Science Research in the Universities of Anhui Provence,No.KJ2017A202the Research Fund Project of Anhui Institute of Transforming Medicine,No.2017zhyx04
文摘BACKGROUND Inflammatory bowel disease(IBD) is characterized by chronic and non-specific inflammation of the intestinal mucosa and mainly includes ulcerative colitis and Crohn’s disease.AIM To explore the beneficial effect of Toxo ROP16Ⅰ/Ⅲ-induced M2 phynotype macrophages in homeostasis of IBDs through downregulation of M1 inflammatory cells.METHODS RAW264.7 macrophages stimulated by lipopolysaccharide(LPS)(M1 cells) were co-cultured with Caco-2 cells as an inflammatory model of IBD in vitro.The expression of Toxo ROP16Ⅰ/Ⅲ was observed in RAW264.7 macrophages that were transfected with p EGFP-rop16Ⅰ/Ⅲ.The phenotypes of M2 and M1 macrophage cells were assessed by quantitative real-time reverse transcriptase polymerase chain reaction and the expression of tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,transforming growth factor(TGF)-β1,IL-10,inducible nitric oxide synthase(i NOS),and arginase-1(Arg-1) was detected.The expression of i NOS,Arg-1,signal transducer and activator of transcription 3(Stat3),p-Stat3,Stat6,pStat6,programmed death ligand-2(PD-L2),caspase-3,-8,and-9 was analyzed by Western blotting,and Griess assays were performed to detect nitric oxide(NO).TNF-α,IL-1β,IL-6,TGF-β1,and IL-10 expression in the supernatants was detected by enzyme-linked immunosorbent assay,and Caco-2 cell apoptosis was determined by flow cytometry after mixing M1 cells with M2 cells in a Caco-2 cell co-culture system.RESULTS M1 cells exhibited significantly increased production of i NOS,NO,TNF-α,IL-1β,and IL-6,while Toxo ROP16Ⅰ/Ⅲ induced macrophage bias to M2 cells in vitro,showing increased expression of Arg-1,IL-10 and TGF-β1 and elevated production of p-Stat3 and p-Stat6.The mixed M1 and M2 cell culture induced by Toxo ROP16 Ⅰ/Ⅲ exhibited decreased production of NO and i NOS and upregulated expression of Arg-1 and PD-L2.Accordingly,Caco-2 cells became apoptotic,and apoptosis-associated proteins such as caspase-3,-8 and-9 were dampened during co-culture of M1 and M2 cells.Flow cytometry analysis showed that co-culture of M1 cells with Caco-2 cells facilitated the apoptosis of Caco-2 cells,but co-culture of M1 and M2 cells alleviated Caco-2 cell apoptosis.CONCLUSION Toxo ROP16 Ⅰ/Ⅲ-induced M2 macrophages inhibited apoptosis of Caco-2 cells caused by M1 macrophages.This finding may help gain a better understanding of the underlying mechanism and represent a promising therapeutic strategy for IBDs.
文摘OBJeCTIve:To assess the efifcacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis. DATA ReTRIvAL: We searched the main databases for eligible trials including Medline (from 1966 to June 2014), Embase (from 1980 to June 2014), Cochrane Library (Issue 6, 2014), Chinese National Knowledge Infrastructure (from 1995 to June 2014), Current Controlled Trials (http://controlled-trials.com), Clinical Trials.gov (http://clinicaltrials.gov), and Chinese Clinical Trial Registry (http://www.chictr.org). All studies regarding prevention and treatment of symptomatic intracranial arterial stenosis by cilostazol were collected. The Mesh or text keywords were the En-glish words: “cilostazol, phosphodiesterase 3 inhibitor, atherosclerosis, and ischemic stroke.” No restrictions were put on publications or publication language. SeLeCTION CRITeRIA:Grade A or B randomized controlled trials were selected according to the quality of evaluation criteria from the Cochrane Collaboration, in which cilostazol and aspi-rin were used to evaluate the effects of cilostazol in the treatment of patients with symptomatic intracranial artery stenosis. The quality of study methodology was evaluated based on criteria de-scribed in Cochrane Reviewer’s Handbook 5.0.1. RevMan 5.2 software was used for data analysis. MAIN OUTCOMe MeASUReS: Clinical efifcacy and safety of cilostazol in stopping progression and promoting regression of symptomatic intracranial artery stenosis were measured by magnet-ic resonance angiography and transcranial Doppler. ReSULTS:Two randomized controlled trials with a total of 203 patients were included in this study. The results showed that while cilostazol was associated with a significantly reduced progression of intracranial artery stenosis (OR = 0.21, 95%CI: 0.09–0.47,P 〈 0.01), it had no beneifcial effect on symptom regression (OR = 1.42, 95%CI: 0.80–2.51,P = 0.24). During the follow-up period, although some adverse effects developed, including headache, gastrointestinal disturbance, and dizziness, incidences of bleeding were lower than in aspirin-treated patients. CONCLUSION:Cilostazol may prevent the progression of symptomatic intracranial artery ste-nosis, which could reduce the incidence of ischemic stroke.
文摘Ophiocordyceps sinensis and Cordyceps militaris both contain many bioactive compounds that confer potential therapeutic benefits. This review discusses the possible use of cultivated C. militaris as an effective substitute for native O. sinensis in the face of ever-increasing prices of O. sinensis because of its short supply. On the one hand, cultivated C. militaris contains higher levels of cordycepin when compared with that of wild-type O. sinensis and cultivation of C. militaris has been shown to be capable of reducing the risk of heavy metal contamination. On the other hand, there is a paucity of robust in vivo studies and randomized controlled tests comparing the pharmacology and use of C. militaris and O. sinensis. For extraction of cordycepin as western-style tablets, the use of cultivated C. militaris rather than O. sinensis represents the most appropriate future approach. For many other purposes, comparative pharmacology and clinical trials are in urgent needs.
基金Supported by The Key Projects of Natural Science Research of Anhui Province in China,No.201904a07020043.
文摘BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unknown.AIM To study the relationship between VDR,Jmjd3 and H3K27me3 in patients with active UC.METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study.The patients with active UC were divided into groups according to mild(n=29),moderate(n=32)and severe(n=29)disease activity based on the modified Mayo score.Vitamin D levels were measured by radioimmunoassay.Colonic mucosal tissues from UC patients and controls were collected by colonoscopy.The expression of VDR,Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining.RESULTS Patients with active UC had lower levels of serum vitamin D(13.7±2.8 ng/mL,P<0.001)than the controls(16.2±2.5 ng/mL).In the UC cohort,serum vitamin D level was negatively correlated with disease activity(r=-0.323,P=0.001).VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues(P<0.001)and negatively correlated with disease activity(r=-0.868,P<0.001).Similar results for VDR expression were noted in the most serious lesion(defined as UC diseased)and 20 cm proximal to the anus(defined as UC normal)(P<0.05).Simultaneously,Jmjd3 expression significantly increased in UC patients(P<0.001),but no difference was found between the different sites in UC patients.H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues(P<0.001),but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients(P<0.05).Jmjd3 Level was negatively correlated with the level of VDR(r=-0.342,P=0.002)and H3K27me3(r=-0.341,P=0.002),while VDR level was positively correlated with H3K27me3(r=0.473,P<0.001).CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC.Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.
基金supported by grants from the National Natural Science Funds for Distinguished Young Scholars of China (81625003)the Key Program,National Natural Science Foundation of China (81930016)the Key Research&Development Plan of Zhejiang Province (2019C03050)。
文摘Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC(recurrence HR = 0.306, P = 0.011;mortality HR = 0.325, P = 0.031).Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.
文摘Background:To analyze the medication and methods of ancient traditional Chinese medicine for the prevention of plague and seasonal pathogen in order to reduce the spread of infectious diseases such as flu and protect the susceptible people.Methods:Search the medication and the methods for preventing plague and seasonal pathogen in the Chinese Medical Code,classify and summarize the methods,perform frequency analysis and efficacy cluster analysis on Chinese medicines of involved medicines.Results:The methods of preventing ancient plague were as follows:burning and fumigating Chinese medicines,medicating nostrils,wearing bags filled with Chinese medicines,oral Chinese medicines and applying medicines to skin.The 3 main ways for drugs to work were external medication,nostril inhalation,and internal absorption.The Chinese medicines for preventing plague are mostly warm in nature and pungent in flavour,belonging to the spleen,stomach,liver,lung meridian.The 3 categories of drugs obtained by cluster analysis are C1:drugs for facilitating lung,relieving exterior and dissipating cold,such as Cangzhu(Atractylodis rhizoma)-Qianghuo(Notopterygh rhizoma et radix)-Xixin(Asari radix et rhizoma)-Baizhi(Angelicae dahuricae radix)-Fangfeng(Saposhnikoviae radix)-Zaojiao(Gleditsiae sinensis fructus);C2:drugs for promoting blood circulation and removing blood stasis,such as Xionghuang(Realgar)-Zhusha(Cinnabaris)-Dahuang(Rhei radix rhizoma)-Chuanxiong(Chuanxiong rhizoma)-Jiegeng(Platycodonis radix);C3:drugs for replenishing Qi(it is the most basic element that constitutes human body and maintains life activities in traditional Chinese medicine)and tonifying the spleen,such as Gancao(Glycyrrhizae radix et rhizoma)-Dazao(Jujubae fructus)-Ganjiang(Zingiberis rhizoma)-Rougui(Cinnamomi cortex)-Gansong(Nardostachyos radix et rhizoma)-Chenpi(Citri reticulatae pericarpium)-Baizhu(Atractylodis macrocephalae rhizoma).Conclusion:Through analysis the medication and methods of ancient traditional Chinese medicine for the prevention of plague,we can provide reference for modern research from the original plague prevention methods,and make an important contribution to the use of traditional Chinese medicine in the prevention and treatment of epidemic infectious diseases in modern clinic.
基金supported by the National Key R&D Program of China(2018YFA0801404,2023YFC3403400)National Natural Science Foundation of China(81941006,32371190,32370878)+2 种基金Guangdong Special Support Program(2019BT02Y276,2024A1515012868)Double First-Class Discipline Promotion Project(2023B10564003)Program for Scientific Research Start-up Funds of Guangdong Ocean University(060302052408)。
文摘As an essential transcriptional activator,PDX1 plays a crucial role in pancreatic development andβ-cell function.Mutations in the PDX1 gene may lead to type 4 maturityonset diabetes of the young(MODY4)and neonatal diabetes mellitus.However,the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models.In this study,three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology,all of which succumbed shortly postpartum,exhibiting pancreatic agenesis.Notably,one tri-allelic PDX1-mutant cynomolgus macaque(designated as M4)developed a pancreas,whereas the two monoallelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation.RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions,indicating developmental delay and PDX1haploinsufficiency.A marked change in m6A methylation was identified in the M4 pancreas,confirmed through cultured PDX1-mutantisletorganoids.Notably,overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids.This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.
文摘Background: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS. Methods: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation. The intracellular calcium concentration and ROS level were measured using flow cytometry, and the gene expressions of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), encoding sarcoplasmic reticulum Ca2+-ATPase 2a, encoding sodium-calcium exchanger (NCX), andp47phox encoding a subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were examined using real-time quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Results: We found that the calcium accumulation and ROS generation in the coronary artery smooth muscle cells isolated from either the ischemic or the nonischemic part of the CAL coronary artery vessel were significantly increased irrespective of blood supply (all P 〈 0.01 ). Moreover, these were accompanied by the increased expressions of NCX and p47phox, the decreased expression of S ERCA2a, and the increased amount of phosphorylated forms of p47phox in NADPH oxidase (all P 〈 0.05). Conclusions: Our results demonstrated that the disordered calcium clearance and the increased ROS generation occurred in the coronary artery smooth muscle cells in rats with chronic HF produced by ligation of the left anterior descending coronary artery (CAL), and which was found to be disassociated from blood supply, and the increased generation of ROS in the ceils was found to make concomitancy to the increased activity of NADPH oxidase in cytoplasm.
基金grants from The National Key Research and Development Program of China (No.2016YFC0901505)National Natural Science Foundation of China (No.81500979)+3 种基金CAMS Initiative for Innovative Medicine (CAMS-I2M-1-008)Central Research Institutes of Basic Research and Public Service Special Operations (No.2016ZX310182-6)a SpecialFund for Capital Health Research and Development (No.2011-1008-03)the Natural Science Foundation of Beijing Municipality (No.5163028).
文摘Background: Spinal muscular atrophy (SMA) is caused by homozygous deletion or compound heterozygous mutation of survival motor neuron gene 1 (SMN1), which is the key to diagnose SMA. The study was to establish and evaluate a new diagnostic method for SMA. Methods: A total of 1494 children suspected with SMA were enrolled in this study. Traditional strategy, including multiplexed ligation-dependent probe amplification (MLPA) and TA cloning, was used in 1364 suspected SMA children from 2003 to 2014, and the 130 suspected SMA children were tested by a new strategy from 2015 to 2016, who were also verified by MLPA combined with TA cloning. The SMN1 and SMN2 were simultaneously amplified by polymerase chain reaction using the same primers. Mutation Surveyor software was used to detect and quantify the SMN1 variants by calculating allelic proportions in Sanger sequencing. Finally, turnaround time and cost of these two strategies were compared. Results: Among 1364 suspected SMA children, 576 children had SMN1 homozygous deletion and 27 children had SMN1 compound heterozygous mutation. Among the 130 cases, 59 had SMN1 homozygous deletion and 8 had heterozygous deletion: the SMN1-specific peak proportion on exon 7 was 34.6 ± 1.0% and 25.5 ± 0.5%, representing SMN1:SMN2 to be 1:2 and 1:3, respectively. Moreover, five variations, including p.Ser8Lysfs *23 (in two cases), p.Leu228*, p.Pro218Hisfs *26, p.Ser143Phefs*5, and p.Tyr276His, were detected in 6/8 cases with heterozygous deletion, the mutant allele proportion was 31.9%, 23.9%, 37.6%, 32.8%, 24.5%, and 23.6%, which was similar to that of the SMN1-specific site on exon 7, suggesting that those subtle mutations were located in SMN1. All these results were consistent with MLPA and TA cloning. The turnaround times of two strategies were 7.5 h and 266.5 h, respectively. Cost of a new strategy was only 28.5% of the traditional strategy. Conclusion: Sanger sequencing combined with Mutation Surveyor analysis has potential application in SMA diagnosis.
基金financially supported by the Science and Technology Department of Guangxi Zhuang Autonomous (No.GuiKeAD21238022)the Natural Science Foundation of Guangxi Province (No.2019GXNSFBA185004)National Natural Science Foundation of China (Nos.52001079,51961005 and 52261038)。
文摘Many MXenes are efficient catalysts for MgH_(2)hydrogen storage material.Nevertheless,the synthesis of MXenes should consume a large amount of corrosive HF to etch out the Al layers from the transition metal aluminum carbides or nitrides(MAX) phases,which is environmentally unfriendly.In this work,Ti_(3)AlCN MAX without HFetching was employed directly to observably enhance the kinetics and the cycling stability of MgH_(2).With addition of10 wt% Ti_(3)AlCN,the onset dehydrogenation temperature of MgH2 was dropped from 320 to 205℃,and the rehydrogenation of MgH2 under 6 MPa H2 began at as low as50℃.Furthermore,at 300℃,it could provide 6.2 wt% of hydrogen in 10 min.Upon cycling,the composite underwent an activation process during the initial 40 cycles,with the reversible capacity increased from 4.7 wt% to 6.5 wt%.After that,the capacity showed almost no attenuation for up to 100 cycles.The enhancing effect of Ti_(3)AICN on MgH_(2) was comparable to many MXenes.It was demonstrated that Ti_(3)AICN did not destabilize MgH_(2) but acted as an efficient catalyst for MgH_(2).Ti_(3)AICN was observed to be the active sites for the nucleation and growth of MgH_(2)and might also help in dissociation and recombination of hydrogen molecules.Such two factors are believed to contribute to the improvement of MgH_(2).This study not only provides a promising strategy for improving the hydrogen storage performances of MgH_(2) by using noncorrosive MAX materials,but also adds evidence of nucleation and growth of MgH_(2) on a catalyst.
文摘Background:Little is known about the risk factors for sudden cardiac death (SCD) in the overall hospitalized cardiac department population.This study was conducted to investigate the risk factors and develop a predictive model for SCD in a hospitalized cardiac department population.Methods:We conducted a retrospective study of patients admitted to the cardiac department of the First Affiliated Hospital of Xinjiang Medical University from June 2015 to February 2017.We collected the clinical data from medical records.Multiple stepwise logistic regression analysis was carried out to confirm the risk factors for SCD and develop a predictive risk model.The risk score was assessed by the area under receiver operating characteristic (AUROC) curve and the Hosmer-Lemeshow goodness-of-fit test.Results:A total of 262 patients with SCD and 4485 controls were enrolled in our study.Logistic regression modeling identified eight significant risk factors for in-hospital SCD:age,main admitting diagnosis,diabetes,corrected QT interval,QRS duration,ventricular premature beat burden,left ventricular ejection fraction,and estimated glomerular filtration rate.A predictive risk score including these variables showed an AUROC curve of 0.774 (95% confidence interval:0.744–0.805).The Hosmer-Lemeshow goodness-of-fit test showed the chi-square value was 2.527 (P= 0.640).The incidence of in-hospital SCD was 1.3%,4.1%,and 18.6% for scores of 0 to 2,3 to 5 and ≥6,respectively (P<0.001).Conclusions:Age,main admitting diagnosis,diabetes,QTc interval,QRS duration,ventricular premature beat burden,left ventricular ejection fraction,and estimated glomerular filtration rate are factors related to in-hospital SCD in a hospitalized cardiac department population.We developed a predictive risk score including these factors that could identify patients who are predisposed to in-hospital SCD.
基金financially supported by the National Natural Science Foundation of China(No.51802276,21878257)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.18KJB480009)。
文摘Rare earth(La,Pr,Sm,Ce and Yb)-doped porous In_(2)O_(3) nanosheets are prepared by a solvothermal method.The effect of rare earth elements on the structure,morphologies and gas-sensing performance of In_(2)O_(3) nanosheets is systematically investigated.The mixed phase composed of c-In_(2)O_(3) and rh-In_(2)O_(3) can be transformed into rh-In_(2)O_(3) by doping with rare earth elements.After doping with rare earth elements,the morphology can be changed from compact nanosheets to porous sheets.Compared with pure In_(2)O_(3) and La,Pr,Sm,Ce-doped porous In_(2)O_(3) nanosheets,Yb-doped In_(2)O_(3) nanosheets present the best gas-sensing performance.Among 3%-10%Yb-doped samples,6%Yb-doped In_(2)O_(3) porous nanosheets exhibit the optimal gas-sensing performance to 5×10^(-6)-750×10^(-6) acetone,giving a high response of 15.3 toward 50×10^(-6) acetone and fast response/recovery time at the operating temperature of 220℃.Moreover,6% Yb-doped porous In_(2)O_(3) nanosheet sensor also exhibits excellent selectivity and stability,indicating its potential in the nextgeneration gas sensor.
基金supported by China Mega-Project on Infectious Disease Prevention(No.2017ZX10303401,2018ZX10713002,2018ZX10101003 and 2018ZX10201001)National Natural Science Foundation of China(No.81825019),and the National Institutes of Health of United States(R01 All 39761 and R01 AI116770)YY was supported by US National Institutes of Health grants R01 Al 139761 and R56 Al 148284.
文摘Background:The ongoing transmission of the Middle East respiratory syndrome coronavirus(MERS-CoV)in the Middle East and its expansion to other regions are raising concerns of a potential pandemic.An in-depth analysis about both population and molecular epidemiology of this pathogen is needed.Methods:MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports,supplemented by other reliable sources.Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models,respectively.Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV.Results:A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7%(95%Cl:30.9-34.6%).Saudi Arabia accounted for 83.6%of the cases.Age of>65 years old,underlying conditions and>5 days delay in diagnosis were independent risk factors for death.However,a history of animal contact was associated with a higher risk(adjusted OR=297,95%Cl:1」0-7.98)among female cases<65 years but with a lower risk(adjusted OR=0.31,95%Cl:0.18-0.51)among male cases>65 years old.Diffusion of the disease was fastest from its origin in Saudi Arabia to the east,and was primarily driven by the transportation network.The most recent subclade C5.1(since 2013)was associated with non-synonymous mutations and a higher mortality rate.Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV.Conclusions:MERS-CoV remains primarily locally transmitted in the Middle East,with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases.Animal contact is associated with a higher risk of death,but the association differs by age and sex.Transportation network is the leading driver for the spatial diffusion ofthe disease.These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic.
文摘Quercetin (QE) and resveratrol (RSV) are powerful antioxidants with the potential to protect the testes against ischemia/reperfusion (I/R) injury. We compared their effects in testicular torsion/detorsion (T/D) in adult rats. Twenty-four male Wistar rats were divided into four groups: sham (group A), T/D (group B), T/D treated with QE (group C), and T/D treated with RSV (group D). QE (20 mg kg-1) and RSV (20 mg kg-1) were injected intra-peritoneally at 60 min of torsion. After 90 rain of surgically induced torsion, the testicular cord was restored to its anatomical position. Twenty-four hour after torsion, blood and tissue samples were obtained for further examination. Testicular tissue malondialdehyde (MDA) and nitric oxide (NO) levels and serum total oxidant status (TOS) were higher in group B than in group A (P 〈 0.05). Group A had higher serum total antioxidant status (TAS) than group B. (P 〈 0.05) QE and RSV significantly lowered MDA, NO, and TOS levels and TAS consumption (P 〈 0.05). QE reduced the MDA and TOS levels more than RSV (P〈 0.05), but their effects on NO reduction and TAS consumption were similar (P〉 0.05). Group A had normal testicular architecture (grade 1). Groups C (mean grade 2.60) and D (mean grade 3.00) had lower testicular injury grades than group B (mean grade 3.45) (P 〈 0.05). Group C had lower testicular injury grade than group D (P 〈 0.05). Treatment with QE and RSV protects against I/R injury after testicular T/D. QE may exhibit better function than RSV at the doses tested in this study.
文摘Coronavirus disease 2019(COVID-19)is a challenging health crisis and has strained medical capacities worldwide.The clustering of cases in families is a characteristic trait of COVID-19.E Many patients are admitted with family members also infected with the causative virus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Here,we describe companion of family members with COVID-19 and its potential benefit for the treatment of the disease.
基金funded by the National Key Research and Development Program of China(2022YFC2303200)Capital Development Key Grant of China(2022-1-5091).
文摘The Omicron variant of the severe acute respiratory syndrome coronavirus 2(SARS‑CoV‑2)infected a substantial proportion of Chinese population,and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment.We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles,plus viral,bacterial,and fungal content,as well as virulence factors and examined their relationships to 28-day mortality were examined.In addition,the bronchoalveolar lavage fluid(BALF)samples from invasive ventilated hospital/community-acquired pneumonia patients(HAP/CAP)sampled in 2019 were included for comparison.Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages,with no difference in 28-day mortality between them.Compared to HAP/CAP cohort,invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract;and in the COVID-19 non-survivors,we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane,higher abundance of opportunistic pathogens including bacterial Alloprevotella,Caulobacter,Escherichia-Shigella,Ralstonia and fungal Aspergillus sydowii and Penicillium rubens.Correlational analysis further revealed significant associations between host immune responses and microbial compositions,besides synergy within viral,bacterial,and fungal pathogens.Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients,providing the basis for future clinical treatment and reduction of fatality.