血清残粒脂蛋白胆固醇和甘油三酯水平与中年人群发生冠心病的相关性

[目的]探讨血清残粒脂蛋白胆固醇(RLP-C)和甘油三酯(TG)水平与中年人群发生冠心病的相关性。[方法]选取2015年1月—2022年12月在柳州市人民医院心血管内科住院行冠状动脉造影的439例中年人群为研究对象。根据冠状动脉造影结果将研究对象分为冠心病组(190例)和对照组(249例)。收集两组一般资料和实验室检查指标,根据血脂谱计算RLP-C。采用双变量Spearman相关、多因素Logistic回归、限制性立方样条图分析RLP-C、TG与中年人群发生冠心病的相关性。采用受试者工作特征(ROC)曲线评估RLP-C、TG对中年人群发生冠心病的预测效度。[结果]冠心病组年龄大于对照组,男性占比、吸烟史占比、高血压发生率、糖尿病发生率、高脂血症发生率、体质指数(BMI)、收缩压(SBP)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、RLP-C高于对照组,高密度脂蛋白胆固醇(HDLC)低于对照组(P<0.05)。Spearman相关分析结果显示,RLP-C、TG、LDLC与中年人群发生冠心病呈正相关关系(r=0.227、0.279、0.105,P均<0.05);HDLC与中年人群发生冠心病呈负相关关系(r=-0.340,P<0.001)。多因素Logistic回归分析结果显示,无论作为连续变量还是分类变量,RLP-C、TG均是中年人群发生冠心病的独立危险因素(P<0.05),HDLC是中年人群发生冠心病的独立保护因素(P<0.05)。与最低四分位数组比较,RLP-C位于第3、4四分位数组的人群发生冠心病的OR(95%CI)分别为2.648(1.364~5.144)、2.847(1.468~5.520);TG位于第3、4四分位数组的人群发生冠心病的OR(95%CI)分别为3.043(1.520~6.092)、3.520(1.811~6.842)。限制性立方样条图显示,RLP-C、TG与冠心病呈正非线性相关关系(P_(总体)均<0.001,P_(非线性)=0.002、0.001)。亚组分析显示,女性人群RLP-C、TG与冠心病的关系较男性人群更为显著。ROC曲线分析显示,RLP-C、TG预测总体人群发生冠心病的曲线下面积(95%CI)分别为0.632(0.580~0.685)(P<0.001)、0.663(0.612~0.713)(P<0.001);预测女性人群发生冠心病的曲线下面积(95%CI)分别为0.735(0.659~0.811)(P<0.001)、0.740(0.666~0.813)(P<0.001)。[结论]RLP-C、TG是中年人群发生冠心病的独立危险因素,两者与发生冠心病的相关性大于LDLC,有可能成为冠心病防治的主要靶点,应引起临床重视。

BMSC-derived Exosomes Ameliorate Peritoneal Dialysis-associated Peritoneal Fibrosis via the Mir-27a-3p/TP53 Pathway

Objective:Peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on PF in response to PD.Methods:Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing.C57BL/6J mice were infused with 4.25%glucose-based peritoneal dialysis fluid(PDF)for 6 consecutive weeks to establish a PF model.A total of 36 mice were randomly divided into 6 groups:control group,1.5%PDF group,2.5%PDF group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF.HE and Masson staining were performed to evaluate the extent of PF.The therapeutic potential of BMSC-Exos for PF was examined through pathological examination,RT-qPCR,Western blotting,and peritoneal function analyses.Epithelial-mesenchymal transition(EMT)of HMrSV5 was induced with 4.25%PDF.Cells were divided into control group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Cell Counting Kit-8 assay was used to measure cell viability,and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells.Results:Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs.The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos,but decreased in PD mice.We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice.Compared with the control mice,the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response,with markedly increased peritoneal thickness and higher expression ofα-SMA,collagen-I,fibronectin,and ECM1.The mice with PD showed decreased miR-27a-3p.Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment,while PF and mesothelial damage were significantly ameliorated.Additionally,markers of fibrosis(α-SMA,collagen-I,fibronectin,ECM1)and profibrotic cytokines(TGF-β1,PDGF)were downregulated at the mRNA and protein levels after BMSC-Exos treatment.In HMrSV5 cells,BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF.Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin(epithelial marker)and decreased expression ofα-SMA,Snail,and vimentin(mesenchymal markers)compared to those of the 4.25%PDF-treated cells.Importantly,a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p.TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos.Conclusion:The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53.

Leaf nitrogen and phosphorus are more sensitive to environmental factors in dicots than in monocots,globally

Leaf nitrogen(N)and phosphorus(P)levels provide critical strategies for plant adaptions to changing environments.However,it is unclear whether leaf N and P levels of different plant functional groups(e.g.,monocots and dicots)respond to environmental gradients in a generalizable pattern.Here,we used a global database of leaf N and P to determine whether monocots and dicots might have evolved contrasting strategies to balance N and P in response to changes in climate and soil nutrient availability.Specifically,we characterized global patterns of leaf N,P and N/P ratio in monocots and dicots,and explored the sensitivity of stoichiometry to environment factors in these plants.Our results indicate that leaf N and P levels responded to environmental factors differently in monocots than in dicots.In dicots,variations of leaf N,P and N/P ratio were significantly correlated to temperature and precipitation.In monocots,leaf N/P ratio was not significantly affected by temperature or precipitation.This indicates that leaf N,P and N/P ratio are less sensitive to environmental dynamics in monocots.We also found that in both monocots and dicots N/P ratios are associated with the availability of soil total P rather than soil total N,indicating that P limitation on plant growth is pervasive globally.In addition,there were significant phylogenetic signals for leaf N(λ=0.65),P(λ=0.57)and N/P ratio(λ=0.46)in dicots,however,only significant phylogenetic signals for leaf P in monocots.Taken together,our findings indicate that monocots exhibit a“conservative”strategy(high stoichiometric homeostasis and weak phylogenetic signals in stoichiometry)to maintain their growth in stressful conditions with lower water and soil nutrients.In contrast,dicots exhibit lower stoichiometric homeostasis in changing environments because of their wide climate-soil niches and significant phylogenetic signals in stoichiometry.

Dynamical distribution of continuous service time model involving non-Maxwellian collision kernel and value functions

The distribution of continuous service time in call centers is investigated.A non-Maxwellian collision kernel combining two different value functions in the interaction rule are used to describe the evolution of continuous service time,respectively.Using the statistical mechanical and asymptotic limit methods,Fokker–Planck equations are derived from the corresponding Boltzmann-type equations with non-Maxwellian collision kernels.The steady-state solutions of the Fokker–Planck equation are obtained in exact form.Numerical experiments are provided to support our results under different parameters.

Kaempferol ameliorated levodopa-induced dyskinesia in experimental rats: A role of brain monoamines, cFOS, FosB, Parkin, Pdyn, TH, and p-JNK

Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinflammation.Kaempferol is anotherflavonoid bearing these potentials.Aim:To evaluate neuroprotective activity of kaempferol in dyskinetic rats.Methods:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 days.Rats were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor function.Kaempferol administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in SNr.Additionally,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with AIMs.Conclusion:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.

Serum urate is associated with an increased risk of inflammatory bowel disease: A bidirectional Mendelian randomization study

BACKGROUND Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD).However,it remains unclear whether the observations are causal because of confounding factors.AIM To investigate the causal associations between urate levels and IBD using bidirec-tional Mendelian randomization(MR).METHODS Independent genetic variants for urate levels and IBD were selected as instru-mental variables from published genome-wide association studies(GWASs).Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD(the UK Biobank,the FinnGen database and a large GWAS meta-analysis)and one for urate levels(a large GWAS meta-analysis).MR analyses included the inverse-variance-weighted method,weighted-median estimator,MR-Egger and sensitivity analyses(MR-PRESSO).A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model.RESULTS Genetically higher serum urate levels were strongly associated with an increased risk of UC[odds ratio(OR):1.95,95%confidence interval(CI):1.86-2.05]after outlier correction,and the ORs(95%CIs)for IBD and CD were 0.94(95%CI:0.86-1.03)and 0.91(95%CI:0.80-1.04),respectively.Animal studies have confirmed the positive association between urate levels and UC.Moreover,genetically predicted IBD was inversely related to urate levels(OR:0.97,95%CI:0.94-0.99).However,no association was observed between genetically influenced UC or CD and urate levels.CONCLUSION Urate levels might be risk factors for UC,whereas genetically predicted IBD was inversely associated with urate levels.These findings provide essential new insight for treating and preventing IBD.

Mediating role of inflammatory indicators in the association between sleep status and blood pressure in centenarians:evidence from China Hainan Centenarian Cohort Study

Objectives To conduct a comprehensive analysis in Hainan centenarians on the link between sleep status and their blood pressure status.Furthermore,the study also aims to explore how inflammatory indicators may mediate the relationship.Methods The China Hainan Centenarians Cohort Study(CHCCS)collected baseline data on sleep status,inflammatory indicators,and blood pressure data.The study used a mediation model to investigate how inflammatory indicators mediate the relationship between sleep status and blood pressure status.Result In this study,a total of 967 centenarians were included.The prevalence of hypertension among the centenarians was 71.4%.The analysis showed that centenarians with poor sleep quality had a 43%higher risk of hypertension compared to those with normal sleep quality(OR=1.43,95%CI:1.03-1.97).Additionally,centenarians with nighttime sleep durations of≤6 h or>9 h had higher proportions of high pulse pressure(PP),with OR values of 1.76(95%CI:1.18-2.63)and 2.07(95%CI:1.34-3.19),respectively.Mediation analysis illustrated that complement C3 played a mediating role in the relationship between sleep quality and hypertension,with an effect ratio of 2.4%.Similarly,lymphocyte count,the neutrophil-to-lymphocyte ratio(NLR),and the systemic immune-inflammation index(SII)were identified as mediating factors in the association between nighttime sleep duration and high PP,with effect ratios of 91.22%,36.93%,and 0.20%,respectively.Conclusion In centenarians,poor sleep quality raises the risk of hypertension,with complement C3 as a mediator.Additionally,nighttime sleep durations of≤6 h or>9 h increases the risk of high PP,mediated by lymphocyte count,NLR,and SII.

野生美味扇菇菌株生物学特性及驯化栽培分析

以采自吉林省白山市野生美味扇菇菌株为试材,采用单因素试验与出菇试验相结合,优化培养基配方并对菌株进行驯化栽培。结果表明:美味扇菇菌丝生长的最适碳源为40 g/L麦芽糖,最适氮源为2 g/L酵母膏,最适无机盐为1 g/L硫酸镁,最适pH为5,最适培养温度为25℃。驯化后的菌株与野外采集的菌株在菌丝体阶段和子实体阶段形态基本一致,可作为栽培育种材料使用。

血清骨钙素水平与冠状动脉病变程度及冠状动脉钙化的相关性研究

目的探讨血清骨钙素水平与冠状动脉粥样硬化性心脏病(冠心病,CAD)患者冠状动脉(冠脉)病变程度及冠脉钙化的相关性。方法选取柳州市人民医院心血管内科疑似CAD患者286例,具有完整资料的受试者作为整体研究,根据冠脉造影结果分为CAD组及Non-CAD组;对CAD患者行冠脉双源螺旋CT扫描,采用Agatston修正法计算冠脉血管钙化积分。并收集受试者一般临床资料,检测血清骨钙素水平。结果CAD组患者血清骨钙素水平低于Non-CAD组[(22.31±6.89)μg/ml vs.(27.23±3.05)μg/ml],且急性冠脉综合征患者血清骨钙素水平低于稳定型心绞痛组患者[(20.35±4.13)μg/ml vs.(23.30±5.44)μg/ml],差异有统计学意义(P<0.05)。校正混杂因素后,经多因素模型分析,血清骨钙素水平≤19.05μg/ml是冠心病发生的独立危险因素(OR=1.59,95%CI:1.00~3.62,P<0.05)。对CAD组患者,多支病变亚组患者血清骨钙素水平低于单支病变亚组患者[(23.83±5.26)μg/ml vs.(20.34±4.25)μg/ml](P<0.05);经Pearson相关性分析,CAD组患者血清骨钙素水平与Gensini评分呈负相关性(r=-0.619,P=0.000);而且随着冠脉钙化程度的加重,血清骨钙素水平逐渐降低(P<0.05)。经多元逐步回归分析,血清骨钙素则是冠脉钙化的独立保护因素(OR=0.454,95%CI:0.147~0.685,P<0.05)。结论CAD患者血清骨钙素水平降低,且与冠脉病变程度及冠脉钙化的发生和发展存在一定相关性,对预测冠脉钙化具有一定参考价值。

Simulating the Stress-Strain Response of Building under Oscillating Wind Conditions

Wind load is one of the main lateral control loads that need to be considered in the design of high-rise building structures. It is also of great engineering significance to study the influence of static wind load or time-varying wind load on the dynamic response of structures. In this paper, a high-rise building with a rectangular section (46.8 m × 27 m × 33 m) is simulated based on Ansys18.0 APDL software. The real situation of its response under no lateral wind load and different fluctuating wind load conditions is simulated and the stress and strain response of the building under steady-state and time-varying wind load is given. The results show that the upper strain of the structure under wind load is about 1/1000 of the bottom strain, and the strain of the structure shows obvious accumulation from the top to the bottom, that is, the bottom strain of the building will be higher than the top strain. The influence of time-varying wind load on building structure is related to the loading position of wind load on the structure. The results provide a basis for the structural wind resistance design of this type of building.

内镜下切除大肠息肉术后迟发性出血的危险因素分析

目的探讨大肠息肉内镜下切除术后迟发性出血(DPPB)的危险因素。方法对2014年7月-2017年7月在湖北省肿瘤医院行内镜下切除术治疗的大肠息肉1 098例患者的临床资料进行回顾性分析,研究术后DPPB的危险因素。结果纳入研究的患者1 098例,治疗息肉2 169枚,18例患者(1.6%)出现术后DPPB,单因素分析发现患者有高血压病史(P=0.007)、息肉直径≥10 mm(P=0.009)、右半结肠息肉(P=0.015)、腺瘤性息肉(P=0.045)是DPPB的危险因素。多因素分析显示高血压病史(P=0.002,O■=4.654,95%CI:1.755~12.343)、息肉直径≥10 mm(P=0.009,O■=3.637,95%CI:1.390~9.517)、右半结肠息肉(P=0.016,O■=3.656,95%CI:1.273~10.504)是内镜下切除术后DPPB的独立危险因素。结论有高血压病史、息肉直径≥10 mm、息肉位于右半结肠的患者内镜下切除术后易出现迟发性出血,建议采取措施进行预防性止血。

心力衰竭靶向治疗的研究进展

心血管疾病是严重威胁我国居民健康的主要疾患之一,致死率长期居于我国疾病谱首位。随着人口老龄化的飞速进展,心血管疾病患病率和死亡率仍有上升趋势,然而,目前心力衰竭的治疗效果及预后并不理想,故探究心力衰竭潜在的致病机制并挖掘新的治疗靶点尤为重要。该综述就近年来心力衰竭靶向治疗的研究进展进行综述,为延缓心力衰竭的进程提供新的思路。

Intervention effect of neuromuscular electrical stimulation on ICU acquired weakness: A meta-analysis

Objective:The early use of neuromuscular electrical stimulation(NMES)to prevent intensive care unit-acquired weakness(ICU-AW)in critical patients is still a controversial topic.We conducted a systematic review to clarify the effectiveness of NMES in preventing ICU-AW.Methods:The Cochrane Library,PubMed,EMBASE,MEDUNE,Web of Science,Ovid,CNKI,Wanfang,VIP,China Biology Medicine disc(CBMdisc)and other databases were searched for randomized controlled trials on the influence of NMES on ICU-AW.The studies were selected according to the inclusion and exclusion criteria.After data and quality were evaluated,a meta-analysis was performed by RevMan 5.3 software.Results:A total of 11 randomized controlled trials with 576 patients were included.The meta-analysis results showed that NMES can improve muscle strength[MD=1.78,95%CI(0.44,3.12,P=0.009);shorten the mechanical ventilation(MV)time[SMD=-0.65,95%CI(-1.03,-0.27,P=0.001],ICU length of stay[MD=-3.41,95%CI(-4.58,-4.24),P<0.001],and total length of stay[MD=-3.97,95%CI(-6.89,-1.06,P=0.008];improve the ability of patients to perform activities of daily living[SMD=0.9,95%CI(0.45,1.35),P=0.001];and increase walking distance[MD=239.03,95%CI(179.22298.85),P<0.001].However,there is no evidence indicating that NMES can improve the functional status of ICU patients during hospitalization,promote the early awakening of patients or reduce mortality(P>0.05).Conclusion:Early implementation of the NMES intervention in ICU patients can prevent ICU-AW and improve their quality of life by enhancing their muscle strength and shortening the MV duration,length of stay in the ICU and total length of stay in the hospital.

利用谱系追踪方法探究Lgr5在胰腺组织及其类器官中的表达

富含亮氨酸重复序列G蛋白偶联受体5(leucine-rich repeat containing G protein-coupled receptor 5,Lgr5)在体内分布广泛,可以作为多种上皮组织(包括小肠、结肠、胃和毛囊)中干细胞的标记物。为了探究小鼠(Mus musculus)胰腺发育过程中导管上皮细胞及体外培养的胰腺导管类器官中Lgr5的表达情况,本研究利用Lgr5-Cre^(ERT2+/–)和Rosa26-mTmG杂交后的转基因小鼠,经Tamoxifen(他莫昔芬)诱导后,观察不同发育阶段胰腺组织切片的荧光表达情况,并通过三维培养建立成体小鼠胰腺导管类器官,观察诱导后类器官细胞中的荧光变化。结果显示:Tamoxifen诱导的正常成体转基因小鼠胰腺导管内未检测到表达Lgr5的细胞;通过对孕鼠及哺乳母鼠注射Tamoxifen,在胚胎发育15.5 d和新生小鼠胰腺中也未发现Lgr5阳性细胞;但是将4-hydroxy-Tamoxifen(4-羟基–他莫昔芬)添加到培养基中,在Lgr5-Cre^(ERT2+/–);Rosa26-mTmG转基因小鼠胰腺导管来源的类器官中检测到部分细胞表达Lgr5。本研究结果证实,在成体及胚胎胰腺组织中没有检测到Lgr5表达,但在体外培养的胰腺导管类器官细胞中检测到Lgr5表达。本研究为探索胰腺发育过程中干/祖细胞特异性表达基因奠定了基础。

PKM2 promotes reductive glutamine metabolism

Objective:Pyruvate kinases M(PKM),including the PKM1 and PKM2 isoforms,are critical factors in glucose metabolism.PKM2promotes aerobic glycolysis,a phenomenon known as"the Warburg effect".The purpose of this study was to identify the roles of PKM2 in regulating cellular metabolism.Methods:The CRISPR/Cas9 system was used to generate the PKM-knockout cell model to evaluate the role of PKM in cellular metabolism.Lactate levels were measured by the Vitros LAC slide method on an autoanalyzer and glucose levels were measured by the autoanalyzer AU5800.The metabolism of ^(13)C_6-glucose or ^(13)C_5-glutamine was evaluated by liquid chromatography/mass spectrometry analyses.The effects of PKM on tumor growth were detected in vivo in a tumor-bearing mouse model.Results:We found that both PKM1 and PKM2 enabled aerobic glycolysis,but PKM2 converted glucose to lactate much more efficiently than PKM1.As a result,PKM2 reduced glucose levels reserved for intracellular utilization,particularly for the production of citrate,and thus increased theα-ketoglutarate/citrate ratio to promote the generation of glutamine-derived acetylcoenzyme A through the reductive pathway.Furthermore,reductive glutamine metabolism facilitated cell proliferation under hypoxia conditions,which supports in vivo tumor growth.In addition,PKM-deletion induced a reverse Warburg effect in tumorassociated stromal cells.Conclusions:PKM2 plays a critical role in promoting reductive glutamine metabolism and maintaining proton homeostasis.This study is helpful to increase the understanding of the physiological role of PKM2 in cancer cells.

Microvesicles derived from hypoxia/reoxYgenation-treated human umbilical vein endothellal cells impair relaxation of rat thoracic aortic rings

Objective To investigate the effects of microvesicles(MVs) derived from hypoxia/reoxygenation(H/R)-treated human umbilical vein endothelial cells(HUVECs) on endothelium-dependent relaxation of rat thoracic aortic rings.Methods H/R injury model was established to induce HUVECs to release H/R-EMVs.H/R-EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium.H/R-EMVs were characterized using 1 urn latex beads and anti-PE-CD144 by flow cytometry.Thoracic aortic rings of rats were incubated with 2.5,5,10,20 μg/ml H/R-EMVs derived from H/R-treated HUVECs for 4 hours,and their endothelium-dependent relaxation in response to acetylcholine(ACh) or endothelium-independent relaxation in response to sodium nitroprusside(SNP) was recorded in vitro.The nitric oxide(NO) production of ACh-treated thoracic aortic rings of rats was measured using Griess reagent.The expression of endothelial NO synthase(eNOS) and phosphorylated eNOS(p-eNOS,Ser-1177) in the thoracic aortic rings of rats was detected by Western blotting.Furthermore,the levels of SOD and MDA in H/R-EMVs-treated thoracic aortic rings of rats were measured using SOD and MDA kit.Results H/R-EMVs were induced by H/R-treated HUVECs and isolated by ultracentrifugation.The membrane vesicles(< 1 urn) induced by H/R were CD144 positive.ACh-induced relaxation and NO production of rat thoracic aortic rings were impaired by H/R-EMVs treatment in a concentration-dependent manner(P<0.05,P<0.01).The expression of total eNOS(t-eNOS)was not affected by H/R-EMVs.However,the expression of p-eNOS decreased after treated with H/R-EMVs.The activity of SOD decreased and the level of MDA increased in H/R-EMVs treated rat thoracic aortic rings(P<0.01).Conclusion ACh induced endothelium-dependent relaxation of thoracic aortic rings of rats was impaired by H/R-EMVs in a concentration-dependent manner.The mechanisms included a decrease in NO production,p-eNOS expression and an increase in oxidative stress.

Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level:A single-center,retrospective cohort study

BACKGROUND Autoimmune pancreatitis(AIP)has been linked with elevated immunoglobulin(Ig)G4 levels.The characteristics and outcomes of AIP based on serum markers have not been fully evaluated.AIM To compare clinical features,treatment efficacy,and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse.METHODS A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021.According to the serum IgG4 level,all patients were divided into two groups,the abnormal group(n=148)with a high level of IgG4[>2×upper limit of normal(ULN)]and the normal group(n=65).The t-test or Mann-Whitney U test was used to compare continuous variables.Categorical parameters were compared by theχ^(2) test or Fisher’s exact test.Kaplan-Meier curves Zhou GZ et al.Clinical characteristics and outcome of AIP WJG https://www.wjgnet.com 5126 September 21,2023 Volume 29 Issue 35 and log-rank tests were established to assess the cumulative relapse rates.Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse.RESULTS Compared with the normal group,the abnormal group had a higher average male age(60.3±10.4 vs 56.5±12.9 years,P=0.047);higher level of serum total protein(72.5±7.9 g/L vs 67.2±7.5 g/L,P<0.001),IgG4(1420.5±1110.9 mg/dL vs 252.7±106.6 mg/dL,P<0.001),and IgE(635.6±958.1 IU/mL vs 231.7±352.5 IU/mL,P=0.002);and a lower level of serum complement C3(100.6±36.2 mg/dL vs 119.0±45.7 mg/dL,P=0.050).In addition,a lower number of cases with abnormal pancreatic duct and pancreatic atrophy(23.6%vs 37.9%,P=0.045;1.6%vs 8.6%,P=0.020,respectively)and a higher rate of relapse(17.6%vs 6.2%,P=0.030)were seen in the abnormal group.Multivariate analyses revealed that serum IgG4[(>2×ULN),hazard ratio(HR):3.583;95%confidence interval(CI):1.218–10.545;P=0.020]and IgA(>1×ULN;HR:5.908;95%CI:1.199–29.120;P=0.029)and age>55 years(HR:2.383;95%CI:1.056–5.378;P=0.036)were independent risk factors of relapse.CONCLUSION AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate.Several factors,such as IgG4 and IgA,are associated with relapse.

Two New Compounds from Schisandra propinqua var.propinqua

Schisanpropinoic acid(1),a new bergamotane sesquiterpenoid,and schisanpropinin(2),a new tetrahydrofuran lignan with a rare epoxyethane unit,were identified from the stems and leaves of Schisandra propinqua var.propinqua.Their structures were determined based on comprehensive spectroscopic and mass spectrometric analysis.The absolute configuration of 1 was determined by X-ray analysis.Compounds 1 and 2 were tested for their cytotoxic activity against five human tumor cell lines.

Work-family conflict and job burn-out among Chinese doctors:the mediating role of coping styles

Background Burn-out among doctors threatens their own health, and that of their patients. To identify risk factors of the doctor burn-out is vital to improving their health and increasing the quality of healthcare services. This study aims to explore the relationship between work-family confict （WFC） and burn-out among Chinese doctors and the mediating role of coping styles in this relationship.Methods A cross-sectional survey was conducted in China, with a questionnaire packet which consisted of the Chinese Maslach Burnout Inventory （CMBI）, WFC Scale and the Simplifed Coping Style Questionnaire （SCSQ）. A total of 2530 doctors participated in the survey. Correlation analysis was performed to explore the relationship between CMBI, WFC and SCSQ scores. A linear regression model was set to determine the mediating role of coping styles on the relationship between WFC and burn-out.Results Doctors who had higher scores on work interfering with family confict, reported more emotional exhaustion （r=0.514, P〈0.001） and had a sense of accomplishment （r= 0.149, P〈0.001）. Simultaneously, family interfering with work （FIW） was positively associated with all dimensions of burn-out （r=0.213, 0.504, 0.088, respectively, P〈0.001）. Coping styles had partial, complete and even mediating effects on the relationship between WFC and burn-out among Chinese doctors.Conclusions WFC was correlated with burn-out, and coping style was a mediator in this relationship among Chinese doctors. Coping style was a positive resource against burn-out.

Iptakalim ameliorates relaxation to acetylcholine in thoracic aortic rings impaired by microvesicles derived from hypoxia/reoxygenation-treated HUVECs

Objective: To investigate the effect of Iptakalim(Ipt) preventing injury of endothelial microvesicles(EMVs) derived from hypoxia/reoxygenation(H/R)-treated HUVECs on the relaxation of rat thoracic aortic rings and explore the underlying mechanism. Methods: H/R injury model was established to release H/R-EMVs from HUVECs. H/R-EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium. H/R-EMVs were characterized by using Transmission Electron Microscope(TEM). Thoracic aortic rings of rats were incubated with 10^(-7)-10^(-3 )mol/L Ipt and co-cultured with 10 μg/ml H/R-EMVs for 4 hours, and their endothelium- dependent relaxation in response to acetylcholine(ACh) was recorded in vitro. The nitric oxide(NO) production of ACh-treated rat thoracic aortic rings was measured by using Griess reagent. The expression of endothelial NO synthase(e NOS), phosphorylated e NOS(p-e NOS, Ser-1177), serine/threonine kinas(Akt) and phosphorylated Akt(p-Akt, Ser-473) in the thoracic aortic rings of rats was detected by Western blotting. Results: H/R-EMVs were induced by H/R-treated HUVECs and isolated by ultracentrifugation. The isolated H/R-EMVs subjected to TEM revealed small, rounded vesicles(100–1 000 nm) surrounded by a membrane. H/R-EMVs impaired relaxation induced by ACh of rat thoracic aortic rings significantly. Compared with H/R-EMVs treatment individually, relaxation and NO production of rat thoracic aortic rings were increased by Ipt treatment in a concentration-dependent manner(P<0.05, P<0.01). The expression of total e NOS(t-e NOS) and total Akt(t-Akt) was not affected by Ipt or H/R-EMVs. However, the expression of p-e NOS and p-Akt increased after treated with Ipt(P<0.01). Conclusion: Based on H/R-EMVs treatment, ACh induced endothelium-dependent relaxation of rat thoracic aortic rings was ameliorated by Ipt in a concentration-dependent manner. The mechanisms involved the increase in NO production, p-e NOS and p-Akt expression.