Single-cell transcriptome profiling of sepsis identifies HLA-DR^(low)S100A^(high)monocytes with immunosuppressive function

Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.Methods We adopted cross-species,single-cell RNA sequencing(scRNA-seq)analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis.Flow cytometry,laser scanning confocal microscopy(LSCM)imaging and Western blotting were applied to identify the presence of S100A9^(+)monocytes at protein level.To interrogate the immunosuppressive function of this subset,splenic monocytes isolated from septic wild-type or S100a9^(–/–)mice were co-cultured with naive CD4^(+)T cells,followed by proliferative assay.Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.Results scRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis,for which distinct monocyte subsets were enriched in disparate subclusters of septic patients.We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR(HLA-DR),which were prominently enriched in septic patients and might exert immunosuppressive function.By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments,we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice,corresponding to HLA-DR^(low)S100A^(high)monocytes in human sepsis.Moreover,we found that S100A9^(+)monocytes exhibited profound immunosuppressive function on CD4^(+)T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.Conclusions This study identifies HLA-DR^(low)S100A^(high)monocytes correlated with immunosuppressive state upon septic challenge,inhibition of which can markedly mitigate sepsis-induced immune depression,thereby providing a novel therapeutic strategy for the management of sepsis.

A new approach for flow simulation in complex hydraulic fracture morphology and its application:Fracture connection element method

Efficient flow simulation and optimization methods of hydraulic fracture morphology in unconventional reservoirs are effective ways to enhance oil/gas recovery.Based on the connection element method(CEM)and distribution of stimulated reservoir volume,the complex hydraulic fracture morphology was accurately described using heterogeneous node connection system.Then a new fracture connection element method(FCEM)for fluid flow in stimulated unconventional reservoirs with complex hydraulic fracture morphology was proposed.In the proposed FCEM,the arrangement of dense nodes in the stimulated area and sparse nodes in the unstimulated area ensures the calculation accuracy and efficiency.The key parameter,transmissibility,was also modified according to the strong heterogeneity of stimulated reservoirs.The finite difference and semi-analytical tracking were used to accurately solve the pressure and saturation distribution between nodes.The FCEM is validated by comparing with traditional numerical simulation method,and the results show that the bottom hole pressure simulated by the FCEM is consistent with the results from traditional numerical simulation method,and the matching rate is larger than 95%.The proposed FCEM was also used in the optimization of fracturing parameters by coupling the hydraulic fracture propagation method and intelligent optimization algorithm.The integrated intelligent optimization approach for multi-parameters,such as perforation number,perforation location,and displacement in hydraulic fracturing is proposed.The proposed approach was applied in a shale gas reservoir,and the result shows that the optimized perforation location and morphology distribution are related to the distribution of porosity/permeability.When the perforation location and displacement are optimized with the same fracture number,NPV increases by 70.58%,which greatly improves the economic benefits of unconventional reservoirs.This work provides a new way for flow simulation and optimization of hydraulic fracture morphology of multi-fractured horizontal wells in unconventional reservoirs.

Diagnostic accuracy of a deep learning approach to calculate FFR from coronary CT angiography

Background The computational fluid dynamics(CFD)approach has been frequently applied to compute the fractional flow reserve(FFR)using computed tomography angiography(CTA).This technique is efficient.We developed the DEEPVESSEL-FFR platform using the emerging deep learning technique to calculate the FFR value out of CTA images in five minutes.This study is to evaluate the DEEPVESSEL-FFR platform using the emerging deep learning technique to calculate the FFR value from CTA images as an efficient method.Methods A single-center,prospective study was conducted and 63 patients were enrolled for the evaluation of the diagnostic performance of DEEPVESSEL-FFR.Automatic quantification method for the three-dimensional coronary arterial geometry and the deep learning based prediction of FFR were developed to assess the ischemic risk of the stenotic coronary arteries.Diagnostic performance of the DEEPVESSEL-FFR was assessed by using wire-based FFR as reference standard.The primary evaluation factor was defined by using the area under receiver-operation characteristics curve(AUC)analysis.Results For per-patient level,taking the cut-off value<0.8 referring to the FFR measurement,DEEPVESSEL-FFR presented higher diagnostic performance in determining ischemia-related lesions with area under the curve of 0.928 compare to CTA stenotic severity 0.664.DEEPVESSEL-FFR correlated with FFR(R=0.686,P<0.001),with a mean di&ference of-0.006士0.0091(P=0.619).The secondary evaluation factors,indicating per vessel accuracy,sensitivity,specificity,positive predictive value,and negative predictive value were 87.3%,97.14%,75%,82.93%,and 95.45%,respectively.Conclusion DEEPVESSEL-FFR is a novel method that allows efficient assessment of the functional significance of coronary stenosis.

New predictors of in-stent restenosis in patients with diabetes mellitus undergoing percutaneous coronary intervention with drug-eluting stent

BackgroundPercutaneous 冠的干预(一种总线标准) 为冠的动脉疾病(CAD ) 成为了主要治疗学的过程，但是 in-stent 狭窄(ISR ) 的高率在临床的实践仍然是一个未解决的临床的问题。增加的证据建议糖尿病 mellitus (DM ) 是为 ISR，而是在有 DM 的 CAD 病人的 ISR 的风险预言者的一个主要风险因素一直不好描绘。这研究的目的是调查临床并且 angiographic 特征预言者显著地在与 drug-eluting stent ( DES )跟随冠的 stenting 的糖尿病的病人与 ISR 的出现联系了诊断了 CAD 并且在北京 Anzhen 经历了冠的 DES 培植的有糖尿病的 920 个病人的 .MethodsA 总数在中国的医院连续地从2012年1月注册了到2012年12月。这些， 440 个病人由于对待的目标损害的前进在 6 个月以内经历了第二 angiography。最后，满足了包括和排除标准的 368 个这些病人被跟随在上面由在基线一种总线标准以后的 angiography。根据是否 ISR 在后续 angiography 被检测，病人们被划分成 ISR 组(n = 74 ) 并且 non-ISR 组(n = 294 ) 。在有 DM 的病人的 ISR 的独立预言者被有一个平均数的 368 个病人(260 个女人和 108 个男人) 全部的回归 models.ResultsA 58.71 变老的 multivariate 艇长比例的危险探索#

Obstructive sleep apnea is associated with severity and long-term prognosis of acute coronary syndrome

BackgroundObstructive 睡觉呼吸暂停(OSA ) 是在有急性冠的症候群(交流) 的病人的普通疾病并且与致命、非致命的心血管的事件的增加的风险联系。然而，在以前的学习的大多数病人与赤裸的金属 stents 被对待，样品尺寸是相对低的。学习是在病人的严厉和预后上评估 OSA 的影响的这的目标为 ACS.MethodsIn 承认了这未来的队研究，我们与交流注册了病人为冠的 angiogram/percutaneous 被就医冠的干预和经历的 polysomnography。我们把病人划分了成二个组：对严重 OSA 组中等[呼吸暂停呼吸过慢过浅索引(AHI )> 15 events/h ] 并且控制组(AHI 15 events/h ) 。他们被跟随在上面为在 32 个月上面。然后，我们在病人把 ACS 严厉和长期的主要不利心血管的事件(向) 与 OSA.ResultsFive 的不同严厉作比较百和 29 个病人总之被包括，与他们中的 76% 个一起是人和一般水准 59

Elevated IL-37 levels in the plasma of patients with severe coronary arterycalcification

Background Coronary artery calcification （CAC） is a predictor of cardiovascular events and plaque burden and is closely associatedwith chronic inflammation. Intedeukin （IL）-37 is a newly discovered member of the IL-1 family and is considered an anti-inflammatorycytokine. Our recent study on mice indicated that IL-37 could attenuate atherosclerosis and vascular calcification, which suggests that IL-37could be associated with the development of atherosclerosis and related diseases. The aim of this study was to investigate if IL-37 plays arole in the progression of CAC in patients. Methods Two hundred participants with suspected cardiovascular disease were recruited. Thelevels of plasma IL-37, osteoprotegerin （OPG）, hypersensitive C-reactive protein （hsCRP） together with other biochemical parameters weremeasured, and a coronary calcium assessment was carried out by multi-detector row CT. A score of 〈 10 AU （Agatston units） denotes anabsence of CAC, a score of 11-100 AU denotes mild CAC, 101-400 denotes moderate CAC, and 〉 400 AU denotes severe CAC. ResultsOur initial data showed that there were no apparent differences in plasma IL-37 levels among patients with or without mild or moderate CAC.However, IL-37 levels were significantly increased in patients with severe CAC （P 〈 0.001）. Similar results were observed for plasma OPGand hsCRP levels. When IL-37 levels in patients with severe calcification were compared with that in all of the other non-severe CAC groups,it became apparent that there was a significant positive correlation between IL-37 level and severe CAC （r = 0.360, P 〈 0.001; OR = 1.033）using Spearrnan＇s correlation and binary logistic regression analysis. Conclusions This study demonstrates that the anti-inflammatory cy-tokine IL-37 is associated with high coronary calcium levels, suggesting that IL-37 expression may be caused by the activation ofinf/amma-tion and that IL-37 might become a predictor of severe CAC in the future, which requires further investigation.

The serum anion gap is associated with disease severity and all-cause mortality in coronary artery disease

ObjectiveTo 与 .MethodsWe 测量了的冠的动脉疾病(CAD ) 的严厉和在 18,115 个 CAD 病人的浆液电解质由冠的 angiography 显示了的预后评估在浆液阴离子差距(AG ) 之间的协会。浆液 AG 根据方程被计算：AG = Na +[(mmol/L)+ K +(mmol/L )][Cl (mmol/L )+ HCO3 (mmol/L )] 4510 的 .ResultsA 总数(24.9%) 参加者有他们比 16 mmol/L 大的 AG 层次。浆液 AG 独立地与 CAD 严厉的措施被联系，包括 CAD 的更严重的临床的类型(P < 0.001 ) 并且更坏的心脏的功能(P = 0.004 ) 。病人在第 4 浆液 AG (15.92 mmol/L ) 方照 5.171 褶层增加了 30 天所有原因死亡的风险(P < 0.001 ) 。这个协会好久是柔韧的，甚至在调整以后，性，评估 glomerular 过滤率[危险比率(HR ) ：4.861， 95% 信心间隔(CI ) ：2.150-10.993， P < 0.001 ] ，临床的诊断，冠的动脉狭窄的严厉，心脏的功能等级，和另外的 confounders (HR：3.318， 95% CI：1.76-2.27， P = 0.009 ).ConclusionIn 这大基于人口的研究，我们的调查结果在 CAD 揭示增加的浆液 AG 的一个高百分比。更高的 AG 与 CAD 和更坏的心脏的功能的更严重的临床的类型被联系。而且，增加的浆液 AG 是所有原因死亡的一个独立、重要、强壮的预言者。这些调查结果支持为在 CAD 的风险层化的浆液 AG 的一个角色。

A deep-learning-based prediction method of the estimated ultimate recovery(EUR)of shale gas wells

The estimated ultimate recovery(EUR)of shale gas wells is influenced by many factors,and the accurate prediction still faces certain challenges.As an artificial intelligence algorithm,deep learning yields notable advantages in nonlinear regression.Therefore,it is feasible to predict the EUR of shale gas wells based on a deep-learning algorithm.In this paper,according to geological evaluation data,hydraulic fracturing data,production data and EUR evaluation results of 282 wells in the WY shale gas field,a deep-learning-based algorithm for EUR evaluation of shale gas wells was designed and realized.First,the existing EUR evaluation methods of shale gas wells and the deep feedforward neural network algorithm was systematically analyzed.Second,the technical process of a deep-learning-based algorithm for EUR prediction of shale gas wells was designed.Finally,by means of real data obtained from the WY shale gas field,several different cases were applied to testify the validity and accuracy of the proposed approach.The results show that the EUR prediction with high accuracy.In addition,the results are affected by the variety and number of input parameters,the network structure and hyperparameters.The proposed approach can be extended to other shale fields using the similar technic process.

Effects and mechanisms of glucose-insulin-potassium on post-procedural myocardial injury after percutaneous coronary intervention

Objective To evaluate the effects and mechanisms of glucose-insulin-potassium(GIK)on post-procedural myocardial injury(PMI)after percutaneous coronary intervention(PCI).Methods A total of 200 non-diabetic patients with documented coronary heart disease(CHD)were divided into the Group GIK and Group G,with 100 patients in each group.Patients in Group G were given intravenous infusion of glucose solution 2 hours before PCI.As compared,patients in Group GIK were given GIK.Results Both post-procedural creatine phosphokinase isoenzyme MB(CK-MB;62.1±47.8 vs.48.8±52.6 U/L,P=0.007)and cTnI(0.68±0.83 vs.0.19±0.24 ng/mL,P<0.001)in Group GIK were significantly higher than those in Group G.In Group G,9.0%and 4.0%of patients had post-procedural increases in CK-MB 1-3 times and>3 times,which were significantly lower than those in Group GIK(14.0%and 7.0%,respectively;all P values<0.01);13.0%and 7.0%of patients had post-procedural increases in cTnI 1-3 times and>3 times,which were also significantly lower than those in Group GIK(21.0%and 13.0%,respectively;all P<0.001).Pre-procedural(10.2±4.5 vs.5.1±6.3,P<0.001)and post-procedural rapid blood glucose(RBG)levels(8.9±3.9 vs.5.3±5.6,P<0.001)in Group G were higher than those in Group GIK.In adjusted logistic models,usage of GIK(compared with glucose solution)remained significantly and independently associated with higher risk of post-procedural increases in both CK-MB and cTnI levels>3 times.Furthermore,pre-procedural RBG levels<5.0mmol/L were significantly associated with higher risk of post-procedural increases in both CK-MB and cTnI levels.Conclusions In non-diabetic patients with CHD,the administration of GIK may increase the risk of PMI due to hypoglycemia induced by GIK.

Optical coherence tomography-guided excimer laser coronary angioplasty in overlapping stents with severe under-expansion and underlying calcification

Excimer laser coronary angioplasty(ELCA)modifies atherosclerotic plaques through its photochemical,photothermal and photodynamic characteristics,while making up for the limitations of intimal disassembly and restenosis of balloon angioplasty without causing significant damage.The American Food and Drug Administration approved of the first clinical application of ELCA in 1992.Since then,ELCA has been used as an adjunct therapy in the treatment of various subsets of coronary artery lesions.ELCA considered to be a relatively safe and effective technique for coronary lesions when routine angioplasty is technically insufficient.

Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients:A systematic review

BACKGROUND Gut microbiome(GM)composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy(ICB)and of ICBrelated colitis.AIM To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB.METHODS The review protocol was registered in PROSPERO:CRD42021228018.From a total of 300 studies,nine studies met inclusion criteria.Two studies were phase I clinical trials,while the remainder were prospective observational studies.All but one study has moderate risk of bias.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).RESULTS Fecal samples enriched in Firmicutes phylum were associated with good response to ICB,whereas the Bacteroidales family was associated with poor response to ICB.Samples with greater GM diversity were associated with more favorable response to ICB[hazard ratio(HR)=3.57,95%confidence interval=1.02-12.52,P<0.05].Fecal samples with a higher abundance in Firmicutes were more susceptible to ICB-related colitis(P<0.01)whereas samples enriched in Bacteroidetes were more resistant to ICB-related colitis(P<0.05).Overall,there was limited concordance in the organisms in the GM identified to be associated with response to ICB,and studies evaluating GM diversity showed conflicting results.CONCLUSION This highlights the need for further prospective studies to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.

The sirtuin family in health and disease

Sirtuins(SIRTs)are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes,and are involved in numerous biological processes.Currently,seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified.Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions.Notably,this protein family plays a variety of important roles in cellular biology such as inflammation,metabolism,oxidative stress,and apoptosis,etc.,thus,it is considered a potential therapeutic target for different kinds of pathologies including cancer,cardiovascular disease,respiratory disease,and other conditions.Moreover,identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules,which can modify SIRT activity.Furthermore,several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples,and supplementation of SIRT modulators might have diverse impact on physiological function in different participants.In this review,we introduce the history and structure of the SIRT protein family,discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family,elaborate on the regulatory roles of SIRTs in human disease,summarize SIRT inhibitors and activators,and review related clinical studies.

Synthesis and densification of zirconium diboride prepared by carbothermal reduction

Using boron powder as additive, the preparation of zirconium diboride(ZrB 2) by carbothermal reduction was investigated. The results show that the carbothermal reduction cannot be completely done until the temperature is more than 1900 ℃. The ZrB2 particles prepared without boron(B) additive at 1900 ℃ for 3 h are rodlike and show a preferential grain growth along [001] direction. B additive changes the heat effect of the raw materials. With B additive, the morphology of ZrB2 particles turns to be regular shape. The average particle size is about 3.6 μm with 2.5 wt% B additives. With more B additive, the shape of particles turns to be round like and the average particle size is decreased to 2.3 μm when 5 wt% B is added. The existence of oxides in grain boundary is a key factor to keep ZrB2 ceramic from deep densification. Using ZrB2 powder prepared with 5 wt% B additives, by controlling carbon content in ZrB2 powder, ZrB2 ceramic with 93%relative density is hot-pressed.

Electrolytic silicon/graphite composite from SiO_(2)/graphite porous electrode in molten salts as a negative electrode material for lithium-ion batteries

Nano-silicon(nano-Si)and its composites have been regarded as the most promising negative electrode materials for producing the next-generation Li-ion batteries(LIBs),due to their ultrahigh theoretical capacity.However,the commercial applications of nano Si-based negative electrode materials are constrained by the low cycling stability and high costs.The molten salt electrolysis of SiO_(2)is proven to be suitable to produce nano-Si with the advantages of in-situ microstructure control possibilities,cheap affordability and scale-up process capability.Therefore,an economical approach for electrolysis,with a SiO_(2)/graphite porous electrode as cathode,is adopted to produce nano-Si/graphite composite negative electrode materials(SGNM)in this study.The electrolytic product of the optimized porous electrode is taken as the negative electrode materials for LIBs,and it offers a capacity of 733.2 mAh·g^(-1)and an initial coulombic efficiency of 86.8%in a coin-type cell.Moreover,the capacity of the SGNM retained 74.1%of the initial discharging capacity after 50 cycles at 0.2C,which is significantly higher than that of the simple mixture of silicon and graphite obtained from the formation of silicon carbide(SiC)between nano-Si and graphite particles.Notably,this new approach can be applied to a large-scale production.