Clinical significance of platelet mononuclear cell aggregates in patients with sepsis and acute respiratory distress syndrome

BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.

Adipose tissue macrophages:implications for obesity-associated cancer

Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression.However,the functions of ATMs on the progression of obesity-associated cancer remain unclear.In this review,we describe the origins,phenotypes,and functions of ATMs.Subsequently,we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment,including the direct exchange of dysfunctional metabolites,inordinate cytokines and other signaling mediators,transfer of extracellular vesicle cargo,and variations in the gut microbiota and its metabolites.A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.

Synchronous colonic mucosa-associated lymphoid tissue lymphoma found after surgery for adenocarcinoma:A case report and review of literature

BACKGROUND Mucosa-associated lymphoid tissue (MALT) lymphoma is a subtype of non-Hodgkin lymphoma that is mainly involved in the gastrointestinal tract. Thesynchronous occurrence of colonic MALT lymphoma and adenocarcinoma in thesame patient is extremely rare. We here report a case of synchronous colonicMALT lymphoma found on surveillance colonoscopy five months after surgeryand chemotherapy for sigmoid adenocarcinoma.CASE SUMMARY A 67-year-old man was admitted because of hematochezia for two months.Colonoscopy suggested a colonic tumor before hospitalization. Abdominalcomputed tomography (CT) revealed local thickening of the sigmoid colon. Thepatient underwent a left hemicolectomy with local lymph node dissection. Thehistopathology revealed moderately differentiated adenocarcinoma and partiallymucinous adenocarcinoma. The pTNM stage was T3N1Mx. The patient receivedchemotherapy with six cycles of mFOLFOX6 after surgery. Colonoscopy wasperformed five months later and revealed single, flat, polypoid lesions of thecolon 33 cm away from the anus. Subsequently, the patient underwent endoscopic mucosal resection for further diagnosis. The pathological diagnosis was MALTlymphoma. Positron emission tomography /CT suggested metastasis. The patientrefused further treatment and died ten months later.CONCLUSION Colonic MALT lymphoma may occur after surgery and chemotherapy foradenocarcinoma as a synchronous malignancy. Regular surveillance colonoscopyand careful monitoring after surgery are critical.

蝶形视网膜色素上皮营养不良患者的多模式眼底影像学特征

目的:探讨蝶形视网膜色素上皮营养不良(BPD)患者的多模式眼底影像特征。方法:回顾分析2016-01/2019-07经多模式影像检查确诊BPD的患者18例36眼的眼底彩照、红外照相、自发荧光、荧光造影、脉络膜造影、光学相干断层扫描(OCT)及眼底血流成像OCT(OCTA)等多模式眼底影像检查。结果:典型的眼底彩色照相可显示色素异常沉着而呈现的蝶翅样病变外观,病变进展后蝶形外观不明显,而相应区域萎缩;红外照相显示BPD患者的眼底黄色病灶,表现为白色高亮影像;自发荧光可有斑片状、点状所勾勒的蝶翅表现,也可有以上特征重叠的表现,当病变进展萎缩明显时,自发荧光不能显示典型的蝶形改变,但可以反映出色素上皮细胞的破坏程度范围;眼底荧光血管造影和脉络膜造影除了显示蝶形病变外,能更为精准地显示血管病变情况,尤其是脉络膜新生血管(CNV)的检查;OCT显示病变位于视网膜色素上皮(RPE)之上与光感受器之间。随病变进展,色素上皮表现相应扩大的损伤,继发CNV者可见突破RPE的高反射信号;OCTA显示病变对视网膜深层和浅层损伤不明显,但脉络膜血流信号不同程度丢失,可敏感检出CNV的血流影像。结论:多模式眼底影像技术提供了BPD患者病变发生发展的影像特征,有助于临床医生更加深入地认识该病。

乳腺X射线摄影非立体定位在乳腺微钙化灶活检中的临床应用

目的探讨乳腺X射线摄影非立体定位在乳腺微钙化灶切除中的临床应用。方法选取2015年1月—2019年1月广东省中西医结合医院常规乳腺X射线摄影中发现有病灶的患者84例,按随机数字表法分为实验组和对照组,每组42例。手动定位所有患者的微钙化灶,分别画线,收集所有患者的乳腺X射线片,测量钩针与最近钙化点的距离进行统计学分析。结果实验组和对照组平均每位患者行乳腺X射线摄影分别为5.5次和6.12次,两组比较,差异有统计学意义(P<0.05)。实验组和对照组钩针与最近钙化点的距离分别为(6.13±0.59)和(6.79±0.58)mm,两组比较,差异有统计学意义(P<0.05)。两组定位中均无出血、定位导丝折断等并发症发生,定位过程顺利。实验组术中均一次性活检成功。结论乳腺X射线摄影手动定位乳腺微钙化灶简单、易行,精确度高,具有令人满意的定位效果。

CASTING: A Potent Supramolecular Strategy to Cytosolically Deliver STING Agonist for Cancer Immunotherapy and SARS-CoV-2 Vaccination

Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase I clinical trials as a monotherapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral injection.These deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and therapy.Here,we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue retention.CASTING efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor recurrence.More importantly,CASTING displays a superior adjuvant activity on SARSCoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo.Collectively,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.

Calixarenes enabling well-adjusted organic-inorganic interface for inverted organic solar cells with 18.25%efficiency and multifold improved photostability under max power point tracking

Compared with organic solar cells(OSCs) adopting conventional architecture,inverted OSCs have offered generally better stability,where Zn O is the most widely used electron transporting layer(ETL) material.For ZnO-based inverted OSCs,a welltuned interface of organic(active layer)-inorganic(Zn O film) with matched surface energy(γS) is critical for both high performance and high stability.In this work,two typical calixarenes,C4A and Bu C4A,were employed as the tuning agents to adjust this organic-inorganic interface for ZnO-based inverted OSCs.As a result,with PM6:L8-BO as the active layer,significantly promoted power conversion efficiencies(PCEs) from 17.14%(for ZnO) to 18.25%(for ZnO/C4A) and 17.80%(for ZnO/Bu C4A) were achieved.Photodynamic studies indicate that the enhanced performance is due to the faster charge extraction process,the suppressed recombination and more ideal internal electric field in ZnO/calixarene-based devices.In addition,wellmatched interface energy and more ordered molecular aggregation in active layer effectively improved photostability and thermal stability for ZnO/calixarene-based devices.These results indicate that calixarenes could act as effective modifying agents of ZnO to improve inverted OSCs’ performance and stability simultaneously,and likely also stimulate calixarenes’ and other macromolecules’ broader studies in other organic electronic devices.

Containment of high-speed rotating disk fragments

Disk burst accidents sometimes happen in aeroengines.To avoid tragic consequences,aeroengine casings must have sufficient containment capability.Experiments and simulations need to be conducted to study the impact,distortion,and perforation caused by disk burst and which may give important clues to potential failure mechanisms.This paper presents some containment tests of high-speed rotating disk fragments,in which the original disks were burst into three equal fragments within a predetermined rotating speed range.The failure modes of the containment casing varied significantly with the thickness of the containment casing.Shearing,tearing,tensile fracture,and large plastic stretching deformation occurred in a thin-walled containment casing,while a thick-walled casing could contain disk fragments and withstand large plastic deformation.Numerical simulations were carried out to study the impact process and failure modes further.Good agreement was found between the results of the simulations and the tests.

Penetration of disk fragments following impact on thin plate

To investigate the ballistic resistance and failure pattern of aeroengine casing following the impact of disk fragments, and to determine the optimum case structure, the phenomena of a 1/3rd disk fragment impact on single and double-layered thin plate targets were simulated using nonlinear dynamical analysis software MSC.Dytran. Strain rate effect was introduced in a Johnson-Cook (JC) material model for the disk fragment and the plate. Impact modeling was based on the Arbitrary Lagrange-Eulerian method, and simulated using explicit finite element method (FEM). Simulation results showed that the major failure pattern of the plate is shearing and tensile fracture with large plastic deformation. It was also concluded that the ballistic limit velocity increases with the standoff distance when it is beyond a certain value, and that greater resistance is obtained when the front plate has either a proportionately low or high thickness. The impact resistance of a double-layered plate may exceed that of a single plate if the thicknesses and standoff distance of the two plates are set appropriately.

Synthesis and biological evaluation of novel 1,2,4-triazole containing 1,2,3-thiadiazole derivatives

A series of novel 1,2,4-triazoles containing 1,2,3-thiadiazole derivatives were designed and synthesized. Their structures were confirmed by melting points, IR, 1H NMR, and elemental analysis and ESI-MS or HRMS. Preliminary bioassays indicated that these compounds exhibited very good insecticidal activity against Aphis laburni at 100 μg/mL, with mortality no less than 95%. Compounds 6a, 6c, 6f, 61 showed higher curative activity against TMV and compound 6h showed a higher induction effects against TMV in vivo at 100 μg/mL. Collectively, our data demonstrate a new strategy for control of insects and viruses.