Conservative management of multi-trauma induced peritonitis:Experience,outcomes,and indications

BACKGROUND The concept of mandatory laparotomy in treating traumatic peritonitis has been increasingly questioned recently.AIM To summarize and share the experience of conservative treatment of patients with multi-trauma induced peritonitis.METHODS A retrospective review was performed on patients with multiple injury induced traumatic peritonitis.RESULTS A total of 184 patients with multiple injury induced traumatic peritonitis were reviewed.46 of them underwent conservative treatment.None of the 46 patients with conservative treatment switched to surgical treatment,and all of them were cured and discharged after successful conservative treatment.No significant abnormal findings were observed at regular follow-up after discharge.CONCLUSION Conservative management is safe,effective,feasible,and beneficial in hemodynamically stable patients with traumatic peritonitis if there is no definite evidence of severe abdominal visceral organ injury.

Platelets in hemostasis and thrombosis:Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis

Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.

Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells： potential roles in airway inflammation

航线发炎是许多呼吸障碍的特点，例如气喘和膀胱的纤维变性。在发炎触发的航线基因表示的变化在这些疾病的致病起一个关键作用。基因连接研究建议 ESE-2 和 ESE-3，编码上皮特定的 Ets-domain-containing 抄写因素，是候选人气喘危险性基因。我们这里报导 et 家庭抄写因素 ESE-1 的另一个成员的表示，以及 ESE-3，起来在支气管的上皮的房间线由煽动性的 cytokines interleukin-1beta (IL-1beta ) 和肿瘤坏死 factor-alpha (TNF-alpha ) 调整了。有 IL-1beta 和 TNF-alpha 的这些房间的处理为 ESE-1 和 ESE-3 导致了信使 rna 表示的戏剧的增加。我们证明导致的表示被抄写因素 NF-kappaB 的激活调停。我们描绘了 ESE-1 和 ESE-3 倡导者并且识别了为导致 cytokine 的表达式被要求的 NF-kappaB 有约束力的序列。另外，我们也表明那 ESE-1 在上面调整 ESE-3 表示， down 由 cytokines 调整它的自己的正式就职。最后，我们在 Elf3 显示出那(对人的 ESE-1 相应) 猛烈老鼠，煽动性的 cytokine interleukin-6 (IL-6 ) 的表示是调整的 down。我们的调查结果建议 ESE-1 和 ESE-3 在航线发炎起一个重要作用。

Establishment of an optimized CTC detection model consisting of EpCAM,MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics

Objective:Emerging studies have demonstrated the promising clinical value of circulating tumor cells(CTCs)for diagnosis,disease assessment,treatment monitoring and prognosis in epithelial ovarian cancer.However,the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards.Methods:We enrolled 160 patients with epithelial ovarian cancer as the experimental group,and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group.We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens(EpCAM and MUC1),and used multiple reverse transcription-polymerase chain reaction(RT-PCR)detecting three markers(EpCAM,MUC1 and WT1)for quantification.And then we used a binary logistic regression analysis and focused on EpCAM,MUC1 and WT1 to establish an optimized CTC detection model.Results:The sensitivity and specificity of the optimized model is 79.4%and 92.2%,respectively.The specificity of the CTC detection model is significantly higher than CA125(92.2%vs.82.2%,P=0.044),and the detection rate of CTCs was higher than the positive rate of CA125(74.5%vs.58.2%,P=0.069)in early-stage patients(stage I and II).The detection rate of CTCs was significantly higher in patients with ascitic volume≥500 mL,suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy(P<0.05).The detection rate of CTC;and CTC;was significantly higher in chemo-resistant patients(26.3%vs.11.9%;26.4%vs.13.4%,P<0.05).The median progression-free survival time for CTC;patients trended to be longer than CTC;patients,and overall survival was shorter in CTC;patients(P=0.043).Conclusions:Our study presents an optimized detection model for CTCs,which consists of the expression levels of three markers(EpCAM,MUC1 and WT1).In comparison with CA125,our model has high specificity and demonstrates better diagnostic values,especially for early-stage ovarian cancer.Detection of CTC;and CTC;had predictive value for chemotherapy resistance,and the detection of CTC;suggested poor prognosis.

Genome-wide identification of functional enhancers and their potential roles in pig breeding

Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,development and disease.Genome-wide quantification of functional enhancers in the pig is needed.Results:We performed self-transcribing active regulatory region sequencing(STARR-seq)in the porcine kidney epithelial PK15 and testicular ST cell lines,and reliably identified 2576 functional enhancers.Most of these enhancers were located in repetitive sequences and were enriched within silent and lowly expressed genes.Enhancers poorly overlapped with chromatin accessibility regions and were highly enriched in chromatin with the repressive histone modification H3K9me3,which is different from predicted pig enhancers detected using ChIP-seq for H3K27ac or/and H3K4me1 modified histones.This suggests that most pig enhancers identified with STARR-seq are endogenously repressed at the chromatin level and may function during cell type-specific development or at specific developmental stages.Additionally,the PPP3CA gene is associated with the loin muscle area trait and the QKI gene is associated with alkaline phosphatase activity that may be regulated by distal functional enhancers.Conclusions:In summary,we generated the first functional enhancer map in PK15 and ST cells for the pig genome and highlight its potential roles in pig breeding.

Duplication and diversification of insulin genes in ray-finned fish

Insulin is a key hormone for the regulation of metabolism in vertebrates.Insulin is produced by pancreatic islet cells in response to elevated glucose levels and leads to the uptake of glucose by tissues such as liver and adipose tissue to store energy.Insulin also has additional functions in regulating development.Previous work has shown that the proglucagon gene,which encodes hormones counter regulating insulin,is duplicated in teleost fish,and that the peptide hormones encoded by these genes have diversified in function.I sought to determine whether similar processes have occurred to insulin genes in these species.Searches of fish genomes revealed an unexpected diversity of insulin genes.A triplication of the insulin gene occurred at the origin of teleost fish,however one of these three genes,insc,has been lost in most teleost fish lineages.The two other insulin genes,insa and insb,have been retained but show differing levels of selective constraint suggesting that they might have diversified in function.Intriguingly,a duplicate copy of the insa gene,which I named insab,is found in many fish.The coding sequenee encoded by insab genes is under weak selective constraint,with its predicted protein sequences losing their potential to be processed into a two-peptide hormone.However,these sequences have retained perfectly conserved cystine residues,suggesting that they maintain insulin's three-dimensional structure and therefore might modulate the processing and secretion of insulin produced by the other genes.

Genomic organization and evolution of ruminant lysozyme c genes

Ruminant stomach lysozyme is a long established model of adaptive gene evolution. Evolution of stomach lysozyme function required changes in the site of expression of the lysozyme c gene and changes in the enzymatic properties of the enzyme. In ruminant mammals, these changes were associated with a change in the size of the lysozyme c gene family. The recent release of near complete genome sequences from several ruminant species allows a more complete examination of the evolution and diversification of the lysozyme c gene family. Here we characterize the size of the lysozyme c gene family in extant ruminants and demonstrate that their pecoran ruminant ancestor had a family of at least 10 lysozyme c genes, which included at least two pseudogenes. Evolutionary analysis of the ruminant lysozyme c gene sequences demonstrate that each of the four exons of the lysozyme c gene has a unique evolutionary history, indicating that they participated independently in concerted evolution. These analyses also show that episodic changes in the evolutionary constraints on the protein sequences occurred, with lysozyme c genes expressed in the abomasum of the stomach of extant ruminant species showing the greatest levels of selective constraints.

Complex role of autophagy in regulation of hepatic lipid andlipoprotein metabolism

Discovering new therapeutic interventions to treat lipid and lipoprotein disorders is of great interest and the discovery of autophagy as a regulator of lipid metabolism has opened up new avenues for targeting modulators of this pathway. Autophagy is a degradative process that targets cellular components to the lysosome and recent studies have indicated a role for autophagy in regulating hepatic lipid metabolism(known as lipophagy) as well as lipoprotein assembly. Autophagy directly targets apolipoprotein B-100(apoB100), the structural protein component of very lowdensity lipoproteins(VLDLs), and further targets lipid droplets(LDs), the cellular storage for neutral lipids.Autophagy thus plays a complex and dual role in VLDL particle assembly by regulating apoB 100 degradation as well as aiding the maturation of VLDL particles by hydrolyzing lipid from LDs. The purpose of this article is to review our current understanding of molecular and cellular mechanisms mediating authophagic control of hepatic lipid biogenesis and VLDL production as well as dysregulation in insulin resistance and dyslipidemia.

Unveiling the functional and evolutionary landscape of RNA editing in chicken using genomics and transcriptomics

The evolutionary and functional features of RNA editing are well studied in mammals,cephalopods,and insects,but not in birds.Here,we integrated transcriptomic and whole-genomic analyses to exhaustively characterize the expansive repertoire of adenosine-to-inosine(A-to-I)RNA editing sites(RESs)in the chicken.In addition,we investigated the evolutionary status of the chicken editome as a potential mechanism of domestication.We detected the lowest editing level in the liver of chickens,compared to muscles in humans,and found higher editing activity and specificity in the brain than in non-neural tissues,consistent with the brain’s functional complexity.To a certain extent,specific editing activity may account for the specific functions of tissues.Our results also revealed that sequences critical to RES secondary structures remained conserved within avian evolution.Furthermore,the RNA editome was shaped by purifying selection during chicken domestication and most RESs may have served as a selection pool for a few functional RESs involved in chicken domestication,including evolution of nervous and immune systems.Regulation of RNA editing in chickens by adenosine deaminase acting on RNA(ADAR)enzymes may be affected by non-ADAR factors whose expression levels changed widely after ADAR knockdown.Collectively,we provide comprehensive lists of candidate RESs and non-ADAR-editing regulators in the chicken,thus contributing to our current understanding of the functions and evolution of RNA editing in animals.

Mesh-Related SIN Syndrome. A Surreptitious Irreversible Neuralgia and Its Morphologic Background in the Etiology of Post-Herniorrhaphy Pain

Purpose: The ubiquitous use of synthetic materials in hernia surgery has brought about a new clinical syndrome: Surreptitious Irreversible Neuralgia (SIN). It is surreptitious because it is of slow onset, unsuspected and enigmatic to clinicians;irreversible because the pain is progressive, unrelenting and unresponsive to treatment. Removal of the mesh does not guarantee pain relief. Neuralgia following mesh insertion, when it occurs, remains a poorly understood phenomenon. Methods: Ten specimens in each group: virgin tissue, scar tissue and explanted mesh from the posterior inguinal wall were examined histologically to assess nerve density, nerve size and nerve and vessel ingrowth into the deformed mesh and within its pores. Results: There was no significant difference in nerve density between virgin, scar and mesh samples. All of the explanted meshes had nerves within the scar tissue encasing the mesh (interstitial infiltration). Nerve ingrowth through the pores of the mesh (micro-entrapment) was detected in 90% of the explanted mesh specimens. Additionally, nerves were detected entrapped within the folds and deformations of mesh explants. Ingrown vessels showed congestion and focal fibrin thrombi. Conclusion: The presence of mesh does not significantly affect nerve density, while the nerves and their terminal ends are in a vulnerable position about the mesh and within its pores. These pores need to be viewed as “mini-compartments” of biological tissue where the vasculature, nerves and their receptors are exposed to potential mechanical and chemical factors: scarring, entrapment, compression, tugging, deformation, contraction, hypoxia/acidosis, inflammation and edema.

The interaction of versican with its binding partners

Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within theextracellular matrix (ECM). Versican, like other members of its family, has unique N- and C-terminal globular regions,each with multiple motifs. A large glycosaminoglycan-binding region lies between them. This review will begin byoutlining these structures, in the context of ECM proteoglycans. The diverse binding partners afforded to versican byvirtue of its modular design will then be examined. These include ECM components, such as hyaluronan, type Icollagen, tenascin-R, fibulin-1, and -2, fibrillin-1, fibronectin, P- and L-selectins, and chemokines. Versican also binds tothe cell surface proteins CD44, integrin β1, epidermal growth factor receptor, and P-selectin glycoprotein ligand-1.These multiple interactors play important roles in cell behaviour, and the roles of versican in modulating such processesare discussed.

IL-17RD （Sef or IL-17RLM） interacts with IL-17 receptor and mediates IL-17 signaling

Interleukin-17 (IL-17 或 IL-17A ) 生产是 TH17 房间的一个特点，贡献多重自体免疫、煽动性的疾病的致病的 CD4+ T 淋巴细胞的一个新唯一的系。IL-17 受体(IL-17R 或 IL-17RA ) 为 IL-17 生物活动是必要的。新兴的数据建议 heteromeric 或 homomeric 受体建筑群的形成为 IL-17 发信号被要求。这里，我们证明孤儿受体 IL-17RD (Sef，类似的表示到 FGF 基因或 IL-17RLM ) 被联系并且有 IL-17R 的 colocalized。重要地， IL-17RD 调停 IL-17 发信号，用一个酶记者评估了由 24p3 的本国的倡导者开车， IL-17 目标基因。另外，主导否定地缺乏细胞内部的领域的 IL-17RD 异种压制 IL-17R-mediated IL-17 发信号。而且，象 IL-17R 一样的 IL-17RD 与 TRAF6 被联系，一个 IL-17R 下游的分子。这些结果显示 IL-17RD 是表明建筑群的 IL-17 受体的部分，因此为通过 heteromeric 或 homomeric 受体建筑群发信号的 IL-17 提供新奇证据。

Postprandial dyslipidemia in insulin resistant states in adolescent populations

Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults,but also in adolescents.The metabolic syndrome,a complex cluster of metabolic abnormalities,increases one’s risk of developing type 2 diabetes and cardiovascular disease(CVD).Dyslipidemia,a key component of the metabolic syndrome,is highly associated with insulin resistance and contributes to increased CVD risk.Dyslipidemia has traditionally been assessed using a fasting lipid profile [i.e.fasting triglycerides,total cholesterol,low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)].However,the postprandial state predominates over the course of a day and non-fasting triglycerides independently predict CVD risk.In insulin resistant states,the intestine overproduces triglyceride-rich lipoprotein(TRL) particles,termed chylomicrons(CMs),following ingestion of a fat-containing meal,as well as in the fasting state.Along with elevated hepatic TRLs(i.e.very-low density lipoproteins),CMs contribute to remnant lipoprotein accumulation,small dense LDL particles,and reduced HDL-C,which collectively increase CVD risk.Given the early genesis of atherosclerosis and physiological metabolic changes during adolescence,studying postprandial dyslipidemia in the adolescent population is an important area of study.Postprandial dyslipidemia in the pediatric population poses a significant public health concern,warranting a better understanding of its pathogenesis and association with insulin resistance and CVD.This review discusses the metabolic syndrome,focusing on the link between insulin resistance,postprandial dyslipidemia,and CVD risk.Furthermore,the clinical significance and functional assessment of postprandial dyslipidemia,specifically in the adolescent population,is discussed in more detail.

The therapeutic potential of nerve growth factor combined with blood-brain barrier modulation by focused ultrasound for neurodegenerative disorders

Nerve growth factor(NGF) is a neurotrophic factor critical for cholinergic neuronal survival, phenotypic maintenance and plasticity in the mammalian brain. NGF has been implicated in the pathogenesis of neurodegenerative disorders, with direct administration of NGF into the brain capable of facilitating neuroprotection and repair.

Gut-associated lymphoid tissue or so-called “dome” carcinoma of the colon: Review

AIM To present a comprehensive review of the etiology, clinical features, macroscopic and pathological findings, and clinical significance of Gut-associated lymphoid tissue or "dome" carcinoma of the colon.METHODS The English language medical literature on gut-or gastrointestinal-associated lymphoid tissue(GALT) or "dome" carcinoma of the colon was searched and appraised.RESULTS GALT/dome-type carcinomas of the colon are thought to arise from the M-cells of the lymphoglandular complex of the intestine. They are typically asymptomatic and have a characteristic endoscopic plaque-or "dome"-like appearance. Although the histology of GALT/dome-type carcinomas displays some variability, they are characterized by submucosal localization, a prominent lymphoid infiltrate with germinal center formation, tumor-infiltrating lymphocytes, absence of desmoplasia, and dilated glands lined by columnar epithelial cells with bland nuclear features and cytoplasmic eosinophilia. None of the patients reported in the literature with follow-up have developed metastatic disease or local recurrence.CONCLUSION Increased awareness amongst histopathologists of this variant of colorectal adenocarcinoma is likely to lead to the recognition of more cases.

Hepatocellular adenoma in the paediatric population:Molecular classification and clinical associations

Hepatocellular adenomas(HCAs)represent rare,benign liver tumours occurring predominantly in females taking oral contraceptives.In children,HCAs comprise less than 5%of hepatic tumours and demonstrate association with various conditions.The contemporary classification of HCAs,based on their distinctive genotypes and clinical phenotypes,includes hepatocyte nuclear factor 1 homeobox alpha-inactivated HCAs,beta-catenin-mutated HCAs,inflammatory HCAs,combined beta-catenin-mutated and inflammatory HCAs,sonic hedgehogactivated HCAs,and unclassified HCAs.In children,there is a lack of literature on the characteristics and distribution of HCA subtypes.In this review,we summarized different HCA subtypes and the clinicopathologic spectrum of HCAs in the paediatric population.

Molecular genetics of ependymoma

Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effective treatments other than surgical resection have all remained elusive.Until recently,ependymoma research was hindered by the small number of tumors available for study,low resolution of cytogenetic techniques,and lack of cell lines and animal models.Ependymoma heterogeneity,which manifests as variations in tumor location,patient age,histological grade,and clinical behavior,together with the observation of a balanced genomic profile in up to 50% of cases,presents additional challenges in understanding the development and progression of this disease.Despite these difficulties,we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic(copy number) and transcriptome profiling platforms.Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin.This review summarizes our current knowledge in the molecular genetics of ependymoma and proposes future research directions necessary to further advance this field.

Regulation of Parkin-dependent mitophagy by Bcl-2-associated athanogene(BAG)family members

Mitochondria are essential organelles that play a central role in cellular metabolism and physiology.Their broad range of functions include supplying energy,regulating signaling pathways,and maintaining control of cell proliferation and apoptosis.As defective mitochondria can perturb cellular homeostasis,quality control mechanisms have evolved to preserve mitochondrial fidelity in response to stress and aging(Palikaras et al.,2018).Persistent defects,however,trigger elimination of the entire organelle by an evolutionarily conserved set of cellular processes that specifically remove dysfunctional or surplus mitochondria.This selective degradation of the mitochondria through autophagy,termed mitophagy,is important in fine-tuning mitochondrial number.

Platelets in Thrombosis and Atherosclerosis

Platelets are anucleate cells generated from megakaryocytes in the bone marrow. After being released into the blood,platelets play essential roles in hemostasis and preserving vessel wall integrity. However,the processes of platelet adhesion,activation,and aggregation at the site of vascular injury may also cause vessel occlusion,and lead to thrombotic diseases.

Protein seeding in Alzheimer's disease and Parkinson's disease: Similarities and differences

Neurodegenerative pathology can be seeded by introduction of misfolded proteins and peptides into the nervous system. Models of Alzheimer's disease(AD) and Parkinson's disease(PD) have both demonstrated susceptibility to this seeding mechanism, emphasizing the role of misfolded conformations of disease-specific proteins and peptides in disease progression. Thinking of the amyloidogenic amyloid-beta peptide(Aβ) and alpha-synuclein(α-syn), of AD and PD, respectively, as prionoids requires a comparison of these molecules and the mechanisms underlying the progression of disease. Aβ and α-syn, despite their size differences, are both natively unstructured and misfold into β-structured conformers. Additionally, several studies implicate the significant role of membrane interactions, such as those with lipid rafts in the plasma membrane, in mediating protein aggregation and transfer of Aβ and α-syn between cells that may be common to both AD and PD. Examination of inter-neuronal transfer of proteins/peptides provides evidence into the core mechanism of neuropathological propagation. Specifically, uptake of aggregates likely occurs by the endocytic pathway, possibly in response to their formation of membrane pores via a mechanism shared with pore-forming toxins. Failure of cellular clearance machinery to degrade misfolded proteins favours their release into the extracellular space, where they can be taken up by directly connected, nearby neurons. Although similarities between AD and PD are frequent and include mechanistically similar transfer processes, what differentiates these diseases, in terms of temporal and spatial patterns of propagation, may be in part due to the differing kinetics of protein misfolding. Several examples of animal models demonstrating seeding and propagation by exogenous treatment with Aβ and α-syn highlight the importance of both the environment in which these seeds are formed as well as the environment into which the seeds are propagated. Although these studies suggest potent seeding effects by both Aβ and α-syn, they emphasize the need for future studies to thoroughly characterize "seeds" as well as analyze changes in the nervous system in response to exogenous insults.