Research Progress of Systemic Immune Inflammatory Index in Prostate Cancer

Prostate cancer has gradually risen to become the second most common cancer threatening men’s health, and prostate-specific antigen (PSA), as the main screening indicator for prostate cancer, has the defects of low specificity and insufficient diagnostic efficacy. As a novel inflammatory index based on neutrophil, lymphocyte and platelet counts, the systemic immune-inflammation index (SII) has recently become a more powerful biomarker for predicting the occurrence and progression of various malignancies. SII reflects the systemic inflammatory response of prostate cancer patients in a more balanced manner, and has higher predictive value than neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). High SII values are often associated with cancer progression and poor prognosis. This article reviews the research progress of SII in prostate cancer, in order to provide guidance for clinical practice.

Inflammatory/immune-suppressive microenvironment characteristics of pancreatic cancer patients with Shi-Re syndrome identified by extracellular vesicle long RNA profiling

Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.

Study on the correlation between TCM syndrome differentiation and immune inflammation index of Sjogren's syndrome

Objective:To observe the relationship between the distribution of TCM Syndromes of primary Sjogren's syndrome(pSS)and the changes of erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM.Methods:157 diagnosed PSS patients were divided into dampness heat obstructing collaterals syndrome,dryness evil invading lung syndrome,Qi blood stasis syndrome,liver kidney yin deficiency syndrome and Qi Yin deficiency syndrome according to TCM syndrome differentiation standard.The age,course of disease,general health score in international universal quality of life scale,self rating Anxiety scale(SAS),self rating Depression Scale(SDS)and erythrocyte sedimentation rate were observed and detected(ESR,C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM and other immune inflammatory indexes were detected.The relationship between different TCM Syndromes of PSS and molecular level changes of immune inflammatory indexes was analyzed and compared,as well as the impact on quality of life and mental emotion.Results:The overall health score of patients with Qi Yin deficiency syndrome was significantly lower than that of patients with dampness heat obstructing collaterals and dampness evil invading lung syndrome(P<0.01),while the SAS and SDS scores of patients with Qi Yin deficiency syndrome were significantly higher than those of patients with dampness heat invading lung syndrome and dampness heat obstructing collaterals syndrome(P<0.05,P<0.01);ESR,CRP,RF,TNF-α,IL-6,IgA,IgG and IgM related laboratory indexes of patients with dampness heat obstructing collaterals syndrome were significantly higher than those of patients with dry evil invading lung syndrome,liver kidney yin deficiency syndrome and liver kidney yin deficiency syndrome Qi Yin deficiency syndrome and Qi blood stasis syndrome(P<0.05,P<0.01).Correlation test found that the above five syndrome types were positively correlated with hs-CRP,IL-6,TNF-ɑindicators(P<0.05).Conclusion:The overall health,SAS,SDS and related hs-CRP,IL-6,TNF-ɑand some others indexes of SS patients are associated with TCM syndromes.

COVID-19 and liver dysfunction in children:Current views and new hypotheses

Coronavirus disease 2019(COVID-19)poses an extremely serious global impact on public healthcare for individuals of all ages,including children.Increasing evidence has shown that liver abnormalities are commonly found in children with COVID-19,and age-related features in innate and adaptive response have been demonstrated.However,there are few reports and studies on COVID-19 related liver injury in children,and the data are scattered.So that many contradictions have arose.This situation is not only due to the serious ethical issues in studying pediatric patients with COVID-19,but also because of the short duration and wide coverage of the COVID-19 epidemic,the severity and complexity of clinical cases varied,as did the inclusion criteria for case reporting and patient outcomes.Therefore,we totaled the incidences,characteristics and pathomechanism of liver injury in children since the COVID-19 outbreak.The etiology of COVID-19-related liver injury is divided into three categories:(1)The direct mechanism involves severe acute respiratory syndrome coronavirus 2 binding to angiotensin-converting enzyme 2 in the liver or bile duct to exert direct toxicity;(2)the indirect mechanisms include an inflammatory immune response and hypoxia;and(3)COVID-19-related treatments,such as mechanical ventilation and antiviral drugs,may cause liver injury.In summary,this minireview provides fundamental insights into COVID-19 and liver dysfunction in children.

Neurological complications of hematopoietic cell transplantation in children and adults

Hematopoietic cell transplantation（HCT） is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen（HLA）-matched donor（allogeneic） or from the patient（autologous）. Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease（Gv HD）. Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, Gv HD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT：（1） early complications（in the first month）-related to harvesting of stem cells, during conditioning（drug toxicity, posterior reversible encephalopathy syndrome）, related to pancytopenia,（2） intermediate phase complications（second to sixth month）-central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus,（3） late phase complications（after sixth month）-neurological complications of Gv HD, second neoplasms and relapses of the original disease.

Oxygen-glucose deprivation of neurons transfected with toll-like receptor 3-siRNA Determination of an optimal transfection sequence

Toll-like receptor 3 protein expression has been shown to be upregulated during cerebral ische- mia/reperfusion injury in rats. In this study, rat primary cortical neurons were subjected to oxy- gen-glucose deprivation to simulate cerebral ischemia/reperfusion injury. Chemically synthesized small interfedng RNA （siRNA）-1280, -1724 and -418 specific to toll-like receptor 3 were transfected into oxygen-glucose deprived cortical neurons to suppress the upregulation of toll-like receptor 3 protein expression. Western blotting demonstrated that after transfection with siRNA, toll-like re- ceptor 3 protein expression reduced, especially in the toll-like receptor 3-1724 group. These results suggested that siRNA-1724 is an optimal sequence for inhibiting toll-like receptor 3 expression in cortical neurons following oxygen-glucose deprivation.

Effects of postoperative immune-enhancing enteral nutrition on the immune system,inflammatory responses,and clinical outcome

Objective This study was conducted to evaluate the effects of postoperative immune enhancing enteral nutrition on the immune system,inflammatory responses,and clinical outcome of patients undergoing major abdominal surgery. Methods This study was designed as a multicenter,prospective,randomized and controlled clinical trial. One hundred twenty-four patients undergoing major abdominal surgery were randomly assigned to receive either an immune enhancing enteral diet or an isocaloric and isonitrogenous control enteral diet for seven days. Enteral feeding was initiated 24 hours after surgery. Host immunity was evaluated by measuring levels of IgG,IgM,IgA,CD4,CD8,and CD4/CD8,and the inflammatory response was determined by assessing IL-1α, IL-2, IL-6, IL-10, and TNF-α levels. Infectious complications were also recorded. Results One hundred twenty patients completed the study and four patients were excluded. On postoperative day 9,among patients receiving an immune enhancing diet,IgG,IgA,CD4 and CD4/CD8 levels were significantly higher and TNF-α and IL-6 concentrations were significantly lower compared to the control group. Moreover,among patients receiving an immune enhancing diet,when comparing preoperation to day 9 postoperation levels,increases in IgA,CD4,and CD4/CD8 levels were significantly higher than in control patients and increases in TNF-α concentrations were significantly lower. No statistically significant differences were found between the two groups with regard to infectious complications. Conclusions Postoperative administration of immune enhancing enteral nutrition in patients undergoing major abdominal surgery can positively modulate postoperative immunosuppressive and inflammatory responses.

Sequential gastrodin release PU/n-HA composite scaffolds reprogram macrophages for improved osteogenesis and angiogenesis

Wound healing is a highly orchestrated process involving a variety of cells,including immune cells.Developing immunomodulatory biomaterials for regenerative engineering applications,such as bone regeneration,is an appealing strategy.Herein,inspired by the immunomodulatory effects of gastrodin(a bioactive component in traditional Chinese herbal medicine),a series of new immunomodulatory gastrodin-comprising biodegradable polyurethane(gastrodin-PU)and nano-hydroxyapatite(n-HA)(gastrodin-PU/n-HA)composites were developed.RAW 264.7 macrophages,rat bone marrow mesenchymal stem cells(rBMSCs),and human umbilical vein endothelial cells(HUVECs)were cultured with gastrodin-PU/n-HA containing different concentrations of gastrodin(0.5%,1%,and 2%)to decipher their immunomodulatory effects on osteogenesis and angiogenesis in vitro.Results demonstrated that,compared with PU/n-HA,gastrodin-PU/n-HA induced macrophage polarization toward the M2 phenotype,as evidenced by the higher expression level of pro-regenerative cytokines(CD206,Arg-1)and the lower expression of pro-inflammatory cytokines(iNOS).The expression levels of osteogenesis-related factors(BMP-2 and ALP)in the rBMSCs and angiogenesis-related factors(VEGF and BFGF)in the HUVECs were significantly up-regulated in gastrodin-PU/n-HA/macrophage-conditioned medium.The immunomodulatory effects of gastrodin-PU/n-HA to reprogram macrophages from a pro-inflammatory(M1)phenotype to an anti-inflammatory and pro-healing(M2)phenotype were validated in a rat subcutaneous implantation model.And the 2%gastrodin-PU/n-HA significantly decreased fibrous capsule formation and enhanced angiogenesis.Additionally,2%gastrodin-PU/n-HA scaffolds implanted in the rat femoral condyle defect model showed accelerated osteogenesis and angiogenesis.Thus,the novel gastrodin-PU/n-HA scaffold may represent a new and promising immunomodulatory biomaterial for bone repair and regeneration.

Advances in classification of aortic dissection

Background Aortic dissection remains one of the most acute and critical diseases in cardiac surgery,with high mortality and disability rates.In the 1960s,DeBakeyfirst proposed the classification of aortic dissection.Subsequently,various classifications of aortic dissection have been proposed.To facilitate clinicians and medical staff involved in the treatment of aortic dissection to make better assessment of the condition of aortic dissection patients and to make reasonable clinical decisions,we reviewed several current mainstream classification schemes.We hope that this paper inspires other researchers to propose a new,more suitable classification scheme for use in the clinical setting.

Non-genetic mechanisms of diabetic nephropathy

Diabetic nephropathy （DN） is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomeruIar basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial-mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte-endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.

Subacute ruminal acidosis in dairy herds:Microbiological and nutritional causes,consequences,and prevention strategies

Dairy cattle are frequently fed high-concentrate(HC)diets in modern intensive feeding systems,especially in the transition period.During this period,cows face many alterations that include hormonal changes and shifting to a lactating state.Switching to a HC diet that may disrupt the ruminal microbiota balance can lead to subacute ruminal acidosis(SARA).Moreover,the main factor shaping the rumen microbiota is dietary composition,especially the ratio of starch to fibrous carbohydrates.Feeding highly fermentable carbohydrate diets after adaptation to forage diets leads to a rumen fermentation rate that exceeds rumen absorption and buffering rates,resulting in a reduction in ruminal pH.As a result of Gram-negative bacterial cell lysis,an increase in harmful ruminal bacterial metabolites,including lipopolysaccharide,lactic acid,and histamine,is observed.The interactions between the host immune system and the ruminal microbiota play an essential role in many physiological processes and the development of the disorder.Progress in DNA sequencing and bioinformatics platforms provides new opportunities to investigate the composition of ruminal microbes and yields unique advances in understanding ecology of the rumen.Subacute ruminal acidosis is linked with a change in the ruminal microbiota structure and richness and with other metabolic disorders;such as rumenitis,milk fat depression,laminitis,and liver abscesses.Therefore,this review aims to explore a better understanding of the crosstalk between diet and microbiota in the prevalence of rumen acidosis and its consequences,which is crucial for control strategies such as feeding management,and supplementation with thiamine,prebiotics,and probiotics.

Immunostimulation in the era of the metagenome

Microbes are increasingly being implicated in autoimmune disease.This calls for a re-evaluation of how these chronic inflammatory illnesses are routinely treated.The standard of care for autoimmune disease remains the use of medications that slow the immune response,while treatments aimed at eradicating microbes seek the exact opposite-stimulation of the innate immune response.Immunostimulation is complicated by a cascade of sequelae,including exacerbated inflammation,which occurs in response to microbial death.Over the past 8 years,we have collaborated with American and international clinical professionals to research a model-based treatment for inflammatory disease.This intervention,designed to stimulate the innate immune response,has required a reevaluation of disease progression and amelioration.Paramount is the inherent conflict between palliation and microbicidal efficacy.Increased microbicidal activity was experienced as immunopathology-a temporary worsening of symptoms.Further studies are needed,but they will require careful planning to manage this immunopathology.

Research progress on the pathogenesis of aortic dissection

Aortic dissection(AD) is a cardiovascular emergency with a high mortality rate, and the risk of death is estimated to increase by 1%-2% per hour. AD is complicated by variable clinical manifestations, and early detection and treatment can give more time for the treatment of patients.Hypertension is the most common cause of AD. In China, 65%-75% of patients with AD have poor blood pressure control. Patients with AD who are less than40 years of age are more likely to suffer from genetic diseases. Connective tissue disease(CTD) plays a dominant role in genetic diseases. Recently, inflammatory immunity, oxidative stress, obstructive sleep apnea-hypopnea syndrome(OSAHS), and other risk factors are being further studied. The new pathogenic factors should be explored to provide an accurate and effective prevention and treatment basis and new diagnostic methods and targets for drug therapy for AD.