Chelidonine reduces IL-1β-induced inflammation and matrix catabolism in chondrocytes and attenuates cartilage degeneration and synovial inflammation in rats

Chondrocyte inflammation and catabolism are two major features in the progression of osteoarthritis (OA). Chelidonine, a principal alkaloid extracted from Chelidonium majus, is suggested to show anti-inflammation, anti-apoptosis, and anti-oxidation activities in various diseases. However, its potential effects on OA cartilage degeneration remains unclear. To evaluate the effect of chelidonine on OA and its underlying mechanism, we incubated chondrocytes with interleukin (IL)-1β and chelidonine at varying concentrations. Then, we performed the CCK-8 assay, fluorescence immunostaining, reverse transcription PCR, ELISA, and western blotting to evaluate cell viability, catabolic/inflammatory factors, levels of extracellular matrix (ECM)-related proteins, and the involved pathways. H&E and Safranin-O staining and ELISA were performed to measure cartilage degradation and synovial inflammation. Chelidonine suppressed the IL-1β-mediated catabolism and inflammation of chondrocytes. Chelidonine suppressed the NF-κB pathway activation. Similarly, our in vivo experiment showed that chelidonine partially attenuated cartilage degradation while inhibiting synovial inflammation. Chelidonine inhibited inflammation and catabolism through modulation of NF-κB pathways in vitro, thereby avoiding rat cartilage degeneration and synovial inflammation within OA.

Influencing factors for persistent inflammation, immunosuppression, and catabolism syndrome in patients with severe acute pancreatitis and establishment of a predictive model / 临床肝胆病杂志

Objective To investigate the influencing factors for persistent inflammation, immunosuppression, and catabolism syndrome (PICS) in patients with severe acute pancreatitis(SAP), and to establish a predictive model. Methods A retrospective analysis was performed for the clinical data of 163 patients who were admitted to the intensive care unit and the emergency intensive care unit due to SAP in The First Affiliated Hospital of Guangxi Medical University from May 2012 to May 2022, and according to the diagnostic criteria for PICS, these patients were divided into PICS group (65 SAP patients with PICS) and non-PICS group (98 SAP patients without PICS). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Variance inflation factor and correlation matrix heatmap were used to evaluate multicollinearity between variables, and Lasso regression and multivariate logistic regression were used to identify independent risk factors and establish a nomogram predictive model. The receiver operating characteristic (ROC) curve, the calibration curve, and the Hosmer-Lemeshow goodness-of-fit test were used for the internal validation of the model, and the decision curve was used to evaluate the clinical practicability of the model. Results The univariate analysis showed that there were significant differences between the PICS group and the non-PICS group in mean arterial pressure, hemoglobin, hematocrit (HCT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), blood urea nitrogen, creatinine, Glasgow coma score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation, acute respiratory distress syndrome, acute kidney injury (AKI), acute liver injury, hypovolemic shock, sepsis, intra-abdominal hypertension, intra-abdominal hemorrhage, and multiple organ dysfunction syndrome (all P < 0.05). The Lasso regression analysis showed that related predictive variables included PLR, HCT, APACHE Ⅱ, SOFA, mechanical ventilation, AKI, hypovolemic shock, and intra-abdominal hypertension, and the multivariate logistic regression analysis showed that PLR (odds ratio [ OR ]=1.006, P < 0.05), mechanical ventilation ( OR =4.324, P < 0.05), AKI ( OR =3.432, P < 0.05), and hypovolemic shock ( OR = 6.910, P < 0.05) were independent risk factors for PICS in patients with SAP. Model fitting was performed for the above factors, and bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.874 (95% confidence interval: 0.822-0.925); the calibration curve of the model was close to the reference curve, and the Hosmer-Lemeshow goodness-of-fit test showed that the model was well fitted ( χ 2 =8.895, P =0.351). The decision curve analysis showed that the predictive model had good clinical practicability. Conclusion PLR, mechanical ventilation, AKI, and hypovolemic shock are independent risk factors for PICS in patients with SAP, and the nomogram model established has good discriminatory ability, calibration, and clinical practicability.

Taking the mechanism of glucose catabolism disorder in depression as an example to explore the research ideas and strategies of stable isotope tracer metabolomics / 药学学报

Stable isotope tracer metabolomics tracks and analyzes the whole metabolic process of the body through the tracer atoms, which belongs to the frontier technology in the field of biomedicine. This technology is of great significance and value for explaining the pathogenesis of diseases, finding biomarkers of diseases and drug action targets. Taking the mechanism of glucose catabolism disorder in depression as an example, this paper systematically expounds the stable isotope tracer metabolomics technology and its application. The research idea of stable isotope tracer metabolomics based on unmarked metabolomics was put forward, and the research strategy of biological significance interpretation from four dimensions of metabolite isotope abundance, key metabolic enzymes, metabolic flow direction and metabolite flow was given, which broke through the bottleneck of stable isotope tracer metabolomics research technology based on overall animal experiment, and provided scientific basis for the promotion and application of this technology.

GPRC5B protects osteoarthritis by regulation of autophagy signaling

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

Research advances in the therapeutic potential of xanthine oxidoreductase inhibitors for periodontitis / 口腔疾病防治

@#Periodontitis is associated with abnormal purine metabolism, which is manifested by increased uric acid in host blood and increased expression of the purine-degrading enzyme, xanthine oxidoreductase (XOR), in periodontal tissues. Both XOR and uric acid are pro-oxidative and pro-inflammatory mediators under pathological conditions. Animal studies have found that injection of uric acid promotes the progression of periodontitis and that febuxostat (an XOR inhibitor) improves tissue destruction in periodontitis. Therefore, blocking the source of uric acid may be a therapeutic strategy to control the progression of periodontitis. In this article, the rationality of XOR inhibitors as potential therapeutic drugs for periodontitis is reviewed. The literature review results suggest that XOR inhibitors show antioxidative, anti-inflammatory, and anti-osteoclastic effects, and XOR inhibitors show clinical efficacy in the treatment of infectious, inflammatory and osteolytic diseases. Although there is no direct evidence to support the finding that XOR inhibitors can ameliorate periodontal microecological dysbiosis, these drugs can modulate intestinal microflora dysbiosis, and there is indirect evidence to support a beneficial effect of XOR inhibitors on periodontal microecological dysbiosis. In conclusion, XOR inhibitors may be used as immunomodulators for the adjuvant treatment of periodontitis by inhibiting inflammation, oxidative stress and anti-osteoclast effects.

Biological characteristics and functions of glutathione cytoplasmic degrading enzyme ChaC1 / 中国生物化学与分子生物学报

Glutathione is a tri-peptide that plays key roles in antioxidation and detoxification. At present, research on glutathione metabolism mainly focuses on anabolism. And little is known about its catabolismin the cytoplasm. With the discovery of glutathione-specific γ-glutamylcyclotransferase ChaC1, thecatabolism of glutathione in the cytoplasm has gradually been unveiled. ChaC1 is one member of the γ-glutamylcyclotransferase (GGCT) family, catalyzing the degradation of glutathione and production of Cys-Gly and 5-oxoproline. ChaC1 is highly conserved, with a ~ 88% identity between human and mousegenes. Mutation of E115 in human ChaC1 or E116 in mouse ChaC1 abolishes its enzymatic activity. Notably, ChaC1 deficiency leads to embryonic lethality in the mouse and zebrafish, indicating ChaC1 isessential for embryo development. On the other side, ChaC1 is highly expressed in different types ofcancer and correlates with a poor prognosis, suggesting that ChaC1 also has important pathophysiologicalfunction. In this paper, we review the research progress on the structure, enzymatic activity andexpression pattern of ChaC1 in recent years, and summarize the role of ChaC1 in development anddiseases, providing new insights on the mechanisms and therapeutic strategies.

Early risk factors for persistent inflammation immunosuppression and catabolism syndrome in patients with severe polytrauma / 中华急诊医学杂志

Objective:To retrospectively assess early risk factor of persistent inflammation, immunosuppression and catabolism syndrome (PICS) in patients with severe polytrauma, in order to deepen the understanding of the pathological changes of chronic critical illness (CCI) after severe polytrauma.Methods:A total of 276 patients with severe polytrauma admitted to Department of Trauma Surgery of Tongji Hospital from March 2019 to December 2020 were enrolled. Inclusion criteria included patients who suffered severe polytrauma, and injury severity score (ISS) ≥27, age ≥18 years old, and had length of hospital stay >15 days. Exclusion criteria included previous medical history of malignancy, or immunological, consumptive, and metabolic diseases. The patient’s clinical characteristics, ISS scores, Glasgow coma scale (GCS), sequential organ failure assessment, APACHEⅡ scores, and nutrition and immune indexes on day 3 after injury were collected. The difference between the PICS group and N-PICS group were performed by Student’s t test, χ2 test or Mann-Whitney U test. The early risk factors were assessed in patients with PICS after severe polytrauma by logistic regression analysis. Results:According to the diagnostic criteria of PICS, all enrolled patients were divided into two groups: PICS group ( n=102) and N-PICS group (without PICS, n=174). Compared with the N-PICS group, patients in the PICS group were older and associated with more brain and chest injuries. On the third day after injury, serum levels of IL-6 and IL-10, and the ratio of Treg cells were significantly higher, the number and ratio of NK cells subset, and the ratio of activated T lymphocyte were significantly lower in the PICS group than in the N-PICS group ( P<0.05). Logistic regression analysis showed that the age>65 years old ( OR=2.375, 95% CI: 1.442-4.531), GCS ≤8 scores ( OR=3.431, 95% CI: 1.843-8.512), IL-10 >10 pg/mL ( OR=2.173, 95% CI: 1.751-5.614), the ratio of Treg cells >7% ( OR=3.871, 95% CI: 1.723-6.312), and the occurrence of traumatic brain and chest injuries ( OR=2.846, 95% CI: 1.522-5.361) were the early risk factors in patients with PICS after severe polytrauma. Conclusions:Age>65 years old, GCS score, IL-10, the ratio of Treg cells, and the occurrence of traumatic brain and chest injuries could be used as the early risk factors in patients with PICS after severe polytrauma. The discovery of early risk factors will help identify patients at high risk of PICS after severe polytrauma, and create the possibility for early intervention.

Research progress on tryptophan metabolism involved by gut microbiota in the diagnosis and treatment of acute radiation-induced intestinal injury / 中华放射肿瘤学杂志

Gut microbiota not only affects the activity of tryptophan metabolism rate limiting enzymes in intestinal cells, but also cooperatively produces a variety of catalytic enzymes, which directly affects the type and quantity of tryptophan metabolites in the intestine. Multiple tryptophan-associated indole compounds originating from the gut microbiome are significantly decreased in the peripheral blood of mice, and negatively correlated with radiation dose ranging from 2 to 10.4 Gy, which might be biomarkers for acute radiation-induced intestinal injury. Recent studies have reported that indole 3-propionic acid (IPA), indole-3-carboxaldehyde (I3A) and kynurenic acid (KYNA), which are tryptophan catabolites derived from gut microbiota, aryl hydrocarbon receptor, which is one of the receptors for tryptophan catabolites, and inhibition of indoleamine 2,3 dioxygenase-1, which is a main rate-limiting enzyme in intestinal tryptophan catabolism, can protect against radiation-induced intestinal toxicity. A more comprehensive understanding of the dynamics of tryptophan catabolites and their roles in acute radiation-induced intestinal injury is needed to deepen the understanding of the pathogenesis in radiation-induced intestinal injury and exploration of effective diagnostic and therapeutic approaches.

A prospective study of clinical characteristics and prognosis in patients with persistent inflammation, immunosuppression and catabolism syndrome after polytrauma / 中华急诊医学杂志

Objective:To prospectively assess clinical characteristics, potential causes and prognosis in patients with persistent inflammation, immunosuppression and catabolism syndrome (PICS) after polytrauma.Methods:Totally 1 083 patients with polytrauma admitted to Department of Traumatic Surgery of Tongji Hospital from Janury 2019 to July 2020 were enrolled. Exclusion criteria included age<18 years old, length of hospital stay<15 days, previous medical history of malignancy, or immunological, consumptive, and metabolic diseases. According to the diagnostic criteria of PICS, all enrolled patients were divided into two groups: PICS group and N-PICS group (without PICS). The patient’s clinical characteristics, ISS score, GCS score, SOFA score, and prognosis were collected. The χ2 test or Student’s t test was uesd to compare the difference between the PICS group and N-PICS group. Results:The incidence of PICS in patients with polytrauma was 11.7% (127/1 083). The majority of PICS patients were middle-aged and elderly men, 68.5% with traumatic brain injury and 59% with thoracic injury. GCS score was significantly lower, while ISS, APACHE II and SOFA scores were significantly higher in the PICS group than in the N-PICS group ( P<0.01, P<0.05). Among PICS patients, 79.5% were treated with mechanical ventilation and 76.3% were associated with pulmonary infection, with a 28-day mortality of 5.5% and a 180-day mortality of 16.5%, which were siginifcantly different from those without PICS. Conclusions:PICS has a high incidence after polytrauma and is commonly seen in middle-aged and elderly male patients with severe polytrauma, especially accompanied by traumatic brain injury or/and thoracic injury. Patients with PICS after polytrauma have poor long-term prognosis, so early identification and intervention should be strengthened in clinical practice.

Target-responsive subcellular catabolism analysis for early-stage antibody-drug conjugates screening and assessment

Events including antibody‒antigen affinity, internalization, trafficking and lysosomal proteolysis combinatorially determine the efficiency of antibody-drug conjugate (ADC) catabolism and hence the toxicity. Nevertheless, an approach that conveniently identifies proteins requisite for payload release and the ensuing toxicity for mechanistic studies and quality assessment is lacking. Considering the plethora of ADC candidates under development, we developed a target-responsive subcellular catabolism (TARSC) approach that examines ADC catabolism and probes changes in response to targeted interferences of proteins of interest. We firstly applied TARSC to study the commercial T-DM1 and the biosimilar. We recorded unequivocal catabolic behaviors regardless of the absence and presence of the targeted interferences. Their negligible differences in TARSC profiles agreed with their undifferentiated anti-tumoral efficacy according to further

Application of stable isotope-resolved metabolomics in glucose catabolism / 药学学报

With the rapid development of high sensitivity detection techniques such as nuclear magnetic resonance and mass spectrometry, stable isotope-resolved metabolomics has been widely used in elucidating the regulatory mechanism of metabolic pathways and metabolic flow analysis, and some breakthroughs have been made. In this paper the application of stable isotope-resolved metabolomics in glucose catabolic regulation, metabolic flow analysis and functional interpretation of key metabolic pathways is reviewed, providing references for the wider use and application of this technology.

Metabolism and function of lipids in the adipose and liver tissues of production ruminants: a review / Función y metabolismo de ácidos grasos en el tejido adiposo y hepático de rumiantes en producción: una revisión / Função e metabolismo de ácidos graxos no tecido adiposo e hepático de ruminantes em produção: uma revisão

Abstract The adipose and liver tissues influence the fatty acid metabolism, being largely responsible for regulating their biosynthesis, degradation and storage in body tissues, as well as for their secretion in milk and meat production from ruminants. Therefore, a better understanding of the functionality of fatty acid metabolism in these tissues and the factors that affect it, could provide the basis for the design of productive strategies in ruminants. Thus, the aim of this review is to present a general overview of the functionality and metabolism of fatty acids in the adipose and liver tissues in production ruminants. From the review, it could be established that fatty acids and triglycerides are the main lipid types in adipose and liver tissues. Adipose tissue is the main energy storage site for both ruminants and non-ruminants. Adipose tissue is metabolically associated with liver tissue through an equilibrium that regulates the processes of β-oxidation, de novo synthesis, and fatty acid transport at a tissue level. Finally, it was established that the fatty acids metabolism in adipose and liver tissue is affected by several factors, including nutrition and level of dietary restriction, genetics, physiological state, and environment, being nutrition the main factor.

Resumen El tejido adiposo (TA) y hepático influencian el metabolismo de ácidos grasos (AG), al ser en gran parte los responsables de regular su biosíntesis, degradación y almacenamiento en tejidos corporales, como también de su secreción en leche y carne de animales en producción. De esta forma, un mejor entendimiento de la funcionalidad del metabolismo de AG en estos tejidos y los factores que lo afectan, podría dar las bases para el diseño de estrategias productivas en rumiantes. Así, el objetivo de esta revisión es presentar un panorama general de la funcionalidad y metabolismo de los AG en el TA y hepático en rumiantes de producción. A partir de la revisión, se pudo establecer, que el tipo de lípidos mayoritarios en TA y hepático, lo forman los AG y triglicéridos. El TA es el principal sitio de almacenamiento energético tanto en rumiantes como en no rumiantes. El TA se encuentra metabólicamente asociado con el tejido hepático mediante un equilibrio que regula los procesos de β-oxidación, síntesis de novo y transporte de AG a nivel tisular. Finalmente, se pudo establecer que el metabolismo de AG en TA y hepático es afectado por diversos factores, tales como la nutrición, nivel de restricción dietaria, genética, estado fisiológico y medio ambiente, de los cuales, la nutrición tiene el mayor impacto.

Resumo O tecido adiposo (TA) e hepático influenciam o metabolismo dos ácidos graxos (AG), sendo amplamente responsável pela regulação de biossíntese, degradação e armazenamento destes nos tecidos corporais, bem como sua secreção no leite e na carne de animais em produção. Desta forma, uma melhor compreensão da funcionalidade do metabolismo dos AG nesses tecidos e os fatores que o afetam, poderia fornecer a base para o planejamento de estratégias produtivas em ruminantes. Assim, o objetivo desta revisão é apresentar uma visão geral da funcionalidade e metabolismo dos AG no TA e hepático em ruminantes de produção. A partir da revisão, foi estabelecido que o tipo de lipídios principais no TA e hepático, são os AG e triglicerídeos. O TA é o principal local de armazenamento de energia para ruminantes e não ruminantes. O TA está metabolicamente associado ao tecido hepático através de um equilíbrio que regula os processos de β-oxidação, síntese de novo e transporte de AG ao nível dos tecidos. Finalmente, foi estabelecido que o metabolismo da AG no TA e no hepatócito é afetado por vários fatores, como nutrição, nível de restrição alimentar, genética, estado fisiológico e ambiente, dos quais a nutrição tem o maior impacto.

Aspectos epidemiológicos del síndrome de inmunosupresión, inflamación y catabolismo persistente en pacientes crónicos críticamente enfermos / Epidemiological aspects of the syndrome of immunosuppression, inflammation and persistent catabolism in critical chronic ill patients / Aspectos epidemiológicos da síndrome de imunossupressão, inflamação e catabolismo persistente em pacientes crônico em estado crítico

Resumen: Los pacientes crónicos críticamente enfermos mantienen un ambiente inflamatorio persistente, inmunidad reducida y consumo progresivo de reservas fisiológicas. Se caracterizan por ingresos hospitalarios con estadías más prolongadas, mayor mortalidad y costos. Objetivo general: Describir las características del síndrome de inflamación, inmunosupresión y catabolismo persistente en pacientes críticos crónicamente enfermos hospitalizados en la Unidad de Cuidados Intensivos del Hospital General La Villa. Con el fin de conocer los aspectos epidemiológicos. Material y métodos: Estudio clínico prospectivo, descriptivo y observacional, analítico. Se ingresaron 25 pacientes con criterios de PICS acorde a la escala NUTRIC y cuadro clínico de enero-abril de 2018. Se realizaron pruebas de estadística descriptiva para variables cualitativas y para cuantitativas se utilizaron medidas de tendencia central. Pruebas inferenciales para contrastar variables cualitativas y para cuantitativas tablas de 2 x 2 para el cálculo de la odds ratio. Resultados: 25 pacientes cumplieron criterios de PICS, incidencia de 37.9%, la distribución por sexos fue 60% hombres y 40% mujeres. Edad promedio fue 48.8. Los diagnósticos más comunes fueron choque hipovolémico (28%), choque séptico (16%), 68% de los pacientes tenían un riesgo nutricional bajo y 32% riesgo alto, 84% de los pacientes requirieron algún tipo de soporte, el más común fue ventilación mecánica, Las complicaciones más comunes fueron las infecciosas (80%) principalmente NAVM. La mortalidad fue de 20%. Conclusiones: Los resultados en este estudio no difieren de los reportados en la bibliografía a nivel internacional, el síndrome de PICS se presenta en pacientes con mayor edad, mayor estancia hospitalaria y carencias nutricionales superiores en quienes las reservas biológicas no son suficientes para evitar la inmunosupresión que conlleva y genera el círculo vicioso que finalmente conduce a la muerte no sólo dentro de la UCI.

Abstract: Critically ill chronic patients maintain a persistent inflammatory environment, reduced immunity and progressive consumption of physiological reserves. They are characterized by hospital admissions with longer stays, higher mortality and costs. General objective: To describe the characteristics of the syndrome of inflammation, immunosuppression and persistent catabolism in critically ill critically ill patients hospitalized in the Intensive Care Unit of the La Villa General Hospital. In order to know the epidemiological aspects. Material and methods: Prospective, descriptive and observational clinical, analytical study. Patients were admitted with PICS criteria according to the NUTRIC score and clinical features from January-April 2018. Descriptive statistics tests were performed for qualitative variables, quantitative measures were used for quantitative central. Inferential tests to compare qualitative variables and for quantitative 2 x 2 tables for calculating the odds ratio. Results: 25 patients met criteria of PICS, incidence of 37.9%, the distribution by sex was 60% men and 40% women. Average age was 48.8. The most common diagnoses hypovolemic shock (28%), septic shock (16%), 68% of patients had a low nutritional risk and 32% high risk, 84% of patients required some kind of support the most common was ventilation mechanical, the most common complications were infectious (80%) mainly VAP. The mortality was 20%. Conclusions: The results in this study do not differ from those reported in the literature at the international level, the syndrome of PICS is presented in patients with older age, longer hospital stay and higher nutritional deficiencies in which biological reserves are not sufficient to avoid immunosuppression that leads to and generates the vicious circle that ultimately leads to death not only within the ICU.

Resumo: Os pacientes crônicos em estado crítico mantêm um ambiente inflamatório persistente, imunidade reduzida e consumo progressivo de reservas fisiológicas. Eles são caracterizados por internações hospitalares com estadias prolongadas, maior mortalidade e custos. Objetivo geral: Descrever as características da síndrome de inflamação, imunossupressão e catabolismo persistente em pacientes críticos cônicos internados na Unidade de Terapia Intensiva do Hospital Geral La Villa, com a finalidade de conhecer os aspectos epidemiológicos. Métodos: Estudo clínico prospectivo, analítico, descritivo e observacional. Foram admitidos 25 pacientes com critérios da PICS segundo a escala NUTRIC e quadro clínico de janeiro a abril de 2018. Realizou-se testes estatísticos descritivos para variáveis qualitativas e medidas de tendência central foram utilizadas para variáveis quantitativas. Testes inferenciais para comparar variáveis qualitativas e para quantitativas tabelas 2 x 2 para calcular o Odds Ratio. Resultados: 25 pacientes preencheram os critérios da PICS, incidência de 37.9%. A distribuição por sexo foi de 60% homens e 40% mulheres sendo que a idade média foi de 48.8 anos. Os diagnósticos mais comuns foram: choque hipovolêmico (28%) e choque séptico (16%) sendo que 68% dos pacientes apresentaram baixo risco nutricional e 32% risco elevado. 84% dos pacientes necessitaram de algum tipo de suporte sendo o mais comum a ventilação mecânica. As complicações mais comuns foram infecciosas (80%) principalmente a PAVM. A mortalidade foi de 20%. Conclusões: Os resultados deste estudo não diferem dos relatados na literatura a nível internacional. A síndrome PICS ocorre em pacientes com idade avançada, maior tempo de internação e deficiências nutricionais graves em que as reservas biológicas não são suficientes para evitar imunossupressão. Isso implica e gera o círculo vicioso que finalmente leva à morte não apenas dentro da UTI.

Persistent inflammation, immune-suppression and catabolism syndrome secondary to sepsis in elderly patients in medical intensive care unit:a retrospective study / 中华老年医学杂志

Objective To investigate the clinical characteristics,risk factors and prognosis of patients with persistent inflammation,immune-suppression and catabolism syndrome(PICS)secondary to sepsis in medical intensive care unit(MICU)in initial stage,in order to increase the understanding of PICS and provide the reference experience for the early screening of high-risk patients.Methods A total of 298 elderly patients diagnosed as sepsis admitted into MICU from Aug.2013 to Dec.2016 were retrospectively studied.Of them,97 patients meeting inclusion criteria were ultimately enrolled and separated into the PICS group and the non-PICS group.General and clinical data and laboratory indexes at first day admitted into MICU were compared between the two groups.The indexes between the two groups were analyzed statistically by multivariate logistic regression analysis.The survival-time distributions were estimated by Kaplan-Meier model,and the difference in prognosis was compared between the two groups.Results Of 97 patients,36 patients (37.1％)met the diagnosis of PICS.The acute physiological function and chronic health evaluation Ⅱ (APACHE Ⅱ) score had a significant difference between the two groups(27.7±5.8 vs.22.9±6.0,P＜0.01).The grade of acute gastrointestinal injury(AGI)were significantly higher in the PICS group than in the non-PICS group(P ＜0.05).Platelet counts,helper T cell counts and CD4+/CD8+ ratios were significantly lower in the PICS group than in the non-PICS group[(164.39 ± 84.29) × 109/L vs.(235.16 ± 126.89) × 109/L,(238.97± 181.11)/μl vs.(385.93±308.22)/μl,(1.58 ± 1.13) vs.(2.12± 1.23),all P ＜0.05)].Multivariable logistic regression analysis revealed that APACHE Ⅱ score was an independent risk factor for PICS and its optimal cut-off value for predicting PICS was 26.5.Kaplan-Meier analysis showed that the overall survival was poorer in the PICS group than in non-PICS group in the whole observation phase.The further Kaplan-Meier analysis on survival time of subdivisions showed that the survival of patients at 90-day and 180-day after admission and in stage 1-3 during one year had significant differences between the two groups (P ＜ 0.05).While the survival of patients at 28-day after admission had no significant difference between the two groups(P＞0.05).Conclusions The elderly patients with persistent inflammation,immune-suppression,and catabolism syndrome(PICS) secondary to sepsis in medical intensive care unit(MICU)show the higher levels of APACHE Ⅱ score and AGI grade,and lower values of platelet counts,CD4+ T cell counts and CD4+/CD8+ ratio in initial stage.And APACHE Ⅱ score is an independent risk factor for PICS in elderly sepsis patients,and the optimal cut-off value of APACHE Ⅱ score for predicting PICS is 26.5.The prognosis for advanced stage and long term prognosis are poor.It is essential to use APACHE Ⅱ and so on,to timely identify and intervene PICS.

Research progress in the diagnosis and treatment of persistent inflammation-immunosuppression catabolism syndrome in severe acute pancreatitis / 中华消化外科杂志

Severe acute pancreatitis (SAP) has a severe attack and high incidence of case fatality rate.Almost all the SAP patients would undergo some different immune status including systemic inflammatory response syndrome,compensatory anti-inflammatory response syndrome and mixed antagonistic response syndrome.With more acknowledgement of the pathophysiology of SAP,come researches have revealed that a few SAP patients may gradually come into a terribly and durably consumptive phase,and ultimately progress to persistent inflammation-immunosuppression catabolism syndrome (PICS).Now the morbidity of PICS has increased in recent years,therefore,it is helpful to recognize PICS early and improve the prognosis by discussing the pathophysiology deeply.Based on the new research progress at home and abroad,this article reviewed the diagnostic criteria,occurrence and development,and treatent of PICS in SAP,in order to offer treatment strategy for the SAP.

Nutritional support therapy during treatment of chronic critical illness / 中华胃肠外科杂志

Chronic critical illness (CCI) refers to a group of critically ill patients who survive the acute phase of intensive care, but with persistent organ dysfunction, thus entering a chronic period of continuous dependence on life support system, and still need to stay in intensive care unit (ICU) for a long time. Persistent inflammatory response-immunosuppression-catabolic syndrome (PICS) is the main pathophysiological feature of CCI. Three factors interact to form a vicious circle, leading to poor prognosis. Nutritional support therapy is a key link in the comprehensive treatment of CCI. Enteral nutrition (EN) should be started as soon as possible if conditions permit. If EN can not be implemented, temporary or transitional parenteral nutrition (PN) should be used, and EN should be added gradually in time. At the same time, the amount of PN should be gradually reduced. When EN meets more than 60% of patients’ energy and protein requirements, PN can be considered to be discontinued. The main strategies and functions of CCI nutritional support therapy are as follows: strengthening high protein supply to correct negative nitrogen balance and inhibit catabolism, selecting branched chain amino acids (BCAA) to promote anabolism, using immunomodulators (arginine, ω3 polyunsaturated fatty acids) to improve immune suppression and inflammatory response, supplementing micronutrients (vitamins and trace elements) to counteract the decrease in intake and the increase in consumption, and adding probiotics to maintain the intestinal microecological balance, and so on. Reasonable nutritional support therapy not only improve malnutrition of CCI patients, but also help to reduce complications, thus speeding up rehabilitation, improving prognosis, shortening ICU hospitalization time, and even reducing mortality.

Advances in the research of severe burn-related corticosteroid insufficiency / 中华烧伤杂志

Despite considerable advances in diagnosis and treatment of the critical illness-related corticosteroid insufficiency (CIRCI), it is still not clear that whether it is common in severe burn patients or not, and how clinical diagnosis, treatment, and research progress. Severe burn is a systemic disease involving the damage of multiple organs of the whole body. The course of the disease is relatively long, and there often exists persistent inflammation, immunosuppression, and catabolism. On the basis of CIRCI study, the epidemiological evidence, possible mechanism, suspicious clinical manifestations, diagnosis and treatment of severe burn-related corticosteroid insufficiency (SBRCI) were briefly reviewed in this article in order to help clinical diagnosis and treatment of SBRCI.

Risk factors and prognosis of persistent inflammation-immunosuppressive catabolism syndrome in malignant tumor patients with lung infection after chemotherapy / 肿瘤研究与临床

Objective To investigate the risk factors and prognosis of persistent inflammation-immunosuppressive catabolism syndrome (PICS) in malignant tumor patients with lung infection after chemotherapy.Methods A total of 128 malignant tumor patients with pulmonary infection after chemotherapy from January 2014 to January 2018 in Jilin Cancer Hospital were collected.According to whether the patients were complicated with PICS,the patients were divided into the PICS group (44 cases) and the control group (84 cases).The clinical characteristics and prognosis of the two groups were compared,and the risk factors of PICS during hospitalization were analyzed.Results The acute physiology and chronic health evaluation (APACHE) Ⅱ score and sequential organ failure assessment (SOFA) score in the PICS group were higher than those in the control group [(18.6±3.8) vs.(15.9±4.0),t =3.598,P ＜ 0.01;(4.8±1.5) vs.(4.0±1.6),t =2.832,P =0.005].When compared with the control group,the proportion of lung cancer in the PICS group was increased [47.7％ (21/44) vs.23.8％ (20/84),x2 =8.378,P =0.006],and the albumin was decreased [(28.8±3.3) g/L vs.(30.8±2.9) g/L,t =3.695,P ＜ 0.01],the C reactive protein was increased [(60±8) mg/L vs.(45±8) mg/L,t =9.520,P ＜ 0.01],hospital duration was prolonged [(33±7) d vs.(26±7) d,t =4.820,P ＜ 0.01],hospital mortality was increased [22.7％ (10/44) vs.4.8％ (4/84),x2 =9.567,P =0.002].Multiple factor logistic regression analysis showed that the APACHE Ⅱ score ＞ 20,lung cancer and the albumin ＜ 30 g/L were the risk factors for PICS in the malignant tumor patients with lung infection after chemotherapy (all P ＜ 0.05).Conclusion The incidence of PICS in malignant tumor patients with pulmonary infection after chemotherapy is high,and the risk factors for the poor prognosis include APACHE Ⅱ score ＞20,lung cancer and the albumin ＜30 g/L.

Inhibition of gastrin on catabolism of rat chondrocytes induced by interleukin-1β / 上海交通大学学报（医学版）

Objective:To investigate the protective effect of gastrin on rat chondrocytes treated with interleukin-1β (IL-1β) and underlying mechanism. Methods:Chondrocytes of knee joint of newborn rats were isolated and cultured. The effect of gastrin on cell viability was determined by MTT assay. In addition, after being induced with 10 ng/mL of IL-1β for 2 d, the chondrocytes were treated with 1×10-7 mol/L of gastrin for 3 d. The expressions of chondrocyte catabolic genes, i.e., matrix metalloproteinase 3 (MMP3) and MMP13, and the key proteins in gastrin-related signaling pathway, i.e., cholecystokinin B receptor (CCKBR), extracellular regulated protein kinases (ERK), phospho-ERK (p-ERK) and p65 were detected by real-time PCR and Western blotting, respectively. Results:Gastrin with the concentration of 1×10-7 mol/L had no cytotoxic effects on the viability of chondrocytes. Based on IL-1β induction, the expressions of MMP3 and MMP13 genes were significantly downregulated by gastrin. Meanwhile, the expression of CCKBR in the IL-1β induction group and gastrin treatment groups was higher than that in the normal control group. Gastrin also facilitated the phosphorylation of ERK and resulted in the inhibition of P65. Conclusion:Gastrin increases the phosphorylation level of ERK by activating its receptor CCKBR, thereby inhibiting the activity of P65 in NF-κB pathway, antagonizing the chondrocyte catabolic activity induced by IL-1β. Accordingly, gastrin may possess the potentials of cartilage matrix protection via inhibiting mRNA expressions of MMP3 and MMP13 and catabolism in rat chondrocytes.

Establishment of a high-throughput analysis method for the identification of key proteases of peptide drugs in vitro / 中国药科大学学报

@#In order to establish an effective analytical method to detect the key proteases which affect the metabolism and the plasma half-life of peptides in vivo, a method to analyze the key proteases of peptide drugs based on high performance liquid chromatography in vitro was established. The general enzymatic reaction conditions in vitro were as follows: pH was 7. 8 or 9. 0 and the buffer system was 0. 01 mol/L PBS or 50 mmol/L Tris buffer. The results of pramlintide detected by this method showed that kallikrein-related peptidase 5 and dipeptidyl peptidase 4 had the strongest hydrolysis on pramlintide. The result was consistent with that determined by microscale thermophoresis, which indicated that kallikrein-related peptidase 5 and dipeptidyl peptidase 4 were the key proteases of pramlintide. This analytical method provides the basis for high-throughput stability screening of peptides and can be used to analyze key proteases of peptide drugs. It can also provide guidance for optimizing the protease stability of peptide drugs.