Objective To investigated the role of antithrombin Ⅲ (AT-Ⅲ) levels in the early diagnosis of disseminated intravascular coagulation (DIC) in patients with sepsis and the predictive effect of AT-Ⅲ on the development of DIC.Methods A retrospective study was conducted. Patients admitted to intensive care unit (ICU) of the First Affiliated Hospital of China Medical University from January to December in 2015 were enrolled. The patients were divided into sepsis group and non-sepsis group according to the diagnostic criteria of sepsis. In addition, sepsis patients were divided into 3 subgroups according to the international society on thrombosis and haemostasis (ISTH) scores on the first day: overt DIC (ISTH ≥ 5), non-overt DIC (ISTH 1-4) and none DIC group (ISTH = 0). Blood routine test, prothrombin time (PT), fibrinogen (Fib), D-dimer, fibrin degradation products (FDP), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores, sequential organ failure assessment (SOFA) scores and ISTH scores were recorded on the first ICU day. AT-Ⅲ was recorded during 7 days. The differences were compared among these 3 groups. Correlations of AT-Ⅲ with various parameters were calculated by using Pearson correlation analysis in sepsis group and overt DIC group. Receiver operating characteristic (ROC) curves for diagnosis of DIC with AT-Ⅲ, AT-Ⅲ+PT were drawn to evaluate the diagnostic efficiency. The AT-Ⅲ levels of DIC patients were compared between early-onset DIC and late-onset DIC during their ICU stay. The change of AT-Ⅲ levels with time and prognosis in patients with early-onset DIC was compared between groups.Results Totally 445 patients were recruited, with 138 patients in sepsis group, and 307 in non-sepsis group. There were 20 patents diagnosed with overt DIC on the first ICU day, 115 patients non-overt DIC and 3 patients of none DIC. Twenty-five sepsis patients were diagnosed overt DIC during the ICU days. AT-Ⅲ level in sepsis patients on the first ICU day were lower than that in non-sepsis patients [(55.29±13.92)% vs. (76.54±12.31)%,P < 0.01]. Patients with overt DIC had a lower AT-Ⅲ level than non-overt DIC or none DIC patients [(43.85±13.00)% vs. (56.95±13.03)%, (68.00±16.52)%, bothP < 0.05]. It was shown by Pearson correlation analysis that AT-Ⅲ level of sepsis patients on the first ICU day was negatively correlated to ISTH score and PT (r value were -0.467, -0.654, bothP < 0.01). AT-Ⅲ level of overt DIC patient on the first ICU day was negatively correlated with PT (r = -0.675,P = 0.001). It was shown by ROC curve that area under ROC curve (AUC) of AT-Ⅲ combined with PT for diagnosis overt DIC in sepsis patients was higher than that of AT-Ⅲ or PT alone (0.843 vs. 0.763, 0.834), the sensitivity 90.0%, specificity 73.7%. The cut-off value for overt DIC diagnosis in sepsis patients of AT-Ⅲ level alone was 48.5%, sensitivity was 78.0%, specificity was 70.0%. On the first ICU day, AT-Ⅲ level was risen when ISTH score improved in patients with sepsis. There was similar change of AT-Ⅲ level between patients with early-onset DIC and late-onset DIC. AT-Ⅲ level increased with DIC improvement.Conclusion AT-Ⅲ level can be used for diagnosing sepsis-associated overt DIC independently or with a combination of PT. When ISTH score improved, AT-Ⅲ level was risen in patients with sepsis associated DIC.

Objective To investigate the content of intestinal fatty acid binding protein (IFABP) and its clinical significance in patients with severe sepsis.Methods A prospective observational study was conducted.Fifty patients with severe sepsis admitted to intensive care unit (ICU) of the First Affiliated Hospital of China Medical University from July to December 2012 were enrolled,and 20 healthy patients served as control group.The concentrations of serum IFABP,interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α) were determined with enzyme-linked immunosorbent assay (ELISA) on days 0,1 and 3 after ICU admission.Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score,28-day prognosis,acute gastrointestinal injury (AGI) grade were recorded at the same time.Furthermore,the contents of IFABP were compared between control group and the severe sepsis group,abdominal infection group and non-abdominal infection group,the survival group and the death group,as well as among different AGI-grade groups.Correlation analysis of IFABP and inflammatory factors,IFABP and two scores,and IFABP and time of stay in ICU and mechanical ventilation were studied.Multivariate logistic regression and analysis of 28-day outcome of the patients were also studied.Results IFABP levels were increased in severe sepsis patients on days 0,1 and 3 compared with those of healthy control group (mg/L:731.90 ±53.91,592.07 ±41.94,511.85 ±47.97 vs.439.88 ±23.68,all P =0.000).There was no statistical significance of IFABP levels between abdominal infection group and non-abdominal infection group,the survival group and the death group,or among different AGI-grade groups.The correlation analysis showed that IFABP was statistically related with IL-6 (r=0.794,P=0.000),TNF-α (r=0.878,P=0.010),APACHE Ⅱ score (r=0.428,P=0.000) in patients with severe sepsis.Significant correlations were also found between IFABP and IL-6 (r=0.812,P=0.000),TNF-α (r=0.885,P=0.000) in abdominal infection group,as well as in non-abdominal infection group (IL-6:r=0.739,P=0.000; TNF-α:r=0.828,P=0.000).As shown by multivariate logistic regression analysis,SOFA scores on days 0,1,3 were the independent risk factors for death [odds ratio (OR) was 1.624 (P=0.004),1.411 (P=0.027),1.740 (P=0.012),respectively],but IFABP level,AGI grade,and APACHE Ⅱ score had no influence on death rate.Conclusion IFABP concentrations in patients with severe sepsis were significantly increased,and it is correlated well to IL-6,TNF-α and APACHE Ⅱ score,but did not related obviously with AGI grade and the prognosis of the patients.

As a co-stimulatory blocker against CD28 receptor, belatacept has been approved and applied to the treatment of rejection in organ transplantation in Europe and America. Belatacept has been proven to outperform calcineurin inhibitor (CNI) in improving the long-term survival rate of recipients and grafts, and enhancing graft function. Nevertheless, it might cause a high incidence of rejection. To resolve this issue, transplant workers have attempted to optimize belatacept immunosuppressive regimen and achieved good clinical efficacy. Although belatacept has been proven to exert poor effect on memory T cells, it has potential value in exploring new co-stimulatory molecular targets to optimize immunosuppressive regimes due to its specificity for immune cells and mild adverse effects. In this article, the advent of co-stimulatory blocker, clinical efficacy and application of belatacept, and the causes of belatacept-resistant rejection were reviewed.

Objective To explore whether Rho kinase inhibitor protects endotoxemia mice from kidney injury,and to investigate the mechanism underlying this effect. Methods Adult male C57BL/6 mice were randomly divided into three groups (n = 8 for each group): control,lipopolysaccharide (LPS),and LPS+ Y-27632 (Rho kinase inhibitor). For induction of acute kidney injury,mice were administered 30 mg/kg LPS intraperitoneally. Y-27632 (10 mg/kg body weight) was injected intraperitoneally 18 h and 1 h before injection of LPS,and an equal volume of sterile saline was administered at the corresponding time point in each group. The mice were killed 8 h after LPS administration. Blood samples and kidney tissues were taken and preserved for subsequent analysis. Results Pretreatment with Y-27632 significantly attenuated LPS-induced kidney injury;pretreatment with Y-27632 markedly reduced renal expression of inflammatory cytokines (TNF-α and IL-1β) in endotoxemia mouse,and also significantly inhibited LPS-induced caspase-3 expression in the kidney; and Y-27632 pretreatment dramatically reduced TLR4 protein expression and NF-κBp65 phosphorylation in kidney tissues of endotoxemia mouse. Conclusion Rho kinase inhibitor may inhibit TLR4 and NF-κB signaling pathway to reduce the inflammatory response in the kidneys of endotoxemia mice and alleviate acute renal injury induced by LPS.

Area Under Curve ; Breast Neoplasms ; Breast ; Diagnosis ; Diagnosis, Differential ; Elasticity Imaging Techniques ; Estrogens ; Female ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Population Characteristics ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; ROC Curve ; Sensitivity and Specificity ; Ultrasonography

“Deficiency cause， cold accumulation， and qi stagnation” originates from Essentials from the Golden Cabinet （《金匮要略》）， which is a guiding principle for the pathogenesis of women's diseases， pioneering the differentiation and treatment of women's diseases based on patterns， and having a profound influence on future generations. Following the classical principles and simplifying the complexities， this paper explored the pathogenesis and mechanism of polycystic ovary syndrome （PCOS） from the perspective of “deficiency cause， cold accumulation， and qi stagnation”， and believed that depletion of essence and blood， long-term accumulation of internal cold， and qi constraint and blood stasis are the causes of PCOS， with depletion of essence and blood， and lack of nourishment of zang-fu （脏腑） organs as the root， and cold pathogen invasion， qi constraint and blood stasis as the branch. The main treatment principle is “treating deficiency with supplementation”， and dispelling pathogen while reinforcing healthy qi， along with “treatment of cold by warming” and “treatment of stagnation by dispersing”. This is of great significance for the treatment of polycystic ovary syndrome. Clinically， these methods can be used flexibly to guide treatment and formula selection for PCOS， with the goal of harmonizing qi and blood and regulating menstruation.

As a vital part of acupuncture and moxibustion,the theory of penetration needling obviously lags behind the practice. This article summarizes the thoughts andmethods of penetration needling by professor . Based on the three basic elements of penetrating acupuncture, including the acupoint, needle and manipulation, the academic origins, the application of penetrating acupuncture at present and the clinical cases are reviewed; the essential content and the extension meaning of needle penetration are summarized, which is based on the identification of the location, pathology and characteristics of disease, combined with the characteristics of acupoints and the tissue structure of the part, we quantify the intensity of stimulation, so as to provide featured reference clinical practice.
Acupuncture ; instrumentation ; Acupuncture Points ; Acupuncture Therapy ; Moxibustion ; Needles

Hemophagocytic syndrome (HPS), which is currently named as hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome characterized by persistent fever, hepatosplenomegaly, pancytopenia and hemophagocytosis found in bone marrow, liver, spleen and lymph nodes due to excessive activation of macrophages and cytotoxic T cells. Macrophage activation syndrome (MAS) is a specific form of HLH induced by autoinflammatory/autoimmune disorders which can be life-threatening and requires multiple disciplines. In order to improve clinicians′ understanding of MAS and standardize the clinical diagnosis and treatment practice of MAS, the rheumatology branch of Chinese Rheumatology Association organized domestic experts to formulate the diagnosis and treatment standard, in order to improve the diagnosis and treatment level of MAS and improve the prognosis of patients.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*