Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Acid-sensing ion channels (ASICs), the main H

The human UDP-glucuronosyltransferase 1A1 (UGT1A1), one of the most essential conjugative enzymes, is responsible for the metabolism and detoxification of bilirubin and other endogenous substances, as well as many different xenobiotic compounds. Deciphering UGT1A1 relevance to human diseases and characterizing the effects of small molecules on the activities of UGT1A1 requires reliable tools for probing the function of this key enzyme in complex biological matrices. Herein, an easy-to-use assay for highly-selective and sensitive monitoring of UGT1A1 activities in various biological matrices, using liquid chromatography with fluorescence detection (LC-FD), has been developed and validated. The newly developed LC-FD based assay has been confirmed in terms of sensitivity, specificity, precision, quanti-tative linear range and stability. One of its main advantages is lowering the limits of detection and quantification by about 100-fold in comparison to the previous assay that used the same probe substrate, enabling reliable quantification of lower amounts of active enzyme than any other method. The precision test demonstrated that both intra- and inter-day variations for this assay were less than 5.5％. Further-more, the newly developed assay has also been successfully used to screen and characterize the regu-latory effects of small molecules on the expression level of UGT1A1 in living cells. Overall, an easy-to-use LC-FD based assay has been developed for ultra-sensitive UGT1A1 activities measurements in various biological systems, providing an inexpensive and practical approach for exploring the role of UGT1A1 in human diseases, interactions with xenobiotics, and characterization modulatory effects of small mole-cules on this conjugative enzyme.

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.
Adolescent ; Adult ; Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease ; HLA Antigens ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Receptors, KIR ; Retrospective Studies ; Young Adult

Adult ; Altitude Sickness ; Arousal ; Electroencephalography ; Emotions ; Humans ; Hypoxia ; Male ; Young Adult

Objective:To explore systematic implementation of World Health Organization Family International Classifications (WHO-FICs) in the field of rehabilitation: the theoretical and policy framework at macro level, governance and management mechanism at meso level, and implementation modules at micro levels, respectively. Methods:The policy and theoretical framework of rehabilitation development was discussed based on the international rehabilitation policy documents of WHO, mainly as World Report on Disability, Global Action Plan on Disability and Rehabilitation in Health Service System. Protocol and roadmap of systematic implementation of WHO-FICs, including International Classification of Diseases (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHIβ-2) was proposed. Results:With the use of WHO-FICs, the theoretical and policy framework of rehabilitation was constructed, and the contents and principles of modern rehabilitation services were clarified at macro-level. Rehabilitation is an important part of health service, there are six building blocks: i.e. leadership and governance, financing, human resources for health, service providing, medical technology and health information system. It proposed to use knowledge management system of WHO-FICs, including the classification, nomenclature, definitions, descriptions, terminology and coding systems, to standardize rehabilitation evaluation and statistics. The management and governance system of rehabilitation should be implemented using WHO-FICs. Rehabilitation services are based on the bio-psycho-social model and implemented the principles of people-centered and functioning-oriented. The systematic implementation of WHO-FICs in rehabilitation abide by the model of "Evaluation (ICHI)－Evaluation, Description, Classification and Coding of Functioning (ICF)－Disease Classification, Diagnosis and Coding (ICD)－Rehabilitation Intervention (ICHI)", and with the standardized process of "Evaluation (Functioning and unmet needs)－Diagnose (Disease and Functioning)－Planning of Rehabilitation－Intervention－Evaluation of Outcome". The mic-modules of implementation of WHO-FICs in rehabilitation had been constructed. There were 28 categories of diseases, 7 categories of functioning and 6 categories of rehabilitation interventions in rehabilitation proposed by International Society of Physical and Rehabilitation Medicine. According to ICD-11 and ICF, it proposed to use WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), Brief Model Disability Survey (MDS-B) and VB40 Generic Functioning Domains (VB40), and the ICF core-sets in evaluation of functioning and rehabilitation outcome. The implementation of WHO-FICs in management of medical records and reporting realized the standardized management of medical record, encoding of diseases, functioning and intervention, reporting of performance, and provided tools for billing, reimbursement and payment management of rehabilitation. It proposed to develop WHO-FICs based clinical data sets and big data to implement functioning-related Diagnosis Related Groups and case-mix statistics. Conclusion:With the systematic implementation of WHO-FICs in rehabilitation, the policy and theoretical framework at macro level had been developed. The mechanism of management and governance at meso level had been explored. The application modules and approaches at micro level had been established. A scientific and effective overall solution had been proposed to enhance the scientific, standardized, refined and informatization level, strengthen the level and governance capacity, and improve the quality, safety and the coverage of rehabilitation services.

Schisandra is the mature fruit of Schisandra chinensis(known as "north Schisandra") or S. shenanthera(known as "south Schisandra"). S. chinensis contains a variety of lignans, volatile oils, polysaccharides, organic acids and other chemical constituents; among them, lignans are recognized as the characteristic active components. Clinical studies have found that Schisandra and Schisandra-related products have a better effect in the prevention and treatment of viral hepatitis, drug-induced liver injury, liver cirrhosis, liver failure and other liver diseases. Modern pharmacological studies have demonstrated that Schisandra has a variety of pharmacological activities, such as anti-inflammation, antioxidation, anticancer, regulation of nuclear receptor, antivirus, regulation of cytochrome P450 enzyme, inhibition of liver cell apoptosis and promotion of liver regeneration. This paper reviews the studies about the applications and mechanism of Schisandra in the prevention and treatment of liver diseases, in the expectation of providing guidance for the development of hepatoprotective drugs from Schisandra and the clinical applications of Schisandra-related products.
Chemical and Drug Induced Liver Injury ; Drugs, Chinese Herbal ; Fruit ; chemistry ; Humans ; Lignans ; analysis ; Protective Agents ; Schisandra

BACKGROUND: It is important to modulate the expression of glucocorticoids receptor (GR) in tress and maintain the immunity homeostasis in sepsis process. Rhubarb have been shown to have potential effects on anti-inflammatory and immune modulation. The present study was designed to investigate the effects of rhubarb on the expression of GR and cellular immunity in burn-induced septic rats. METHODS: Sixty-six healthy male Sprague Dawley (SD) rats were randomized into sepsis group (n = 24), rhubarb group (n = 24), and control group (n = 18); each group were further randomized into 12, 24, and 72 h subgroups according to different time points. During onset of the sepsis model, the rats in the rhubarb group were infused with 50 mg/kg rhubarb powder dissolved into 1 mL saline through gastric tube, while sepsis and control groups were treated with saline. The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were analyzed by radiation ligands binding assay. The percentages of CD4,CD8,CD4CD25T cells, CD19B cells as well as natural killer (NK) cells in the lymphocytes in peripheral blood were detected by flow cytometer. For assessing the differences among groups, one-way analysis of variance (ANOVA) with Scheffe multi-comparison techniques were employed. Comparisons between time-based measurements within each group were performed with ANOVA repeated measurement. RESULTS: The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were significantly decreased in a time-dependent manner in sepsis group (t = 23.045, P < 0.01; t = 24.395, P < 0.05, respectively), which were increased in a time-dependent manner after rhubarb administration (t = 19.965, P < 0.05; t = 17.140, P < 0.05, respectively). Twelve hours after sepsis, the percentages of CD4 T cells, CD4/CD25 T cell ratio, and CD19 B cells in the peripheral blood were significantly increased in the sepsis group (t = -3.395, P < 0.01; t = 2.568, P < 0.05; t = 2.993, P < 0.05, vs. control mice, respectively). However, the percentage of NK cells in the peripheral blood were significantly decreased in the sepsis group (t = -2.022, P < 0.05, vs. control mice). Twelve hours after sepsis, the percentage of CD8 T cells were significantly decreased in the peripheral blood in the sepsis group (t = -2.191, P < 0.05, vs. control mice) and were significantly increased in the rhubarb group (t = 2.953, P < 0.05, vs. sepsis mice). Seventy-two hours after sepsis, the ratio of CD4/CD25 T cell in peripheral blood were significantly increased in the sepsis group (t = 2.508, P < 0.05, vs. control mice) while were significantly decreased in the rhubarb group (t = 3.378, P < 0.05, vs. control mice). Furthermore, the percentages of CD19 B cell in peripheral blood were significantly decreased at 72 h in the rhubarb group (t = 2.041, P < 0.05 vs. sepsis group). CONCLUSIONS Rhubarb might play potential anti-inflammatory and immunomodulatory roles in the sepsis processes.

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.
Cord Blood Stem Cell Transplantation ; Core Binding Factor Alpha 2 Subunit ; Graft vs Host Disease ; Humans ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; Oncogene Proteins, Fusion ; Peripheral Blood Stem Cell Transplantation ; RUNX1 Translocation Partner 1 Protein ; Transplantation Conditioning