Antithrombotic drugs are important means to prevent and treat thrombotic diseases. With the wider use of antithrombotic drugs, the incidence of antithrombotic drug-related bleeding has increased year by year. Anticoagulant drugs, antiplatelet drugs and thrombolytic drugs can all cause subcutaneous hemorrhage, gastrointestinal hemorrhage and even intracranial hemorrhage, resulting in death or disability. Therefore, the Chinese Society of Thrombosis, Hemostasis and Critical Care organized multidisciplinary experts to jointly write this specification to help clinicians regulate the treatment of antithrombotic drug-related bleeding. This specification includes four parts: antithrombotic drug monitoring, bleeding evaluation, reversal treatment and restart of antithrombotic treatment.

Objective To explore the phenotypes of erythroblastic island-like (EBI-like) macrophages during erythroid differentiation from human embryonic stem cells in vitro and the function of EBI-like macrophages in the differentiation of erythroid. Methods To study the function of EBI- like macrophages in the differentiation of erythroid, we used the Spin-EB method to induce human embryonic stem cells (hESCs) to differentiate into red blood cells. The expression of specific surface markers of erythrocytes and macrophages and the cell morphology were tested by flow cytometry and imaging flow cytometry. Multiple gene expressions were detected by qRT-PCR. An immunofluorescence assay was used to identify the phenotype of EBI-like macrophages. Results Erythroid cells were induced by embryonic stem cells in vitro. Giemsa staining revealed that EBI-like structures derived from the hESCs were similar to natural EBI. Immunofluorescence staining confirmed that the erythroid cells (CD235a) were surrounded by macrophages (CD68); CD45⁺CD235a⁺CD163⁺CD169⁺CD106⁺ EBI-like macrophage (0.092%±0.013%) resembles in vivo EBI macrophage. Imaging flow cytometry observed that CD45⁺CD235a⁺CD163⁺CD106⁺CD169⁺ EBI-like macrophages were surrounded by CD235a⁺ erythroid cells. The proportion of induced CD71⁺CD235a⁺ cells was 37.37%±1.68% after removing the EBI structure, which was significantly lower than the untreated group (46.97%±4.16%). We found that central macrophages of EBI-like may play a role in promoting erythroid differentiation through the interaction of CD169 and CD43. Conclusions EBI-like structure in the erythroid induction system of hESCs is similar to the natural EBI. The central EBI-like macrophages maybe promote the differentiation of erythrocytes in vitro through the interaction of CD169 and CD43. We provided a theoretical and practical reference for optimizing the erythroid induction system in vitro.

Objective To explore the molecular mechanism of a classic traditional Chinese medicine compatibility combination of Astragalus membranaceus (A.m) and Angelica sinensis (A.s) in treatment of diabetes mellitus with cardiovascular complications. Methods The BATMAN database was used to analyze A.m and A.s respectively. The chips data related to diabetes mellitus with cardiovascular complications were retrieved from GEO database. The differential genes were analyzed by GEO2R to construct the protein-protein interaction (PPI) network, and the key target genes of A.m-A.s were obtained by topology, and DAVID database was used for gene ontology (GO) and KEGG pathway enrichment analysis of key genes. A total of 20 SD rats were randomly divided into healthy control group, diabetes mellitus complicated with cardiovascular complications group, metformin group, and A.m-A.s group (5 each). All the rats except those in HC group were fed with high fat and high sugar feeds, and used to establish the model of diabetes mellitus with cardiovascular complications. The expressions of PI3K and Akt3 in cardiomyocytes of the rats in each group were observed. Results (1) A total of 1332 target genes related to A.m-A.s combination were analysis obtained from BATMAN database, and 3 chip data files related to diabetes with cardiovascular diseases (GSE26887, GSE43950 and GSE46262)were retrieved from GEO database including 2759 differential genes screened by GEO2R analysis and 247 key genes of A.m-A.s combination in treatment of diabetes mellitus with cardiovascular complications. (2) The protein-protein interaction (PPI) network diagram of key targets was constructed by STRING database, and the "A.m-A.s- active ingredients-targets" network was constructed by Cytoscape 3.7.2. The functional enrichment analysis with DAVID database showed that the biological process of A.m-A.s in treatment of diabetes mellitus and cardiovascular complications was mainly concentrated in positive and negative regulation of RNA polymerase II promoter transcription, redox process, signal transduction, apoptosis process, inflammatory reaction, and positive regulation of cell proliferation, etc. The signaling pathways mainly include metabolic pathway, cancer pathway, TNF signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway, PI3K-Akt signaling pathway, non-alcoholic fatty liver disease pathway, and insulin resistance pathway and so on. (3) The animal model experiment with SD rats in vivo of A.m-A.s combination in treatment of diabetes mellitus with cardiovascular complications suggested that, compared with healthy control group, the expressions of PI3K and Akt3 decreased in cardiomyocytes of the untreated model group, and the difference was statistically significant (P<0.05, P<0.01); the expressions of PI3K in the treatment groups were higher than that in the model group, but lower than that in the healthy control group, and the difference was statistically significant (P<0.01). Conclusion The characteristics of A.m-A.s combination in treatment of diabetes mellitus with cardiovascular complications are "multi-components, multi-targets and multi-pathways", and multiple key genes and signal pathways can play important roles. Further research is expected to broaden the ideas of diagnosis and treatments of diabetes with traditional Chinese medicine.

Objective To explore the effect and mechanism of silybin on improving pulmonary fibrosis and oxidative stress in mice. Methods A total of 120 mice were randomly divided into sham operation group, lung injury model group, dexamethasone group, low-dose, medium-dose and high-dose silybin groups (20 mice each). The models of pulmonary injury mice were induced by bleomycin. Mice in dexamethasone group, low-, medium- and high-dose silybin groups were given intragastric administration of dexamethasone (3 mg/kg) and silybin (120, 240, 480 mg/kg), while sham operation group and lung injury model group were given the same volume of normal saline for 28 d. The bronchoalveolar lavage fluid (BALF) and pulmonary tissues of each group were collected. The count of inflammatory cells in BALF was examined by microscopy. The pathological damage of pulmonary tissues was observed by HE staining. The pulmonary wet/dry weight ratio (W/D) was detected by wet-dry weighting method. The content of hydroxyproline (HYP) in pulmonary tissues, and levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in BALF were detected by ELISA. The expressions of bone morphogenetic protein 9 (BMP9)/bone morphogenetic protein receptor 2(BMPR2)/SMAD signaling pathways-related proteins were detected by Western blotting. Results Compared with sham operation group, count of BALF inflammatory cells, scores of pulmonary injury and fibrosis, W/D, HYP, and MDA, TNF-α, IL-1β and IL-6 levels in BALF increased significantly, while SOD, GSH-Px activity, T-AOC levels in BALF, as well as the relative expression levels of BMP9, BMPR2 and p-SMAD1/5/9 in lung tissues decreased significantly in lung injury model group (P<0.05). Compared with lung injury model group, count of BALF inflammatory cells, scores of pulmonary injury and fibrosis, W/D, HYP, and MDA, TNF-α,IL-1β and IL-6 levels in BALF decreased significantly, while SOD, GSH-Px activity, T-AOC level in BALF, and BMP9, BMPR2 and p-SMAD1/5/9 expression levels in lung tissues increased significantly in high-dose silybin group and dexamethasone group(P<0.05). Conclusion The silybin may improve bleomycin-induced pulmonary fibrosis and oxidative stress in lung injury mice by mediating BMP9/SMAD signaling pathways, and thereby repairing pulmonary injury.

Objective To investigate the role and mechanism of neutrophil extracellular traps (NETs) in acute liver injury from heatstroke (HS) mouse model. Methods Fifty-six C57BL/6 mice were randomly (random number table) assigned into sham heated control group (control group, n=8), sham heated with Chlorine amidine (CA) treatment group (CA group, n=8), heatstroke group (HS, n=32), and heatstroke with CA treatment group (HS+CA, n=8). In the HS group, after heat-shock treatment, mice were further subgrouped into HS 0 h, HS 3 h, HS 6 h, and HS 9 h (n=8/subgroup). Another forty-eight mice were randomized into the control group, CA group, HS(9 h) group, and HS+CA group (n=12/group). We tracked the survival rate of these mice up to 216 h. Mice were prepared with the pre-warm chamber to initiate HS. The change in rectum temperature (Tr) was monitored and the time point reaching 42.9 ℃ was recorded. At the end of heat stress, the mice were sacrificed according to the group time point, and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured by the automatic biochemical analyzer. HE staining was used to observe the pathological injury of liver tissue. Plasma-free DNA and myeloperoxidase (MPO)-DNA complex concentrations were detected by the kit. The expression of citrullinated histone (Cit H3) and MPO in liver tissue was observed by a laser confocal microscope. The concentration of IL-1β in liver tissue homogenate was determined by ELISA.The activation level of Nlrp3 inflammasome in liver tissue was detected by Western blotting. Results There was no significant difference in heat exposure time and core body temperature rise rate between HS+CA group and HS group at the end of heat shock(P>0.05), but the survival time of HS+CA group was longer than that of HS group (P<0.05). At 3 h, 6 h, and 9 h after heat shock, the activities of serum ALT and AST, and the pathological scores of liver tissue increased progressively with time and were significantly higher than those in control group (P<0.001). At 3 h, 6 h, and 9 h after heat shock, the concentrations of plasma-free DNA and MPO-DNA, the levels of Cit H3 and MPO in liver tissue increased progressively with time and were significantly higher than those in control group (P<0.001). HE staining of liver tissue showed that, compared with HS group, the degeneration of hepatocytes in HS+CA group was significantly alleviated, inflammation was significantly alleviated, and there was little blood stasis in hepatic sinuses without bleeding. Inhibition of NETs release significantly alleviated heat stress-induced liver injury (HS+CA group vs. HS 9 h group, P<0.001). Survival analysis showed that the survival rate of mice in HS+CA group was higher than that in HS group (χ²=4.719,P<0.05). The expression levels of Nlrp3 and cleaved caspase-1 and IL-1β in liver tissue of HS+CA group were lower than those in HS group (P<0.001). Conclusion NETs may play an important role in the pathogenesis of HS liver injury through the Nlrp3 inflammasome/IL-1β signal pathway.

Objective To reveal the pattern of multimorbidity in the middle-aged and elderly population in China by visual cluster analysis. Methods Using the 2015 data of China Health and Retirement Longitudinal Study, the age, gender, place of residence, and 14 kinds of non-communicable chronic diseases of the study population were extracted. A total of 18 542 subjects with complete information were included. A two-step clustering algorithm combining self-organizing map and K-Means was used to visually cluster the existence of chronic diseases among the middle-aged and elderly population. Results There were 8044 patients with 2 or more chronic diseases. The prevalence of multimorbidity was 43.38% in those patients, and 52.28% in the elderly population aged 60 years or above. Among the 14 chronic diseases, arthritis or rheumatism had the highest prevalence (33.02%),followed by hypertension (31.07%), stomach or other digestive diseases (23.60%). The patterns of multimorbidity included the following four categories: (1) 97.72% of patients in group A had chronic lung diseases, with more than half (55.05%) suffering from arthritis or rheumatism; (2) the prevalence of hypertension in group B was 98.21%; (3) the prevalence of dyslipidemia in group C was as high as 99.49%, and 91.72% of patients had hypertension; (4) 73.39% of patients in group D suffered from arthritis or rheumatism, and 68.11% had stomach or other digestive diseases. The patterns of multimorbidity were slightly different in women and urban populations. Conclusions The situation of chronic diseases in the middle-aged and elderly population in China is not optimistic, and the patterns of multimorbidity among different genders, urban and rural populations are different. Those results based on visual cluster analysis are of great significance for co-prevention of multiple conditions and reducing the burden of chronic diseases.

Objective To explore the role of mitochondrial copy number (MCN) of embryos in the outcome of embryo transfer in patients with poor ovarian response (POR) and the correlation with mother's age, embryonic karyotype and blastocyst grade. Methods A retrospective analysis was performed of 75 patients with normal ovarian reserve (NOR) and 74 patients with POR who underwent in vitro fertilization (IVF) and preimplantation genetic testing for aneuploidies (PGT-A) in the Sixth Medical Center of Chinese PLA General Hospital from September 2018 to October 2020. The blastocysts obtained after IVF were biopsied(NOR group: 205; POR group: 135), and 116 and 44 euploid blastocysts were obtained, respectively. The MCN of embryos in different clinical outcomes of each group were analyzed and compared, and the correlations of embryo MCN with maternal age, embryo karyotype and blastocyst grade were analyzed by multiple linear regression analysis. Results The mean MCN of biopsy blastocysts and euploid blastocysts were lower in POR group than those in NOR group with statistically significant difference (biopsy blastocysts: 267.4±174.0 vs. 319.0±264.8, P<0.05; euploid blastocysts: 216.0±95.7 vs. 305.4±273.2, P<0.01). Regardless POR group or NOR group, the MCN of early aborted embryos was higher than that of live embryos with statistically significant difference(POR group: 303.3±95.4 vs. 158.9±36.3, P<0.01; NOR group: 486.0±356.7 vs. 258.0±137.9, P<0.05). Multiple linear regression analysis showed the MCN of embryos in POR and NOR groups had no correlation with embryo karyotype and blastocyst grade, but was positively correlated with the mother's age (POR group: β=0.185, P=0.035; NOR group: β=0.215, P=0.002). Conclusion Higher MCN may be more likely to cause early miscarriage in POR patients, and the embryonic MCN was correlated with maternal age.

Objective To explore the factors influencing hospitalized new-onset overt hepatic encephalopathy (OHE) in hospitalized patients with hepatitis B-associated acute-on-chronic liver failure (HBV-ACLF), and to construct an individualized risk prediction model. Methods A total of 310 HBV-ACLF patients admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from December 2016 to December 2020 were selected, and divided into non-hepatic encephalopathy group(n=236), hepatic encephalopathy group (n=74) according to whether OHE occurred after admission. The general data, laboratory test indicators, and model of end-stage liver disease (MELD) scores were compared between the two groups; univariate and multivariate logistic regressions were used to analyze the factors influencing the hospitalized new-onset OHE in HBV-ACLF patients after admission. A nomogram model was constructed with the influencing factors. The receiver operating characteristic (ROC)curve and the calibration curve was used to evaluate the discrimination and calibration of the model, and decision curve analysis(DCA) was used to evaluate the clinical validity of the model. Results Compared with the non-hepatic encephalopathy group, the baseline international normalized ratio [2.71(2.20, 3.44) vs. 1.98(1.70, 2.55)], serum alanine aminotransferase [987.50(450.50,1538.00) U/L vs. 561.00(191.00, 1090.50) U/L], blood aspartate aminotransferase [830.00(257.75, 1518.25) U/L vs. 381.00(153.50, 872.00) U/L], plasma Ammonia [71.75(57.75, 109.50) μmol/L vs. 57.00(41.80, 79.60) μmol/L], white blood cell count [7.93(6.43, 9.74)×10⁹/L vs. 6.62(5.33, 8.16)×10⁹/L], hemoglobin [136.50 (126.25, 151.50) g/L vs. 126.00(115.00,143.00) g/L], and the proportion of patients in intermediate and advanced stages (56.8% vs. 23.3%) of the hepatic encephalopathy group were higher, the difference was statistically significant; the alpha-fetoprotein level was lower [56.33(23.61, 139.03) ng/L vs. 88.25(31.32, 216.88) ng/L, P=0.033], the difference was statistically significant (P<0.001). The results of multivariate logistic regression analysis showed that baseline international normalized ratio (OR=2.56, 95%CI 1.61-4.30, P<0.001), age (OR=1.06, 95%CI 1.02-1.10, P=0.003), plasma ammonia (OR=1.02, 95%CI 1.01-1.03, P=0.005), blood white blood cell count (OR=1.24, 95%CI 1.07-1.43, P=0.003), hemoglobin (OR=1.03, 95%CI 1.00-1.05, P=0.026) were the independent influencing factors of hospitalized new-onset OHE in HBV-ACLF patients. The area under the ROC curve (AUC) of the nomogram model established in this study was 0.848(95%CI 0.798-0.897), and the MELD model was 0.723(95%CI 0.654-0.793). The maximum bias (Emax)=0.143 and the minimum bias (Eavg=0.041 between the nomogram model and the ideal model, the model has a good degree of discrimination,S:p=0.676. Through the calibration test, the model predicted value is consistent with the actual value. The performance was good, the decision curve showed that the threshold was in the range of 0.05 to 1.0, and the net benefit rate of the nomogram model was higher than that of the MELD model. Conclusions Age, international normalized ratio, white blood cell count, plasma ammonia, and hemoglobin are the factors influencing hospitalized new-onset OHE in HBV-ACLF patients. Nomogram constructed from five independent influencing factors can more accurately predict the risk of hospitalized new-onset OHE in this population, thus having a good clinical application value.

Objective To investigate the clinical characteristics and related factors of patients with fat liquefaction of approach wounds after thoracic endovascular aortic repair (TEVAR). Methods The clinical data of 939 patients undergone TEVAR from August 2005 to June 2021 were consecutively enrolled in present study, and divided into fat liquefaction group (n=73)and non-fat liquefaction group (n=866) according to whether fat liquefaction occurs in the wound after operation. The clinical characteristics such as age, gender, overweight, past medical history, imaging findings, anemia, renal insufficiency, approach and laboratory indicators were compared between the two groups. Univariate and multivariate binary logistic regression were performed to analyze the factors associated with fat liquefaction of approach wounds. Results No significant difference existed between the two groups in age, gender, history of hypertension, coronary heart disease, diabetes, combined with pleural effusion and other clinical characteristics (P>0.05). The proportions of overweight and renal insufficiency were higher in fat liquefaction group than those in non-fat liquefaction group with significant differences (82.8% vs. 67.4%, P=0.011; 22.9% vs. 13.3%, P=0.028). While the levels of creatine kinase isoenzyme [10.00(7.00, 14.00) U/L vs. 11.00(8.00, 15.00) U/L, P=0.018] and hemoglobin [(130.64±17.33) g/L vs. (134.96±16.42) g/L, P=0.032], and the proportion of patients with femoral artery puncture (4.2% vs. 16.1%, P=0.007) were lower in fat liquefaction group than those in non-fat liquefaction group with statistical significance (P<0.05). Multivariate binary logistic regression analysis showed that overweight (OR=2.226, 95%CI 1.135-4.364, P=0.020) and renal insufficiency (OR=2.116,95%CI 1.119-4.003, P=0.021) were the independent risk factors for fat liquefaction in approach wounds after TEVAR. Femoral artery puncture (OR=0.273, 95%CI 0.084-0.889, P=0.031) was an independent protective factor for fat liquefaction of surgical approach after TEVAR. Conclusion Overweight combined with renal insufficiency can increase the risk of fat liquefaction in approach wounds after TEVAR, and femoral artery puncture may reduce such risk.

Objective To study and evaluate the cardiovascular function of patients with psoriasis vulgaris (PV) by analyzing the dynamic Korotkoff's sound trend diagram data from visual blood pressure measurements. Methods A total of 52 PV patients, visiting and/or admitted in the Department of Dermatology of Air Force Medical Center of PLA during July 14 to August 31, 2021, were recruited as PV group, and another 51 examiners in the Health Examination Center of Air Force Medical Center of PLA during August 2-31, 2021 were levied as healthy control group. Routine blood tests and visual blood pressure measurements were performed. The general data blood pressure indicators and systemic inflammatory indicators neutrophil/lymphocyte ratio(NLR) and platelet/lymphocyte ratio (PLR) of the two groups were collected and compared. Pearson correlation analysis was used to analyze the relationship between the clinical factors and blood pressure indicators in PV patients, univariate and multivariate logistic regression analysis was used to analyze the related factors of PV incidence, and receiver operating characteristic (ROC) curve was used to analyze the predicted value and cut-off value of each factor in PV incidence. Results After adjustment of interference factors, compared with the healthy control group, the peripheral blood PLR, NLR, cardiac ejection ability (systolic blood pressure,K-D), peripheral arteriole resistance (diastolic blood pressure, mean blood pressure) and degree of vascular sclerosis (K-A) increased significantly in PV patients (P<0.05), and the vascular elasticity of aorta and great artery (pulse pressure difference) and the ability of autonomic nerve to control blood pressure stability (DKT morphology) were decreased significantly (P<0.05). Multivariate logistic regression analysis showed that BMI, PLR, systolic blood pressure, DKT morphology were the independent risk factors for PV (OR=1.270, 1.014, 1.078, 6.084, P<0.05). ROC curve analysis showed that systolic blood pressure (AUC=0.798, P<0.001), mean blood pressure (AUC=0.748, P<0.001), pulse pressure difference (AUC=0.719, P=0.001), diastolic blood pressure (AUC=0.696,P=0.002), NLR (AUC=0.718, P=0.001), PLR (AUC=0.716, P=0.001), K-D (AUC=0.637, P=0.030), and DKT morphology(AUC=0.638, P=0.029) were the early predicted indicators of PV, the cut-off values are 109 mmHg, 86 mmHg, 35 mmHg, 86 mmHg,1.3, 97, 68 and morphology 2, respectively. Conclusion Based on DKT, PV patients have abnormal cardiovascular function, which is related to the occurrence and severity of PV. Abnormal cardiovascular function and systemic inflammatory indexes NLR and PLR have early predictive significance for the occurrence of PV.

Co-culture is an important technique to study specific biological problems, and has been widely applied recent years in the field of nervous system diseases which are characterized by diversity, commonality and intractability, and have always been a medical problem that researchers are committed to overcoming. The co-culture of mesenchymal stem cells (MSCs) and nerve cells provides hope for treatment of nervous system diseases. As a systemically designed and controlled environment, co-culture technology can be used to explore the morphology and function of nerve cells under physiological, pathological or toxic conditions, as well as the molecular events of intercellular interaction. Neurogenesis and nerve regeneration directed by MSCs will have a significant impact on therapeutic strategies for neurological diseases in the future. The research progress in co-culture of MSCs and nerve cells has been systematically reviewed in present paper, and described the application prospect of co-culture model, so as to provide ideas for the treatment of nervous system diseases.

Chronic obstructive pulmonary disease (COPD) is a common pulmonary disease in elderly, in which the pulmonary respiratory mechanics has gradually changed, while surgery, general anesthesia and conventional mechanical ventilation will seriously affect the pulmonary respiratory mechanics of COPD patients, which are more likely to have severe perioperative pulmonary complications. Therefore, according to the features of the respiratory mechanics of COPD patients and the characteristics of changes in respiratory mechanics during mechanical ventilation, to select individualized ventilation strategies to improve their respiratory mechanics and apply different monitoring methods to optimize the interaction between human and ventilator during ventilation of COPD patients for achieving the purpose of lung protection are very important for patients with COPD during the perioperative period. This review describes in detail the physiological status of the patients with COPD patients and the characteristics of respiratory mechanics during mechanical ventilation, and through the summary and discussion of recent literature, describes different ventilation strategies and various respiratory mechanics monitoring methods in COPD patients in recent years. It is expected to provide new ideas and references for the ventilation management of COPD patients who require mechanical ventilation in clinical practice.