Effect of proprotein convertase subtilisin/kexin type 9 on platelet activation associated with sepsis / 中华危重病急救医学

Objective:To investigate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on platelet activation in sepsis.Methods:① Clinical trial: a prospective study was conducted. Patients with sepsis and septic shock aged ≥ 18 years old who met the diagnostic criteria of Sepsis-3 admitted to the department of intensive care medicine of the Affiliated Hospital of Binzhou Medical College from January to October in 2021 were selected as subjects. Healthy subjects in the same period were taken as healthy control group. Platelet count (PLT) in the first routine blood test after admission was recorded. Venous blood was taken 1 day after diagnosis, and serum PCSK9 level was determined by enzyme-linked immunosorbent assay (ELISA). The differences of PCSK9 level and PLT between the two groups were compared, and subgroup analysis was conducted based on PLT for patients with sepsis. The correlation between PCSK9 level and PLT in septic patients was analyzed by Pearson correlation method. ② Animal experiment: 80 male C57BL/6 mice were randomly divided into control group, sepsis model group [lipopolysaccharide (LPS) group], PCSK9 inhibitor pretreatment group (PCSK9 inhibitor+LPS group) and PCSK9 inhibitor control group (PCSK9 inhibitor group), with 20 mice in each group. The mouse model of sepsis was reproduced by intraperitoneal injection of LPS 12 mg/kg, and the control group and PCSK9 inhibitor group were intraperitoneally injected with the same amount of sterile normal saline. PCSK9 inhibitor+LPS group and PCSK9 inhibitor group were pretreated with PCSK9 inhibitor 5 mg/kg intraperitoneal injection for 7 days before injection of LPS or normal saline, respectively, and the control group and LPS group were injected with an equal amount of sterile normal saline. The lung tissues were taken for pathological and immunohistochemical observation 24 hours after modeling. Blood was taken from the heart for determining PLT. Platelet activation was detected by flow cytometry. The expression level of platelet-activation marker CD40L was detected by Western blotting.Results:① Clinical trial: there were 57 cases in the sepsis group and 27 cases in the healthy control group. Serum PCSK9 level in the sepsis group was significantly higher than that in the healthy control group (μg/L: 232.25±72.21 vs. 191.72±54.92, P < 0.05), and PLT was significantly lower than that in the healthy control group [×10 9/L: 146.00 (75.50, 204.50) vs. 224.00 (194.00, 247.00), P < 0.01]. Subgroup analysis showed that the serum PCSK9 level in the thrombocytopenia patients ( n = 20) was significantly higher than that in the non-thrombocytopenia patients ( n = 37; μg/L: 264.04±60.40 vs. 215.06±72.95, P < 0.01). Correlation analysis showed a significant negative correlation between serum PCSK9 levels and PLT in septic patients ( r = -0.340, P = 0.010). ② Animal experiment: there were no significant pathological changes in lung tissue in the control group and PCSK9 inhibitor group under light microscope, and no significant differences in PLT, platelet activation and plasma CD40L protein expression was found between the two groups. In the LPS group, a large number of inflammatory cells were infiltrated in the pulmonary interstitium, the alveolar structure was damaged obviously, the alveolar septum was widened, the alveolar cavity was extensively bleeding, the capillary dilatation with bleeding and platelet aggregation were found, the PLT was significantly decreased, the platelet activation and the expression level of CD40L protein in plasma were significantly increased. The infiltration of inflammatory cells in lung tissue of mice in the PCSK9 inhibitor+LPS group was reduced to a certain extent, the thickening of alveolar septa was reduced, the platelet aggregation in lung tissue was decreased as compared with the LPS group, the PLT was significantly increased (×10 9/L: 515.83±46.60 vs. 324.83±46.31, P < 0.05), the platelet activation and the expression level of CD40L protein in plasma were significantly decreased [positive expression rate of platelet activation dependent granule surface facial mask protein CD62P: (12.15±1.39)% vs. (18.33±2.74)%, CD40L protein (CD40L/β-actin): 0.77±0.08 vs. 1.18±0.10, both P < 0.05]. Conclusion:PCSK9 level has a certain effect on promoting platelet activation in sepsis, and inhibition of PCSK9 level may have potential research value in improving adverse outcomes caused by sepsis thrombocytopenia.

Effect of continuous blood purification on immunity and endothelial cell function in patients with sepsis / 中华危重病急救医学

Objective:To explore the effect of continuous blood purification (CBP) on the immunity and endothelial cell function of patients with sepsis.Methods:A prospective study was conducted. The patients aged ≥18 years old and meeting the diagnostic criteria of sepsis admitted to the department of critical care medicine of Binzhou Medical University Hospital from March 2019 to October 2020 were selected as the research subjects, and the patients were divided into standard treatment group and CBP treatment group according to random number table method. Both groups were given standard treatment including initial fluid resuscitation, infection source control and antibiotics according to the 2016 international guidelines for the management of sepsis and septic shock. CBP treatment group was additionally given continuous veno-venous hemofiltration (CVVH) at a dose of 25-30 mL·kg -1·h -1 and blood flow rate of 150-200 mL/min for more than 20 hours a day for 3 days. The clinical data of patients including blood lactic acid (Lac), procalcitonin (PCT), lymphocyte count (LYM), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score were recorded before treatment and 1 day and 3 days after treatment. At the same time, the venous blood was collected, and the immune function related indexes [interleukins (IL-4, IL-7), programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), interferon-γ (IFN-γ)] and endothelial cell injury related markers [soluble thrombomodulin (sTM), angiopoietin-2 (Ang-2), von Willebrand factor (vWF), heparan sulfate (HS), syndecan-1 (SDC-1)] levels in serum were determined by enzyme-linked immunosorbent assay (ELISA). The length of intensive care unit (ICU) stay of patients in the two groups was recorded, and the outcomes of patients in the two groups were followed up for 28 days. Results:Finally, 20 patients were enrolled in the standard treatment group, and 19 patients were enrolled in the CBP treatment group. There were no significant differences in gender, age and infection site between the two groups. The length of ICU stay in the standard treatment group was (10±5) days, and 5 patients died and 15 patients survived after 28 days. The length of ICU stay in the CBP treatment group was (9±4) days, and 8 patients died and 11 patients survived after 28 days. There were no significant differences in the length of ICU stay and number of patients who died within 28 days between the two groups (both P > 0.05). There were no significant differences in the Lac, PCT, LYM, APACHEⅡ score, SOFA score and immune function and endothelial cell injury related indexes before treatment and 1 day after treatment between the two groups. After 3 days of treatment, the Lac, PCT, APACHEⅡ score and SOFA score of the CBP treatment group were significantly lower than those before treatment, and pro-inflammatory and anti-inflammatory cytokines such as IFN-γ and IL-4, apoptosis-related indicators such as PD-1 and IL-7, and endothelial injury related factors such as sTM, SDC-1 and HS were significantly improved compared with the pre-treatment, the improvement degree of the above indicators was more obvious than that of the standard treatment group, and LYM was significantly higher than that of the standard treatment group (×10 9/L: 1.3±0.3 vs. 0.9±0.4, P < 0.05), IL-4, IFN-γ, IFN-γ/IL-4 ratio, IL-7, PD-1, sTM, SDC-1, HS, and Ang-2 were significantly lower than those of the standard treatment group [IL-4 (ng/L): 2.8 (1.5, 3.2) vs. 3.3 (2.7, 5.2), IFN-γ (ng/L): 6.3 (5.4, 106.5) vs. 217.9 (71.4, 517.1), IFN-γ/IL-4 ratio: 3.7 (1.8, 70.3) vs. 59.1 (18.3, 124.9), IL-7 (ng/L): 4.6 (3.2, 5.1) vs. 6.3 (5.2, 8.0), PD-1 (μg/L): 0.04 (0.03, 0.06) vs. 0.08 (0.05, 0.12), sTM (μg/L): 4.9 (4.3, 7.4) vs. 8.7 (6.0, 10.8), SDC-1 (μg/L): 0.6 (0.3, 1.1) vs. 0.9 (0.8, 2.5), HS (ng/L): 434.8 (256.2, 805.0) vs. 887.9 (620.1, 957.3), Ang-2 (ng/L): 934.0 (673.3, 1 502.1) vs. 2 233.9 (1 472.5, 3 808.4)], the differences were statistically significant (all P < 0.05). Conclusion:CBP treatment can eliminate the patient's immunosuppressive state, reduce a variety of endothelial injury markers and the degradation of glycocalyx, but cannot decrease the 28-day death risk or shorten the length of ICU stay.

Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia / 中华内科杂志

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.

Prognostic value of PCSK9 and blood lipid in patients with sepsis / 中华危重病急救医学

Objective:To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis.Methods:Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn.Results:There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95% CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. Conclusions:PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.

The overall action molecular mechanism of anti-hepatitis B active extracts in Flos chrysanthemi indici based on epigenetics and metabonomics / 药学学报

Using the concepts and methods of epigenetics and metabolomics, to investigate the overall action molecular mechanism of Chrysanthemi indici C (CIC), the anti-hepatitis B virus (HBV) active extracts from Flos chrysanthemi indici. The inhibitory effects of CIC on proliferation and hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg) and HBV-DNA of HepG2.2.15 cells were detected by CCK-8 and antigen kit. The DNA methyltransferases (DNMTs)/ten-eleven-translocation-2 (TET2) equilibrium was detected by ELISA. Illumina 850K methylation chip, pyrosequencing and qPCR were used to determine the action pathway and target of CIC by GO and KEGG analysis. Cell metabolites were extracted with 80% methanol, and the changes of differential metabolites, differential metabolic pathways and cell microenvironment were detected by LC-MS and other metabolomics methods. The results showed that CIC could inhibit the proliferation, HBsAg, HBeAg and HBV-DNA of HepG2.2.15 cells obviously, down-regulate DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3a (DNMT3a) and DNA methyltransferase 3b (DNMT3b), up-regulate TET2, and restore the balance of DNMTs/TET2. The action targets of CIC were phospholipase C gamma 2 (PLCG2), phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), 5-hydroxytryptamine receptor 2B (HTR2B), nerve growth factor (NGF), mainly involved in lipid metabolism, inflammation mediated regulation of transient receptor potential (TRP), phospholipase D signaling and advanced glycation end product-receptor for AGE (AGE-RAGE) signaling in diabetic complications pathways. CIC could significantly affect fatty acid metabolism and had great influence on phenolic acid, alkaloid and lipid metabolites in cell microenvironment. These results suggest that the action mechanism of CIC may be the synergistic action of multiple pathways and multiple targets, including related inflammatory pathways, immune pathways and lipid metabolism, through regulating epigenetic expression balance and restoring the balance of cell microenvironment.

Research advances on signaling pathways affecting sweat gland development and their involvement in the reconstitution of sweat adenoid cells in vitro / 中华烧伤杂志

The damage of sweat glands in patients with extensive deep burns results in the loss of thermoregulation, which seriously affects the quality of life of patients. At present, there are many researches on the repair of sweat gland function, but the mechanism of human sweat gland development has not been fully clarified. More and more studies have shown that the cascaded pathways of Wnt/β-catenin, ecto- dysplasin A/ectodysplasin A receptor/nuclear factor-κB, sonic hedgehog, and forkhead box transcription factor jointly affect the development of sweat glands, and it has been reported that the cascaded signaling pathways can be used to achieve the reconstruction of sweat adenoid cells in vitro. This article reviews the signaling pathways that affect the development of sweat glands and their involvement in the reconstruction of sweat adenoid cells in vitro.

Assistant role of manifestations under tracheoscopy in the diagnosis of invasive pulmonary aspergillosis in severe patients / 中华危重病急救医学

Objective:To evaluate the assistant role of manifestations under tracheoscopy in the diagnosis of invasive pulmonary aspergillosis (IPA) in severe patients.Methods:A retrospective study was conducted. The patients with suspected IPA admitted to intensive care unit (ICU) of Affiliated Hospital of Binzhou Medical College from January 2015 to December 2019 were enrolled. The diagnosis, clinical diagnosis and suspected diagnosis were made according to the grading criteria of Guidelines for the diagnosis and treatment of invasive fungal infection in severe patients (2007). Those who met the criteria were enrolled in the IPA group, and those who did not meet the criteria or other pathogens were enrolled in the non-IPA group. The general data of the patients were collected, and the changes of tracheal and bronchial mucosa under tracheal microscope before and after treatment were recorded, as well as the results of galactomannan (GM) test and aetiology culture of bronchoalveolar lavage fluid (BALF). The baseline, bronchoscopy and pulmonary CT manifestations and their dynamic changes were compared in each group. Results:A total of 142 patients with suspected IPA were finally enrolled. Among them, 12 were pathologically proven IPA, 77 were probable IPA, 22 were possible IPA, and 31 were undefined IPA. Of the 142 patients, 60 had typical manifestations of mucosal injury under bronchoscopy, including 7 proven IPA patients (58.3%), 52 probable IPA patients (67.5%), and 1 possible IPA patient (4.5%), but none undefined IPA patient. The patients undergoing lung CT scan were 12 proven IPA patients (100%), 73 probable IPA patients (94.8%), and 21 possible IPA patients (95.5%), respectively. Most of the Chest CT showed patchy or strip density increasing and other non-specific manifestations. There were 3 proven IPA patients (25.0%), 7 probable IPA patients (9.0%), and 0 possible IPA patient (0%) who had typical IPA CT manifestations (halo sign and cavity or crescent sign). Among the patients of proven IPA and probable IPA (89 cases), there were a total of 35 cases with endoscopic airway mucosal injury and tracheoscopy reexamination ≥ 3 times. All the 35 patients received anti-aspergillus treatment, among which 16 survived and 19 died. Among the 16 patients who survived, the microscopic appearance of mucosal injury was gradually reduced and the clinical manifestations were gradually improved. Of the 19 patients who died, 16 had deteriorated endoscopic airway mucosal injury.Conclusions:The specific manifestations of severe patients with bronchial mucosal injury are of great significance in the diagnosis of IPA. In the case of severe patients who cannot receive pathological examination or chest CT in time, dynamic observation of the changes of airway mucosal injury is a simple auxiliary method to discover the changes of patients' condition in time, evaluate the effect of antifungal therapy and the prognosis of IPA.

Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

A Thyroid Ultrasound Image-based Artificial Intelligence Model for Diagnosis of Central Compartment Lymph Node Metastasis in Papillary Thyroid Carcinoma / 中国医学科学院学报

Objective To establish an artificial intelligence model based on B-mode thyroid ultrasound images to predict central compartment lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC). Methods We retrieved the clinical manifestations and ultrasound images of the tumors in 309 patients with surgical histologically confirmed PTC and treated in the First Medical Center of PLA General Hospital from January to December in 2018.The datasets were split into the training set and the test set.We established a deep learning-based computer-aided model for the diagnosis of CLNM in patients with PTC and then evaluated the diagnosis performance of this model with the test set. Result The accuracy,sensitivity,specificity,and area under receiver operating characteristic curve of our model for predicting CLNM were 80%,76%,83%,and 0.794,respectively. Conclusion Deep learning-based radiomics can be applied in predicting CLNM in patients with PTC and provide a basis for therapeutic regimen selection in clinical practice.

Tweety-Homolog 1 Facilitates Pain via Enhancement of Nociceptor Excitability and Spinal Synaptic Transmission / 神经科学通报·英文版

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.

Significance of high mobility group box 1, von Willebrand factor and other cytokines in the evaluation of severity and prognosis of sepsis patients / 中华危重病急救医学

Objective:To explore the value of high mobility group box 1 (HMGB1), von Willebrand factor (vWF) and other cytokines in predicting the severity and prognosis of sepsis patients.Methods:Patients with sepsis and septic shock who ≥18 years old and met the Sepsis-3 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to June 2019 were taken as the research objects. The healthy individuals for regular health examination in the same period were taken as the control. The basic information, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) scores were recorded. The venous blood was taken within 24 hours after the patients were diagnosed. The levels of HMGB1, vWF, tumour necrosis factor-α (TNF-α), interleukin-10 (IL-10), soluble thrombomodulin (sTM), vascular endothelial growth factor receptor 2 (VEGFR-2), angiopoetin-2 (Ang-2) and other cytokines in serum were determined by enzyme linked immunosorbent assay (ELISA). Differences among patients with sepsis, septic shock, healthy physical examinees, and patients who died in 28-day and those who survived, were compared. Spearman rank correlation method was used to analyze the correlation among each cytokine and APACHEⅡ, SOFA scores. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of cytokines on the prognosis of patients with sepsis/septic shock. Logistic regression was used to analyze the risk factors of 28-day death.Results:Eleven patients with sepsis, 25 patients with septic shock and 30 healthy individuals were enrolled. Among the patients with sepsis/septic shock, 15 died in 28-day and 21 survived. The serum levels of TNF-α, IL-10, HMGB1, vWF, sTM and VEGFR-2 in patients with sepsis were significantly higher than those in the healthy control group. The levels of TNF-α, IL-10, HMGB1, vWF, sTM in septic shock group were higher than those in the sepsis group, while the Ang-2 level decreased significantly. The serum levels of TNF-α, IL-10, HMGB1, vWF and sTM in the death group were higher than those in the survival group, while Ang-2 was lower than the survival group. Spearman correlation analysis showed that HMGB1, TNF-α, sTM, IL-10, vWF were positively correlated with APACHEⅡ score when patients with sepsis/septic shock were enrolled ( r values were 0.652, 0.666, 0.445, 0.430 and 0.355, respectively, all P < 0.05), and HMGB1, TNF-α also positively correlated with SOFA score ( r values were 0.433, 0.479, both P < 0.05). Ang-2 was negatively correlated with APACHEⅡ and SOFA scores ( r values were -0.519, -0.440, both P < 0.05). ROC curve analysis showed that the predictive value of HMGB1, vWF, IL-10, sTM for 28-day death in patients with sepsis/septic shock were higher than the APACHEⅡ score [the area under ROC curve (AUC) and 95% confidence interval (95% CI): 0.946 (0.870-1.000), 0.902 (0.790-1.000), 0.877 (0.745-1.000), 0.868 (0.734-1.000) vs. 0.846 (0.700-0.991)]. Logistic regression analysis showed that APACHEⅡ score, vWF, sTM, and IL-10 were independent risk factors for 28-day death in patients with sepsis/septic shock (β values were 4.731, 0.407, -7.058, -0.887, all P < 0.05). Conclusion:HMGB1, vWF, IL-10, sTM and other cytokines all can be used to evaluate the severity and prognosis of sepsis patients.

Effect of disinfectant with benzethon chloramine and isopropanol as main active ingredients on the accuracy of dental impression / 北京大学学报(医学版)

OBJECTIVE@#To assess the effect of disinfectant (Cavicide) with benzethon chloramine and isopropanol as main active ingredients disinfectant on dental impression accuracy.@*METHODS@#The effect of Cavicide on three impression materials (alginate, polyether and vinylpolysiloxane) were assessed using a standard model. The standard model was digitized by an extraoral scanner (IScan D103i, Imetric). For each kind of impression materials, thirty impressions were taken following the manufactures' instruction in the same conditions. Subsequently, the impressions were randomly divided into three groups, with ten impressions in each group. After the impression taking was completed, the three groups underwent pure water rinse for 1 min (blank control, BC), 2% glutaraldehyde solution immersion disinfection for 30 min (glutaraldehyde, GD), and Cavicide solution spray disinfection for 5 min (Cavicide, CC), respectively. All the impressions were digitized by the extraoral scanner (IScan D103i, Imetric) after disinfection and exported to a dedicated three-dimensional analysis software (Geomagic Qualify 2014, Geomagic, USA). In the software, the digital models of the impressions were trimmed to teeth and then superimposed with the digitized standard model via best-fit alignment. Root mean square (RMS) was used to evaluate the deviations between the impression and the standard model. The deviation in the anterior and posterior regions was evaluated respectively. One-way ANOVA test and the LSD post-hoc test were used to compare the deviations between the three groups (P < 0.05). The color map of each superimposition was saved for visual analysis.@*RESULTS@#For the polyether and vinylpolysiloxane materials, the difference between the three groups was not statistically significant (P=0.933, P=0.827). For the alginate material, the difference in posterior region between group GD and group BC, as well as group GD and group CC were statistically significant (GD vs. BC, P=0.001; GD vs. CC, P=0.002), while the difference between group BC and group CC was not statistically significant (P=0.854). The visual analysis showed an obvious deviation in the buccal-lingual direction in group GD.@*CONCLUSION@#Disinfectant (Cavicide) with benzethon chloramine and isopropanol as main active ingredients using spray disinfection has no effect on the accuracy of the alginate, polyether and vinylpolysiloxane impressions.

Comparative Study on Dpph Free Radical Scavenging Activity of 25 Kinds of Traditional Chinese Medicinal Plants

Aims: To determine and compare the antioxidant activity of water and ethanol extract of 25 kinds of traditional chinese medicinal plants. Results: The ethanol extract of 4 kinds of medicinal herbs had the strongest scavenging activity. They were Magnolia officinalis, Rheum officinale, Psoralea corylifolia and Radix Bupleuri. In addtion, Rheum laciniatum, Chrysanthemum morifolium, Magnolia officinalis and Salvia miltiorrhiza had the strongest scavenging activity of their water extract. On the basis of the above comparison, we evaluated EC50 and total phenolic content of their ethanol extract. The EC50 of Magnolia officinalis, Rheum officinale, Psoralea corylifolia and Radix Bupleuri were 2.75mg·mL-1, 11.82mg·mL-1, 25.22mg·mL-1and 42.67mg·mL-1. The total phenlic content of them were 4.80μg·L-1 , 1.19μg·L-1, 1.07μg·L-1 and 0.75μg·L-1, respectively. Conclusion: The results showed the correlation between the antioxidant activity and the total phenol content. Furthermore, the reaction time of the DPPH test affected the free radical scavenging, which reflected the difference of the extract component would impact the test method.

Buttress plate fixation of coronoid process fractures via a medial approach / 中华创伤杂志(英文版)

PURPOSE@#To assess the clinical and radiographic outcomes of coronoid process fractures surgically managed with buttress plate fixation via a medial approach.@*METHODS@#A retrospective review of all coronoid fractures surgically fixed in our institution using a buttress plate technique via a medial approach between June 2012 and April 2015 by the senior author was performed. These fractures were all sizeable fractures contributing to persistent elbow instability in terrible triad or varus posteromedial rotatory instability injury patterns. A prospective telephone questionnaire was conducted to assess patient outcomes using the disabilities of the arm, shoulder and hand (DASH) score and Mayo hlbow performance score (MEPS).@*RESULTS@#Twelve patients were included in the study, comprising 10 males and 2 females with an average age of 39 years (range, 19-72 years). Mean follow-up was 16 months (range, 4-18 months). The average time to radiographic union was 4 months (range, 3-7 months). Range of motion measurements at final follow-up were obtained in 11 out of 12 patients, with one patient defaulting follow-up. All 11 patients displayed a functional elbow range of motion of at least 30°-130°, with an average arc of motion of 130° (range, 110° -140°), mean elbow flexion of 134° (range, 110° -140°) and mean flexion contracture of 3° (range, 0° -20°). The mean DASH score was 16 (range, 2.5-43.8) and the mean MEPS was 75 (range, 65-100). Complications observed included one patient with a superficial wound infection which resolved with a course of oral antibiotics and one patient with radiographic evidence of heterotopic ossification which was conservatively managed. No residual elbow instability was observed and no reoperations were performed.@*CONCLUSION@#Buttress plate fixation via a medial approach of coronoid process fractures that contribute to persistent elbow instability represents a reliable method of treatment that produces satisfactory and predictable outcomes.

Lengthening of a below knee amputation stump with Ilizarov technique in a patient with a mangled leg / 中华创伤杂志(英文版)

A below knee amputation (BKA) requires sufficient stump length for the fitting of a modern prosthesis. In cases of trauma where the levels of injury are unpredictable, achieving sufficient stump length can be a challenge. We described a case report of using the Ilizarov technique for bone lengthening at the residual BKA stump for a patient who sustained a mangled limb following a road traffic accident. Using this technique, we have successfully lengthened the tibial stump adequately for a functioning prosthesis. As shown in this case, we believe that this technique could attain an excellent outcome for a selected group of patients with short residual BKA stump.

Effect of docetaxel combined with chemotherapy on the survival time, serum tumor markers and metastasis related factors in patients with esophageal cancer after operation / 中国基层医药

Objective@#To investigate the application effect of docetaxel combined with capecitabine and oxaliplatin (XELOX) chemotherapy in patients with esophageal cancer undergoing radical operation.@*Methods@#From February 2013 to December 2015, 69 cases of esophageal cancer in Heji Hospital Affiliated to Changzhi Medical College were treated with radical operation, and they were divided into two group according to the random number table.Thirty-four cases in the control group were treated with XELOX chemotherapy, and 35 cases in the observation group were treated with XELOX chemotherapy + docetaxel.The clinical therapeutic effect and the levels of serum tumor markers[carcinoembryonic antigen(CEA) and squamous cell carcinoma associated antigen(SCC)], serum transfer related factors[interleukin-6(IL-6), nitric oxide synthase(NOS), nitric oxide(NO)]before and after treatment of the two groups were observed and compared.The occurrence and life cycle of the two groups were also analyzed.@*Results@#The control rate of the disease in the observation group was 74.29% (26/35), which was higher than that in the control group [50% (17/34)](χ2=4.332, P<0.05). The serum levels of CEA and SCC in the observation group were lower than those in the control group(t=15.835, 10.872, all P<0.05). The serum levels of IL-6 and NOS in the observation group were lower than those in the control group, and the level of NO was higher than that in the control group(t=12.200, 8.209, 7.460, all P<0.05). There was no statistically significant difference in the incidence of side effects between the observation group and the control group(P>0.05). The median survival time of the observation group was 12.50 months, while that of the control group was 8.70 months, and the difference was statistically significant(P<0.05).@*Conclusion@#Docetaxel combined with XELOX chemotherapy can prolong the postoperative life cycle of the patients.

Effective Components and Mechanisms of Drynariae Rhizoma Anti-osteoporosis Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To predict the target of active components of Drynariae Rhizoma by the network pharmacology, map related targets of osteoporosis (OP), and analyze key nodes of interaction topologically, so as to comprehensively explore the pharmacological mechanism of anti-op of osteoclasts. Method:Firstly, the main active components of Drynariae Rhizoma were screened out from TCMSP based on the pharmacokinetic characteristics, and the related targets were predicted by Pubchem and Swiss Target Prediction database according to the Two-dimensional/Three-dimensional(2D/3D)structural similarity. Then, through Online Mendelian Inheritance in Man (OMIM) and Pubmed text, known OP therapeutic targets were mined, based on putative targets, String database was imported to build Drynariae Rhizoma treatment target OP interaction network diagram. With the help of CytoNCA software, the interaction key nodes were topologically identified according to relevant node parameters, and then imported into String database to build the protein interaction network graph. Finally, biological functions and metabolic pathways of key nodes were analyzed through DAVID database. Result:Sixteen active components of Drynariae Rhizoma were screened out, and 118 related targets were predicted according to the target prediction technique. Totally 316 known therapeutic targets for OP were retrieved. The protein interaction network was constructed according to the String network database. A total of 97 key nodes were screened via CytoNCA topology. The enrichment analysis showed that Drynariae Rhizoma may play an anti-osteoporosis role by regulating stem cells, osteoblasts, osteoclasts and immune cells through multiple signaling pathways in aspects of proliferation, differentiation, immunity and oxidative stress. Conclusion:Studies based on network pharmacology have shown that Drynariae Rhizoma may play an anti-op role through direct or indirect targets and multiple major signaling pathways and affect the proliferation and differentiation of multiple types of cells, in order to provid a scientific basis for explaining the material basis and mechanism of Drynariae Rhizoma's anti-osteoporosis effect.

Effect of carrier size and surface morphology on the aerosolization of formulation in a capsule-based dry powder inhaler / 药学学报

The size and surface morphology of carrier lactose had influence on the aerosolization performance of dry powder inhalers. In this article, chlorpheniramine maleate was blended with two types of commercial carrier lactose, which were Lactohale 100® and Respitose SV003® (SV003), as formulation model. In vitro experiments were conducted using fast screening impactor at 30 L·min-1 and 60 L·min-1 respectively. Meanwhile, computational fluid dynamics (CFD) coupling with discrete element modelling (DEM) was applied to discuss the movements of those two carrier particles in Handihaler® at the flow rate mentioned above. The dispersion characteristics of two formulations and the dispersion mechanism of Handihaler® were analyzed by establishing the relationship between in vitro experiments and numerical simulation. The results of in vitro experiments and CFD-DEM demonstrated that the aerosolization performance of formulation with SV003 was better. The linear correlation (R2 = 0.940 1) between fine particle dose and total energy loss by carrier collision within the wall of device was found by comparing the in vitro experimental results with CFD-DEM results. It revealed that particle-wall collision in Handihaler® had direct impact on the dispersion results of formulation.

Effect of docetaxel combined with chemotherapy on the survival time,serum tumor markers and metastasis related factors in patients with esophageal cancer after operation / 中国基层医药

Objective To investigate the application effect of docetaxel combined with capecitabine and oxaliplatin (XELOX) chemotherapy in patients with esophageal cancer undergoing radical operation.Methods From February 2013 to December 2015,69 cases of esophageal cancer in Heji Hospital Affiliated to Changzhi Medical College were treated with radical operation,and they were divided into two group according to the random number table.Thirty-four cases in the control group were treated with XELOX chemotherapy,and 35 cases in the observation group were treated with XELOX chemotherapy + docetaxel.The clinical therapeutic effect and the levels of serum tumor markers[ carcinoembryonic antigen ( CEA) and squamous cell carcinoma associated antigen ( SCC)],serum transfer related factors [ interleukin -6 ( IL -6),nitric oxide synthase ( NOS), nitric oxide ( NO)] before and after treatment of the two groups were observed and compared.The occurrence and life cycle of the two groups were also analyzed.Results The control rate of the disease in the observation group was 74.29%(26/35),which was higher than that in the control group [50%(17/34)](χ2 =4.332,P＜0.05).The serum levels of CEA and SCC in the observation group were lower than those in the control group(t=15.835,10.872,all P＜0.05).The serum levels of IL-6 and NOS in the observation group were lower than those in the control group,and the level of NO was higher than that in the control group ( t =12. 200, 8. 209, 7. 460, all P ＜0. 05 ). There was no statistically significant difference in the incidence of side effects between the observation group and the control group(P>0.05).The median survival time of the observation group was 12.50 months,while that of the control group was 8.70 months,and the difference was statistically significant(P＜0.05).Conclusion Docetaxel combined with XELOX chemotherapy can prolong the postoperative life cycle of the patients.