OBJECTIVE: To investigate the potential mechanisms of sepsis pathogenesis in intensive care unit (ICU), with a specific focus on the role of skin microbiota, and to evaluate the causal relationships between skin microbiota and ICU sepsis using Mendelian randomization (MR). METHODS: A two-sample MR analysis was performed using skin microbiota genome-wide association study (GWAS) summary data from German population cohorts as exposures, combined with ICU sepsis susceptibility and 28-day mortality GWAS summary data from the IEU OpenGWAS database as outcomes. The primary causal effect estimates were generated using the inverse variance weighted (IVW) method, supplemented by validation through MR-Egger and weighted median approaches. Heterogeneity and pleiotropy tests, along with sensitivity analyses, were conducted to evaluate the robustness of the results. RESULTS: Regarding risk of ICU sepsis, IVW analysis showed that order Pseudomonadales [odds ratio (OR) = 0.93, 95% confidence interval (95%CI) was 0.88-0.98], family Flavobacteriaceae (OR = 0.93, 95%CI was 0.90-0.96), and genus Acinetobacter (OR = 0.96, 95%CI was 0.93-0.99) were significantly negatively correlated with the risk of ICU sepsis (all P < 0.05). There was a significant positive correlation between the risk of ICU sepsis and the presence of β-Proteobacteria (OR = 1.05, 95%CI was 1.00-1.11) and Actinobacteria (OR = 1.05, 95%CI was 1.00-1.11), both P < 0.05. Regarding 28-day mortality of ICU sepsis, IVW analysis showed that phylum Bacteroidetes (OR = 0.92, 95%CI was 0.86-0.99), family Streptococcaceae (OR = 0.92, 95%CI was 0.85-0.98), family Flavobacteriaceae (OR = 0.90, 95%CI was 0.83-0.97), genus Streptococcus (OR = 0.92, 95%CI was 0.86-0.99), ASV016 [Enhydrobacter] (OR = 0.92, 95%CI was 0.87-0.98), and ASV042 [Acinetobacter] (OR = 0.92, 95%CI was 0.88-0.97) were significantly negatively correlated with the 28-day mortality of ICU sepsis (all P < 0.05); family Moraxellaceae (OR = 1.09, 95%CI was 1.00-1.18) and ASV008 [Staphylococcus] (OR = 1.08, 95%CI was 1.03-1.14) was significantly positively correlated with the 28-day mortality of ICU sepsis (both P < 0.05). Sensitivity analysis and MR-PRESSO showed no heterogeneity, pleiotropy, or horizontal pleiotropy between skin microbiota and ICU sepsis risk and 28-day mortality rate. Analysis of confounding factors showed that single nucleotide polymorphisms (SNPs) associated with relevant skin bacteria could independently and causally affect the risk of ICU sepsis or ICU sepsis related mortality rate, independent of other confounding factors. The Steiger test results indicated that the established causal relationship was not due to reverse causality. CONCLUSIONS Skin microbiota composition may influence both sepsis susceptibility and 28-day mortality in ICU settings. Family Flavobacteriaceae demonstrated protective effects against sepsis onset and mortality. These findings provide new perspectives for early detection and management strategies.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Mendelian Randomization Analysis ; Microbiota ; Skin/microbiology* ; Genome-Wide Association Study ; Risk Factors ; Skin Microbiome

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

【Objective】 To evaluate the efficacy and safety of human coagulation factor Ⅷ developed by Shenzhen Weiguang Biological products Co, Ltd in the treatment of patients with hemophilia A. 【Methods】 A prospective, multi-center, open, single-group clinical study was conducted. A total of 65 subjects with hemophilia A were enrolled, and human coagulation factor Ⅷ(FⅧ) was injected according to the patients’ bleeding severity. The improvement score of bleeding symptoms and signs after the first infusion of the first bleeding event and the transfusion efficiency of FⅧ activity at 10 min and 1 hour after infusion were taken as the main efficacy indexes. The improvement scores of bleeding symptoms and signs after the first infusion and the increase of FⅧ activity at 10 min and 1 hour after infusion were the secondary efficacy indexes. 【Results】 The 65 subjects were enrolled in safety analysis set (SS) and full analysis set (FAS), and 58 of them were enrolled in protocol analysis set (PPS). Ten minutes and one hour after the first infusion, the level of factor Ⅷ activity in the subjects increased significantly, and the FⅧ activity increased by 100% or more in more than 79% of the subjects. The average infusion efficiency of FⅧ activity in all subjects was more than 100%. In 70% of the subjects, the pain was relieved rapidly and /or the bleeding symptoms were significantly improved 8 hours after each bleeding infusion, and the improvement rate of bleeding symptoms and signs reached 100% 72 hours after infusion. 【Conclusion】 After infusion of human coagulation factor Ⅷ, the activity level of factor Ⅷ in patients with hemophilia A significantly increased. The infusion efficiency can reach a optimal level, and the bleeding symptoms can be significantly improved.

【Objective】 To evaluate the clinical efficacy and safety of one kind of human prothrombin complex concentrate in treatment of patients with hemophilia B. 【Methods】 The clinical data of 36 patients with hemophilia B treated with human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. from May 2018 to April 2019 were retrospectively analyzed, and its clinical efficacy and safety were analyzed. 【Results】 A total of 35 subjects entered the full analysis set (FAS)and safety set (SS), 33 subjects entered the per protocol Set (PPS). Thirty minutes after the first infusion of FAS subjects, the activity of coagulation factor Ⅸ increased from (3.93±0.975) IU/dL to (25.61±9.337) IU/dL, and the infusion efficiency was (96.43±22.007)%. The increased value of coagulation factor Ⅱ activity was (73.25±14.874) IU/dL. The activity of coagulation factor Ⅶ was (42.79±16.847) IU/dL. The increased value of coagulation factor Ⅹ activity was (65.29±17.042) IU/dL. The increased value of coagulation factor Ⅸ activity was (21.68±9.434%) IU/dL. Twenty-four hours after the first infusion of FAS subjects, the improvement of bleeding symptoms and signs was excellent in 21 cases (60%), improved in 14 cases (40.0%), and the effective rate was 100%. The incidence of adverse reactions was 2.9%(1/35), and there was no antibody to human coagulation factor Ⅸ and new virus infection. 【Conclusion】 Infusion of human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. in the treatment of hemophilia B has significant clinical efficacy and good safety.

OBJECTIVETo explore the anesthetic effects of repeated administration of propofol combined with vitamin C in mice.

METHODSForty mice were subjected to daily intraperitoneal injections of 80 mg/kg propofol (P80 group), 70 mg/kg propofol and 50 mg/kg vitamin C (P70+Vc50 group), 55 mg/kg propofol and 100 mg/kg vitamin C (P55+Vc100 group), or 50 mg/kg propofol and 200 mg/kg vitamin C (P50+Vc200 group) for 6 consecutive days, and the anesthesia induction time and anesthesia duration were recorded.

RESULTSCompared with the P80 group, the mice in P55 + Vc100 group and P50 + Vc200 group showed significantly shorter anesthesia duration on the first 3 days (P<0.05). In all the groups, anesthesia duration was significantly shortened in the following days compared with that on day 1 (P<0.01); anesthesia duration was shorter on day 3 than on day 2 in P50 + Vc200 group (P<0.01), and was shorter on days 4, 5, and 6 than on day 2 in all the groups (P<0.01). In all the groups, the rate of loss of righting reflex (LORR) decreased gradually with time in a similar pattern.

CONCLUSIONVitamin C can reduce the dose of propofol without obviously affecting the anesthetic effect to reduce the incidence of drug tolerance and potential dose-related side effects of propofol.

Anesthesia ; Anesthesia Recovery Period ; Anesthetics, Intravenous ; administration & dosage ; pharmacology ; Animals ; Ascorbic Acid ; administration & dosage ; pharmacology ; Drug Tolerance ; Mice ; Propofol ; administration & dosage ; pharmacology

Objective To investigate the extraction and purification methods of serum specific endothelial cell antibody of renal transplant recipients with rejection after renal transplantation.Methods Human umbilical vein endothelial cell (HUVEC)was isolated and cultured.The serum samples of the renal transplant recipients with poor renal function after renal transplantation were collected.Specific endothelial cell antibody was screened out with flow cytometry;antibodies against human leukocyte antigen (HLA)and major histocompatibility complex class Ⅰ-related chain A (MICA)were detected by Luminex platform.After the existence of specific endothelial cell antibody in the serum sample was confirmed,specific endothelial cell antibody was absorbed with HUVEC.The cell was washed and then the absorbed antibody was eluted from the cell membrane.Antibody IgG in the eluent was purified and concentrated again with Protein-A /G magnetic beads.Antibody activity in the eluent was detected by flow cytometry and the purified specific endothelial cell antibody (IgG)was identified by SDS-polyacrylamide gel (SDS-PAGE)and Western blot.Results In the serum of 386 renal transplant recipients,the serum samples of 5 renal transplant recipients with serum creatinine (Scr) >400 μmoI /L,negative anti-HLA antibody,negative anti-MICA antibody and median fluorescence intensity (MFI) >16 were selected.Purified specific endothelial cell antibody IgG showed immunoglobulin heavy chain (purity > 95%)by SDS-PAGE gel.Flow cytometry showed that the purified antibody had the feature of rebinding with the surface antigen of vascular endothelial cell.Conclusions The purification method of using human umbilical vein endothelial cell to absorb specific endothelial cell antibody in the serum of renal transplant recipients may obtain good effect.

Objective To explore the anesthetic effects of repeated administration of propofol combined with vitamin C in mice. Methods Forty mice were subjected to daily intraperitoneal injections of 80 mg/kg propofol (P80 group), 70 mg/kg propofol and 50 mg/kg vitamin C (P70+Vc50 group), 55 mg/kg propofol and 100 mg/kg vitamin C (P55+Vc100 group), or 50 mg/kg propofol and 200 mg/kg vitamin C (P50+Vc200 group) for 6 consecutive days, and the anesthesia induction time and anesthesia duration were recorded. Results Compared with the P80 group, the mice in P55 + Vc100 group and P50 + Vc200 group showed significantly shorter anesthesia duration on the first 3 days (P<0.05). In all the groups, anesthesia duration was significantly shortened in the following days compared with that on day 1 (P<0.01);anesthesia duration was shorter on day 3 than on day 2 in P50+Vc200 group (P<0.01), and was shorter on days 4, 5, and 6 than on day 2 in all the groups (P<0.01). In all the groups, the rate of loss of righting reflex (LORR) decreased gradually with time in a similar pattern. Conclusions Vitamin C can reduce the dose of propofol without obviously affecting the anesthetic effect to reduce the incidence of drug tolerance and potential dose-related side effects of propofol.

Objective To explore the anesthetic effects of repeated administration of propofol combined with vitamin C in mice. Methods Forty mice were subjected to daily intraperitoneal injections of 80 mg/kg propofol (P80 group), 70 mg/kg propofol and 50 mg/kg vitamin C (P70+Vc50 group), 55 mg/kg propofol and 100 mg/kg vitamin C (P55+Vc100 group), or 50 mg/kg propofol and 200 mg/kg vitamin C (P50+Vc200 group) for 6 consecutive days, and the anesthesia induction time and anesthesia duration were recorded. Results Compared with the P80 group, the mice in P55 + Vc100 group and P50 + Vc200 group showed significantly shorter anesthesia duration on the first 3 days (P<0.05). In all the groups, anesthesia duration was significantly shortened in the following days compared with that on day 1 (P<0.01);anesthesia duration was shorter on day 3 than on day 2 in P50+Vc200 group (P<0.01), and was shorter on days 4, 5, and 6 than on day 2 in all the groups (P<0.01). In all the groups, the rate of loss of righting reflex (LORR) decreased gradually with time in a similar pattern. Conclusions Vitamin C can reduce the dose of propofol without obviously affecting the anesthetic effect to reduce the incidence of drug tolerance and potential dose-related side effects of propofol.

Objective To evaluate the predictive performance of neuro-mechanical coupling (NMC) and neuro-ventilatory coupling (NVC) in the weaning outcome in patients with chronic obstructive pulmonary disease (COPD). Methods Sixteen patients were enrolled when the criteria for their first spontaneous breathing trial (SBT) was met. A 30-minute SBT was attempted, with the measurement of electrical activity of the diaphragm (Edi) , NMC, NVC, NVC ×NMC, index of rapid shallow breathing (f/Vt) , airway occlusion pressure (P0.1) and f/Vt ×P0.1 at 0, 5 and 30 min. The receiver operating characteristic (ROC) curve was calculated to evaluate the predictive performance of each index. Results Successful weaning(S group) was observed in 6 patients while weaning failure(F group) in 10 patients. (1)The predictive capacity of Edi: at 30 min of SBT, Edi showed higher values in the F group (P ＜ 0. 05), the area under the ROC curves(AUC) was 0. 817(P ＜0. 05). (2) The predictive capacity of NVC and NMC:at 5, 30 min of SBT, NVC and NMC showed higher values in the S group (P ＜0. 05); at 30 min of SBT NVC presented the largest AUC than any other time of SBT (0. 822, P ＜ 0. 05), while the AUC of NMC was 0. 800 (P ＞ 0. 05). (3) The predictive capacity of NVC × NMC: at 30 min of SBT, the AUC of NVC × NMC was larger than NVC (0. 864, P ＜ 0. 05) , showing greater sensitivity (100. 0%) and specificity (83. 3%) .(4) The predictive capacity of f/Vt and P0.1: f/Vt and f/Vt × P0.1 presented poor predictive performance in the failed patients. Conclusions Edi, NVC and NVC × NMC were good predictor for the weaning outcome in patients with COPD.

OBJECTIVETo study the correlation among the morphological characteristics and the spica yield of various germplasm of Prunella vulgaris.

METHODThe various P. vulgaris germplasm from all over the country were investigated by analysis of correlation analysis, path analysis and principle component analysis in a randomized block experiment.

RESULTThe 6 morphological characteristics were greatly different from each other in various germplasm. The spica yield per plant had a very significantly positive correlation with the number of spica per plant and fresh leaves weight per plant, meanwhile the correlation between the spica yield per plant and spica length was very significantly. Three principal components which accounted for 87.533% of total variance were extracted from the principal component analysis.

CONCLUSIONThe strong growth potential, the number of spica per plant and spica length were main factors for the selection of high yield breeding of P. vulgaris.

Genetic Variation ; Principal Component Analysis ; Prunella ; anatomy & histology ; chemistry ; genetics ; growth & development