Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

Objectives:This study aims to explore the causal relationships between immune cells and serum metabolites in the development of coronary heart disease(CHD)using Mendelian randomization(MR)methods.Methods:We conducted a two-sample MR analysis utilizing data from the FinnGen Project's genome-wide association study(GWAS)on CHD,alongside data on metabolites and immune cells from the GWAS catalog.For the identified associated metabolites,we further employed mediation MR methods to evaluate their mediating roles in the influence of immune cells on CHD.Results:The MR analysis indicated that three immune cells(IgD-CD24-%B cell,CD11b on CD14+monocyte,HLA DR on DC)had stable causal relationship with CHD(under the premise of inverse variance weighted[IVW]method P<0.05,both MR-Egger and weighted median methods also showed P<0.05).Furthermore,these immune cells were associated with CHD through four metabolites(N-acetylneuraminic acid levels,the ratio of desmethyltaurine to taurine,X-24801 and X-18779).Conclusions:This study reveals the causal relationships between immune cells and serum metabolites in the pathogenesis of CHD,providing new biomarkers for early prediction and risk assessment of CHD.

The incidence of chronic venous disease(CVD)is significantly higher in the elderly population compared to non-elderly individuals,with more severe disease manifestations.Additionally,elderly CVD patients often have comorbid conditions such as cardiovascular diseases,making the evaluation process more complex and increasing treatment difficulty.Currently,there are no established recommendations in China for the diagnosis and treatment of CVD in individuals aged 60 and above.Against this backdrop,the Peripheral Vascular Disease Management Branch of the Chinese Geriatric Society has developed the Chinese Expert Consensus on the Diagnosis and Treatment of Chronic Venous Disease in the Elderly based on domestic and international guidelines,relevant evidence-based medical research,and the physiological and clinical characteristics of the elderly population in China.This consensus aims to provide an important reference for improving the diagnosis and treatment of CVD in elderly patients in China.

Objective To investigate the utility of dual-energy computed tomography(DECT)virtual non-contrast(VNC)images instead of true non-contrast(TNC)images in the quantitative analysis of emphysema.Methods A retrospective selection was con-ducted on 59 patients who underwent chest CT plain scan plus dual-phase enhanced scan on APEX-CT.VNC images of arterial phase(VNCart)and venous phase(VNCven)were generated on AW4.7 workstation.Volume CT dose index(CTDIvol)and dose length product(DLP)were recorded respectively.In a double-blind manner,two physicians graded the severity of each patient's emphysema according to the Fleischner Society's emphysema visual classification system.The"digital lung"detection and analysis platform was used to quantitatively measure emphysema at three thresholds(-950 HU,-930 HU and-910 HU),and the difference in meas-urement results between VNC images and TNC images was compared.Quantitative differences in low attenuation volume(LAV),percentage of low attenuation area(LAA%)and mean lung density(MLD)at the-950 HU threshold were compared using Bland-Altman plots.Results Using TNC images as the standard,there was no significant difference in the results of the visual classifica-tion evaluation of emphysema between TNC and VNC images(χ2=2.80,P=0.247).In quantitative measurement,there was no significant difference in total lung volume(TLV)(χ2=3.26,P=0.196)between the three groups images.Compared to TNC ima-ges,there were no statistically significant differences in LAV,LAA%and MLD of VNCven images at 15th percentile lung density(Perc 15%)and different thresholds(P>0.05).Compared to the TNC mode,the VNC mode could reduce the effective dose(ED)by approximately 32.6%.Conclusion The use of DECT VNCven images on chest has the potential to replace TNC for the quantitative analysis of emphysema,thereby streamlining scans and reducing radiation dose.

Objective To investigate the utility of dual-energy computed tomography(DECT)virtual non-contrast(VNC)images instead of true non-contrast(TNC)images in the quantitative analysis of emphysema.Methods A retrospective selection was con-ducted on 59 patients who underwent chest CT plain scan plus dual-phase enhanced scan on APEX-CT.VNC images of arterial phase(VNCart)and venous phase(VNCven)were generated on AW4.7 workstation.Volume CT dose index(CTDIvol)and dose length product(DLP)were recorded respectively.In a double-blind manner,two physicians graded the severity of each patient's emphysema according to the Fleischner Society's emphysema visual classification system.The"digital lung"detection and analysis platform was used to quantitatively measure emphysema at three thresholds(-950 HU,-930 HU and-910 HU),and the difference in meas-urement results between VNC images and TNC images was compared.Quantitative differences in low attenuation volume(LAV),percentage of low attenuation area(LAA%)and mean lung density(MLD)at the-950 HU threshold were compared using Bland-Altman plots.Results Using TNC images as the standard,there was no significant difference in the results of the visual classifica-tion evaluation of emphysema between TNC and VNC images(χ2=2.80,P=0.247).In quantitative measurement,there was no significant difference in total lung volume(TLV)(χ2=3.26,P=0.196)between the three groups images.Compared to TNC ima-ges,there were no statistically significant differences in LAV,LAA%and MLD of VNCven images at 15th percentile lung density(Perc 15%)and different thresholds(P>0.05).Compared to the TNC mode,the VNC mode could reduce the effective dose(ED)by approximately 32.6%.Conclusion The use of DECT VNCven images on chest has the potential to replace TNC for the quantitative analysis of emphysema,thereby streamlining scans and reducing radiation dose.

Room temperature stored platelets are associated with a higher risk of sepsis and related fatality. The risk of bacterial contamination of platelets is a leading risk of infection from blood transfusion. U.S. Food and Drug Administration recently issued a guidance on bacterial risk control strategies for blood collection establishments and transfusion services to enhance the safety and availability of platelets for transfusion. The prevention and control strategies in the guidance would be informative and instructive for further development of risk control strategies of platelet bacterial contamination in China.

Objective:To describe the clinical characteristics of the urinary system involvement in patients with IgG4-related disease (IgG4-RD), and to identify the risk factors for progression to glomerular filtration rate (GFR) less than 60 ml/min.Methods:A retrospective review was carried out using the medical records of 71 cases with IgG4-RD complicated with renal and urinary lesions diagnosed in the First Affiliated Hospital of Zhejiang University School of Medicine between January 2017 and December 2021. Cox proportional hazards model was performed to assess the factors associated with the risk of GFR<60 ml/min.Results:We studied 71 patients with IgG4-RD who had renal and urinary lesions with a mean follow-up of (31.5±19.5)months. Among these, 60 patients were male, and the mean disease onset age was (63.1±10.8)years, and 41(57.7%) patients had IgG4-related kidney disease (IgG4-RKD). Twenty-four patients had IgG4-RKD confirmed after kidney biopsy, with all biopsies showing tubulointerstitial nephritis and one showing membranous nephropathy. Urine immunoglobulin G[ HR(95% CI)=1.218(1.026, 1.446), P=0.025] was associated with a higher risk of GFR less than 60 ml/min. Conclusion:The most common type of urinary system involvement in patients with IgG4-RD is IgG4-RKD. Meanwhile the most common pathological type of IgG4-RKD is TIN. Urine immunoglobulin G is associated with a higher GFR less than 60 ml/min rate.

One of the technical bottlenecks limiting the high yield of 1,4-butanediamine is the insufficient tolerance of strains to 1,4-butanediamine. Enhancing the tolerance of strains to 1,4-butanediamine is therefore a primary challenge that needs to be addressed for the construction of strains with high yields of 1,4-butanediamine. Staphylococcus pasteuri 326180 exhibits exceptional tolerance to high-concentration 1,4-butanediamine, serving as both an ideal model for studying the mechanism underlying the 1,4-butanediamine tolerance and a novel host for constructing strains capable of efficiently producing 1,4-butanediamine. However, for both the research on the tolerance mechanism and the modification of chassis strains, gene editing of S. pasteuri needs to be carried out at the molecular level. The research objective of this paper is to establish a genetic manipulation system for S. pasteuri, laying foundation for subsequent studies on tolerance mechanism and the modification of chassis strains. This study systematically optimized the electroporation conditions, including key parameters such as the growth phase of cells, electric field strength, electroporation buffer, and recovery medium, successfully establishing an electroporation method for S. pasteuri. Additionally, we constructed the gene editing plasmid pCpfOA by replacing the resistance expression cassette, optimized the selection markers for gene editing, and finally established a CRISPR/Cpf1-based gene editing technology for S. pasteuri, achieving an editing efficiency of 90%. The genetic manipulation system of S. pasteuri established in this study provides technical support for research into the tolerance mechanism of this bacterium and the genetic modification of chassis strains.
Staphylococcus/drug effects* ; Gene Editing/methods* ; Electroporation/methods* ; Plasmids/genetics* ; CRISPR-Cas Systems ; Genetic Engineering/methods*

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.