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 investigate the diagnostic value of high-resolution magnetic resonance black blood technology imaging (MRBTI) and CT angiography (CTA) in detecting carotid plaque in predicting stroke.Methods:A prospective study was conducted on 135 patients with carotid artery disease diagnosed and treated in Handan Central Hospital from January 2020 to June 2022, all patients underwent cervical MRBTI and CTA examinations. Digital subtraction angiography (DSA) was used as the gold standard to compare the diagnostic value of the two detection methods for carotid plaque properties. Patients were followed up for 2 years and divided into stroke and non-stroke according to the result of follower-up. Imaging indexes of the two groups were compared, and the predictive value of MRBTI combined with CTA for stroke was evaluated by receiver operation characteristic (ROC) curve.Results:The relevant data of 134 patients were included in statistical analysis. For severe carotid stenosis and ulcerative plaques, the accuracy of CTA examination was 85.11% and 84.91% separately, that of MRBTI examination was 91.49% and 92.45%, the combined examination was 95.74% and 96.23%, and the above three examination methods was not statistically significant ( P>0.05). The detection accuracy rates of CTA for mild, moderate carotid artery stenosis and smooth, irregular plaque, were 73.08%, 86.89%, 73.91% and 86.21%, those of MRBTI detection were 92.31%, 91.80%, 86.96% and 93.10%, and those of combined detection were 100.00%, 98.36%, 100.00% and 98.28%, the combined detection was higher than those of CTA and MRBTI alone ( P<0.05); there was no statistically significant difference in the level of tube wall area between the stroke patients and the non-stroke patients ( P>0.05), but the total vascular area and lumen area in stroke patients were significantly higher than those in non-stroke patients: (103.48 ± 22.48) mm 2 vs. (92.51 ± 16.26) mm 2, (46.18 ± 11.03) mm 2 vs. (41.32 ± 10.52) mm 2, and normal wall index was significantly lower: (0.54 ± 0.12) mm 2 vs. (0.61 ± 0.09) mm 2 ( P<0.05); ROC curve analysis showed that MRBTI combined with CTA had the best predictive efficacy for stroke, with area under the curve (AUC) value as high as 0.82, and its sensitivity (79.00%) was significantly higher than that predicted by MRBTI indexes (total vascular area, lumen area and normal wall index) (51.90%, 39.50%, 56.80%) or CTA (30.90%) alone, with statistically significant difference ( P<0.05). Conclusions:The combination of MRBTI and CTA can improve the diagnostic efficiency of carotid artery disease and the prediction efficiency of stroke, and can be used as an auxiliary examination means of DSA to provide a more reliable clinical basis for the assessment of plaque characteristics in patients with carotid artery disease and the prediction of stroke.

Objective Through reviewing the herbs,medical books and classic prescriptions of the past dynasties,the herbal examination of Gypsum fibrosum and its analogs was carried out to clarify the relationship between them.The qualitative analysis was carried out by single-point Raman,infrared,near infrared and XRD techniques,the quantitative analysis of the main components was carried out by EDTA titration and Raman surface scanning technique,the elemental analysis was carried out by ICP-OES,and the differences between gypsum and argillite were observed by scanning electron microscope.Results Gypsum fibrosum is mixed with marble,feldspar,north cold-water stone,south cold-water stone and xuanjing stone and so on.Before the Ming Dynasty,there was no differentiation between soft and anhydrite,and after the Ming Dynasty,it was clear that gypsum was soft gypsum and feldspar was anhydrite;in modern times,marble is also made to be gypsum for medicinal use;Feldspar is anhydrite and is no longer made to be used for medicinal use,north cold-water stone is red gypsum,and south cold-water stone is calcite.Gypsum,south coldwater stone is calcite.The peaks of argillite appeared to be buried in the Raman spectrum compared with Gypsum fibrosum,and the original profiles of both infrared and near-infrared were basically the same,and the near-infrared model established by the preprocessing method of the first-order derivatives plus vector normalization(5-point smoothing)could effectively differentiate between Gypsum fibrosum and its analogues,but it could not differentiate between argillite and Gypsum fibrosum with high content.XRD showed that there are differences in the relative intensities of the peaks of argillite and Gypsum fibrosum,and some XRD shows that there are differences in the relative intensities of the peaks of basalt and Gypsum fibrosum,and some of the peaks of basalt are characterized by impurities such as quartz,and the contents of trace elements such as Fe,Mn,Cr,Pb,Hg and As are higher in basalt.The peak shapes of XRD,Raman spectra,infrared spectra and near-infrared spectra of Gypsum fibrosum and calcined gypsum are closer but can still be distinguished,and the Ca content of calcined gypsum is higher than that of gypsum.Commercially available south chrysocolla and stalactite source are carbonate minerals calcite calcite.Spectral detection can not be distinguished,the trace element content is basically the same,but the traits are different.North chrysocolla(red gypsum)is higher than the Fe content of commercially available white gypsum.Raman surface scanning not only can be a qualitative and quantitative determination of minerals such as gypsum and other minerals,and the results of the content of the titration is basically similar,but also to determine the state of Gypsum fibrosum and calcined gypsum calcined water loss status and the degree of calcined gypsum.The results of Raman surface scanning are similar to the titration results.Conclusion This study can provide a scientific basis for the traceability of Gypsum fibrosum,and can better guide the clinical use of medicine and the rational use of resources.

We report a 30-year-old woman who presented with intermittent gross hematuria and left flank pain，and CT revealed a left staghorn stones. The initial percutaneous nephrolithotomy（PCNL）left a 6 mm fragment，and both stone and urine cultures yielded extended-spectrum β-lactamase（ESBL）-producing Escherichia coli. Seven months later，the stone increased to 6 cm and urine culture revealed Proteus mirabilis. Endoscopic combined intrarenal surgery（ECIRS）achieved complete clearance. At 6-month follow-up，the patient remained asymptomatic，culture-negative，and stone-free. This case highlights that small residual fragments after PCNL may rapidly enlarge with secondary urease-producing infection，underscoring the need for early re-intervention and standard follow-up.

Objective To explore the mechanism of GS-9620 in improving imiquimod(IMQ)-induced psoriasis-like inflammation by regulating the Th1/Th17-related immune response,and to investigate its regulatory effect on the gut microbiota in mice.Methods An IMQ-induced psoriasis-like inflammation model was established in BALB/c mice.The severity of the skin lesions was evaluated by psoriasis area and severity index(PASI)score.The proportions of CD4+interleukin(IL)-17+and CD4+interferon(IFN)-γ+cells in spleen tissue were detected by flow cytometry.Levels of the inflammatory factors tumor necrosis factor(TNF)-α,IL-1β,and IL-6 in skin tissues were determined by enzyme-linked immunosorbent assay,and pathological analysis was performed by hematoxylin/eosin staining.The effects of GS-9620 on the structure of the gut microbiota in control,IMQ model,and GS-9620-treated mice were detected by 16S rRNA sequencing.Results GS-9620 significantly reduced the PASI score in IMQ-induced mice and effectively reduced the proportions of CD4+IL-17+and CD4+IFN-γ+cells in the spleen.GS-9620 also significantly down-regulated the expression levels of TNF-α,IL-1β,and IL-6 in skin tissues.16S rRNA sequencing showed that GS-9620 significantly regulated the abundance of gut microbiota related to inflammation,including the relative abundances of bacteria such as Lachnospiraceae_NK4A136_group,Lachnospiraceae_UCG-008,Alloprevotella,Desulfovibrio,Prevotellaceae_UCG-001,and Alistipes.Conclusions GS-9620 effectively alleviates IMQ-induced psoriasis-like skin inflammation in mice by regulating the expression of Th1/Th17-related inflammatory factors.It may also improve IMQ-induced clinical symptoms by regulating the structure of the gut microbiota,thus providing a new theoretical basis for the treatment of psoriasis.The result of this study provide important experimental evidence to support further investigations into the application of GS-9620 for the treatment of psoriasis.

Objective:To investigate the role of mRNA expression in the pathogenesis of gout by analyzing the difference of gene expression in peripheral blood mononuclear cells(PBMCs)among acute gouty(AG),intermittent gouty(IG)and health con-trols(HC).Methods:AG patients,IG patients and HC were enrolled in this study.RNA-seq and bioinformatics techniques were used to observe the differences of mRNA expression in PBMCs of different groups,and to explore the genes and signaling pathways as-sociated with gout attack.GO and KEGG databases were used to investigate the biological functions of differentially expressed genes and the relationship between genes and signaling pathways.Genes involved in the KEGG enriched PPAR signaling pathway(CYP27A1,ACSL1,CD36,PPARG,ANGPTL4,PLIN2)were validated in PBMCs from 35 patients with AG,35 patients with IG,and 35 normal healthy subjects using real-time PCR.Results:Compared with HC group,there were 222 significant differential genes in AG group,including 193 up-regulated genes and 29 down-regulated genes.GO analysis showed that the genes differentially ex-pressed in AG group were mainly enriched in the regulation of multicellular biological processes such as inflammation,trauma,and stress response and immune response regulation compared with HC group.However,KEGG analysis showed that the up-regulated genes in AG group were enriched in"Toll-like receptor signaling pathway""complement and coagulation cascades""PPAR signaling pathway""lipid and atherosclerosis""osteoclast differentiation""cytokine-cytokine receptor interaction""chemokine signaling path-way""IL-17 signaling pathway",and"cholesterol metabolism"compared with HC group.The results of PCR validation of related genes in the PPAR signaling pathway showed that the expression levels of ACSL1,CD36,PPARG,and PLIN2 in the AG group were higher than those in the control group(P<0.05),and the expression levels of CYP27A1 and ANGPTL4 in the AG group were not dif-ferent from those in the HC group(P>0.05).Conclusion:PPAR signaling pathway may be involved in the pathogenesis of AG,of which ACSL1,CD36,PPARG,and PLIN2 may be used as potential therapeutic targets for acute gouty arthritis;CYP27A1 and ANG-PTL4 may not be associated with the pathogenesis of AG.

Objective To explore the mechanism of GS-9620 in improving imiquimod(IMQ)-induced psoriasis-like inflammation by regulating the Th1/Th17-related immune response,and to investigate its regulatory effect on the gut microbiota in mice.Methods An IMQ-induced psoriasis-like inflammation model was established in BALB/c mice.The severity of the skin lesions was evaluated by psoriasis area and severity index(PASI)score.The proportions of CD4+interleukin(IL)-17+and CD4+interferon(IFN)-γ+cells in spleen tissue were detected by flow cytometry.Levels of the inflammatory factors tumor necrosis factor(TNF)-α,IL-1β,and IL-6 in skin tissues were determined by enzyme-linked immunosorbent assay,and pathological analysis was performed by hematoxylin/eosin staining.The effects of GS-9620 on the structure of the gut microbiota in control,IMQ model,and GS-9620-treated mice were detected by 16S rRNA sequencing.Results GS-9620 significantly reduced the PASI score in IMQ-induced mice and effectively reduced the proportions of CD4+IL-17+and CD4+IFN-γ+cells in the spleen.GS-9620 also significantly down-regulated the expression levels of TNF-α,IL-1β,and IL-6 in skin tissues.16S rRNA sequencing showed that GS-9620 significantly regulated the abundance of gut microbiota related to inflammation,including the relative abundances of bacteria such as Lachnospiraceae_NK4A136_group,Lachnospiraceae_UCG-008,Alloprevotella,Desulfovibrio,Prevotellaceae_UCG-001,and Alistipes.Conclusions GS-9620 effectively alleviates IMQ-induced psoriasis-like skin inflammation in mice by regulating the expression of Th1/Th17-related inflammatory factors.It may also improve IMQ-induced clinical symptoms by regulating the structure of the gut microbiota,thus providing a new theoretical basis for the treatment of psoriasis.The result of this study provide important experimental evidence to support further investigations into the application of GS-9620 for the treatment of psoriasis.

This study systematically collated and textual researched realgar from aspects such as name,origin,and quality by consulting ancient herbal texts,classic medical books,and modern literature.The textual research shows that current herbal works all take"realgar"as the official name,with aliases including"Huangshi shi","Shihuang","Tianyang shi","Jiguan shi","Xunhuang","Chouhuang",and"Mingxiong",etc.Ancient herbal records indicate that Xunhuang,Chouhuang,and Shuiku Realgar are all Realgar,while Orpiment is its associated mineral.In ancient times,the main production areas of Realgar were in Gansu,with outputs also seen in Shandong and Hunan.Nowadays,it is mainly produced in Hunan,Guizhou,Hubei,Gansu,Yunnan,Sichuan and other regions.Ancient herbal works mentioned characteristics like"cockscomb color","non-stinky","solid","red and bright"in their quality evaluation,while modern herbal works mostly evaluate its quality by color and texture,such as"red color","large blocks","brittle texture","glossy".The traditional efficacy of Realgar is to dry dampness,kill insects,detoxify various poisons,treat sores and activate blood.Modern studies have shown it also has anti-tumor,antibacterial and antiviral effects.Processing methods in past dynasties included water grinding,vinegar processing,refining,etc.,and currently,water grinding and acid water grinding are commonly used.This paper observed the properties of Realgar,detected the content of As?S?,and analyzed the microscopic characteristics and far-infrared spectral characteristics of qualified batches of Realgar.It was finally found that the As?S? content of qualified batches of Realgar was all more than 90%;under the scanning electron microscope,it showed massive shape,uniform distribution,obvious particles,and no agglomeration;a small amount of associated mineral Orpiment crystals were observed under the polarizing microscope;the characteristic peaks of Realgar(343-344 cm?1,224-225 cm?1,372-374 cm?1,367-369 cm?1,359 cm?1,207-208 cm?1,193-194 cm?1,168-170 cm?1)and Orpiment(390 cm?1,380 cm?1,347 cm?1,311 cm?1,300 cm?1,201 cm?1,182 cm?1,158 cm?1 and 139 cm?1)were determined."Red color and glossy"can be used as property references,"Realgar is a sulfide mineral of the Realgar family,with the main chemical component As?S?,associated with Orpiment"can be used as origin references,and"Shimen in Hunan,Wanshan in Guizhou,Yunnan,Gansu,Sichuan"can be used as production area references,which are consistent with the results of herbal textual research.This study provides a basis for the identification and analysis of Realgar,with a view to better guiding clinical medication and resource utilization.

We report a 30-year-old woman who presented with intermittent gross hematuria and left flank pain，and CT revealed a left staghorn stones. The initial percutaneous nephrolithotomy（PCNL）left a 6 mm fragment，and both stone and urine cultures yielded extended-spectrum β-lactamase（ESBL）-producing Escherichia coli. Seven months later，the stone increased to 6 cm and urine culture revealed Proteus mirabilis. Endoscopic combined intrarenal surgery（ECIRS）achieved complete clearance. At 6-month follow-up，the patient remained asymptomatic，culture-negative，and stone-free. This case highlights that small residual fragments after PCNL may rapidly enlarge with secondary urease-producing infection，underscoring the need for early re-intervention and standard follow-up.

Objective To investigate the clinical efficacy and safety of two thrombus thrombectomy devices,AcoStream and AngioJet,in the treatment of acute iliofemoral vein thrombosis(AIFVT).Methods A total of 97 AIFVT patients were treated with different thrombus clearing devices according to their states of illness,and patients were divided into the AcoStream group(41 cases)and the AngioJet group(56 cases).The thrombus clearing status,degree of swelling reduction in affected limb,surgical time and intraoperative blood loss were compared between the two groups,and the need for assisted catheter contact thrombolysis(CDT)treatment,urokinase dosage,iliac vein stent placement,incidence of complications,length of hospital stay and hospitalization costs were also compared between the two groups.Regular follow-up was conducted to record for recurrence of thrombosis,the patency of the stent,deep vein thrombosis syndrome(PTS)and PTS degree were evaluated in lower limbs.Results There were no significant differences in age,gender,affected limb,time of illness,site of illness and causes of illness between the two groups(P＞0.05).The operation was successful in both groups and the thrombus removal effect was satisfactory.There were no significant differences in terms of thrombus clearance rate,the degree of swelling reduction in the limb 48 hours after surgery and assisted CDT rate between the two groups(P＞0.05).Compared with the AcoStream group,the AngioJet group had a longer surgical time,reduced intraoperative blood loss,increased hospitalization costs and higher rates of complications(P＜0.05).There was no significant difference in the recurrence rate of thrombosis between the two groups(P＞0.05),and there was no occurrence of iliac vein stent occlusion or PTS in either patients.Conclusion Two mechanical thrombus clearing devices of AcoStream and AngioJet are safe and effective for treating AIFVT.