This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

Objective To compare the positioning errors and the motion of acromioclavicular joint in breast cancer patients with integrated cervicothoracic thermoplastic membrane and breast bracket fixation,and to provide reference for accurate irradiation of upper and lower clavicular region.Methods Sixty-three pa-tients with breast cancer who were treated in the radiotherapy center of the hospital from November 1,2021 to August 9,2023 were selected as the study objects,and were divided into the integrated cervicothoracic thermo-plastic membrane group(n=32)and breast bracket group(n=31)according to different positioning meth-ods.The translation errors of left and right direction(X),head and foot direction(Y)and ventral and dorsal direction(Z)and the rotation errors of sagittal plane(Rx),cross section(Ry)and coronal plane(Rz)of the two groups were analyzed,and the movement amplitude and three-dimensional displacement of acromioclavic-ular joint were measured respectively.Results Compared with the breast bracket group,X translation errors[(0.18±0.14)cm vs.(0.15±0.12)cm]and Z translation errors[(0.19±0.14)cm vs.(0.16±0.14)cm]of the cervicothoracic thermoplastic memberane group were greater,Z translation error[(0.21±0.17)cm vs.(0.22±0.21)cm]and Rx rotation error of cervical and sternoclavicular joints[(0.93±0.87)° vs.(1.08±0.92)°]were smaller,Rz rotation error[(1.00±0.94)° vs.(0.95±0.86)°]was greater,and the motion ΔX of acromioclavicular joint[(0.18±0.15)cm vs.(0.25±0.21)cm]was smaller,the difference was statistically significant(P＜0.05).Conclusion Integrated cervicothoracic thermoplastic membrane can be used as a solu-tion for prophylactic irradiation of breast cancer in the upper and lower clavicular region and for radiation leak-age in the presence of metastasis.

Objective : To investigate the effects of astragalus mongholicus extract ( AME) on lung injury and the myeloid differentiation factor 88 ( MyD88 ) / Toll-like receptor 4 ( TLR4 ) / nuclear factor kappa B ( NF-κB) p65 pathway in rheumatoid arthritis induced interstitial lung disease (RA-ILD) rats． Methods : SD rats were randomly divided into a control group，RA-ILD group，low-dose AME group (5 g / L) ，high-dose AME group ( 10 g / L) ，and high-dose AME + lipopolysaccharide (LPS) group ( 10 g / L AME + 1 mg / L TLR4 activator LPS) ．Except for the control group，rats in all other groups were injected with bovine type Ⅱ collagen，Freund ’s complete adjuvant， and bleomycin to establish the RA-ILD model．The arthritis index and lung tissue wet-dry weight ratio of rats were tested．ELISA was applied to detect the levels of inflammatory factors interleukin (IL) -1 β , IL-6 and tumor necrosis factor-α ( TNF-α) in bronchoalveolar lavage fluid． Hematoxylin eosin staining was used to observe pathological changes of rat knee joint tissue and lung tissue．Western blot was applied to detect the expression of autophagy fac- tors Beclin 1，microtubule-associated protein 1A /1B-light chain 3 (LC3) Ⅱ / Ⅰ , and MyD88 /TLR4 /NF-κB p65 pathway related proteins in lung tissue． Results : Compared with control group，knee joint tissue and lung tissue of rats in RA-ILD group were damaged，the arthritis index，lung tissue wet-dry weight ratio，levels of IL-1 β , IL-6， and TNF-α , the expression levels of MyD88 and TLR4 proteins ，and p-NF-κB p65 /NF-κB p65 ratio increased (P＜0. 01) ，the expression of Beclin 1 and LC3 Ⅱ / Ⅰ proteins decreased (P＜0. 01) ．Compared with RA-ILD group，the low-dose and high-dose AME groups showed reduced tissue damage in rats，the arthritis index，lung tis- sue wet-dry weight ratio，levels of IL-1 β , IL-6，and TNF-α , the expression levels of MyD88 and TLR4 proteins， and p-NF-κB p65 /NF-κB p65 ratio showed a dose-dependent decrease (P＜0. 05 or P＜0. 01) ，the expression of Beclin 1 and LC3 Ⅱ / Ⅰ proteins showed a dose-dependent increase (P＜0. 05 or P＜0. 01) ．Compared with high- dose AME group，the tissue damage of rats in the high-dose AME + LPS group was worsened，the arthritis index， lung tissue wet-dry weight ratio，levels of IL-1 β , IL-6，and TNF-α , the expression levels of MyD88 and TLR4 pro- teins，and p-NF-κB p65 /NF-κB p65 ratio were higher (P＜0. 01) ，the expression of Beclin 1 and LC3 Ⅱ / Ⅰ pro- teins was lower (P ＜0. 01 ) ． Conclusion AME inhibits the MyD88 /TLR4 /NF-κB p65 pathway and alleviates lung injury in RA-ILD rats．

Objective Epigenetics,which changes the expression of DNA or protein by chemical modification,affects the regulation of genes and plays an important role in the interaction between genetic and environmental factors in diseases.This review focuses on the development trend and research hotspots of epigenetic modification in ulcerative colitis from 2003 to 2023.Methods Literature related to epigenetic modification in UC was obtained from the Web of Science Core Collection database,and bibliometric analyses and visualization were performed using VOSviewer,CiteSpace and R software.Results 1359 papers published from 2003-2023 were retrieved for inclusion in the analysis.The United States dominated the field of epigenetic modification,with the University of Chicago being the most published and cited institution,and Wu Feng of the Meyerhoff Center for Inflammatory Bowel Disease being the most cited author.The journals Inflammatory Bowel Diseases and Gastroenterology have high influence,screening for high-frequency keywords related to UC epigenetic modifications,including microRNA,inflammation,biomarker,azathioprine,DNA methylation,long noncoding RNA,circular RNA,received wide attention.Conclusion Epigenetics continues to evolve in the field of UC,providing important avenues in elucidating the pathogenesis of UC,in elucidating the interactions between genetics and the environment,and in giving new ideas for simplifying diagnosis,improving inflammation,and developing new drugs.

Objective:To investigate the expressions and prognostic value of lysyl oxidase like protein 2(LOXL2),chemo-kine c-c-motif ligand 18(CCL-18)and chitinase protein 40(YKL-40)in connective tissue disease with pulmonary interstitial lesions.Methods:A total of 308 patients with connective tissue disease who were treated in the First Affiliated Hospital of Hebei North Univer-sity from July 2021 to February 2022 were selected,including 108 patients with pulmonary interstitial disease(pathological group),200 patients without pulmonary interstitial disease(non pathological group),and another 35 healthy volunteers as the control group.Serum levels of LOXL2,CCL-18 and YKL-40 were detected by ELISA;Logistic regression analysis was applied to analyze the factors affecting the prognosis of patients with connective tissue disease and pulmonary interstitial disease;the predictive value of serum LOXL2,CCL-18 and YKL-40 levels on the prognosis of patients with connective tissue disease and pulmonary interstitial disease was analyzed by receiver operating characteristic(ROC)curve analysis.Results:Compared with control group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the non pathological group and the pathological group were obviously increased(P<0.05);the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the le-sion group were higher than those in the non lesion group(P<0.05);compared with the survival group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease in the death group were obviously higher(P<0.05);Logistic regression analysis showed that LOXL2,CCL-18 and YKL-40 were risk factors for the prognosis of patients with connective tissue disease and pulmonary interstitial disease(P<0.05);the area under the ROC curve(AUC)of the combined detection of serum LOXL2,CCL-18 and YKL-40 in predicting the prognosis of patients with connective tissue disease and pulmonary interstitial disease was 0.967,which was better than their respective independent prediction(Zcombined detection-LOXL2=1.735,P=0.041;Zcombined detection-CCL-18=2.481,P=0.007;Zcombined detection-YKL-40=2.008,P=0.022).Conclusion:The serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease are elevated,which has certain value in the prognosis evaluation of patients with connective tissue disease combined with pulmonary interstitial disease.

Objective Epigenetics,which changes the expression of DNA or protein by chemical modification,affects the regulation of genes and plays an important role in the interaction between genetic and environmental factors in diseases.This review focuses on the development trend and research hotspots of epigenetic modification in ulcerative colitis from 2003 to 2023.Methods Literature related to epigenetic modification in UC was obtained from the Web of Science Core Collection database,and bibliometric analyses and visualization were performed using VOSviewer,CiteSpace and R software.Results 1359 papers published from 2003-2023 were retrieved for inclusion in the analysis.The United States dominated the field of epigenetic modification,with the University of Chicago being the most published and cited institution,and Wu Feng of the Meyerhoff Center for Inflammatory Bowel Disease being the most cited author.The journals Inflammatory Bowel Diseases and Gastroenterology have high influence,screening for high-frequency keywords related to UC epigenetic modifications,including microRNA,inflammation,biomarker,azathioprine,DNA methylation,long noncoding RNA,circular RNA,received wide attention.Conclusion Epigenetics continues to evolve in the field of UC,providing important avenues in elucidating the pathogenesis of UC,in elucidating the interactions between genetics and the environment,and in giving new ideas for simplifying diagnosis,improving inflammation,and developing new drugs.

Objective:To investigate the expressions and prognostic value of lysyl oxidase like protein 2(LOXL2),chemo-kine c-c-motif ligand 18(CCL-18)and chitinase protein 40(YKL-40)in connective tissue disease with pulmonary interstitial lesions.Methods:A total of 308 patients with connective tissue disease who were treated in the First Affiliated Hospital of Hebei North Univer-sity from July 2021 to February 2022 were selected,including 108 patients with pulmonary interstitial disease(pathological group),200 patients without pulmonary interstitial disease(non pathological group),and another 35 healthy volunteers as the control group.Serum levels of LOXL2,CCL-18 and YKL-40 were detected by ELISA;Logistic regression analysis was applied to analyze the factors affecting the prognosis of patients with connective tissue disease and pulmonary interstitial disease;the predictive value of serum LOXL2,CCL-18 and YKL-40 levels on the prognosis of patients with connective tissue disease and pulmonary interstitial disease was analyzed by receiver operating characteristic(ROC)curve analysis.Results:Compared with control group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the non pathological group and the pathological group were obviously increased(P<0.05);the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease in the le-sion group were higher than those in the non lesion group(P<0.05);compared with the survival group,the serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease in the death group were obviously higher(P<0.05);Logistic regression analysis showed that LOXL2,CCL-18 and YKL-40 were risk factors for the prognosis of patients with connective tissue disease and pulmonary interstitial disease(P<0.05);the area under the ROC curve(AUC)of the combined detection of serum LOXL2,CCL-18 and YKL-40 in predicting the prognosis of patients with connective tissue disease and pulmonary interstitial disease was 0.967,which was better than their respective independent prediction(Zcombined detection-LOXL2=1.735,P=0.041;Zcombined detection-CCL-18=2.481,P=0.007;Zcombined detection-YKL-40=2.008,P=0.022).Conclusion:The serum levels of LOXL2,CCL-18 and YKL-40 in patients with connective tissue disease and pulmonary interstitial disease are elevated,which has certain value in the prognosis evaluation of patients with connective tissue disease combined with pulmonary interstitial disease.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.

Purpose/Significance To design a comprehensive data platform to meet the needs of collecting and sharing survey data on meteorological sensitive diseases,so as to enhance monitoring capabilities for meteorological sensitive diseases in China.Method/Process Through various methods such as data extraction,data exchange,data import and customized collection,disease data,meteoro-logical data,environmental data and diagnosis and treatment data are processed and integrated into the platform for unified management.Result/Conclusion This platform realizes the functions of data collection,aggregation,visualization display and data sharing,which can provide support for scientific researchers in various bases across the country to better manage and utilize meteorological sensitive disease survey data.