Objective To generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

In line with the rising global incidence of cancer,tumor metastasis has become the leading cause of mortality among cancer patients.Formation of the pre-metastatic niche(PMN)creates an optimal microenvironment for tumor cell colonization and metastasis,thus facilitating tumor dissemination.In this context,cancer-associated fibroblasts(CAFs)have garnered significant attention as a result of their multifaceted roles in tumor progression.CAFs enhance the formation of the PMN and promote the invasive behavior of tumor cells by remodeling the extracellular matrix,inducing epithelial-mesenchymal transition,stimulating angiogenesis and modulating the tumor immune microenvironment.These processes not only expedite metastasis but also enable tumor immune evasion.This paper reviews the fundamental mechanisms and functions of CAFs in tumor metastasis,examines their potential applications in cancer research and therapy,and offers new perspectives and directions for the development of anti-tumor metastasis strategies.

Objective To investigate the protective effect of hederagenin(HDG)on cisplatin(Cis)-induced acute kidney injury(AKI)in mice and its potential mechanism.Methods 24 male C57BL/6J mice were randomly divided into a control group,AKI model group,HDG low-dose group,and HDG high-dose group,with six mice in each group.AKI model was established by intraperitoneal injection of 20 mg/kg cisplatin(Cis).The HDG low-dose and HDG high-dose groups were given 20,40 mg/kg HDG by intragastric administration,respectively,and samples were collected 3 days later.The kidneys of the mice were collected for hematoxylin-eosin(HE)and periodic-acid-schiff(PAS)staining to evaluate the kidney pathology,and serum was collected to detect changes in serum creatinine(Scr)and blood urea nitrogen(BUN).The expression of p-P65,P65,IL-6,TNF-α,IL-1β,and other inflammatory-related proteins was detected by Western Blot.A TCMK1(renal tubular epithelial cell)inflammatory cell model was established by Cis(200 ng/mL)stimulation in vitro.Blank group,Cis model group,HDG low-dose group,HDG high-dose group,Axin2 overexpression group,HDG+Axin2 overexpression group were set up.In the Axin2-overexpression group,the expression of p-P65,P65,IL-6,TNF-α,IL-1β,Axin2,and AREG was detected among total cell proteins.Results Compared with the control group,AKI model mice exhibited significantly elevated serum creatinine and blood urea nitrogen levels(P<0.05),accompanied by pathological alterations including vacuolar degeneration of renal tubules,inflammatory cell infiltration,and glycogen deposition,and the expression of inflammation-related proteins(p-P65,TNF-α,IL-6,IL-1β)and Axin2 was markedly upregulated in AKI mice(P<0.05).HDG treatment induced a dose-dependent reduction in serum creatinine and blood urea nitrogen levels(high-dose>low-dose,P<0.05),alleviated renal histopathological damage,and concurrently suppressed the expression of these inflammatory mediators and Axin2(P<0.05).HDG was confirmed that dose-dependently inhibited Cis-induced upregulation of Axin2,and inflammatory cytokines in vitro experiments.Transcriptome sequencing revealed that Axin2 overexpression significantly increased amphiregulin(AREG)expression(P<0.05).Mechanistically,HDG reduced p-P65 phosphorylation by suppressing the Axin2/AREG axis(P<0.05),while Axin2 overexpression abolished the protective effects of HDG against Cis-induced renal tubular cell injury.Conclusions HDG protects against renal injury in AKI mice by reducing inflammation through the inhibition of Axin2/AREG axis activation.

Objective To evaluate the protective effects of the traditional Chinese medicine formula Shenxiankang on renal injury and fibrosis,and to explore its potential mechanisms of action.Methods Chronic kidney disease(CKD)model was established in mice using unilateral ureteral obstruction(UUO).The mice were randomly divided into four groups:sham,UUO,and Shenxiankang(SXK)Low/High dose groups(1500,4500 mg/(kg·d)),each comprising eight mice.The each SXK groups received daily oral administration of Shenxiankang,and the remaining mice were gavaged equivalent volumes of saline for 7 d.After the experiment,renal tissues were collected for assessment of renal injury and fibrosis using HE and Masson staining.The expression levels of fibrosis markers and proteins involved in the epithelial membrane protein 3(Emp3)and Tgf-β/Smad3 signaling pathway were determined by Real-time PCR,immunohistochemistry,and Western Blot.In cell-based experiments,the effects of Shenxiankang on the Emp3/Tgf-β/Smad3 pathway and its interaction with TGF-beta receptor R2(Tgfβ2)were further analyzed using an Emp3 knockdown and Co-IP assays.Results Shenxiankang significantly reduced immune cell infiltration and tubular atrophy in the UUO model group and decreased the expression of kidney injury markers kidney injury molecule 1(Kim1)and Lipocalin 2(Lcn2),confirming its efficacy in alleviating renal injury.Masson staining and analysis of fibrosis markers Fibronectin(Fn)and α-smooth muscle actin(α-SMA)indicated that Shenxiankang effectively suppressed fibrosis induced by UUO.Mechanistic studies revealed that Shenxiankang exerted its effects by selectively downregulating the abnormal activation of the Emp3/Tgf-β/Smad3 signaling pathway,a finding further supported by cellular experiments showing that Shenxiankang modulates Tgf-β/Smad3 signaling through Emp3 regulation.Moreover,the Co-IP experiment result indicate that Shenxiankang exerts its effects by regulating the interaction between Emp3 and Tgfβ2.Conclusions Shenxiankang exhibits significant protective effects in a mouse model of chronic kidney disease,effectively reducing renal injury and fibrosis.These effects are likely mediated through the downregulation of the Emp3/Tgf-β/Smad3 signaling pathway,suggesting Shenxiankang's potential therapeutic value in renal protection.

Objective:To assess the current status of geriatrics department development in public general hospitals at or above the second grade in Shandong province.Methods:A cross-sectional survey was conducted from October 27 to November 3, 2023 using a web-based electronic questionnaire to investigate the current status of geriatrics department development in all public general hospitals at or above the second grade across 16 prefecture-level cities in Shandong province.The survey included participation from medical department staff and managers of geriatric medicine departments.Results:Shandong province has 355 public general hospitals at or above the second grade, of which 337 completed the questionnaire.Among these 337 hospitals, 92.28%(311/337)have established geriatric departments, 83.09%(280/337)have set up geriatric clinics, 69.14%(233/337)have independent geriatric wards, and 71.51%(241/337)have implemented comprehensive geriatric assessments(CGA).Regarding the configuration of geriatric departments, 60.24%(203/337)of hospitals met the requirement of having at least 20 ward beds, 34.42%(116/337)met the doctor-to-bed ratio requirement of at least 0.3, and 22.26%(75/337)met the nurse-to-bed ratio requirement of at least 0.6.Only 13 hospitals met all the requirements for geriatric wards, beds, doctors, and nurses, accounting for 3.86%(13/337)of the participating hospitals.Conclusions:The establishment of geriatrics departments in second-grade or higher public general hospitals in Shandong province has surpassed the national target in China ahead of schedule.Most hospitals have established geriatric clinics and wards and have implemented CGA.However, significant challenges remain, including a shortage of ward beds and a lack of medical staff.

BACKGROUND:During tissue repair and regeneration,macrophages exhibit multiple activities such as promoting inflammation,anti-inflammation,fibrosis,and wound healing at various stages of tissue damage.The heterogeneity and balanced polarization of macrophages are decisive in organ repair. OBJECTIVE:To explore the research hotspots and development trends in the field of macrophage polarization in tissue repair through visualization analysis methods,as well as the research level of global scientific and clinical workers in this field. METHODS:Using bibliometric analysis methods,this study employed Citespace literature visualization analysis software and VOSviewer tools,retrieving related literature from 2013 to 2023 in the Web of Science Core Collection's Science Citation Index Expanded(SCI-Expanded)and Social Sciences Citation Index Expanded(SSCI-Expanded)databases.The analysis results were presented in a dynamic map format,revealing the main trends and focuses of the research. RESULTS AND CONCLUSION:The number of publications in this field had dramatically increased from 2013 to 2023,with a significant rise starting in 2017.Chinese researchers had the highest number of publications,with 642 papers,while American researchers began focusing on this field early on.Professor Elisseeff Hennifer H had made a substantial contribution to the research in this area.Shanghai Jiao Tong University had produced the most publications.In recent years,keywords such as"hyaluronic acid"and"regulation"had been prevalent.Macrophage polarization research in tissue repair primarily concentrates on its multifunctional regulatory mechanisms,interactions with other cell types,and its behavior under specific pathological conditions.The main research areas include the role of macrophages in wound healing,cardiovascular diseases,chronic inflammation,tumor microenvironments,and regenerative medicine.A deeper understanding of the multifunctionality and polarization mechanisms of macrophages can lead to the development of new therapeutic strategies to enhance tissue repair and regeneration,thereby improving patient treatment outcomes.

AIM:To investigate the efficacy of Shenxiankang(SXK)in mitigating renal fibrosis in unilateral ureteral obstruction(UUO)mice,and elucidate its regulatory mechanism targeting the differentiation antagonizing non-protein coding RNA(DANCR)/TGF-β1/Smad3 signaling axis.METHODS:Mice were randomly assigned to:normal group(NC),model group(UUO),low,medium and high doses(1 500,3 000 and 4 500 mg·kg-1·d-1)of SXK group,and benazepril(10 mg·kg-1·d-1)group.Chronic kidney disease was modeled via unilateral ureteral ligation.Renal DAN-CR overexpression was induced using tail vein injection coupled with ultrasound microbubble technology.In vitro,human renal tubular epithelial cells(HK-2)were stimulated with TGF-β1;DANCR was either knocked down or overexpressed,followed by SXK intervention in both in vivo and in vitro models.Renal tissues were harvested for pathological assessment.DANCR expression and localization were analyzed using fluorescence in situ hybridization.Fibrosis deposition was evaluat-ed by immunohistochemistry(IHC).Western blot quantified the expression of fibrosis markers(α-SMA,FN)and key components of the TGF-β1/Smad3 signaling axis(p-Smad3,Smad3,TGF-β1).RESULTS:UUO mice exhibited signifi-cant renal tubular dilation.SXK intervention ameliorated renal lesions and reduced fibrosis.In UUO mice with DANCR overexpression,levels of renal fibrosis markers(α-SMA,FN)and TGF-β1/Smad3 signaling axis proteins(p-Smad3,Smad3,TGF-β1)were increased;these effects were reversed by SXK.In vitro,DANCR knockdown decreased the expres-sion of fibrotic proteins/mRNA and TGF-β1/Smad3 signaling axis components.SXK treatment effectively counteracted the fibrotic injury and TGF-β1/Smad3 signaling axis activation induced by DANCR overexpression.CONCLUSION:SXK ef-fectively mitigates renal fibrosis in UUO mice,potentially through regulation of the DANCR/TGF-β1/Smad3 signaling axis.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.