Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

Purpose To investigate the clinicopathological and molecular genetic characteristics of Warthin-like mucoepidermoid carcinoma(WLMEC).Methods Eight cases of WLMEC were collected.HE staining,immunohisto-chemistry,and fluorescence in situ hybridization were performed to observe their histological morphology,immunophe-notype,and molecular genetic characteristics.Clinical information was analyzed,and follow-up was conducted.Re-sults Among the eight cases of WLMEC,three were male and five were female,aged from 28 to 65 years(median age:47 years),all occurring in the parotid gland.All eight cases had clear boundaries and appeared as polycystic structures.Besides the homogeneously eosinophilic material,blue-stained mucoid material was visible in the cyst cavi-ty.The epithelium was arranged in various ways,including single-layer,double-layer,or multi-layer.The cells had a bland-looking morphology with round or oval nuclei.Compared to Warthin tumor,the cytoplasm was significantly less eosinophilic and flatter.Mitotic figures were rare.A prominent lymphoid stroma with abundant plasma cell infiltration was observed,especially in areas adjacent to the epithelium.The tumor cells expressed CK(AE1/AE3),CK5/6,p63,and CK7.The epithelial arrangement was disordered,unlike the typical double-layered structure seen in Warthin tumor.The Ki67 index ranged from 1％to 5％.MAML2 gene rearrangement was detected in all eight cases.No recur-rence was observed during the follow-up period of 1 to 54 months after surgical resection.Conclusion WLMEC is a rare low-grade malignant tumor originating from salivary glands.Compared with Warthin tumor,patients with WLMEC are younger and more commonly female.The presence of epithelial cells that are not typically arranged in a regular double layer with strong eosinophilia,as well as the abundance of plasma cells beneath the epithelium,serve as impor-tant diagnostic clues.Performing MAML2 gene testing on suspicious cases can aid in the accurate diagnosis of this dis-ease.

Objective To discuss the factors influencing the occurrence of frailty in patients with acute myocardial infarction(AMI)after receiving interventional treatment,and to construct a prediction model,to draw a nomogram,and to make the validation of the model.Methods Using convenient sampling method,a total of 462 patients with AMI,who were admitted to the Department of Cardiovascular Medicine of three Grade Ⅲ-A hospitals in Shandong Province of China from July 2023 to January 2024,were selected as the study subjects.Among them,324 AMI patients encountered from July 2023 to November 2023 were selected as modeling group,and logistic regression was used to construct a risk prediction model and draw a nomogram to visualize the model.The remaining 138 AMI patients encountered from December 2023 to January 2024 were used as the validation group.The receiver operating characteristic(ROC)curve and Hosmer-Lemeshow testing were adopted to verify the predictive effect of the model.Results Of 324 patients in the modeling group,170(52.47％)developed frailty.Univariate analysis showed that significant differences in age,education level,body mass index(BMI),Charlson comorbidity index,grip strength,walking speed,brain natriuretic peptide precursor level,physical exercise,multiple medication,and kinesophobia existed between the two groups(all P＜0.05).Multivariate logistic regression analysis revealed that age,BMI,Charlson comorbidity index,grip strength,walking speed,NT-ProBNP precursor level,physical exercise,multiple medication,and kinesophobia were the influencing factors of frailty in patients with AMI after receiving interventional treatment,with an OR value of 1.061,0.630,1.529,0.931,0.005,0.358,1.783,2.929,and 0.497 respectively.The above nine factors were used as independent variables to draw the nomogram,the area under ROC curve of the model was 0.851(95％CI:0.809-0.892),the optimal critical value was 0.562,the sensitivity was 84.1％,and the specificity was 72.1％.Hosmer-Lemeshow goodness of fit testing showed that the model had anx2=12.957 and P=0.113.Conclusion The frailty condition of AMI patients after receiving interventional treatment is at a low to medium levels.The frailty risk prediction model constructed in this study has good prediction effect,which can provide guidance for clinical nurses to timely identify high-risk patients and to promptly adopt interventional measures.

Purpose To investigate the clinicopathological and molecular genetic characteristics of Warthin-like mucoepidermoid carcinoma(WLMEC).Methods Eight cases of WLMEC were collected.HE staining,immunohisto-chemistry,and fluorescence in situ hybridization were performed to observe their histological morphology,immunophe-notype,and molecular genetic characteristics.Clinical information was analyzed,and follow-up was conducted.Re-sults Among the eight cases of WLMEC,three were male and five were female,aged from 28 to 65 years(median age:47 years),all occurring in the parotid gland.All eight cases had clear boundaries and appeared as polycystic structures.Besides the homogeneously eosinophilic material,blue-stained mucoid material was visible in the cyst cavi-ty.The epithelium was arranged in various ways,including single-layer,double-layer,or multi-layer.The cells had a bland-looking morphology with round or oval nuclei.Compared to Warthin tumor,the cytoplasm was significantly less eosinophilic and flatter.Mitotic figures were rare.A prominent lymphoid stroma with abundant plasma cell infiltration was observed,especially in areas adjacent to the epithelium.The tumor cells expressed CK(AE1/AE3),CK5/6,p63,and CK7.The epithelial arrangement was disordered,unlike the typical double-layered structure seen in Warthin tumor.The Ki67 index ranged from 1％to 5％.MAML2 gene rearrangement was detected in all eight cases.No recur-rence was observed during the follow-up period of 1 to 54 months after surgical resection.Conclusion WLMEC is a rare low-grade malignant tumor originating from salivary glands.Compared with Warthin tumor,patients with WLMEC are younger and more commonly female.The presence of epithelial cells that are not typically arranged in a regular double layer with strong eosinophilia,as well as the abundance of plasma cells beneath the epithelium,serve as impor-tant diagnostic clues.Performing MAML2 gene testing on suspicious cases can aid in the accurate diagnosis of this dis-ease.

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Purpose To investigate the clinicopathological features,molecular genetics and prognosis of high grade B cell lymphoma with concurrent MYC rearrangement and 11q aberra-tions(HGBCL-MYC-11q).MethodsThree cases of HGBCL-MYC-11q were reviewed and analyzed using hematoxylin-eosin staining,immunohistochemistry,EBER in situ hybridization and fluorescence in situ hybridization.Clinical data were collected with follow-up.Results All three patients were male,age was 10,61,and 74 years,respectively.All patients had Ann Arbor stage Ⅳ disease.All three cases were biopsies occurring in the nasopharynx,upper pharynx and ileocecus,respectively.Three cases were morphologically similar to diffuse infiltrative growth of tumor cells,moderate or moderately large cells,round to slightly irregular nuclei and easily visible mitotic figures.Focal necrosis was noted in one case.One case exhibited the distinct"starry sky"pattern.All cases expressed CD20,BCL6 and MUM1 and high Ki67 index,two cases expressed CD10 and two cases ex-pressed BCL2.CD3,CD30 and TDT were all negative.EBER in situ hybridization was all negative.FISH analyses using C-MYC break-apart probes were all positive and all cases had 11q aberrations.One case only had the 11q23.3 amplification;and one case only had the 11q24.3 loss.After a follow-up for 1-18 months,one patient died and two patients survived with disease.ConclusionHGBCL-MYC-11q is rare,morphologically similar to BL/HGBCL,with MYC rearrangement and 11q abnormali-ties.We should enhance awareness of the disease and improve more accurate diagnosis and differential diagnosis of the disease.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective To isolate a Acinetobacter baumannii(Ab)phage from underground sewage,study its prop-erties,and to provide a theoretical basis for phage treatment of Ab infection.Methods Double-layer agar tech-nique was used to isolate phages by using Ab GY-6 as the host strain.Biological characterization and therapeutic effect of the phage was tested.Genetic information of the phage was analyzed.Results Ab phage Abgy202162 was isolated.Transmission electron microscopy(TEM)analysis showed that the morphology of Abgy202162 exhibited an icosahedral structure.Biological characteristic analysis showed that the optimal multiplicity of infection was 1,the latent period was 5 min,and the burst size was approximately 520 PFU per cell.In addition,Abgy202162 re-mained stable at different concentrations of chloroform,pH,and temperatures.Sodium dodecyl sulfate-polyacryl-amide gel electrophoresis(SDS-PAGE)analysis showed that it contained 10 proteins with molecular weights ran-ging from 15 to 100 ku.The double-stranded(ds)DNA genome of Abgy202162 consisted of 40 889 bp and its G+C content was 38.85％.It contained 47 open reading frames(ORFs),of which 26 had specific functions,but no virulence related genes or antibiotic resistance genes were found.Phylogenetic analysis showed that Abgy202162 was a new phage in the Autographiviridae family,Beijerinkvirinae subfamily,and Friunavirus genus.Abgy202162 showed the ability to prevent Ab infection in the Galleria mellonella in vivo model.Conclusion The phage Ab-gy202162 has strong environmental tolerance and high safety,indicating its potential as an antibiotic alternative used in the treatment of infections caused by Ab.

Purpose To investigate the clinicopathological features,diagnosis,differential diagnosis and molecular charac-teristics desmoid fibromatosis the breast(DFB).Methods The clinicopathological data and prognostic information of 26 pa-tients with desmoid fibromatosis of the breast were collected.Their clinical characteristics,histological morphologies,immu-nophenotypes and molecular characteristics were analyzed.Re-sults All the 26 patients were female,with a median age of 34.5 years and an average age of 36.8 years(range from 13 to 69 years).There were 10 cases in left breast,14 cases in right breast and 2 cases in bilateral breast.Isolated and painless breast masses were found in all patients,and 3 cases were ac-companied by nipple depression.Grossly,most of them showed a poorly circumscribed tan-white to gray mass with a trabeculated appearance.Microscopically,all the tumors were composed of mild spindle cells with varying intervals of collagen fiber bun-dles.The boundary between the tumor and the surrounding breast tissue was not clear,and the tumor cells infiltrated adja-cent tissues,such as breast ducts,lobules,adipose tissue,and skeletal muscle.Uniform spindle or oval cells formed in fascicles and interwoven,without atypical or polymorphism;the nuclear chromatin was sparse or vacuolar,with small nucleoli,but mito-ses were rare or absent.Nuclear accumulation of β-catenin was present in 20 of 26 tumors,SMA was variously positive in 20 of 26,desmin was focally positive in 6 of 26;CKpan,CK5/6,p63,CD34,CD10 and S-100 were all negative.The Ki67 index was 5％-10％.The gene mutations of CTNNB1 exon 3 were found in 18 of 26 by Sanger sequencing,including T41A(83.3％),S45P(11.1％)and S45F(5.6％).Two patients also had familial adenomatous polyposis.Local resection was performed in 23 cases,mastectomy was performed in 2 cases,and one case did not require any additional treatment after core needle biopsy.20 cases were followed up for 1-108 months,and no recurrence occurred.Conclusion Desmoid fibromatosis of the breast is rare,and can mimic breast cancer clinically,ra-diologically and histologically.It should be always considered in differential diagnosis for the spindle cell proliferations of the breast.A diagnosis of DFB can be achieved basing on the typi-cal histopathology,immunohistochemistry,history and gene se-quencing.