OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

Wound repair and infection have long posed significant challenges in clinical medicine.Am-phibians,adapting to complex environments through long-term natural selection,have evolved skin sys-tems with remarkable abilities to resist external damage and promote rapid wound healing,making them an important source for discovering candidate molecules for wound healing.In this study,a novel peptide composed of 22 amino acids,with the sequence"VGKAGLETAACKATNSCFNIDW"and a molecular weight of 2299.6 D,was screened from the cDNA library of Odorrana tormota and named PN-VW22.The peptide was synthesized by solid-phase synthesis,and its effects on cell proliferation were evaluated using the CCK-8 assay and scratch wound healing assay in human keratinocytes(HaCaT)and mouse em-bryonic fibroblasts(NIH3T3).Antibacterial activity was assessed by determining the minimum inhibitory concentration(MIC).Results showed that PN-VW22 at various concentrations had no significant effect on the cell viability in NIH3T3 cells(P＞0.05),but significantly enhanced HaCaT cell viability at 0.5μmol/L(P＜0.001).Meanwhile,PN-VW22 induced cell proliferation and promoted wound healing in HaCaT cells,with a healing rate of 64.44％after 24 h incubation at 0.5 μmol/L.Furthermore,PN-VW22 exhibited antibacterial activity against Staphylococcus aureus with an MIC value of 13.92 μmol/L.In sum,this study identified PN-VW22 as a novel bifunctional peptide with both wound repair and anti-infective properties,providing a new toxin peptide template for the development of wound healing drugs.

Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

Objective To establish a scientific and objective index system for the function testing and evaluation of scissors surgical instruments in the central sterile supply department to provide systematic and comprehensive function testing and evaluation indexes for the sterile supply personnel.Methods Firstly,an initial pool of items was developed by literature review and semi-structured interview;secondly,an expert correspondence questionnaire was formed based on group discussion,and the final evaluation indexes were determined after 2 rounds of Delphi expert correspondence in March to June 2023;and lastly,the weights of the evaluation indexes were clarified with the hierarchical analysis method.Results The 2 rounds of Delphi expert correspondence had the effective response rate being 85%and 100%,the expert authority coefficient being 0.94 and 0.96 and the Kendall concordant coeffient being 0.339 and 0.350,respectively,and the consistency test showed all P<0.001.The established index system involved in 3 first-level indicators,7 second-level indicators and 20 third-level indicators,of which the first-level indicators of appearance,structure and performance had the weights of 0.171 2,0.384 7 and 0.444 0,respectively.Conclusion The evaluation index system of scissors surgical instruments developed gains advantages in scientificity,rationality and practicality,and facilitates objective function evaluation of scissors surgical instruments in the central sterile supply department.[Chinese Medical Equipment Journal,2025,46(4):76-81]

Purpose To explore the clinicopathological features,diagnosis and differential diagnosis of mantle cell lymphoma(MCL)with aberrant expression of CD10.Methods 14 cases of MCL with aberrant expression of CD10 were analyzed using hematoxylin-eosin,immunohistochemical stains,in situ hybridization,and fluorescence in situ hy-bridization(FISH)techniques to observe the histological morphology,immunophenotype,and molecular genetic char-acteristics.The relevant literatures were reviewed.Results There were 11 males and 3 females,with a male-to-fe-male ratio of 11∶3.The age ranged from 49 to 80 years,with an average age of 64.4 years and a median age of 64 years.10 cases occurred in lymph nodes,1 case in the nasopharynx,1 case in the right colon,1 case in the right eye-lid,and 1 case in the right testis.According to the Ann Arbor staging system,8 cases were classified as stage Ⅳ and 5 cases as stage Ⅲ,and 1 case with undetermined staging.Histologically,there was diffuse effacement of the normal architecture by tumor cells infiltration.Transparent degenerate small blood vessels and scattered individual epithelial-like tissue cells could be observed in the background.Among them,8 cases(8/14,57.14％)were composed of uni-form small to medium-sized lymphocytes with slightly irregular nuclei,unevenly dispersed chromatin,inconspicuous nucleoli,and scant cytoplasm,along with observable mitotic figures.In 3 cases(3/14,21.43％),the tumor cells were large and markedly pleomorphic,with round or irregular nuclei,prominent nucleoli,frequent mitotic figures,and abundant pale cytoplasm.Tumor cells in 3 cases(3/14,21.43％)were resembling lymphoblasts,characterized by round nuclei,fine chromatin,inconspicuous nucleoli,frequent mitotic figures,and scant cytoplasm.Immunophenotyp-ically,CD21 staining showed residual follicular dendritic meshworks.The tumor cells were diffusely and strongly posi-tive for CD20(14/14),PAX5(7/7),CD5(14/14),Cyclin D1(14/14),SOX11(11/11),and BCL2(13/13),partially positive for BCL6(8/14,57.14％)and MUM1(6/9,66.67％),but negative for CD3(14/14)and CD23(14/14).Among 14 cases,10 cases were diffusely and strongly positive for CD10(10/14,71.43％),and 4 cases were partially positive for CD10(4/14,28.57％).The percentage of Ki67 index ranged from 10％to 90％.All cases were negative for EBER(8/8).FISH analysis was performed in 9 cases,among which 7 cases showed CCND1 gene rearrangement,another 2 cases failed to detect due to insufficient tissue samples.Bone marrow biopsy was performed in 13 cases,revealing involvement in 8 cases(8/13,61.54％)and no involvement in 5 cases(5/13,38.46％).Con-clusion MCL with aberrant expression of CD10 is very rare,which commonly exhibits a diffuse growth pattern and blastoid and pleomorphic variants.It often has a high Ki67 proliferation index and poorer prognosis,and should be dis-tinguished from other subtypes of CD1O-positive B-cell lymphomas.

Objective To explore the targets and mechanisms of Tongguanteng Injection in inhibiting the proliferation and migration of cervical cancer.Methods The biological activity of Tongguanteng Injection in inhibiting human cervical cancer SiHa cells was determined by MTT method.Detecting the effect of Tongguanteng Injection on SiHa cell migration through wound healing assay.Using network pharmacology to collect the key targets for treating cervical cancer,and perform molecular docking and enrichment analysis on the targets.Immunohistochemistry and Western blot were used to detect the key proteins to validate the network pharmacology predictions.Result Tongguanteng Injection significantly inhibited the proliferation and migration in a dose-dependent manner in human cervical cancer SiHa cells.Based on the main active ingredients of Marsdenia tenacissima,81 therapeutic targets for cervical cancer were obtained,which may treat cervical cancer by affecting key proteins such as FGF2,MAPK1,and MAPK3.Immunohistochemical results indicated that FGF2,MAPK1 and MAPK3 were expressed in cervical cancer tissues.The western bolt assays showed that Tongguanteng Injection could significantly reduce the FGF2 protein expression.Meanwhile,the MAPK1 and MAPK3 protein expressions were significantly increased.Conclusion Tongguanteng Injection may regulate the FGF2,MAPK1 and MAPK3,effectively impede the proliferation and migration of cervical cancer.

Wound repair and infection have long posed significant challenges in clinical medicine.Am-phibians,adapting to complex environments through long-term natural selection,have evolved skin sys-tems with remarkable abilities to resist external damage and promote rapid wound healing,making them an important source for discovering candidate molecules for wound healing.In this study,a novel peptide composed of 22 amino acids,with the sequence"VGKAGLETAACKATNSCFNIDW"and a molecular weight of 2299.6 D,was screened from the cDNA library of Odorrana tormota and named PN-VW22.The peptide was synthesized by solid-phase synthesis,and its effects on cell proliferation were evaluated using the CCK-8 assay and scratch wound healing assay in human keratinocytes(HaCaT)and mouse em-bryonic fibroblasts(NIH3T3).Antibacterial activity was assessed by determining the minimum inhibitory concentration(MIC).Results showed that PN-VW22 at various concentrations had no significant effect on the cell viability in NIH3T3 cells(P＞0.05),but significantly enhanced HaCaT cell viability at 0.5μmol/L(P＜0.001).Meanwhile,PN-VW22 induced cell proliferation and promoted wound healing in HaCaT cells,with a healing rate of 64.44％after 24 h incubation at 0.5 μmol/L.Furthermore,PN-VW22 exhibited antibacterial activity against Staphylococcus aureus with an MIC value of 13.92 μmol/L.In sum,this study identified PN-VW22 as a novel bifunctional peptide with both wound repair and anti-infective properties,providing a new toxin peptide template for the development of wound healing drugs.

BACKGROUND:In our previous experiments,it was found that transplantation of young adipose stem cells into aged mice would have weight loss effect and improve the inflammatory state in aged mice. Therefore,we speculate that insulin-like growth factor 1 may play an important role in aging and obesity. OBJECTIVE:To explore the anti-obesity effect of insulin-like growth factor 1 in naturally aging mice. METHODS:(1) Bioinformatics analysis:Sequencing of adipose tissue from obese patients in the GEO database and transcriptomic sequencing of young mouse adipose stem cells and old adipose stem cells were conducted to analyze insulin-like growth factor 1 expression. (2) Animal experiment verification:Six young C57BL/6J mice and twelve aged C57BL/6J mice (20 months old) were selected. Abdominal adipose tissue and serum insulin-like growth factor 1 expression in young and aged mice were examined by ELISA and qRT-PCR. All the 12 aged mice were randomly divided into two groups with 6 mice in each group:the experimental group was given insulin-like growth factor 1 (50 μg/kg) for 4 continuous weeks,while the control group was given the same amount of phosphate buffer saline. The body mass changes of mice were monitored regularly,glucose tolerance was measured at the end of the experiment,and serum inflammatory factors and inflammatory factors in abdominal white adipose tissue of mice were detected by ELISA. Hematoxylin-eosin staining was used to observe pathological changes in the mouse liver,kidney and abdominal white adipose tissue. The mRNA expression levels of inflammatory factors and PI3K-Akt signaling pathway in abdominal white adipose tissue of mice were detected by qRT-PCR.RESULTS AND CONCLUSION:Obese patients showed lowly expressed insulin-like growth factor 1 in adipose tissue,but the expression of insulin-like growth factor 1 increased after weight loss surgery. Insulin-like growth factor 1 expressed lowly in aged adipose stem cells. Insulin-like growth factor 1 also showed a low expression in adipose tissue and serum of aged mice. Injection of insulin-like growth factor 1 protein could significantly reduce the body mass of aged mice and improve insulin resistance. Pathological sections of the liver of aged mice revealed fat accumulation. After injection of insulin-like growth factor 1 protein,fat accumulation was significantly improved and the size of fat droplets in adipose tissue was significantly reduced. Insulin-like growth factor 1 injection significantly reduced the expression levels of serum tumor necrosis factor α,interleukin 1β,and interleukin 6 in aged mice,and significantly increased the expression of PI3K-AKT signaling pathway in adipose tissue of aged mice. To conclude,exogenous insulin-like growth factor 1 can reduce body mass,reduce fat droplet size in adipose tissue,and improve liver fat accumulation in aged mice,thereby improving their inflammatory status. Exogenous insulin-like growth factor 1 may activate the PI3K-AKT signaling pathway to improve the inflammatory symptoms in aged mice,thereby improving obesity in naturally aging mice.

Objective:With the help of the advanced ACD Labs/AutoChrom method development software,param-eter simulation design was carried out.Based on the results of software simulation and actual investigation,an HPLC method for the determination of related impurities in safinamide mesylate raw material drug was established.Methods:A Waters Atlantis T3 column(4.6 mm ×250 mm,5 μm)was used.The phosphate buffer with a pH of 7.0 was used as mobile phase A,and acetonitrile was used as mobile phase B.Gradient elution was performed at a flow rate of 1.3 mL·min-1,the detection wavelength was 228 nm,the column temperature was 35 ℃,and the injection volume was 10 μL.Results:Impurities 1-12 in safinamide mesylate could be effectively separated from the main component.The linear ranges were 0.102 1-5.329,0.102 9-5.379 7,0.106 8-4.972 9,0.102 1-5.135,0.103 8-5.314 7,0.097 7-4.869 8,0.095 2-4.760 5,0.095 3-5.109 5,0.050 5-5.287 5,0.098 7-4.885 6,0.102 4-4.997 5,0.050 8-5.134 7 μg·mL-1,respectively.The limits of detection(LOD)were 0.051,0.051 4,0.053 4,0.051 1,0.051 9,0.048 8,0.047 6,0.047 7,0.025 3,0.049 3,0.051 2,0.025 4 μg·mL-1,and the limits of quantification(LOQ)were 0.102 1,0.102 9,0.106 8,0.102 1,0.103 8,0.097 7,0.095 2,0.095 3,0.050 5,0.098 7,0.102 4,0.050 8 μg·mL-1.The accuracy,preci-sion and durability all met the requirements.Conclusion:This method is suitable for the determination and quality control of the related substances of 12 impurities in safinamide mesylate raw materials.

Purpose This study aims to analyze the clinical,pathological,and molecular genetic characteristics of nodal follicular helper T-cell lymphoma,follicular type(nTFHL-F).Methods 7 cases of nTFHL-F were re-viewed.Clinical data were collected,tissue morphology was summarized,and immunohistochemical staining and mo-lecular testing were performed.Results The median age of patients was 62 years with a male-to-female ratio of 6:1.The initial symptoms included neck lymphadenectasis in 6 cases and abdominal discomfort in one.Six cases were in ad-vanced stages,while 1 case was in the localized stage.The tumors exhibited a vague,irregular follicular nodular pat-tern,without significant polymorphic inflammatory background or high endothelial vascular proliferation.Five cases showed a progressive transformation resembling germinal center pattern,and two cases exhibited a follicular lymphoma-like growth pattern.Tumor cells presented three distinct morphologies:centrocyte-like appearance,monocytoid B cell-like appearance,and atypical cells with abundant,transparent cytoplasm.Tumor cells expressed at least three follicu-lar T-cell markers.Testing for ITK::SYK gene fusion was negative in all cases(0/7).Next generation sequencing i-dentified mutations in TET2 gene in two cases(2/2),the RHOA gene in one case(1/2),and VAV1 gene in one case(1/2).The follow-up duration ranged from 2 to 64 months,with three deaths(3/7),and a median survival time of 37 months.Conclusion nTFHL-F predominantly occurs in middle-aged to elderly males,presenting with advanced clinical stages,and has a poor prognosis.nTFHL-F is closely associated with nodal follicular helper T-cell lymphoma,angioimmunoblastic type,and mya coexist within the same individual.