Aim To verify the mechanism of action of Carthami Flos-Lycopodii Herba in treating KOA carti-lage inflammation based on network pharmacology and in vitro and in vivo experiments.Methods The effec-tive ingredients of Carthami Flos-Lycopodii Herba were screened through the database,the core targets of"drug disease"were analyzed,and pathway enrichment analy-sis and molecular docking verification were conducted.Experimental verification:Primary chondrocytes were extracted from mice and divided into the control group,IL-1β group,treatment group,and treatment+TLR4 agonist group.CCK-8 method was used to screen the optimal intervention concentration of Carthami Flos-Ly-copodii Herba.ELISA was used to detect the content of inflammatory factors in chondrocytes.Western blot was employed to detect the protein expression related to cellular pathways.Subsequently,a KOA mouse model was constructed using the DMM method.After admin-istration,the knee joint injury of mice was evaluated u-sing safranin O-green staining.ELISA was used to de-tect the levels of inflammatory factors in serum.West-ern blot was employed to detect collagen Ⅱ,MMP13,Aggrecan,and apoptosis related protein expression in cartilage tissue.TUNEL staining was used to detect the apoptosis rate of cells.Results A total of 26 active ingredients of Carthami Flos-Lycopodii Herba were screened,as well as 123 potential targets for treating KOA.The enrichment analysis results indicated that it mainly involved mechanisms such as Toll like receptors and cell apoptosis.The experimental results showed that Carthami Flos-Lycopodii Herba alleviated the in-flammatory response of chondrocytes and affected the expression of pathway related proteins.Compared with KOA mice,safflower stretched muscle grass could im-prove cartilage damage and reduce the concentration of serum inflammatory factors,regulate the expression of collagen Ⅱ,MMP13,Aggrecan,and apoptosis related proteins in cartilage tissue,and reduce the fluorescence intensity of TUNEL staining in the tissue.Conclusions Carthami Flos-Lycopodii Herba can improve KOA cartilage inflammation,and its mechanism may be relat-ed to the TLR4/MyD88/NF-κB signaling pathway.

Purpose To investigate the clinicopathological features,differential diagnosis,and prognosis of breast carcinoma within fibroadenoma(FA).Methods A retrospective analysis was performed on the clinical and imaging data of 21 cases of FA-associated carcinoma.HE staining,immunohistochemistry using the EnVision method,and next-generation sequencing were employed to assess the clinicopathological characteristics and genetic alterations,with a review of the relevant literature.Results All patients were female,aged 21-67 years,with a median age of 48 years.Clinically,all lesions presented with well-circumscribed mass lesions.On imaging,12 cases demonstrated punctate or coarse calcifications,while 3 cases exhibited locally indistinct margins.Pathological examination revealed that the tumors had an average maximum diameter of 2.25 cm,with a gray-white nodular cut surface resembling FA.Microscopically,there was proliferation of either epithelial or spindle cells.The pathological diagnosis was FA-associat-ed in situ carcinoma in 16 cases(15 cases of low-grade ductal carcinoma in situ and 1 case of lobular carcinoma in si-tu),and invasive carcinoma in 5 cases(comprising 2 cases of invasive carcinoma-no special type,1 case of invasive lobular carcinoma,1 case of low-grade adenosquamous carcinoma and 1 case of fibromatosis-like metaplastic carcino-ma).In 18 cases,the carcinoma was confined within the FA,whereas in 3 cases the tumor locally extended beyond the FA,and 1 case exhibited ipsilateral axillary lymph node metastasis.Immunophenotypically,tumor cells in in situ carcinomas were negative for CK5/6,while the myoepithelial cells were p63-positive,and both estrogen receptor(ER)and progesterone receptor(PR)were diffusely and consistently positive.In invasive carcinoma,both ductal and lobular subtypes were ER and PR positive and HER2 negative.Conversely,in the low-grade adenosquamous carcinoma and fi-bromatosis-like metaplastic carcinoma,ER,PR,and HER2 were all negative,with p63 and CK5/6 positivity.Two ca-ses were negative for mismatch repair protein PMS2.Six cases had a family or personal history of malignant tumors;a-mong the 5 cases that underwent next-generation sequencing,2 cases harbored germline BRCA2 mutations,2 cases had germline PMS2 mutations,and 1 case exhibited no definitive genetic alteration.Conclusion Carcinoma arising within FA exhibits atypical clinical and imaging features.In patients with high-risk factors for breast cancer or family history of malignancy,or when calcifications are observed on imaging,prompt excision and biopsy are recommended.Recogniz-ing the abnormal morphology within FA and the use of immunohistochemistry are essential for accurate diagnosis,with careful differentiation from spindle cell metaplastic carcinoma and low-grade adenosquamous carcinoma.Overall,the prognosis is relatively favorable,and treatment should be tailored according to tumor type,molecular subtype,and stage.

Objective:To investigate the predictive value of thyroid hormone sensitivity indicators for adverse pregnancy outcomes in pregnant women with gestational diabetes mellitus (GDM) complicated by hypothyroidism.Methods:A cross-sectional study was conducted to retrospectively analyze the clinical data of 80 pregnant women with GDM complicated by hypothyroidism who were admitted to the Department of Obstetrics, Second Affiliated Hospital of Shaanxi University of Chinese Medicine from February 2022 to February 2024. The patients were divided into two groups: the adverse outcome group ( n = 48) and the normal outcome group ( n = 32) based on the occurrence of adverse pregnancy outcomes. Logistic regression analysis was conducted to identify the risk factors for adverse pregnancy outcomes in these women. Additionally, receiver operating characteristic curve analysis was performed to evaluate the predictive value of thyroid hormone sensitivity indicators for adverse pregnancy outcomes. Results:In the adverse outcome group, the proportion of women with a pre-pregnancy body mass index ≥ 24 kg/m2, triglyceride level, activated partial thromboplastin time, fibrinogen level, thyroid-stimulating hormone level, and thyroid-stimulating hormone index were 58.33% (28/48), (5.77 ± 0.25) mmol/L, (31.79 ± 2.68) seconds, (4.39 ± 0.37) g/L, (5.05 ± 1.07) mU/L, and (3.15 ± 0.24), respectively, which were significantly higher than those in the normal outcome group ( χ2 = 4.41, t = -3.56, -3.23, -2.61, -4.17, -9.15, all P < 0.05). Conversely, the levels of free thyroxine, free triiodothyronine, thyrotroph T4 resistance index, and thyroid feedback quantile index in the adverse outcome group were (9.32 ± 1.04) pmol/L, (3.17 ± 0.42) pmol/L, (33.09 ± 4.26), and (0.19 ± 0.07), respectively, which were all significantly lower than those in the normal outcome group ( t = 4.44, 3.51, 4.31, 2.21, all P < 0.05). Logistic regression analysis revealed that pre-pregnancy body mass index [ OR = 2.673, 95% CI(1.057,6.761)], triglyceride level [ OR = 25.623, 95% CI(3.208,204.673)], activated partial thromboplastin time [ OR = 1.365, 95% CI(1.106,1.685)], fibrinogen level [ OR = 3.111, 95% CI(1.257,7.701)], thyroid-stimulating hormone level [ OR = 2.969, 95% CI(1.613,5.465)], free thyroxine level [ OR = 0.441, 95% CI(0.280,0.695)], free triiodothyronine level [ OR = 0.172, 95% CI(0.057,0.516)], thyroid-stimulating hormone index [ OR = 6.298, 95% CI(1.099, 36.094)], thyrotroph T4 resistance index [ OR = 0.799, 95% CI(0.704,0.907)], and thyroid feedback quantile index [ OR = 0.057, 95% CI(0.168,0.478)] were all factors that influence adverse pregnancy outcomes in pregnant women with GDM complicated by hypothyroidism (all P < 0.05). The area under the curve for predicting adverse pregnancy outcomes using the combined thyroid hormone sensitivity indicators was 0.809 [95% CI (0.704, 0.915), P < 0.001], with a sensitivity of 0.896, specificity of 0.687, and a maximum Youden index of 0.583. Conclusions:The thyroid hormone sensitivity indicators have a certain predictive value for adverse pregnancy outcomes in pregnant women with GDM complicated by hypothyroidism. These indicators can provide important reference for clinical prediction and intervention of adverse pregnancy outcomes in this patient population.

OBJECTIVE To observe the effect of electroacupuncture on insomnia symptoms and blood pressure levels in patients with hypertension and insomnia.METHODS A randomized controlled clinical trial was conducted.A total of 60 patients with hyper-tension and insomnia were enrolled in Jiangsu Province Hospital of Chinese Medicine from December 2021 to December 2022 and ran-domly divided into a treatment group and a control group at a ratio of 1:1,with 30 cases in each group.During the treatment period,2 cases dropped out of the control group and 1 case dropped out of the treatment group.Both groups of patients received sleep and hy-pertension health education and conventional hypertension drug treatment.The treatment group was given electroacupuncture interven-tion,and the control group was given sham electroacupuncture intervention.The treatment course of both groups was 4 weeks.Before and after treatment,the Pittsburgh Sleep Quality Index(PSQI),Insomnia Severity Index(ISI)scale and portable polysomnography(PPSG)were used to evaluate the changes in sleep quality of the two groups of patients;home blood pressure measurement(HBPM)was adopted to evaluate the changes in blood pressure levels of the two groups of patients.Spearman correlation analysis and linear re-gression analysis were used to study the relationship between blood pressure levels and PPSG parameters.RESULTS After treatment,only the sleep onset latency(SOL)and sleep efficiency(SE)of the control group were significantly improved(P<0.05);the PSQI,ISI scores,morning and night systolic blood pressure(SBP),and diastolic blood pressure(DBP)of the treatment group were signifi-cantly reduced(P<0.01),which was better than that of the control group(P<0.05,P<0.01);the sleep parameters of PPSG were significantly improved(P<0.01),which was better than that of the control group(P<0.05,P<0.01).The results of Spearman corre-lation analysis showed that the morning SBP level of patients before treatment was related to the wake time after sleep onset(WASO)and the number of micro-arousals(MAS).After treatment,the decrease in the morning SBP of patients was related to the reduction of MAS and the shortening of SOL.CONCLUSION Electroacupuncture can effectively improve the insomnia symptoms and blood pres-sure levels of patients with hypertension.Its therapeutic mechanism may be related to reducing the number of MAS and improving the degree of sleep fragmentation.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Aim To investigate the therapeutic effects of cinnamaldehyde on synovial lesions in mice with knee osteoarthritis(KOA)and its regulatory mecha-nism in the phagocytic function of synovial macropha-ges.Methods In the animal experiments,mouse ser-um and synovial tissue were extracted.HE staining was used to evaluate the inflammatory cell infiltration in the synovial tissue.ELISA was employed to detect the lev-els of inflammatory factors such as interleukins in the serum.Western blot was used to detect the expression of Ras homolog family member A(RhoA),Rho-associ-ated protein kinase 1(ROCK1),myosin light chain(MLC),and p-MLC proteins in the synovial tissue.RT-qPCR was utilized to detect the expression of in-flammatory factors and pathway-related mRNA in the synovial tissue.TUNEL staining was used to detect ap-optosis in the synovial tissue.In the cellular experi-ments,after the intervention,RAW267.4 cells were subjected to Western blot and RT-qPCR for the detec-tion of the aforementioned indicators,and confocal mi-croscopy was used to assess phagocytic function.Re-sults After cinnamaldehyde intervention,the synovial inflammatory infiltration was significantly reduced,the protein and mRNA expression of the RhoA/ROCK1/MLC signaling pathway was markedly downregulated,the fluorescence intensity of TUNEL staining signifi-cantly decreased,and the phagocytic function of macro-phages was enhanced.Conclusion Cinnamaldehyde can inhibit RhoA/Rock1/MLC signaling pathway,en-hance macrophage burial,improve synovial inflamma-tion,and delay the progression of KO A mice.

Aim To investigate the therapeutic effects of cinnamaldehyde on synovial lesions in mice with knee osteoarthritis(KOA)and its regulatory mecha-nism in the phagocytic function of synovial macropha-ges.Methods In the animal experiments,mouse ser-um and synovial tissue were extracted.HE staining was used to evaluate the inflammatory cell infiltration in the synovial tissue.ELISA was employed to detect the lev-els of inflammatory factors such as interleukins in the serum.Western blot was used to detect the expression of Ras homolog family member A(RhoA),Rho-associ-ated protein kinase 1(ROCK1),myosin light chain(MLC),and p-MLC proteins in the synovial tissue.RT-qPCR was utilized to detect the expression of in-flammatory factors and pathway-related mRNA in the synovial tissue.TUNEL staining was used to detect ap-optosis in the synovial tissue.In the cellular experi-ments,after the intervention,RAW267.4 cells were subjected to Western blot and RT-qPCR for the detec-tion of the aforementioned indicators,and confocal mi-croscopy was used to assess phagocytic function.Re-sults After cinnamaldehyde intervention,the synovial inflammatory infiltration was significantly reduced,the protein and mRNA expression of the RhoA/ROCK1/MLC signaling pathway was markedly downregulated,the fluorescence intensity of TUNEL staining signifi-cantly decreased,and the phagocytic function of macro-phages was enhanced.Conclusion Cinnamaldehyde can inhibit RhoA/Rock1/MLC signaling pathway,en-hance macrophage burial,improve synovial inflamma-tion,and delay the progression of KO A mice.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Rho proteins and the Rho-associated protein kinase(ROCK)signaling pathway are cruci-al components of intracellular signaling cascades.Rho proteins,which belong to the small GTPase family,play a pivotal role in regulating essential elements of the cytoskeleton within cells.ROCK functions as a downstream effector protein kinase of Rho,modulating various biological processes,including cell morphology,migration,and proliferation.Recent studies have underscored the signifi-cance of the ROCK signaling pathway in the replication of a diverse group of viruses.Furthermore,it has been discovered that some viruses disrupt cellular contraction,adhesion,and migration through the Rho/ROCK pathway,subsequently influencing the immune response triggered by vi-ral infections and affecting the tight junctions between cells.This article primarily reviews the re-search progress regarding the Rho/ROCK signaling pathway and its key signaling molecules,Rho and ROCK,in terms of their activation and regulation of viral replication and tight junction pro-teins between cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.