ObjectiveBased on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway， this study explores the protective effect and mechanism of Taohong Siwutang against retinal vasculitis （RV） from the perspective of angiogenesis. MethodsSPF-grade C57BL/6J mice were used to establish a RV model induced by experimental autoimmune uveitis （EAU）， and the protective effect of Taohong Siwutang on RV was investigated. Fifty mice were randomly assigned to a blank group， model group， and low-， medium-， and high-dose Taohong Siwutang groups （3.315、6.63、13.26 g·kg^-1，10 mice in each group）. After modeling， gavage administration was performed for 20 consecutive days. A small-animal retinal imaging system and fluorescein sodium angiography were used to observe pathological changes in the retinal tissue and vessels. Hematoxylin-eosin （HE） staining was used to assess retinal histopathological changes. Immunohistochemistry was performed to evaluate CD31-positive expression. Western blot was used to detect the protein expression levels of JAK2， phosphorylated （p）-JAK2， STAT3， p-STAT3， and vascular endothelial growth factor receptor 2 （VEGFR2） in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the relative expression level of VEGFR2 mRNA in retinal vessels. ResultsCompared with the blank group， the model group showed relative optic disc swelling， multiple areas of inflammatory cell infiltration around retinal veins with partial vascular occlusion， vessel thickening and morphological alterations， uneven retinal thickness， wrinkling and bending of inner and outer layers， vascular dilation， and disordered cellular arrangement. Compared with the model group， the Taohong Siwutang groups showed markedly reduced CD31-positive expression and effectively improved perivascular inflammatory infiltration， vascular tortuous dilation， angiogenesis， vascular occlusion， and hemorrhage. Western blot results showed that compared with the model group， the expression of VEGFR2 and the phosphorylation levels of JAK2 and STAT3 were significantly decreased in the Taohong Siwutang groups （P0.01）. Real-time PCR results indicated that VEGFR2 mRNA expression was significantly decreased in the Taohong Siwutang groups compared with the model group （P0.05）. ConclusionTaohong Siwutang can effectively alleviate angiogenesis in RV and， through the JAK2/STAT3 signaling pathway， reduce angiogenesis and improve retinal pathological injury， thereby exerting a protective effect on retinal vessels.

ObjectiveBased on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway， this study explores the protective effect and mechanism of Taohong Siwutang against retinal vasculitis （RV） from the perspective of angiogenesis. MethodsSPF-grade C57BL/6J mice were used to establish a RV model induced by experimental autoimmune uveitis （EAU）， and the protective effect of Taohong Siwutang on RV was investigated. Fifty mice were randomly assigned to a blank group， model group， and low-， medium-， and high-dose Taohong Siwutang groups （3.315、6.63、13.26 g·kg^-1，10 mice in each group）. After modeling， gavage administration was performed for 20 consecutive days. A small-animal retinal imaging system and fluorescein sodium angiography were used to observe pathological changes in the retinal tissue and vessels. Hematoxylin-eosin （HE） staining was used to assess retinal histopathological changes. Immunohistochemistry was performed to evaluate CD31-positive expression. Western blot was used to detect the protein expression levels of JAK2， phosphorylated （p）-JAK2， STAT3， p-STAT3， and vascular endothelial growth factor receptor 2 （VEGFR2） in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the relative expression level of VEGFR2 mRNA in retinal vessels. ResultsCompared with the blank group， the model group showed relative optic disc swelling， multiple areas of inflammatory cell infiltration around retinal veins with partial vascular occlusion， vessel thickening and morphological alterations， uneven retinal thickness， wrinkling and bending of inner and outer layers， vascular dilation， and disordered cellular arrangement. Compared with the model group， the Taohong Siwutang groups showed markedly reduced CD31-positive expression and effectively improved perivascular inflammatory infiltration， vascular tortuous dilation， angiogenesis， vascular occlusion， and hemorrhage. Western blot results showed that compared with the model group， the expression of VEGFR2 and the phosphorylation levels of JAK2 and STAT3 were significantly decreased in the Taohong Siwutang groups （P0.01）. Real-time PCR results indicated that VEGFR2 mRNA expression was significantly decreased in the Taohong Siwutang groups compared with the model group （P0.05）. ConclusionTaohong Siwutang can effectively alleviate angiogenesis in RV and， through the JAK2/STAT3 signaling pathway， reduce angiogenesis and improve retinal pathological injury， thereby exerting a protective effect on retinal vessels.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats. METHODS Thirty male SD rats were divided into blank control group， negative control group， positive control group （fluoxetine 10 mg/kg， i.g.）， single drug group （C. saxicola total alkaloids 210 mg/kg， i.g.） and combined drug group （C. saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg， i.g.） according to the random number table method， with 6 rats in each group. By lipopolysaccharide （LPS） induction modeling， except blank control group （no model and no administration） received intraperitoneal injection of the same amount of normal saline， the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression. After 1 week of modeling， each administration group was given relevant drug intragastrically according to the corresponding dose， and blank control group and negative control group （without drug treatment） were administered intragastrically with an equal volume of solvent to dissolve the drug； continued modeling while administering the drug. After two weeks of continuous administration， the effects of C. saxicola total alkaloids versus the combination of C. saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments； the levels of tumor necrosis factor-α， interleukin-1β and interleukin-6 in rats were determined； the histopathological changes of the hippocampus of rats were observed. Blood sample was collected from the orbit at different time points after administration on the 15th day， and the upper plasma was obtained. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in rat plasma. The average plasma concentration-time curve was depicted， the area under the curve （AUC） was calculated， and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group， the negative control group had a decrease in body mass and sugar water preference rate， a decrease in the total distance of open field， a prolonged swimming immobility time， and a increased in the expression of inflammatory factors in serum （P＜0.05）； compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water， increased the total distance of open field， shortened the time of swimming immobility， and decreased the expression of inflammatory factors in serum （P＜0.05）. There was no significant difference in the above indicators between the single drug group and the combined drug group in rats （P＞0.05）. Pharmacokinetic results showed that compared with single drug group， AUC0-t of coptisine， AUC0-t， AUC0-∞， tmax and cmax of jatrorrhizine， AUC0-t， AUC0-∞， t1/2 and cmax of berberrubine， and AUC0-t of epiberberine， cmax of dehydrocarvedine， cmax of palmatine were significantly increased in combined drug group， but there was no significant difference， indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats， reduce serum inflammatory cytokine levels， and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone， the combination with borneol do not show significant pharmacodynamic differences， bu can improve the absorption of coptisine， jatrorrhizine in model rats.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Purpose: This study aimed to identify core domains for pre-registered nurses by comparing licensing competencies with program outcomes (POs) in undergraduate nursing education. This was accomplished in preparation for the transition of the Korean Nurse Licensing Examination (KNLE) from a tradition seven-subject format to a newly integrated, competency-based single-subject format that reflects current trends in nursing assessment. Methods: A literature review and survey were conducted. From 828 studies retrieved via PubMed, CINAHL, and Google Scholar using keywords such as “newly graduated registered nurses” and “competency OR competence,” 18 were selected according to pre-established inclusion and exclusion criteria. Documents from national and international nursing organizations were included to extract relevant licensing competencies. We also reviewed POs from all undergraduate nursing schools in South Korea to align educational outcomes with the identified core domains. Results: The core domains identified were clinical performance and decision-making, professional attitudes and ethics, communication and interpersonal skills, leadership and teamwork, quality improvement and safety, health promotion and prevention, and information technology and digital health. These domains showed strong alignment with POs under the fourth-cycle accreditation standards. Conclusion It concludes the seven core domains will be appropriate for evaluating pre-registered nurses in the integrated KNLE. Based on the seven identified core domains, expert consensus should be sought in the next phase to support the development of integrated, competency-based test items grounded in these domains.

Purpose: This study aimed to identify core domains for pre-registered nurses by comparing licensing competencies with program outcomes (POs) in undergraduate nursing education. This was accomplished in preparation for the transition of the Korean Nurse Licensing Examination (KNLE) from a tradition seven-subject format to a newly integrated, competency-based single-subject format that reflects current trends in nursing assessment. Methods: A literature review and survey were conducted. From 828 studies retrieved via PubMed, CINAHL, and Google Scholar using keywords such as “newly graduated registered nurses” and “competency OR competence,” 18 were selected according to pre-established inclusion and exclusion criteria. Documents from national and international nursing organizations were included to extract relevant licensing competencies. We also reviewed POs from all undergraduate nursing schools in South Korea to align educational outcomes with the identified core domains. Results: The core domains identified were clinical performance and decision-making, professional attitudes and ethics, communication and interpersonal skills, leadership and teamwork, quality improvement and safety, health promotion and prevention, and information technology and digital health. These domains showed strong alignment with POs under the fourth-cycle accreditation standards. Conclusion It concludes the seven core domains will be appropriate for evaluating pre-registered nurses in the integrated KNLE. Based on the seven identified core domains, expert consensus should be sought in the next phase to support the development of integrated, competency-based test items grounded in these domains.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.