In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

The seed kernel of Momordica cochinchinensis, i.e., Momordicae Semen, is used for medicinal purposes, but to date, no research has been reported on its chemical constituents. In this study, the chemical constituents of Momordicae Semen were investigated for the first time using silica gel column chromatography, semi-preparative HPLC, HR-MS, and NMR. As a result, eight compounds were isolated and identified as: p-hydroxybenzoic acid-7-O-trehaloside(mubeside A, 1), 2,6-dimethoxyphenol-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside B, 2), 1-O-p-methoxybenzoyl-1,4-benzenediol-4-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside C, 3), 1-O-p-hydroxybenzoyl-1,4-benzenediol-4-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside D, 4), gypsogenin-3-O-β-D-galactosyl-(1→2)-β-D-glucuronoside(5), quillaic acid-3-O-β-D-galactosyl-(1→2)-β-D-glucuronoside(6), violanthin(7), and kaempferitrin(8). Compounds 1-4 are new compounds, while compounds 5-8 were isolated from Momordicae Semen for the first time.
Glycosides/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; Magnetic Resonance Spectroscopy ; Chromatography, High Pressure Liquid

Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

The effective implementation of clinical practice guideline(CPG), as a crucial vehicle of evidence-based medicine, plays a vital role in improving healthcare quality and patient safety. Currently, there remains a significant gap between the actual implementation outcomes of traditional Chinese medicine(TCM) guidelines and their intended objectives, which necessitates a systematic investigation into their influencing factors to optimize implementation strategies. This study aims to comprehensively identify the factors influencing CPG implementation in China, adapt the theoretical domains framework(TDF) to the local context, and integrate TCM-specific characteristics to provide recommendations for optimizing the development and implementation processes of TCM guidelines. Systematic search was conducted across multiple databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, and EMbase, covering the period from each database's inception to March 2024. Qualitative and mixed-methods studies were included to examine factors affecting the implementation of clinical practice guidelines. The methodological quality of the included studies was assessed using the critical appraisal skills programme(CASP) tool. RESULTS:: were synthesized through framework analysis and thematic synthesis, and expert consensus was achieved via a structured consensus meeting. A total of 16 studies involving 2 388 participants were included with overall good methodological quality. Based on the TDF, 43 influencing factors across 14 domains were identified. The most critical factors included the quality of guideline evidence, training and academic conferences organized by hospitals and academic institutions to promote guideline adoption among medical staff, support from professional leaders for guideline implementation, the applicability and clarity of guideline recommendations, and material resources(supplies, funding, and facilities) required for implementation. Additionally, influencing factors of TCM guideline implementation were identified, including the distinctive advantages of TCM therapies, the applicability of syndrome differentiation, and the feasibility of TCM treatments. Based on these findings, it is recommended that TCM guideline development should incorporate these unique influencing factors to formulate high-quality, clear, and actionable recommendations. Following guideline publication, healthcare and academic institutions should strengthen training and dissemination efforts and ensure the availability of necessary implementation resources to facilitate the successful adoption of guidelines in clinical practice.
China ; Humans ; Practice Guidelines as Topic ; Medicine, Chinese Traditional/standards* ; Evidence-Based Medicine

Objectives: This study aimed to assess the health rights of inmates in correctional facilities from the perspective of unmet needs and to explore institutional improvement plans that could yield substantial qualitative and quantitative advancements.

Methods: Data on capacity and actual occupancy, external and internal medical services, the number of inmates with mental health conditions, and cell area were obtained from the Ministry of Justice. Overall, 1,057 inmates were surveyed, representing 1.84% of the total inmate population of 57,560 as of September 30, 2016. A structured questionnaire was distributed to these inmates, and upon collection, the responses were analyzed. Furthermore, a request was submitted to the Ministry of Justice to survey the status of healthcare personnel and medical services across 52 correctional facilities nationwide.

Results: Between 2014 and 2015, the Ministry of Justice in South Korea allocated approximately 14 to 22 billion Korean won for healthcare services in correctional facilities. The major facilities with the most inmates with mental health conditions had 160 such inmates in 2014 and 161 in 2015. Overcrowding and insufficient cooling pose ongoing health risks. Inmates face challenges accessing medical care, with unmet needs for dental and psychiatric services.

Conclusion: Strategies to improve inmates’ health rights include establishing a primary healthcare system, improving governance, alleviating overcrowding, and introducing mental health programs. Emphases are placed on managing severe illnesses such as cancer, strengthening emergency care, and ensuring oversight by the National Human Rights Commission. Regular education of prison staff is also recommended to improve inmate health management.

This study explores the development, roles, and key initiatives of the Regional Environmental Health Centers in Korea, detailing their evolution through four distinct phases and their impact on environmental health policy and local governance. It chronicles the establishment and transformation of these centers from their inception in May 2007, through four developmental stages. Originally named Environmental Disease Research Centers, they were subsequently renamed Environmental Health Centers following legislative changes. The analysis includes the expansion in the number of centers, the transfer of responsibilities to local governments, and the launch of significant projects such as the Korean Children’s Environmental Health Study (Ko-CHENS ). During the initial phase (May 2007–February 2009), the 10 centers concentrated on research-driven activities, shifting from a media-centered to a receptor-centered approach. In the second phase, prompted by the enactment of the Environmental Health Act, six additional centers were established, broadening their scope to address national environmental health issues. The third phase introduced Ko-CHENS, a 20-year national cohort project designed to influence environmental health policy by integrating research findings into policy frameworks. The fourth phase marked a decentralization of authority, empowering local governments and redefining the centers' roles to focus on regional environmental health challenges. The Regional Environmental Health Centers have significantly evolved and now play a crucial role in addressing local environmental health issues and supporting local government policies. Their capacity to adapt and respond to region-specific challenges is essential for the effective implementation of environmental health policies, reflecting geographical, socioeconomic, and demographic differences.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disorder affecting the sacroiliac joints and axial spine. Along with pharmacotherapy, non-pharmacological interventions for axSpA are crucial and constitute the cornerstone of treatment. Here, we review the evidence for non-pharmacological treatment of axSpA as a basis for the 2023 Korean treatment recommendations for patients with axSpA. The effectiveness of the core non-pharmacological approaches, such as education, smoking cessation, and exercise, has been reaffirmed. High-quality research on surgical treatment is limited. However, total hip replacement is advised in patients with ongoing pain or disability and visible structural damage to the hip on imaging. Urgent spinal intervention should be considered in cases of acute spinal pain with neurological deficiency or concurrent unstable fractures. Evidence for complementary therapies, including spas and acupuncture, remains insufficient.

The 5-hydroxytryptamine type3 (5-HT3 ) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission. It has been implicated in various neuropsychiatric disorders. This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT3 receptor-mediated currents in NCB20 neuroblastoma cells. Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism. Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC50 without altering the maximal response (Emax ), suggesting a competitive inhibition. Quetiapine's IC50 varied with 5-HT concentration and treatment condition. The IC50 value of quetiapine was 0.58 μM with 3μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration. Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC50 from 25.23 μM to 0.20 μM.Interaction kinetics experiments revealed an IC50 of 5.17 μM for an open state of the 5-HT3 receptor, suggesting weaker affinity during receptor activation. Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states. Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics. Inhibition of the 5-HT3 receptor by quetiapine was voltage-independent, and quetiapine exhibited no usedependency, further supporting its role as a competitive antagonist. These findings provide insights into inhibitory mechanism of quetiapine on 5-HT3 receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.