The chemical constituents from the n-butanol fraction of ethanol extract of safflower (Carthamus tinctorius L.) were isolated and purified using chromatographic process including MCI Gel CHP-20, ODS, Sephadex LH-20 column chromatography, and semi-preparative HPLC method, and one alkyne and two phenylpropanoid derivants were obtained. Their structures were identified as (5R,E)-tetradecane-12-ene-8,10-diyne-1,5,14-triol (1), (E)-8-O-β-D-glucopyranosyl n-butyl cinnamate (2), and (7S,8S)-7-(4-hydroxy-3-methoxybenzene)-7-butyl-8,9-diol (3) by modern spectroscopy methods (1D NMR, 2D NMR, UV, IR and MS). 1-3 are all new compounds. Compounds 1-3 were screened for their anti-renal fibrosis activities in vitro, and none of them showed obvious effect.

Six compounds were isolated from the ethyl acetate fraction of Citri Sarcodactylis Fructus by using various column chromatographic methods, such as MCI Gel CHP-20, ODS, Sephadex LH-20, silica gel and semipreparative HPLC. Their structures were identified to be citrusin G (1), citrusin H (2), citrusin E (3), syringin (4), coniferin (5), methylconiferin (6) by NMR, HR-ESI-MS, UV, IR spectra. Compounds 1 and 2 were new secondary metabolism products and 3-6 were obtained from the titled material for the first time. Compound 1 showed anti-renal fibrosis activity in TGF-β1-induced kidney proximal tubular cells.

ObjectiveTo investigate the effects of Xijiao Dihuangtang （XJDHT） on mice with sepsis and cellular models of sepsis and explore its molecular mechanism in alleviating sepsis-induced inflammatory responses via regulating pyruvate kinase M2 （PKM2）-mediated one-carbon metabolism pathway. MethodsForty C57BL/6N mice were randomly divided into four groups： normal group， model group， low-dose XJDHT group （7.7 g·kg^-1）， and high-dose XJDHT group （15.4 g·kg^-1）. After one week of continuous gavage， sepsis was induced using cecal ligation and puncture （CLP） in groups except the normal group. 24 h after the surgery， mortality rates in all groups were recorded， and serum cytokines were measured by enzyme linked immunosorbent assay （ELISA）. Lung histopathology was examined by hematoxylin-eosin （HE） staining. During the in vitro experiment， the human monocytic leukemia cell line （THP-1） was exposed to various concentrations of XJDHT and treated with lipopolysaccharide （LPS） at a final concentration of 2 mg·L^-1 for 24 h. Cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay. Protein levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax） were measured by Western blot. Transcriptome sequencing was performed to analyze differentially expressed genes in all groups and conduct gene ontology （GO） enrichment. Key genes in the one-carbon metabolism pathway， including pyruvate kinase M2 （PKM2）， 5-methyltetrahydrofolate-homocysteine methyltransferase （MTR）， and phosphoglycerate dehydrogenase （PHGDH）， were verified by Western blot. A PKM2 inhibition model was established using shikonin for further protein expression analysis. ResultsAnimal experiments showed that compared with the normal group， the model group exhibited significantly elevated body temperature and lung pathology （P<0.01） and increased serum TNF-α and IL-1β levels （P<0.01）. High-dose XJDHT reduced body temperature and lung tissue damage （P<0.01） and significantly decreased serum TNF-α and IL-1β levels （P<0.01）. Low-dose XJDHT treatment showed no significant temperature change （P<0.01） but reduced serum TNF-α and IL-1β levels （P<0.01）. Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α， IL-1β， and one-carbon metabolism genes （PKM2， MTR， and PHGDH） （P<0.01）. Cell experiments demonstrated that compared to the normal group， the model group showed elevated protein expressions of TNF-α and IL-1β in THP-1 cells （P<0.01）， decreased Bcl-2/Bax ratio， and increased apoptosis （P<0.01）. Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α， IL-1β， and one-carbon metabolism genes （PKM2， MTR， and PHGDH） （P<0.01）. Compared to the model group， high-dose XJDHT significantly increased Bax/Bcl-2 ratio and PHGDH protein expression （P<0.01） and effectively reduced cell apoptosis （P<0.01） while down-regulating protein expressions of TNF-α， IL-1β， PKM2， and MTR （P<0.01）. Low-dose XJDHT moderately increased Bax/Bcl-2 ratio and PHGDH protein expression （P<0.05）， reduced apoptosis （P<0.05）， and decreased IL-1β and MTR protein levels （P<0.05， P<0.01）， but there were no significant changes in TNF-α and PKM2 expression. After PKM2 inhibition by shikonin in THP-1 cells， the expression of protein related to one-carbon metabolism was detected. Compared with the blank group， the LPS-induced model group showed significantly upregulated PKM2 and MTR protein expression （P<0.01） and downregulated PHGDH expression （P<0.01）. Compared with the model group， shikonin treatment significantly reduced PKM2 expression （P<0.05）， increased PHGDH expression （P<0.01）， and decreased MTR expression （P<0.05）. ConclusionXJDHT can inhibit the release of inflammatory factors in sepsis， and its mechanism is related to the intervention of the PKM2-regulated one-carbon metabolism pathway in macrophages.

ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management （MTM） services for patients with coronary heart disease by using Economic， Clinical and Humanistic Outcomes （ECHO） model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 （pre-quality control implementation group， n＝96） and June-August 2023 （post-quality control implementation group， n＝164）. Using propensity score matching analysis， 80 patients were selected from each group. The study subsequently compared the economic， clinical， and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching （P＞0.05）. Compared with pre-quality control implementation group， the daily treatment cost （16.26 yuan vs. 24.40 yuan， P＜0.001）， cost-effectiveness ratio [23.12 yuan/quality-adjusted life year （QALY） vs. 32.32 yuan/QALY， P＜0.001]， and the incidence of general adverse drug reactions （2.50% vs. 10.00%， P＝0.049） of post-quality control implementation group were decreased significantly； the utility value of the EuroQol Five-Dimensional Questionnaire （0.74± 0.06 vs. 0.71±0.07， P＝0.003）， the reduction in the number of medication related problems （1.0 vs. 0.5， P＜0.001）， the medication adherence score （[ 6.32±0.48） points vs. （6.10±0.37） points， P＝0.001]， and the satisfaction score （[ 92.56±1.52） points vs. （91.95±1.56） points， P＝0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups （1.25% vs. 3.75%， P＝0.310）. CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care， and the ECHO model can quantitatively evaluate the effect of MTM services， making pharmaceutical care better priced and more adaptable to social needs， thus being worthy of promotion.

Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases that share similar inflammatory mechanisms and characteristics. Programmed cell death (PCD) has recently garnered attention for its crucial role in regulating inflammation and maintaining tissue homeostasis, as well as for its potential to link these two diseases. The various forms of PCD--including apoptosis, pyroptosis, and necroptosis--are closely controlled by signaling pathways such as Toll-like receptor 4 (TLR4) /NF-κB and MAPK. These pathways determine cell fate and influence inflammatory responses, tissue destruction, and repair, and they both play important roles in the pathogenesis of RA and periodontitis. In periodontitis, periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis) and its virulence factors, including lipopolysaccharide (LPS), induce pyroptosis and necroptosis in immune cells such as macrophages via the TLR4/NF-κB pathway, which leads to an excessive release of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Concurrently, these pathogens inhibit the normal apoptotic process of immune cells, such as neutrophils, prolonging their survival, exacerbating immune imbalance, and aggravating periodontal tissue destruction. Similarly, in RA synovial tissue, fibroblast-like synoviocytes (FLS) acquire apoptosis resistance through signaling pathways such as the Bcl-2 family, JAK/STAT, and NF-κB, allowing for the consistent proliferation and secretion of matrix metalloproteinases and pro-inflammatory cytokines. Meanwhile, the continuous activation of pyroptotic pathways in neutrophils and macrophages results in the sustained release of IL-1β, further exacerbating synovial inflammation and bone destruction. Notably, dysregulated PCD fosters inter-organ crosstalk through shared inflammatory mediators and metabolic networks. Damage-associated molecular patterns (DAMPs) and cytokines that originate from periodontal lesions can spread systemically, influencing cell death processes in synovial and immune cells, thereby aggravating joint inflammation and bone erosion. By contrast, systemic inflammation in RA can upregulate osteoclastic activity or interfere with the normal apoptosis of periodontal cells via TNF-α and IL-6, ultimately intensifying periodontal immune imbalance. This review highlights the pivotal bridging role of PCD in the pathogenesis of both periodontitis and RA, providing a reference for therapeutic strategies that target cell death pathways to manage and potentially mitigate these diseases.

ObjectiveTo observe the effects of electroacupuncture with "tonifying the kidney and dispelling stasis" acupoint prescription on sexual function in diabetic erectile dysfunction （DMED）model rats， and to explore its possible mechanism of action. MethodsSPF male SD rats were randomly divided into 10 each in blank group， model group， Tadalafil group， and electroacupuncture group. DMED rat model was prepared by high glucose and high fat diet combined with intraperitoneal injection of streptozotocin. After successful modelling， rats in the electroacupuncture group were given electroacupuncture intervention of "tonifying the kidney and dispelling stasis" acupoint prescription once every other day； Tadalafil group was given Tadalafil solution 0.5 mg/kg·d by gavage， and the blank group， model group and electroacupuncture group were given 10 ml/kg pure water by gavage once a day. Each group was intervened for 30 days. The body mass and blood glucose level of the rats were detected on the 1st， 8th， 15th， 22nd days and at the end of the intervention， respectively. At the end of the intervention， the penile erection of the rats was observed by using the apomorphine test； the level of plasma endothelial cell microparticles （EMPs）was detected by flow cytometry； the histopathological morphology of the penile cavernous body was observed by HE staining， and the pathological morphology of the endothelial cells of the penile vasculature was observed by electron microscopy. Serum sex hormones including testosterone （T）， follicle stimulating hormone （FSH）， luteinising hormone （LH） and vascular endothelial function-related factors including vascular endothelial growth factor （VEGF）， endothelin-1 （ET-1）， lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1）， soluble E-selectin （sE-selectin）， and soluble intercellular adhesion molecule-1 （sICAM-1） were measured by ELISA method. ResultsCompared with blank group， the model group， Tadalafil group， and electroacupuncture group all had lower body mass and higher blood glucose levels at each time of testing （P＜0.01）. Compared with the blank group， the number of penile erections reduced in the model group， the level of CD31⁺ EMPs increased， the levels of serum T， FSH， LH， and VEGF reduced， and the levels of serum ET-1， LOX-1， sE-selectin， and sICAM-1 increased （P＜0.01）. Compared with the model group， the Tadalafil group and the electroacupuncture group showed an increased number of penile erections decreased level of CD31⁺ EMPs， increased levels of serum T， FSH， LH， and VEGF， and decreased levels of serum ET-1， LOX-1， sE-selectin， and sICAM-1 （P＜0.01）. Compared with the Tadalafil group， serum T， FSH， LH， VEGF levels increased and ET-1， LOX-1 levels decreased in the electroacupuncture group （P＜0.05 or P＜0.01）. HE staining and electron microscopic observation revealed that there was severe pathological damage to the cavernous tissue of the penis and vascular endothelial cells of the rat in the model group， which was ameliorated to a certain degree in both Tadalafil group and electroacupuncture group. ConclusionThe electroacupuncture prescription of "tonifying the kidney and dispelling stasis" can improve the erectile dysfunction of DMED rats， which is comparable to the effect of Tadalafi. Its mechanism of action may be related to the regulation of vascular endothelial function.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective To investigate the prevalence of Anisakis infections in coastal marine fishes and awareness of anisakiasis control knowledge among local residents in Yantai City, Shandong Province in 2021, so as to provide insights into formulation of anisakiasis control interventions. Methods Marine fishes were purchased from Shunxin Port, Yantai City, Shandong Province in November 2021, and the presence of Anisakis was detected in different species of fishes and different fish sites. The correlations between body length and weight of marine fish and intensity of Anisakis infections were examined using Spearman’s rank correlation analysis, and the dietary habits and anisakiasis control knowledge were investigated using questionnaire surveys among local residents. Results A total of 201 marine fishes belonging to 20 species were dissected, and Anisakis was detected in 77 marine fishes (38.31%) belonging to 11 species (55.00%), with a mean infection intensity of 45.04 parasites per fish (3 468/77). Spearman’s rank correlation analysis revealed that the body length (r_s = 0.74, P < 0.05) and weight (r_s = 0.79, P < 0.01) of the monkfish correlated positively with the intensity of Anisakis infections, and the body length (r_s = 0.68, P < 0.05) of the flatfish correlated positively with the intensity of Anisakis infections, while no correlations were examined between the body length or weight of other marine fishes and the intensity of Anisakis infections. Of all respondents, 53.38% men and 56.67% women did not know anisakiasis control knowledge at all, and there was a significant difference in the proportion of respondents using separate chopping boards for raw and cooked food from different villages (χ² = 17.89, P < 0.01), while there was an age-specific proportion of respondents with habitats of eating raw or semi-raw seafood (χ² = 28.27, P < 0.01). Conclusions The prevalence and intensity of Anisakis infections were high in coastal marine fishes in Yantai City in 2021, and the awareness of anisakiasis control knowledge was low among local residents. Intensified health education pertaining to anisakiasis control knowledge is recommended to reduce the risk of Anisakis infections.

Aim To explore the potential targets and related signaling pathways of Agaricus blazei Murill (AbM ) extract in the treatment of chronic myeloid leukemia (CML) based on liquid chromatography mass spectrometry ( LC-MS ), network pharmacology, molecular docking, and were further verified by experiments in vitro. Methods The active components of AbM extract were retrieved from LC-MS, Swiss Target Prediction database was used to predict related targets, and CML disease target genes were obtained from Gen- eCards and DisGeNET databases. After screening the common targets of drug and CML, the protein-protein interaction network of the common targets was performed by STRING, and GO and KEGG enrichment a- nalysis were done by DAVID database. Cytoscape software was used to construct the network of target protein. Molecular docking was carried out by DockThor, and the Pymol software was used to make a visual picture. The inhibitory effect of AbM extract on leukemia cells K562 was determined by CCK-8 experiment, and the effect of AbM extract on the expression and phosphorylation level of related proteins was verified by Western blot. Results The prediction results showed that 126 active components of AbM extract, and 172 common targets were collected. KEGG pathway analysis results showed that PI3K/Akt/mTOR signaling pathway might play an important role in the treatment of CML disease. The IC