Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*

With the rise of digital healthcare in recent years, digital tools, as a new type of health management tool, are expected to become a feasible tool for rehabilitation exercise in stroke patients. The aim of this article is to review the current status of the application of digital tools in self-management of stroke recovery. In addition, the concept, function and application effect of digital tools are introduced, and the existing problems and future research directions are pointed out, in order to provide reference for the self-management of stroke patients in China.

Objective To evaluate the efficacy of an online-to-offline(O2O)health education guided by the'Timing Theory'in improving self-management behaviours among the patients with glaucoma after day surgery.Methods In this randomised controlled study conducted between July and December 2022,70 patients with glaucoma after day surgery in our hospital were assigned to a control group and an experimental group,with 35 patients per group.Patients in control group received routine nursing care,while those in experimental group received O2O health education based on timing theory in addition to the routine nursing care.Outcomes were evaluated using the glaucoma awareness and knowledge questionnaire(GAKQ),self-efficacy to manage chronic disease scale(SEMCD)and glaucoma self-management questionnaire(GSMQ)at baseline,at 1 month and 3 months after surgery.Results A total of 32 patients in the experimental group and 27 in the control group completed the study.The generalised estimating equation(GEE)analysis showed a significant difference,respectively,in total score of GSMQ in interaction effect(F=8.408,P=0.015)and SEMC in time main effect(F=54.660,P<0.001).There were significant differences in total scores of GAKQ in time main effect,inter-group main effect and interaction effect(F=128.483,P<0.001;F=7.991,P<0.05;F=32.652,P<0.001,respectively).At one-month after intervention,the experimental group showed significantly higher GAKQ and SEMCD scores than the control group(Z=-2.004,P<0.05;Z=-2.029,P<0.05,respectively).At 1-and 3-months after intervention,the experimental group demonstrated significantly higher GAKQ scores(Z=-3.987,P<0.001;Z=-4.505,P<0.001,respectively).Conclusion The timing theory based O2O health education significantly improves knowledge of glaucoma,self-efficacy and self-management behaviours among day surgery patients and helps patients better cope with perioperative self-management over day surgery.

Objective To investigate the effects and mechanisms of combined prescriptions of essential oils from five traditional Chinese medicinal herbs,namely peppermint,turmeric,ginger,Tibetan fennel,and cumin,on symptoms related to functional abdominal pain syndrome(FAPS).Methods Gas chromatography-mass spectrometry(GC-MS)was employed to analyze the chemical constituents of five essential oils,while network pharmacology was utilized to predict the key targets and signaling pathways associated with these essential oils in alleviating functional abdominal pain syndrome.A formula design methodology centered on these core targets and signaling pathways was developed for creating new prescriptions.Molecular docking technology was conducted to predict its the underlying mechanisms.Subsequently,animal experiments were performed to assess pharmacological activity,including hot plate tests and acetic acid-induced writhing assays to validate the analgesic effects of the newly formulated prescription,as well as xylene-induced ear swelling tests to evaluate its anti-inflammatory properties.The impact of the essential oil formulation on intestinal peristaltic function was examined through intestinal propulsion experiments.Additionally,enzyme-linked immunosorbent assay(ELISA)methods were employed to measure levels of serotonin(5-HT),prostaglandin E2(PGE2),and gamma-aminobutyric acid(GABA)in brain tissue.Western blot analysis was conducted to determine protein expression levels of TPH1 and SERT in the intestine,along with TPH2 and SERT in the brain.Results The main chemical components in five essential oils were identified and screened(peppermint:12,turmeric:8,ginger:14,cumin:2,fennel:6).Based on the network pharmacology analysis,four new essential oil prescriptions were successfully designed according to the complementary relationship between the five essential oils in improving functional abdominal pain syndrome at the target level,including 4 new prescription named Prescription A,B,C and D,these four prescriptions were all based on ginger and turmeric essential oils,with other essential oils serving as supplements or enhancements.The results of animal experiments showed that Prescription D could significantly reduce the writhe frequency of mice(P<0.05),all the four groups could significantly prolong the pain threshold of mice(P<0.05),and Prescription C had a significant effect on reducing the degree of ear swelling(P<0.05).The prescription of essential oil did not significantly affect the function of peristalsis and the speed of propulsion.The levels of 5-HT and PGE2 in the brain tissue were significantly inhibited(P<0.05),and the level of GABA was significantly increased(P<0.05).Prescription C could reduce the expression of TPH1 in the intestinal tissue(P<0.05),Prescription A,C and D could reduce the expression of TPH2,and all groups had a tendency to increase the expression of SERT in the brain tissue.Conclusion In summary,the therapeutic effects of the four novel prescriptions composed of the five essential oils demonstrated potential in improving symptoms related to FAPS,the mechanism might be through modulating abnormalities in the brain-gut axis system.

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

Objective:To investigate the hepatoprotective effect of N-acetylcysteine(NAC)on rats with liver injury induced by cisplatin and its effect on intestinal flora and the expression of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nuclear factor-kappa B(NF-κB).Methods:Male Sprague-Dawley rats were randomly divided into control group(CG),cisplatin group(CP),and NAC group.The rats in the NAC group were given NAC 15 mg/kg by gavage for 8 consecutive days.At half an hour after intragastric administration on the fifth day,all rats except those in the NC group were given intraperitoneal injection of 8 mg/kg cisplatin to induce acute liver injury.An automatic biochemical analyzer was used to measure the content of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),and total bilirubin(TBIL);liver index was calculated for the rats;Western blot was used to measure the relative expression levels of NF-κB,IL-6,and TNF-α in liver tissue;the 16S rDNA technique was used to measure and analyze the amplification information of the V3-V4 regions of each sample.Results:Compared with the NC group,the CP group had significant increases in the content of AST,ALT,ALP,and TBIL,while NAC reversed the abnormal liver function caused by cisplatin.Compared with the NC group,the CP group had a sig-nificant increase in liver index(P=0.000),while the NAC group had a significant reduction in liver index compared with the CP group(P=0.007).Compared with the NC group,the CP group had signifi-cant increases in the expression levels of IL-6,TNF-α,and NF-κB,while the NAC group showed reductions in the expression of these genes,with significant differences in the expression of IL-6 and TNF-α(P=0.006 and 0.000).Compared with the NC group,the CP group had a significant increase in the α-diversity index of intesti-nal flora,while compared with the CP group,the NAC group tended to have a reduction in the α-diversity index of intestinal flora.Com-pared with the CP group at the phylum level,the NAC group had an increase in the abundance of Actinobacteria and a reduction in the abundance of Firmicutes.Compared with the CP group at the genus level,the NAC group had a reduction in the abundance of Rumino-coccaceae and increases in the abundance of Bifidobacterium and Allobaculum.Conclusion:NAC can alleviate acute liver injury caused by cisplatin,possibly by downregulating the expression of IL-6,TNF-α,and NF-κB and regulating the abundance and diver-sity of intestinal flora.

Objective:To evaluate surgical strategies and clinical outcomes in supra-labyrinthine cholesteatoma management, providing evidence-based guidance for therapeutic decision-making. Methods:Seven patients with supra-labyrinthine cholesteatoma in our hospital from 2021 to 2023 were enrolled in this study. The clinical manifestations, imaging findings, and surgical outcomes of patients were retrospectively analyzed. A systematic literature review focused on surgical anatomy correlations and imaging-based approach selection. Results:All seven cases of supra-labyrinthine cholesteatoma were unilateral. Preoperative otoendoscopy, CT, and intraoperative findings confirmed that they were classified as supral-abyrinthine cholesteatoma according to Sanna's classification. Two cases were operated entirely with otoendoscopy, three cases used a postauricular approach with microscopic assistance, and two cases involved a combined approach with endoscopy and microscopy. Hearing reconstruction with ossicular prosthesis was performed in five cases, while two cases did not undergo hearing reconstruction due to preoperative anacusis confirmed by both subjective and objective hearing tests. In all seven cases, various segments of the facial nerve were exposed during surgery, but postoperative facial nerve function remained intact, hearing was preserved, no cerebrospinal fluid leakage occurred, and no recurrences have been observed to date（as of June 2024）. Conclusion:With the advancement of imaging techniques and microsurgical technology, early diagnosis and surgical methods for supral-abyrinthine cholesteatoma have significantly improved. Compared to traditional approaches, the newer methods reduce unnecessary complications and offer advantages such as minimal surgical trauma, superior hearing preservation rates, and shorter recovery times with better postoperative neural function. This study reviews recent literature on petroclival cholesteatomas, combined with our own cases, to analyze the classification of supral-abyrinthine cholesteatoma and surgical approach selection. The findings aim to optimize treatment strategies and guide appropriate surgical methods, ultimately improving patient prognosis and quality of life.
Humans ; Cholesteatoma/surgery* ; Ear, Inner/surgery* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Objective:To provide theoretical support and practice model for improving the clinical medical education supervision system of university-affiliated hospitals.Methods:This study focused on the group of reserve teaching supervision experts. Through literature research, questionnaire survey, and expert interview, the Competency Evaluation Criteria for Reserve Teaching Supervision Experts was constructed, which was implemented according to the training framework of "theory, practice, summary, and feedback". The paired t-test was performed using SPSS 24.0. Results:The research team formulated the Competency Evaluation Criteria for Reserve Teaching Supervision Experts through expert interviews. Six basic competencies and three advanced competencies for reserve teaching supervision experts were identified and their weights were assigned. A supervision team was established with supervision experts (including reserve teaching supervision experts) and teaching staff at a ratio of 1∶6.9, achieving an increase in the coverage of supervised specialties. A toolkit for enhancing the supervision capabilities of reserve experts was developed, and its effectiveness was analyzed. Statistical analysis showed that the overall score gap between reserve teaching supervision experts and senior supervision experts gradually narrowed. In terms of teaching demeanor and teaching effectiveness, there were no significant differences between the two types of experts. However, in terms of teaching content scores, there was a significant difference between reserve teaching supervision experts and senior supervision experts ( P<0.05). Conclusions:The training mechanism of reserve teaching supervision experts can effectively bridge the structural defects of the traditional supervision team. However, further emphasis is needed on the standardization and professionalization of teaching content supervision.