OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group， model group， dexamethasone group （positive control）， and Ephedrae Herba-Armeniacae Semen Amarum 2∶1， 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g （crude drug）/kg]， dexamethasone suspension （0.5 mg/kg）， or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration， medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration， the nucleus tractus solitarius （NTS） was located using a stereotaxic apparatus. Histamine phosphate （1 μL） was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats； the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor （NGF）， substance P （SP）， norepinephrine （NA）， 5-hydroxytryptamine （5-HT） and acetylcholine （Ach）] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor （NK-1R）， p38 mitogen-activated protein kinase （MAPK）， and c-fos in the medulla oblongata， as well as the protein expressions of NK-1R， p38 MAPK， and c-fos in the NTS region， were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine， pseudoephedrine， and methylephedrine. Compared with blank group， the contents of NGF， SP， NA， 5-HT and Ach， and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein were significantly increased in the model group （ P ＜0.01）. Compared with model group， Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein （ P ＜0.01）， with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Objective: Patients with atherosclerotic cardiovascular disease (ASCVD) following percutaneous coronary intervention (PCI) are classified as very-high-risk individuals in cardiovascular disease (CVD) risk stratification. The distribution pattern of traditional Chinese medicine (TCM) syndromes in this patient population, as well as its association with blood lipid profiles and clinical prognosis, remains unclear. The present prospective cohort study aims to investigate these correlations, thereby providing insights to enrich the research fields. Methods: We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1, 2020 and December 31, 2022. Demographics and clinical characteristics, signs and symptoms defining each TCM syndrome, and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events (MACEs). We analyzed the correlation between TCM syndromes, blood lipid profiles, and MACEs, and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression. The analyses were based on detailed baseline and one-year follow-up data. Results: A per-protocol analysis was performed on 586 patients with complete data ultimately. During the one-year follow-up, 174 patients (29.69%) experienced a MACE. We performed statistical analyses on comorbidities, medication, and biochemical indicators across groups defined by TCM syndrome differentiation. When comparing different TCM syndromes, no significant differences were found in age, body mass index (BMI), history of revascularization, comorbidities, family history of CVD, smoking or drinking, or statin intensity (P > 0.05). Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol (TC, 5.27 ± 1.18 mmol/L, P < 0.001), triglyceride (TG, 1.96 ± 1.33 mmol/L, P = 0.008), low-density lipoprotein cholesterol (LDL-C, 3.35 ± 0.79 mmol/L, P < 0.001), and high-density lipoprotein cholesterol (HDL-C, 1.24 ± 0.81 mmol/L, P < 0.001) compared with those with other TCM syndromes combined. A multivariable logistic regression model was constructed to predict MACEs. The model included TCM syndrome type [with intertwined phlegm and blood stasis as a predictor, adjusted odds ratio (OR) = 1.413, 95% confidence interval (CI): 0.517 – 3.864, P = 0.501], age (adjusted OR = 0.97, 95% CI: 0.955 – 1.001, P = 0.057), male gender (adjusted OR = 0.698, 95% CI: 0.416 – 1.170, P = 0.173), TC (adjusted OR = 1.004, 95% CI: 0.513 – 1.965, P = 0.990), and LDL-C (adjusted OR = 5.825, 95% CI: 2.214 – 15.326, P < 0.001). This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients [the area under the receiver operating characteristic (ROC) curve (AUC) = 0.865, 95% CI: 0.816 – 0.914]. Conclusion The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C. The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters (TC and LDL-C) shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI, underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.

ObjectiveStroke poses a heavy burden due to its high mortality and morbidity rates. Accurate and real-time detection of lesions is pivotal for prompt clinical intervention and favorable prognosis. Electrical impedance tomography (EIT) and microwave tomography (MWT) have emerged as compelling alternatives for stroke screening, owing to their non-ionizing, non-invasive and portable nature. EIT provides information on tissue conductivity, and MWT offers high sensitivity to changes in dielectric properties. However, single-modality imaging is inherently limited, EIT suffers from low sensitivity to deep-seated tissues and severe ill-posedness of inverse problems, whereas MWT is challenged by strong nonlinearity in inverse scattering and susceptibility to modeling errors. Consequently, the clinical utility of standalone EIT or MWT for stroke diagnosis remains constrained by poor spatial resolution and imaging artifacts. To improve the accuracy and robustness of stroke imaging, a dual-modality fusion conditional denoising diffusion probabilistic model (DM-DDPM) was proposed for high-precision dual-modality image reconstruction. MethodsA dual-encoder network with a symmetric architecture and independently trained parameters was constructed to extract heterogeneous features separately from EIT boundary voltage measurements and MWT scattered field signals. Attentional feature fusion (AFF) is employed to integrate complementary information from the two modalities adaptively, generating robust fused priors that suppress redundant noise while preserving key physical characteristics. Subsequently, the fused priors are embedded into a Transformer-based diffusion model via a cross attention mechanism to guide the reverse denoising process. This approach effectively reduces artifacts and enhances the stability of conductivity distribution reconstruction. Time step embedding is introduced to enable the network to perceive the diffusion stage and further improve the accuracy of noise prediction. ResultsSimulated experiments demonstrated that DM-DDPM significantly outperforms single-modality and multi-modality networks under various noise levels. A head model simulation dataset was constructed based on COMSOL Multiphysics, and tests were carried out under 50 dB, 40 dB and 30 dB signal-to-noise ratio levels. At 30 dB, the average relative error (RE) was below 0.20, while the structural similarity index measure (SSIM) and correlation coefficient (CC) remained above 0.90 and 0.89, respectively. Compared with single-modality and multi-modality networks, artifacts were significantly reduced, lesion edges were clearer, and localization was more accurate. The model maintains high reconstruction quality and strong robustness for single, double, and triple lesions simultaneously. Furthermore, physical experiments were conducted using a 16-electrode EIT system and a 16-antenna MWT system with asynchronous data acquisition. These experiments confirmed the feasibility of the method in real-world scenarios and demonstrated that it can robustly reconstruct simulated lesions despite environmental interference and measurement noise, validating its reliability for practical clinical applications. ConclusionThe proposed method effectively combines complementary dual-modality information with a conditional diffusion model. Low accuracy and poor noise resistance in single-modality imaging were effectively addressed, while the noise amplification issue caused by direct multimodal data fusion was avoided. The proposed algorithm exhibits strong anti-noise interference ability and high imaging stability in both simulation and physical experiments. Precise localization of stroke lesions with different quantities was achieved, providing a high-precision, and practical technical support for clinical stroke detection.

OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

AIM To study the chemical constituents from the stems and barks of Maytenus variabilis(Hemsl.)C.Y.Cheng.METHODS The 95％ethanol extract from the stems and barks of M.variabilis was isolated and purified by silica gel,Sephadex LH-20 and semi preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-three compounds were isolated and identified as β-amyrin(1),3β-acetoxyolean-12-en-11-one(2),ursa-12-ene-11-one-3-ol octocosate(3),friedelin(4),canophyllol(5),pinoresinol(6),medioresinol(7),isolariciresinol(8),dihydrodehydrodiconiferyl alcohol(9),vanillic acid(10),7R,8S-5-methoxydihydrodehydroconiferyl alcohol(11),β-hydroxypropiovanillone(12),triptregeline B(13),triptregeline E(14),(+)-evofolin B(15),2,5-dimethoxybenzoquinone(16),olean-12-ene-3,11-dione(17),β-sitosterol(18),(-)-(7R,7'R,7"S,8S,8'S,8"S)-4',4"-dihydroxy-3,3',3",5-tetramethoxy-7,9',7',9-diepoxy-4,8"-oxy-8,8'-sesquineolignan-7",9"-diol(19),phyllostadimer B(20),rayalinol(21),lyoniresinol(22),dihydrobuddlenol B(23).CONCLUSION Compounds 3,9-11,13-14,16,19-21,23 are isolated from genus Maytenus for the first time,and compounds 2,4-5,7-8,12,15,17,22 are first found from this plant.

AIM To study the chemical constituents of Anaphalis margaritacea(L.)Benth.& Hook.f.and their antioxidant activities.METHODS Separation and purification were performed using silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH method and ABTS method.RESULTS Twenty-three compounds were isolated and identified as trans-tilidroside(1),4'-hydroxydehydrokawain(2),apigenin(3),3-O-kaempferol-3-O-acetyl-6-O-(p-coumamoyl)-α-D-glucopyranoside(4),kaempferol(5),quercetin-3-O-β-D-(6-O-Z-p-coumamoyl)-glucopyranoside(6),tiliroside(7),kaempferol-3-O-β-D-glucoside(8),3,5-dihydroxy-7,8-dimethoxyflavone(9),bis(2-ethylhexyl)adipate(10),3,5-dihydroxy-6,7,8-trimethoxyflavone(11),stigmasterol(12),myriophylloside B(13),1-hexadecanol(14),chlorogenic acid(15),4-hydroxy-N-{ 4-[3-(4-hydroxyphenyl)-E-acryloylamino]-butyl}-benzamide(16),3,6-dimethylpiperazine-2,5-dione(17),β-adenosine(18),5,6-dehydrokawain(19),kaempferol-3-O-(2",6"-di-O-E-p-coumaroyl)-β-D-glucopyranoside(20),kaempferol-3-O-(3"-O-E-p-coumaroyl)-(6"-O-E-feruloyl)-β-D-glucopyranoside(21),4,5-di-caffeoylquinic acid butyl ester(22),3,4-di-caffeoylquinic acid butyl ester(23).The IC50 values of compounds 1,7,22-23 against DPPH free radicals were(24.67±1.63)-(53.41±1.61)μmol/L,and the IC50 values of compounds 8,21-23 against ABTS+free radicals were(15.22±0.89)-(41.66±6.29)μmol/L.CONCLUSION Compounds 9,19-23 are isolated from genus Anaphalis for the first time,and 2,10,13,14,16,17,19-23 are first isolated from this plant.Compounds 1,7-8,21-23 have strong antioxidant activity.