OBJECTIVE To establish the high-performance liquid chromatography （HPLC） fingerprint of Sagina japonica ， and to establish a quantitative analysis of multi-components by single-marker （QAMS） method for simultaneous determination of six componen ts in S. japonica ， aiming to provide references for the quality control of this medicinal herb. METHODS HPLC method was used to establish the fingerprints of 12 batches （No. S1-S12） of S . japonica according to Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine . The similarity evaluation and identification of common peaks were conducted， followed by cluster analysis （CA） and principal component analysis （PCA） for 12 batches of samples. Using vicenin-2 as internal reference， the contents of p-hydroxy cinnamic acid， apigenin-6-C-arabinoside-8-C-glucoside， isoorientin， vitexin and 20-hydroxyecdysone were determined by QAMS method. The results were then compared with those obtained by the external standard method. RESULTS The similarities of HPLC fingerprints for 12 batches of S . japonica ranged from 0.828-0.998. A total of 17 common peaks were calibrated， and 6 common peaks were identified. Specifically， peak 5 was identified as vicenin-2， peak 7 as p-hydroxycinnamic acid， peak 10 as apigenin-6-C-arabinoside-8-C-glucoside， peak 11 as isoorientin， peak 13 as vitexin， and peak 15 as 20-hydroxyecdysone. The results of CA showed that S1-S5， S7 and S9-S11 were clustered into one category， S6 was clustered into one category， and S8 and S12 were clustered into one category. The results of PCA revealed that the accumulative contribution rate of the four main components was 89.430%. The content ranges measured by QAMS method for p-hydroxy cinnamic acid， apigenin-6-C-arabinoside-8-C-glucoside， isoorientin， vitexin and 20-hydroxyecdysone were 0.017 4-0.269 4， 0.568 8-4.240 3， 0.503 2-5.040 3， 0.024 0-0.132 0 and 2.551 3-4.881 1 mg/g， respectively. There was no significant difference in the contents of components measured between QAMS method and the external standard method （ P ＞0.05）. CONCLUSIONS The established HPLC fingerprint and QAMS method can be used for quality evaluation and quality control of S . japonica.

Objective To compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR+/HER2− metastatic or advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 articles, involving 8 031 patients and 11 treatment regimens, were included. There was no significant difference in progression-free survival (PFS) or overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant difference in grade 3-4 adverse events was observed among certain types of CDK4/6i (P<0.05). Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR+/HER2− advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual conditions.

AIM: To evaluate the diagnostic value of serum Th1-type cytokine levels and extraocular muscle-related parameters in thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective study was conducted on 45 patients diagnosed with TAO in our hospital from January 2023 to December 2024, and 20 normal volunteers during the same period as controls. Venous blood samples of the patients were collected to detect the concentrations of Th1-type cytokines [interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), and interleukin-12(IL-12)] in the serum. Additionally, the end diastolic velocity(Ved), velocity maximum(Vmax), resistance index(RI)of the central retinal artery, as well as the thickness and left-right diameter of the medial rectus muscle were measured. Logistic regression model was used to analyze the risk factors of TAO, and receiver operating characteristic curve(ROC)was adopted to evaluate the diagnostic efficacy of each index for the occurrence of TAO.RESULTS: The general information of the two groups was comparable. Compared with the normal control group, the serum concentrations of IFN-γ and TNF-α in TAO patients were significantly increased, Ved and Vmax were lower than those in the control group, and RI and the thickness of the medial rectus muscle were higher than those in the control group(all P<0.05). Logistic regression analysis showed that serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle were all risk factors for TAO. ROC curve analysis indicated that the AUCs of serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle for the diagnostic efficacy of TAO were 0.756, 0.769, 0.732, and 0.642, respectively. The combined detection of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle had an AUC of 0.840 and a Youden index of 0.59, which was superior to the detection of a single indicator.CONCLUSION: The levels of serum Th1-type cytokines and extraocular muscle-related ultrasound indicators have certain value in the diagnosis of TAO. The combination of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle has better diagnosis efficiency in TAO, which can provide a certain reference for the early diagnosis of TAO.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Identification of disease-specific cell subtypes (DSCSs) has profound implications for understanding disease mechanisms, preoperative diagnosis, and precision therapy. However, achieving unified annotation of DSCSs in heterogeneous single-cell datasets remains a challenge. In this study, we developed the gPRINT algorithm (generalized approach for cell subtype identification with single cell's voicePRINT). Inspired by the principles of speech recognition in noisy environments, gPRINT transforms gene position and gene expression information into voiceprints based on ordered and clustered gene expression phenomena, obtaining unique "gene print" patterns for each cell. Then, we integrated neural networks to mitigate the impact of background noise on cell identity label mapping. We demonstrated the reproducibility of gPRINT across different donors, single-cell sequencing platforms, and disease subtypes, and its utility for automatic cell subtype annotation across datasets. Moreover, gPRINT achieved higher annotation accuracy of 98.37% when externally validated based on the same tissue, surpassing other algorithms. Furthermore, this approach has been applied to fibrosis-associated diseases in multiple tissues throughout the body, as well as to the annotation of fibroblast subtypes in a single tissue, tendon, where fibrosis is prevalent. We successfully achieved automatic prediction of tendinopathy-specific cell subtypes, key targets, and related drugs. In summary, gPRINT provides an automated and unified approach for identifying DSCSs across datasets, facilitating the elucidation of specific cell subtypes under different disease states and providing a powerful tool for exploring therapeutic targets in diseases.
Humans ; Algorithms ; Single-Cell Analysis ; Databases, Genetic ; Molecular Sequence Annotation

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective:To compare the diagnostic value of semi-quantitative parameters of fluorine 18-labelled prostate-specific membrane antigen( 18F-PSMA)positron emission tomography /computed tomography(PET/CT)and the Prostate-specific Membrane Antigen Reporting and Data System(PSMA-RADS)score for identifying benign and malignant oligo-PSMA-avid bone lesions(1-5 lesions)in elderly patients with prostate cancer. Methods:A retrospective analysis was conducted on 157 prostate cancer patients who underwent 18F-PSMA PET/CT examinations at Beijing Hospital from October 2022 to August 2024.According to the inclusion and exclusion criteria, a total of 63 patients were selected.All patients underwent 18F-PSMA PET/CT examination for the purpose of initial staging or detecting lesions with biochemical recurrence.PSMA-avid bone lesions were evaluated using the PSMA-RADS version 2.0 scoring system and the semi-quantitative parameters were measured on PSMA PET/CT images.According to the comprehensive diagnostic criteria, PSMA-avid bone lesions were divided into metastatic group and non-metastatic group.The differences in PSMA-RADS scores, semi-quantitative parameters, bone density abnormalities, and lesion distribution were compared between the two groups.Multivariate logistic regression analysis was performed to determine the factors related to the bone metastasis in prostate cancer.By plotting the receiver operating characteristic(ROC)curves and calculating the area under the curve(AUC), factors with better diagnostic performance were evaluated and screened, and the optimal diagnostic threshold for each factor in diagnosing bone metastasis was determined. Results:There were a total of 129 PSMA-avid bone lesions for 63 patients(aged 60-84 years, median age 69 years), including 35 lesions(27.1%)in the metastatic group and 94 lesions(72.9%)in the non-metastatic group.The differences between metastatic group and non-metastatic group in PSMA-RADS scores[5(4, 5) vs.3(3, 3)], maximum standardized uptake value(SUV max)[12.6(7.0, 18.4) vs.4.7(3.5, 5.9)], lesion SUV max/mediastinal blood pool SUV max ratio(lesion-to-blood pool ratio, LBR)[5.4(3.0, 8.3) vs.1.7(1.4, 2.2)], lesion SUV max/liver SUV max ratio(lesion-to-liver ratio, LLR)[2.6(1.6, 4.1) vs.0.8(0.7, 1.1)], PSMA receptor expressing tumor volume(PSMA-TV)[0.6(0.3, 1.0) vs.1.0(0.7, 1.5)], total lesion of PSMA(TL-PSMA)[4.4(2.4, 7.0) vs.2.4(1.7, 3.9)], proportion of changes in osteogenic bone density[77.1%(27/35) vs.2.1%(2/94)], proportion of lesions located in the ribs[14.3%(5/35) vs.46.8%(44/94)], and proportion of lesions located in the pelvis[54.3%(19/35) vs.20.2%(19/94)]were all statistically significant(all P<0.05). Multivariate logistic regression analysis indicated that none of the variables with statistically significant differences between groups above were independent risk factors for osseous metastasis in prostate cancer(all P>0.05). Among them, The PSMA-RADS score, LLR, LBR, and SUV max all had good diagnostic efficacy for osseous metastasis, with 0.995(95% CI: 0.987-1.000), 0.923(95% CI: 0.869-0.977), 0.898(95% CI: 0.828-0.967), and 0.890(95% CI: 0.820-0.961), respectively.The cut-off values for diagnosing osseous metastasis were 4 score for PSMA-RADS score, 0.934 for LLR, 1.990 for LBR, and 5.47 for SUV max, respectively.According to Delong's test, there were statistically significant differences in AUC between PSMA-RADS score and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)( Z-values were 2.677, 2.776, and 2.929, respectively, and P-values were 0.007, 0.006, and 0.003, respectively). Conclusions:The PSMA-RADS score(Version 2.0)and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)both have good diagnostic value in differentiating benign and malignant PSMA-avid bone lesions in elderly patients with prostate cancer, among which the PSMA-RADS score has the best diagnostic efficacy.

Objective:To explore the molecular epidemiological characteristics of human metapneumovirus (HMPV) in children with acute respiratory infection (ARI) in Beijing from 2023 to 2024.Methods:In the longitudinal study, 9 834 children with ARI were enrolled from August 2023 to December 2024, including the influenza-like illness (ILI) group from emergency and outpatient department receiving influenza virus (Flu) and HMPV test and the ARI inpatient group for 13 common respiratory pathogen screening test including HMPV, Flu, respiratory syncytial virus, and so on. All respiratory samples positive with HMPV were genotyped by amplifying and sequencing of G gene and further phylogenetic analysis. The χ2 test and Wilcoxon rank-sum test were used to compare the positive rate and basic clinical data of the 2 groups. Results:Among 9 834 enrolled patient, there were 5 276 male and 4 558 female children, with age 5.4 (1.9, 8.2) years. In ILI group of 1 460 patients, there were 83 cases (5.7%) positive for HMPV, with the age 4.9 (3.6, 6.6) years and children under 6.0 years old 59 cases (71.1%). Among 8 374 ARI inpatients, there were 256 cases (3.1%) positive for HMPV, with age 3.5 (1.3, 6.4) years and children under 6.0 years old 188 cases (73.4%). The HMPV positive rate and the age of children positive for HMPV in ARI inpatient group were significantly lower than that in ILI group (both P<0.001). In December, 2024, the HMPV positive rates of ILI and ARI inpatient group (21.3% (17/80), 15.0% (47/314)) were significantly higher than the total positive rates of each group (both P<0.001). Among 279 subtyped specimens, there were 155 cases (55.6%) belonging to genotype A and 124 cases (44.4%) belonging to genotype B. Sub-lineage A2.2.2 containing 111nt-insertions was predominate one in 2023 with positive ratio 89.2% (91/102), and B2 was predominate in 2024 with positive ratio 64.4% (114/177). Conclusions:From 2023 to 2024, the positive rate of HMPV in the ILI group was higher than that in the ARI inpatient group, suggesting a common epidemic of HMPV infection. Children positive for HMPV in the ARI inpatient group were younger than that in the ILI group. A severe epidemic of HMPV was observed in the winter of 2024, which requires attention. Sub-lineage A2.2.2 with 111nt-duplicate insertions and B2 were the predominant epidemic strains in 2023 and 2024, respectively.

Objective:To detect the expression levels of 12 cytokines in the plasma of patients with primary biliary cholangitis (PBC) and explore their association with PBC disease activity and ursodeoxycholic acid (UDCA) therapeutic response.Methods:This study enrolled 127 patients with PBC who visited Peking Union Medical College Hospital between December 2021 and November 2023 (PBC group) and 32 healthy controls who underwent physical examinations during the same period (control group). The expression of 12 cytokines was measured using flow cytometry, and compared between groups. Spearman correlation analysis was performed to assess the relationship between cytokine levels and five laboratory indicators reflecting PBC disease activity [alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBil), aspartate aminotransferase (AST), and total bile acid (TBA)]. Furthermore, the receiver operating characteristic (ROC) curve analysis was performed to evaluate the effectiveness of cytokines in distinguishing between patients who responded to UDCA treatment and those who did not.Results:The plasma interleukin (IL)-8 levels between the PBC group and healthy controls showed no significant differences, and the plasma IFN-γ levels in PBC patients were significantly higher than those in health controls ( P<0.05). Spearman analysis showed that IL-8 was positively correlated with ALP, GGT, TBil, AST, and TBA ( R2=0.348, 0.401, 0.406, 0.495, 0.417; all P<0.01), and negative correlation was observed between IFN-γand ALP, GGT, and TBA levels ( R2=-0.265, -0.253, -0.232; all P<0.05). The plasma IL-8 level in 52 PBC patients who did not respond to UDCA treatment was significantly higher, while the IFN-γ level was significantly lower than those in 56 PBC patients who responded to UDCA treatment (both P<0.05). ROC analysis showed that the area under the curve for distinguishing plasma IL-8 and IFN-γlevels between PBC patients responding to UDCA treatment and not is 0.631 and 0.783, respectively. The sensitivities were 87.5% and 90.5%, and the specificities were 44.2% and 57.9%, respectively. Conclusion:The levels of plasma IL-8 and IFN-γ are correlated with the disease activity of PBC and can be used to reflect the therapeutic responses to UDCA in PBC patients.