ObjectiveTaking Aurantii Fructus Immaturus juice（AFI）-processed Atractylodis Macrocephalae Rhizoma（AMR） as an example， this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products， investigate the key differential components， evaluate their anti-inflammatory activities， and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry（GC-MS） and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology（NIST）17 database， comparison with retention index（RI） and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine （TCM） spectral library， in conjunction with PubChem and MassBank， characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） value >1. Components with high log₂fold change（FC） among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide（NO） production in a lipopolysaccharide（LPS）-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay（ELISA） was used to detect the effects of the differential components on tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6， and monocyte chemotactic protein（MCP）-1 levels， and immunofluorescence（IF） was employed to assess their effects on nuclear transcription factor（NF）-κB p65 translocation， thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR， among which， sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components， 36 compounds were identified， and the main differential components were flavonoids， sesquiterpenoids， and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products， representing compounds directly introduced during processing. Five compounds， including atractylenolide Ⅲ， tangeritin， nobiletin， hesperidin and narirutin， were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L^-1 tangerine and narirutin could significantly inhibit LPS-induced NO production（P<0.01） in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7（P<0.05）， while narirutin significantly inhibited the levels of TNF-α， IL-1β， MCP-1 and IL-6（P<0.01）. IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR， and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.

Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

AIM: To observe the characteristics of best corrected visual acuity(BCVA), microperimetry(MP), multifocal electroretinogram(mfERG), and optical coherence tomography angiography(OCTA)parameters in patients with idiopathic epiretinal membrane(IERM), and conduct a comparative study and correlation analysis on these parameters.METHODS:This was a cross-sectional study. A total of 56 patients(56 eyes)diagnosed with IERM who visited our hospital between February 2021 and November 2024 were collected as IERM group, and 33 healthy individuals(33 eyes)undergoing physical examinations were included as control group. Parameters were compared between the IERM group and the control group, as well as among IERM subgroups at different stages. Additionally, correlations among visual function parameters and between these visual function parameters and vascular structural OCTA parameters were analyzed.RESULTS: The general data of patients in the control group and IERM group were comparable. In the IERM group, BCVA, retinal sensitivity(RS), P1 wave amplitude in ring 1, superficial capillary plexus parafoveal vessel density(SCPpfvd), deep capillary plexus parafoveal vessel density(DCPpfvd), and the foveal avascular zone(FAZ)area were significantly lower than the control group(all P<0.01). In contrast, central retinal thickness(CRT), superficial capillary plexus foveal vessel density(SCPfvd), and deep capillary plexus foveal vessel density(DCPfvd)were significantly increased(all P<0.001). When comparing different stages of IERM, significant differences were observed in BCVA, CRT, RS, SCPfvd, and FAZ(all P<0.01). In eyes affected by IERM, BCVA(LogMAR)was negatively correlated with RS; P1 wave amplitude in ring 1 positively correlated with P1 wave implicit time in ring 1; SCPfvd positively correlated with BCVA(LogMAR)and negatively correlated with RS; DCPfvd negatively correlated with P1 wave implicit time in ring 1; and DCPpfvd positively correlated with RS(all P<0.05).CONCLUSION: Eyes with IERM exhibit abnormalities in visual function parameters and vascular structure, with varying degrees of alteration in BCVA, CRT, RS, SCPfvd, and FAZ across different stages. Comprehensive evaluation of BCVA, MP, mfERG, and OCTA contributes to a deeper understanding of the nature of IERM and aids in formulating appropriate diagnosis and treatment plans.

Gastric cancer is one of the most common malignant tumors worldwide and presents many treatment challenges,especially in relation to late-stage treatment and its high recurrence rate.Angiogenesis is a key process in the growth and metastasis of gastric cancer,and studies aimed at researching and developing anti-angiogenesis therapies are therefore important for the treatment of gastric cancer.Exosomes are nanoscale vesicles released by cells,which serve as important messengers for intercellular communication.They regulate local and distant cell communication by transporting specific exosomes components,and it can also promote or inhibit the development and progression of gastric cancer by regulating the growth,proliferation,and angiogenesis of tumor cells.Exosomes transport bioactive molecules from donor cells to recipient cells,leading to reprogramming of target cells and cascade molecular reactions.This review summarizes the relationship between exosomes and tumor angiogenesis in gastric cancer,and the current research status of exosomes in anti-angiogenic therapy.The importance of the physiological structure and function of exosomes in gastric cancer angiogenesis indicates the potential importance of combining exosomes with anti-angiogenic therapy for the treatment of gastric cancer.

Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

Objective:To explore the trajectory of changes in electronic health literacy in young and middle-aged patients with coronary heart disease (CHD) combined with diabetes mellitus (DM) after percutaneous coronary intervention (PCI), and to analyze its relationship with unplanned readmission within 30 days.Methods:A convenience sample of 210 young and middle-aged CHD patients with DM who underwent PCI in the Department of Cardiology, Xinxiang Central Hospital, from February 2023 to June 2024 was selected. The e-Health Literacy Scale (eHEALS) was used to assess electronic health literacy at the 3rd day (T 1), 15th day (T 2), and 30th day (T 3) after PCI. Unplanned readmission within 30 days after discharge was recorded. Latent class growth model (LCGM) was used to identify categories and characteristics of electronic health literacy trajectories. Kaplan-Meier method was applied to plot the cumulative incidence of 30-day unplanned readmission, and the Log-Rank test was used to compare differences among different trajectory types. Results:A total of 207 patients completed the entire survey and follow-up, with a valid response rate of 98.57% (207/210). eHEALS scores gradually increased after PCI, with scores of (6.75±1.31), (11.55±3.31), and (15.56±5.75) at T 1, T 2, and T 3, respectively. Two potential categories were identified: persistent low-level type (85 cases, 41.06%) and gradually improving type (122 cases, 58.94%). Twenty-six patients experienced unplanned readmission within 30 days, with an incidence of 12.56%. The proportions of unplanned readmission within 30 days were 20.00% (17/85) in the persistent low-level group and 7.38% (9/122) in the gradually improving group, with a statistically significant difference (χ 2=7.268, P=0.007). Kaplan-Meier cumulative risk function analysis showed that the cumulative incidence of 30-day unplanned readmission in the gradually improving group was lower than that in the persistent low-level group, with a statistically significant difference (Log-Rank=7.683, P=0.006) . Conclusions:Young and middle-aged CHD patients with DM after PCI show trajectory characteristics in electronic health literacy. Although the electronic health literacy of some patients gradually improved after PCI, persistent low-level literacy was still common, and patients in the persistent low-level group had a higher risk of 30-day unplanned readmission, which deserves clinical attention.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

We have isolated an intestinal probiotic strain, Pediococcus acidilactici HRQ-1. To improve its gastrointestinal fluid tolerance, transportation and storage stability, and slow-release properties, we employed the extrusion method to prepare the microcapsules with P. acidilactici HRQ-1 as the core material and sodium alginate and chitosan as the wall material. The optimal conditions for preparing the microcapsules were determined by single factor and orthogonal tests, and the optimal ratio was determined by taking the embedding rate, survival rate, storage stability, gastrointestinal fluid tolerance, and release rate as the evaluation indexes. The results showed that under the optimal embedding conditions, the embedding rate reached (89.60±0.02)%. Under the optimal formula of freeze-drying protective agent, the freeze-drying survival rate reached (76.42±0.13)%, and the average size of the microcapsules produced was (1.16±0.03) mm. The continuous gastrointestinal fluid simulation experiments confirmed that the microcapsules ensured the viable bacterial count and can slowly release bacteria in the intestinal fluid. The curve of the viable bacterial count during storage at 4 ℃ and room temperature indicated that the prepared microcapsules achieved strains' live number protection. The formula and preparation process of P. acidilactici microcapsules may provide a technological reserve for the preparation of more live bacterial drugs in the future.
Pediococcus acidilactici/chemistry* ; Probiotics/chemistry* ; Capsules/chemistry* ; Alginates/chemistry* ; Chitosan/chemistry* ; Drug Compounding/methods* ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry* ; Freeze Drying

Objective:To investigate the impact of different CT reconstruction kernels on the quantitative analysis of small pulmonary vessels in patients with chronic obstructive pulmonary disease (COPD) and high-risk patients.Methods:This study was a cross-sectional study. Clinical and imaging data of 73 COPD and high-risk patients visiting the China-Japan Friendship Hospital between March and April 2024 were retrospectively analyzed. All patients underwent high-resolution CT of the chest and pulmonary function tests, with the ratio of forced expiratory volume in one second to forced vital capacity (FEV 1/FVC) obtained. The raw CT data were reconstructed using different kernels: the FC86 group used the adaptive iterative dose reduction(AIDR) 3D standard lung sharp reconstruction algorithm, the FC18 group used the AIDR 3D standard Body standard reconstruction algorithm, the advanced intelligent clear-IQ engine(AiCE) Lung group used the AiCE deep learning reconstruction algorithm for lung, and the AiCE Body group used the AiCE deep learning reconstruction algorithm for body. Image signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image noise were calculated. The pulmonary vessel segmentation & Measurement software was used to segment and extract pulmonary arteries and veins of four groups in thin-slice whole-lung CT imaging, obtaining the ratio of small pulmonary arteries (%V artery<5) and the ratio of small pulmonary veins (%V vein<5). The One-way repeated measures ANOVA or Friedman test was used to compare the differences in SNR, CNR, image noise, %V artery<5, and %V vein<5 among the four groups, followed by Bonferroni post hoc or Bonferroni-Dunn test with P-value correction to analysis differences between subgroups. The correlations between %V artery<5 and FEV 1/FVC, as well as between %V vein<5 and FEV 1/FVC were analyzed using Spearman rank correlation analysis in all four groups. Results:The overall differences in image noise, SNR, and CNR in the AiCE Lung, AiCE Body, FC18, and FC86 groups were statistically significant ( P<0.001). Except for the difference in CNR values between the AiCE Lung group and the FC18 group, which was not statistically significant ( P=0.192), all differences were statistically significant ( P<0.016 7). The overall differences in %V artery<5 values and %V vein<5 values in the AiCE Lung, AiCE Body, FC18, and FC86 groups were statistically significant ( P<0.001). The %V artery<5 and %V vein<5 values in the FC18 group were lower than those in the AiCE Lung, AiCE Body, and FC86 groups ( P<0.016 7), and the rest of the differences were not statistically significant ( P>0.016 7). %V artery<5 and %V vein<5 were positively correlated with FEV 1/FVC in all 4 groups ( P<0.05), with the highest correlation coefficient between %V vein<5 and FEV 1/FVC in the AiCE Body group ( r=0.501, P=0.001). Conclusions:DLR-AiCE-based kernel reconstruction optimizes image quality and significantly affects the results of quantitative parameters of small pulmonary vessels. The reconstruction kernel prioritized for quantitative analysis of small vessels within the lungs in COPD based on the CT scanner in this study is AiCE Body.