OBJECTIVE To evaluate the quality of Euscaphis japonica from different habitats. METHODS The relative correction factors of gallic acid， protocatechuic acid， ellagic acid， isoquercitrin， astragalin and apigenin were calculated with quercetin as the internal reference； the relative correction factors of euscaphic acid， oleanolic acid， stigmasterol and β-sitosterol were also calculated with ursolic acid as the internal reference. The contents of 12 components in 18 batches of samples were calculated by QAMS method and were compared with external standard method. At the same time， the contents of water-soluble extract， alcohol-soluble extract， total ash and acid-insoluble ash were detected. The quality of E. japonica was evaluated by principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， and weighted technique for order preference by similarity to ideal solution （TOPSIS） method. RESULTS There was no significant difference between the results of QAMS method and external standard method for the 12 components in the 18 batches of samples. However， notable content variations were observed among different batches of samples. The results of PCA and OPLS-DA showed that S1-S7， S8- S12， and S13-S18 were clustered into one category respectively. Seven key characteristic components variable importance in projection values ＞1， euscaphic acid， ursolic acid， protocatechuic acid， apigenin， β-sitosterol， isoquercitrin， and oleanolic acid， respectively. The analysis results of the weighted TOPSIS method revealed that the relative closeness for evaluating the quality of 18 batches of samples ranged from 0.283 5 to 0.644 1， with the samples of E. japonica from Fengjie， Chongqing， demonstrating the highest quality. CONCLUSIONS The established method is accurate and feasible， which can be used for the quality evaluation of E. japonica combined with chemometrics and weighted TOPSIS model.

Objective To investigate the correlation between peripheral blood CD14+CD16+monocytes and IgG N-glycosyl levels and disease activity in patients with systemic lupus erythematosus(SLE).Methods A total of 109 SLE patients admitted to Xingtai Cental Hospital from August 2021 to November 2024 were retrospectively selected as the study objects.According to SLE disease activity index(SLE-DAI),the patients were divided into active group(n=52)and stable group(n=57).In addition,56 patients who underwent physical examination during the same period were selected as the control group.Clinical data of patients were collected,CD14+CD16+mononuclear cells were detected by flow cytometry(FCM),and IgG N-glycosyl levels were detected by hydrophilic interaction chromatography-mass spectrometry.Logistic regression analysis was performed to analyze the influencing factors of SLE-DAI,and multicollinearity test[variance inflation factor(VIF)]was performed for independent variables.The prediction model of disease activity was constructed.The effectiveness of the predictive model was evaluated by describing the recviver operator characteristic(ROC)curve and calculating the area under the curve(AUC)value.Hosmer-Lemeshow goodness-of-fit test predicted the calibration degree of the model.Results The levels of WBC,Hb,PLT,ALB,complement C3 and complement C4 in control group were higher than those in SLE group(t=8.917～22.171),and the levels of CRP were lower than those in SLE group(t=-17.359),with differences were statistical significance(all P<0.05).The CRP level and the proportion of CD14+CD16+mononuclear cells in the active group were higher than those in the stable group,and the differences were statistically significant(t=5.449,11.112,all P<0.05).The IgG glycosylation characteristics of galactosylation,sialylation and N-acetylglucosamine modification were lower than those in the stable group,and the differences were statistical significance(Z=-2.432～-0.158,all P<0.05).Spearman correlation analysis showed that the proportion of CD14+CD16+monocytes was significantly negatively correlated with IgG galactosylation,sialylation level and bisection N-acetylglucosamine modification(r=-0.656,-0.531,-0.608,all P<0.01).CD14+CD16+monocyte ratio was positively correlated with SLE-DIA(r=0.581,all P<0.01).IgG galactosylation,sialylation levels and bisection N-acetylglucosamine modification were negatively correlated with SLE-DIA(r=-0.645,-0.609,-0.503,all P<0.01).Logistic regression analysis showed that CRP>8.21mg/L,CD14+CD16+≥16.17%,sialylation<22.05%and isotropic N-acetylglucosamine modification<16.53%were independent risk factors for disease activity in SLE patients(Wald χ2=4.471～12.811,all P<0.05).The VIF values of the above independent variables were all less than 10.By establishing the Logistic regression prediction model and drawing the ROC curve,the AUC value for diagnosing SLE disease activity was 0.821(95%CI:0.733～0.905),the sensitivity,specificity and the Yodon index were 85.37%,75.67%,0.677,respectively.and the P values of Hosmer-Lemeshow goodness-of-fit test models were 0.568,respectively.Conclusion The proportion of CD14+CD16+monocytes in peripheral blood of SLE patients increase significantly,and the level of IgG glycosylation characteristics decrease,both of which are correlated with SLE-DIA.The predictive model constructed based on the two had a good ability to distinguish SLE-DIA from inactive state,with high sensitivity and moderate specificity conducive to early clinical recognition,and the model fitting effect is good.SLE-DIA can be evaluated more accurately.

Objective:To evaluate the effect of ultrasound-guided high ankle block (HAB) on the quality of postoperative recovery of patients undergoing foot and ankle surgery.Methods:In this randomized controlled trial, 90 patients of either sex, aged 18-64 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, scheduled for elective foot and ankle surgery, were divided into 2 groups ( n=45 each) using a random number table method: HAB group and spinal anesthesia group (SA group). Patients underwent ultrasound-guided HAB on the affected side in HAB group, while patients received spinal anesthesia in SA group. The Quality of Recovery-15 (QoR-15) scores were recorded at 24 and 48 h postoperatively. Additional data collected included anesthesia preparation and operation time, sensory and motor grading after anesthesia, anesthetic effect grading, surgery duration, intraoperative tourniquet time, block duration, time to first ambulation, and postoperative length of hospital stay. The time of first rescue analgesia and requirement for rescue algesia within 48 h postoperatively and the occurrence of adverse reactions such as hypotension, headache, nausea and vomiting, and urinary retention after anesthesia were also recorded. Results:Compared to SA group, QoR-15 scores and motor grading after anesthesia were significantly increased, the time to first ambulation and postoperative length of hospital stay were shortened, the duration of block and anesthesia preparation and operation time were prolonged at 24 h postoperatively, the rate of rescue analgesia wthin 48 h after operation and incidence of adverse reactions after anesthesia were decressed, and the time to first rescue analgesia was pronlonged in HAB group ( P<0.05). There were no significant differences between the two groups in sensory grading after anesthesia, anesthetic effect grading, intraoperative use of tourniquet time, and QoR-15 scores at 48 h postoperatively ( P>0.05). Conclusions:Ultrasound-guided HAB provides better quality of postoperative recovery than spinal anesthesia for the patients undergoing foot and ankle surgery.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms. In vivo experiments were conducted using 8-week-old SPF male C57BL/6J mice. The T2DM animal model was established by high-fat and high-sugar diet combined with intraperitoneal injections of streptozotocin (STZ), in compliance with the ethical guidelines set by the Animal Welfare Committee of Beijing University of Chinese Medicine (approval number: BUCM-2022021503-1134). In vitro experiments employed human liver cancer HepG2 cells, which were induced with tunicamycin (TM) to establish the ERS cell model. Transcriptomic sequencing was used to analyze changes in gene expression in the liver samples of T2DM mice following ISL treatment. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess the regulatory effects of ISL on key ERS genes. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunofluorescence techniques were used to evaluate ISL's effects on ERS-related proteins. Results indicate that ISL significantly downregulates the expression of ERS-related genes, reduces the level of glucose-regulated protein 78 (GRP78), and inhibits the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), thereby alleviating abnormal ERS induced by T2DM. Additionally, ISL increases the protein levels of insulin receptor substrate (IRS) 1 and IRS2 and enhances the phosphorylation of protein kinase B (Akt), thereby improving insulin sensitivity. In conclusion, ISL is able to alleviate T2DM associated symptoms by improving abnormal ERS and enhancing insulin sensitivity.

Objective To evaluate the application value of stereotactic robotic surgery driven by a multi scenario AI system in the elderly with severe hypoperfusion in the internal capsule area and minor HTH.Methods A retrospective analysis was conducted on 101 minor HTH patients com-plicated with severe hypoperfusion in the internal capsule area identified by an AI diagnostic sys-tem in our department from January to October 2024.Among them,48 cases who underwent ster-eotactic robotic drainage with AI system support were assigned into the study group,and 53 cases of conventional drug treatment were into the control group.The general clinical data were com-pared between the two group.Improvement rate of rCBF 14 d after treatment,effective rate 90 d after treatment,favorable prognosis rate,and incidence of shunt dependent hydrocephalus were compared between the two groups to evaluate the application value of AI-assisted stereotactic ro-botic surgery in these patients.Results The study group had significantly higher improvement rate of rCBF 14 d after treatment,better effective rate and larger ratio of favorable prognosis 90 d after treatment when compared with the control group(60.4％vs 39.6％,P＜0.05;62.5％vs 41.5％,P＜0.05;64.6％vs 43.4％,P＜0.05).Conclusion Stereotactic robotic assisted drainage driven by multi scenario AI system can significantly improve the prognosis of the elderly minor HTH patients complicated with severe hypoperfusion in the internal capsule area.

Objective To evaluate the application value of stereotactic robotic surgery driven by a multi scenario AI system in the elderly with severe hypoperfusion in the internal capsule area and minor HTH.Methods A retrospective analysis was conducted on 101 minor HTH patients com-plicated with severe hypoperfusion in the internal capsule area identified by an AI diagnostic sys-tem in our department from January to October 2024.Among them,48 cases who underwent ster-eotactic robotic drainage with AI system support were assigned into the study group,and 53 cases of conventional drug treatment were into the control group.The general clinical data were com-pared between the two group.Improvement rate of rCBF 14 d after treatment,effective rate 90 d after treatment,favorable prognosis rate,and incidence of shunt dependent hydrocephalus were compared between the two groups to evaluate the application value of AI-assisted stereotactic ro-botic surgery in these patients.Results The study group had significantly higher improvement rate of rCBF 14 d after treatment,better effective rate and larger ratio of favorable prognosis 90 d after treatment when compared with the control group(60.4％vs 39.6％,P＜0.05;62.5％vs 41.5％,P＜0.05;64.6％vs 43.4％,P＜0.05).Conclusion Stereotactic robotic assisted drainage driven by multi scenario AI system can significantly improve the prognosis of the elderly minor HTH patients complicated with severe hypoperfusion in the internal capsule area.

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

Objective To analyze the changes in optical coherence tomography angiography (OCTA) parameters in patients with essential hypertension，and to explore the effect of blood pressure on OCTA parameters. Methods A total of 164 patients with essential hypertension were selected and divided into controlled blood pressure group (n=92) and uncontrolled blood pressure group (n=72). OCTA examination was performed on the optic disc and macula of all patients, and the right eyes were selected for analysis. Results There were no significant differences in retinal nerve fiber layer (RNFL) thickness, radial peripapillary capillary (RPC) total vascular density, RPC total small vessel density, perifovea superficial capillary plexus (SCP) vascular density, and perifovea deep capillary plexus (DCP) vascular density between the two groups of patients. There were no significant differences in foveal avascular zone (FAZ) area, FAZ diameter, and fovea retinal thickness between the two groups of patients. The density of the parafovea SCP, parafovea DCP, and fractal dimension (FD) in the uncontrolled blood pressure group were significantly lower than those in the controlled blood pressure group (P＜0.05). Multiple linear regression analysis showed that elevation of blood pressure was a independently related factor of reduced parafovea DCP density (P＝0.026), while there was no correlation between the uncontrolled blood pressure and parafovea SCP density and FD level. Conclusions The blood pressure level is correlated with the parafovea DCP density, while has no correlation with other OCTA parameters in hypertension patients.