ObjectiveBased on literature data mining， this study explores the modeling elements of diarrhea-predominant irritable bowel syndrome （IBS-D） animal models in China and abroad， providing references and suggestions for improving modeling methods and evaluation indicators. MethodsRelevant literature on IBS-D animal experiments from 2014 to 2024 was retrieved through computer searches in databases such as China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， Chinese Medical Journals Full-text Database， and PubMed. Information on experimental animal species， gender， body weight， modeling methods， modeling periods， intervention controls， modeling standards， and detection indicators was organized. Microsoft Excel 2021 software was used to establish a database and perform statistical analysis to examine the characteristics of IBS-D animal models. ResultsA total of 398 articles that met the inclusion criteria were reviewed. The IBS-D animal models were predominantly established using SD rats， Wistar rats， and C57BL/6 mice. Male animals were more commonly used， with rats typically aged 6-8 weeks and mice aged 4-6 weeks. In terms of interventions， piverium bromide was the main Western medicine， Tongxieyaofang was the primary Chinese medicine， and electroacupuncture was the primary acupuncture method. Among the modeling methods， the multi-factor combined composite modeling approach was the most common. Modeling periods were mainly concentrated between 1-14 days and 15-30 days. The success criteria for modeling were mainly evaluated based on the animal's general condition， fecal appearance， visceral sensitivity， gastrointestinal motility， behavior， and pathology. Detection indicators included apparent indexes， pathological markers， biochemical indicators， oxidative stress， brain-gut peptides， neurotransmitters， inflammatory factors， immune function， intestinal permeability， autophagy， apoptosis， proteins related to relevant signaling pathways， intestinal microbiota and its metabolites， etc. ConclusionThere are various methods for establishing IBS-D animal models， but no unified and universally accepted method has been established. The operation of the same modeling methods and the evaluation standards of the models vary across studies. Based on the results of data mining， the authors suggest that the multi-factor combined composite modeling approach most closely reflects the pathophysiological processes of IBS-D， better simulating the complex clinical symptoms of IBS-D patients， such as abdominal pain and diarrhea， and has a high degree of clinical relevance. This method is relatively recommended. While animal models in general align with Western medicine standards， models incorporating traditional Chinese medicine （TCM） syndromes are relatively few. Therefore， one of the future directions for research is to establish IBS-D animal models that meet the combined clinical disease and syndrome requirements of both Western and Chinese medicine.

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*

Objective:To investigate the potential characteristic manifestations and application value of the Dynamic Visual Acuity Test（DVAT） in vestibular migraine（VM）. Methods:A total of 50 VM patients（case group） and 50 healthy subjects（control group） diagnosed at the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University between November 1, 2023, and December 31, 2024, were enrolled. The case group underwent DVAT, video head impulse test（vHIT）, caloric test, and Dizziness Handicap Inventory（DHI） assessment, whereas the control group only received DVAT. Group-based analyses were conducted to examine the effect of age on Dynamic Visual Acuity Loss（DVALoss）, as well as the correlations of DVALoss with vestibular function tests and DHI scores. Results:DVALoss in the case group was significantly higher than that in the control group（P<0.001）. In both groups, age was significantly and positively correlated with DVALoss（P<0.001）. Within the case group, DVALoss was strongly and positively correlated with DHI scores（r=0.807, P<0.001）; it was negatively correlated with the vestibulo-ocular reflex（VOR） gain in vHIT, though without clinical significance, and showed no significant association with the caloric test. Age and DVALoss collectively accounted for 71.3% of the variance in DHI scores（R²=0.713）, with age exerting a relatively minor actual impact. Conclusion:DVAT can sensitively identify the core functional impairments of VM. DVALoss, as a direct functional reflection of the pathological mechanism of VM, is strongly correlated with DHI scores. Incorporating DVALoss into standardized assessments may provide an objective basis for the diagnosis and management of VM.
Humans ; Migraine Disorders/diagnosis* ; Visual Acuity ; Case-Control Studies ; Head Impulse Test ; Vestibular Function Tests ; Female ; Male ; Adult ; Vestibular Diseases/physiopathology* ; Middle Aged ; Caloric Tests

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

This study was aimed at investigating the effectiveness of various host nucleic acid removal and non-specific amplifica-tion techniques in animal tissue samples,to increase the accuracy of pathogen identification in tissue samples.Simulated samples were prepared with a mixture of mouse lung tissue homogenates and Klebsiella pneumoniae fluids,and processed with six host nucleic acid removal kits and three non-specific amplification techniques.The effectiveness of each method in removing host DNA and enriching nucleic acids of pathogenic microorganisms was evaluated through real-time fluorescence quantitative PCR and high-throughput se-quencing.For host nucleic acid removal techniques,the method of selective cleavage and quantitative degradation of host DNA(Com-plete5 kit)effectively decreased the host nucleic acid content in tissue samples and increased the relative abundance of pathogen nucleic acids.In contrast,the magnetic bead method for host DNA removal(Next microbiome DNA enrichment Kit kit)was less effec-tive.At lower pathogen concentrations(77 CFU/mL),the Vazyme kit was more effective than the other kits in removing host nucleic acids.Non-specific amplification techniques(MALBAC whole genome amplification,MDA isothermal amplification,and random primer amplification)were not applicable to tissue samples and were not effective in increasing the relative abundance of pathogen nucleic acids.Selective lysis and quantitative degradation of host DNA were suitable for processing tissue samples with high host back-ground and low pathogenic microorganism levels,whereas non-specific amplification methods were not applicable to tissue samples for pre-processing of macro-genome high-throughput sequencing.

Objective This study sought to establish a diarrhea-predominant irritable bowel syndrome(IBS-D)mouse model by gavage different mass concentrations sennae folium combined with chronic restraint stress,and to determine the appropriate mass concentration of sennae folium to establish IBS-D mouse model.Methods The mass concentration of sennae folium used for the IBS-D mouse model followed suggested amounts in the literature and on that basis,the mass concentration gradient was established prior to conducting the experiment.Female C57BL/6 mice were divided into a normal group(Group N),a low-dose group(Group L;0.25 g/mL sennae solution),a medium-dose group(Group M;0.50 g/mL sennae solution),and a high-dose group(Group H;1.0 g/mL sennae solution),with 10 mice per group.After 14 days,the defecation,diarrhea index,visceral sensitivity,and morphological changes in the colonic tissue in each group were observed and recorded to compare the differences among models established with varying mass concentrations of sennae folium.Results Compared with Group N(42.90±11.90)%,Group L(80.30±5.77)%,Group M(80.50±3.44)%,and Group H(81.90±2.68)%had significantly higher 6 h fecal water content(P＜0.01).Compared with Group N(0.00±0.00),the diarrhea index of mice in Group L(0.57±0.16),Group M(0.62±0.23),and Group H(0.60,0.23)also increased significantly(P＜0.01).Compared with Group N(0.65(0.60,0.65)),Group M(0.32(0.24,0.39))and Group H(0.34(0.27,0.47))had significantly lower visceral pain threshold and higher visceral sensitivity(P＜0.01).Additionally,the first blue stool time in Group M(98.15(93.41,100.44)min)was significantly shorter than that in Group N(186.81(109.28,192.05)min)(P＜0.01),and the total number of stools in Group M(22.4±3.73)was significantly higher than that in Group N(17.90±4.48)(P＜0.05).Conclusions Compared with 0.25 and 1.0 g/mL,0.50 g/mL sennae folium gavage,combined with chronic restraint stress,can better simulate the clinical symptoms of IBS-D.

Irritable bowel syndrome(IBS)is a prevalent functional gastrointestinal disorder characterized by a complex etiology involving multiple interacting factors.Accumulating evidence in recent years has indicated that intestinal barrier dysfunction may play a crucial role in the pathogenesis of IBS.This review systematically ex-amines the impact of intestinal barrier dysfunction on IBS,analyzing its associations with the mechanical,im-mune,chemical,and microbial components of the gut barrier,as well as current clinical treatment approaches.Moreover,this paper highlights the potential of intestinal barrier repair mechanisms as therapeutic targets,which may provide novel insights and directions for understanding the underlying pathophysiological mechanisms and de-veloping effective interventions for IBS.

Objective:To compare the value of different imaging modalities in evaluating early efficacy of 90Y-selective internal radiation therapy (SIRT) for liver malignant tumors. Methods:From September 2021 to December 2023, a retrospective analysis was conducted on 43 patients (32 males, 11 females; age (55.8±14.7) years) with liver malignant tumors who received 90Y-SIRT at Hainan Cancer Hospital and Boao Super Hospital. The injection dosage of 90Y was 1.5(1.2, 2.4)GBq. Clinical and imaging data of patients before and after treatment for multimodal evaluation were collected, including MRI plain and enhanced scans, as well as diffusion weighted imaging (DWI). Plain scan images were evaluated for the treatment efficacy by response evaluation criteria in solid tumors (RECIST) 1.1 version, while enhanced MRI was scored into 1-5 based on changes in the target area, including increased low-density range, necrotic features, and decreased enhancement. The minimum apparent diffusion coefficient (ADC min) of DWI increased by 20% compared to baseline was determined to be responsive. Wilcoxon signed rank test was used to analyze data, and ROC curve analysis was used to analyze the diagnostic efficacy of different imaging modalities (Delong test). Results:All patients had baseline MRI data, 39 underwent MRI at 1-month after treatment, and 22 underwent MRI at 3-month after treatment. Based on MRI plain scan images, the target lesions showed partial remission (PR) in 10.26%(4/39) of patients, progressive disease (PD) in 5.13%(2/39) of patients, and stable disease (SD) in 84.61%(33/39) of patients at 1-month after treatment; while there were 40.91%(9/22) PR, 9.09%(2/22) PD and 50.00%(11/22) SD at 3-month after treatment. Based on DWI images, 35.90%(14/39) and 68.18%(15/22) of patients were considered responsive at 1-month and 3-month after treatment, respectively. Compared with baseline, the differences of tumor sizes, enhancement degree of target lesions and ADC min at 1-month and 3-month after treatment were statistically significant ( Z values: from -3.88 to -2.39, all P<0.05). Compared with the tumor size and enhancement degree, the AUCs of ADC min were the highest at 1-month (0.701) and 3-month (0.953) after treatment ( Z values: 0.40-2.29, all P<0.05). Conclusions:MRI plain scan, MRI enhancement and DWI are effective in the evaluation the efficacy of 90Y-SIRT for liver malignant tumors at 1-month and 3-month after treatment. ADC min is superior to tumor size and enhancement degree in diagnostic efficacy.

Objective:To investigate the practical value of pancreatic duct bind with supporting tube combined with single-needle suture for pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 65 patients with pancreatic head or periampullary tumors who underwent LPD at the First Affiliated Hospital of Kunming Medical University between January 2021 and June 2024 were retrospectively analysed. Among them, 31 were male and 34 were female, aged (57.7±13.3) years. The patients were divided into two groups based on the method of pancreaticojejunostomy: 22 patients who underwent pancreatic duct bind with supporting tube single-needle suture pancreaticojejunos-tomy were included in the study group, 43 patients who underwent traditional pancreatic duct-to-mucosa pancreaticojejunostomy were included in the control group. The clinical data of the patients, including gender, age, operation time, pancreaticojejunostomy time, and postoperative complications, etc. were recorded.Results:Compared with the control group, the pancreaticojejunostomy time [(25.3±2.4) min vs. (47.0±3.9) min] and operation time [(425.2±52.1) min vs. (453.7±30.8) min] of the study group were both shortened, and the differences were statistically significant (both P<0.05). There was no statistically significant difference in the postoperative complication rate between the study group and the control group [18.2% (4/22) vs. 34.9% (15/43), P=0.161]. The incidence of clinically relevant pancreatic fistula in the study group was lower than that in the control group [4.5% (1/22) vs. 30.2% (13/43)], and the difference was statistically significant ( P=0.024). Conclusion:Pancreatic duct bind with supporting tube combined with single-needle suture pancreaticojejunostomy is safe and effective in LPD. Compared with traditional pancreatic duct-to-mucosa pancreaticojejunostomy, pancreatic duct bind with supporting tube combined with single-needle suture pancreaticojejunostomy has advantages in terms of clinically relevant pancreatic fistula rate, operation time, and pancreaticojejunostomy time.