Objective To explore the efficacy of endoscopic therapy for esophageal and gastric variceal bleeding(EGVB),investigate the risk factors for rebleeding within 1 year,and establish a predictive model accordingly.Methods A retrospective study was conducted using the clinical and follow-up data of 120 EGVB patients who underwent endoscopy at our hospital between January 2021 and December 2022.The efficacy of endoscopic therapy was analyzed,and the patients were divided into a bleeding group and a non-bleeding group based on whether rebleeding occurred within 1 year after treatment.The factors influencing rebleeding within 1 year after treatment were analyzed,and a predictive model was established using logistic regression analysis.The model's goodness of fit was evaluated using the Hosmer-Lemeshow test,and its clinical value was analyzed using the receiver operating characteristic(ROC)curve.Results The hemostasis success rate within 72 hours after endoscopic therapy was 100％in all 120 patients.Four weeks after endoscopic treatment,endoscopic reexamination showed that the complete and partial disappearance rate of varices was 75.83％(91/120),with rebleeding occurring in 10 cases(8.33％).There were 34 cases(28.33％)of cumulative rebleeding at 6 months and 63 cases(52.50％)at 1 year after endoscopic therapy.Nine patients(7.50％)died within 1 year after endoscopic therapy,all of whom were rebleeding cases.A total of 63 patients with rebleeding were included in the bleeding group,and 57 patients without rebleeding were included in the non-bleeding group.Serum sodium＜135 mmol/L(odds ratio[OR]=3.837,95％confidence interval[CI]:1.095-13.445),Child-Pugh grade C(OR=3.835,95％CI:1.137-12.935),esophageal varices degree G3(OR=5.113,95％CI:1.565-16.707),and main portal vein diameter＞12 mm(OR=5.964,95％CI:2.295-15.497)were identified as risk factors of rebleeding within 1 year after endoscopic therapy in EGVB patients(P＜0.05).The risk prediction model for rebleeding within 1 year after endoscopic therapy in EGVB patients was shown as P=1/{1+e[-(-3.815+1.345×serum sodium+1.344×Child-Pugh grade+1.786×main portal vein diameter+1.632×esophageal varices degree)]}.The Hosmer-Lemeshow x2 was 3.158(P=0.856).The area under the curve(AUC)for predicting rebleeding within 1 year after endoscopic therapy in EGVB patients was 0.815,indicating good predictive performance.Clinical validation showed that the model had an accuracy of 82.30％,with sensitivity and specificity being 81.03％and 83.63％,respectively.Conclusion Endoscopic therapy for EGVB achieves a high rate of acute bleeding control,but patients remain at risk of rebleeding.Rebleeding is associated with serum sodium＜135 mmol/L,Child-Pugh grade C,main portal vein diameter＞12 mm,and esophageal varices degree G3.The logistic regression model can effectively predict the probability of rebleeding within 1 year after endoscopic therapy.

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.

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 explore the molecular mechanism of miR-4508 regulating the inflammatory response of human bronchial epithelial cells induced by representative chrysotile asbestos.Methods:The chrysotile asbestos was ground into ultrafine dust using a horizontal planetary instrument, and human bronchial epithelium (16HBE) cells were taken as the object of infection. Cell survival rate was detected by cell counting kit-8 method, cytotoxicity was detected by lactate dehydrogenase (LDH) kit. The released of inflammatory factor IL-6 was detected by electrochemical luminescence. The released inflammatory factor IL-8 was detected by enzyme-linked immunosorbent assay. The expression level of miR-4508 was screened and verified by reverse transcription-quantitative real-time polymerase chain reaction. After 16HBE cells were treated with AKT inhibitor MK2206, the phosphorylation levels of AKT and PTEN were detected by western blot. The expression levels of AKT and PTEN and the contents of IL-6 and IL-8 were detected in miR-4508 overexpression and interference experiments.Results:With the increase of chrysotile asbestos exposure concentration, the cell survival rate decreased in a concentration-dependent manner, and the LDH content gradually increased. The secretion of IL-6 and IL-8 in chrysotile 25, 50 and 75 μg/ml groups were (325.92±8.61) pg/ml, (331.51±4.96) pg/ml, (378.74±13.77) pg/ml, and (94.95±3.11) pg/ml, (357.60±1.80) pg/ml, (537.19±3.11) pg/ml, respectively, while the group with 0 μg/ml chrysotile was (95.85±1.20) pg/ml and (7.81±0.00) pg/ml ( P＜0.05). In addition, chrysotile asbestos exposure to 16HBE could induce the high expression of miR-4508 . After pretreatment with MK2206, the phosphorylation levels of AKT and PTEN were decreased, the contents of IL-6 and IL-8 were significantly decreased, and the expression level of miR-4508 was significantly reduced. Overexpression of miR-4508 significantly increased the expressions of AKT and PTEN, and the contents of IL-6 and IL-8 ( P＜0.01). After interfering with miR-4508, the expressions of AKT and PTEN were significantly decreased, and the contents of IL-6 and IL-8 were significantly decreased ( P＜0.01). Conclusions:Chrysotile asbestos can induce the inflammatory response of 16HBE cells and up-regulate the expression level of miR-4508. The up-regulation of miR-4508 promotes the 16HBE inflammatory response induced by chrysotile asbestos through the PI3K/AKT pathway.

Objective To investigate the effects of Zhuang medicinal thread moxibustion on apoptosis of interstitial cells of Cajal(ICC)in gastric smooth muscle of diabetic gastroparesis(DGP)rats via regulation of the p38MAPK signaling pathway.Methods Totally 60 rats were randomly divided into a blank group(10 rats)and a modeling group(50 rats).DGP models were established in the modeling group via intraperitoneal injection of streptozotocin.50 successfully modeled rats were further randomized into model group,Western medication group,prevention+treatment group,prevention group and treatment group,with 10 rats in each group.The Western medication group was administered mosapride citrate by gavage for 3 weeks starting at week 10;the prevention+treatment group underwent Zhuang medicinal thread moxibustion("Zhongwan",bilateral"Neiguan"and"Zusanli")intervention for 6 weeks starting at week 7;the prevention group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 7;and the treatment group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 10,3 cones per point,once a day;the blank group and model group received handling only.The random blood glucose and body mass of rats were detected,and the gastric emptying rate and intestinal propulsion rate were calculated.HE staining was used to observe the morphology of gastric smooth muscle tissue,TUNEL staining was used to detect the apoptosis of gastric smooth muscle tissue,ELISA was used to detect the contents of Caspase-3,TNF-α,IL-1β and IL-6 in gastric smooth muscle tissue,immunohistochemistry was used to detect the positive expressions of Cx43 and c-kit in gastric smooth muscle tissue,Western blot was used to detect the expressions of p38MAPK,p-p38MAPK,BAX and Bcl-2 protein in gastric smooth muscle tissue.Results Compared with the blank group,the random blood glucose significantly increased in the model group(P<0.01),and the body mass,gastric emptying rate and small intestinal propulsion rate significantly decreased(P<0.01),the blood vessels of gastric tissue were not clear,the surface was not smooth,the mucosal folds were less,the arrangement of gastric smooth muscle cells was disordered,the nuclear membrane was not clear,and there were vacuole like changes between cells,the apoptosis rate significantly increased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the protein expressions of p38MAPK,p-p38MAPK and BAX in gastric smooth muscle tissue significantly increased(P<0.01),and the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio significantly decreased(P<0.01).Compared with the model group,the random blood glucose of rats in each intervention group decreased,and the body mass,gastric emptying rate and intestinal propulsion rate increased(P<0.01),the blood vessels of gastric tissue were clear,the inner surface of stomach was smooth,the mucosal folds were not rich,no ulcer was found,the shape of gastric smooth muscle cells was complete,the nuclear membrane was clear,and the arrangement of muscle cells was regular,the apoptosis rate significantly decreased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the expressions of p38MAPK,p-p38MAPK,BAX protein in gastric smooth muscle tissue decreased(P<0.05,P<0.01),the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio increased(P<0.05,P<0.01).The overall effect of the prevention+treatment group was better than that of the Western medication group,prevention group and treatment group(P<0.05,P<0.01).Conclusion Zhuang medicinal thread moxibustion may reduce gastric inflammation and ICC apoptosis in DGP rats by inhibiting p38MAPK signaling pathway,so as to improve DGP gastric motility disorder,and the effect of early intervention is more significant.

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.

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 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.

Objective:To explore the value of blood lactic acid (BLA), procalcitonin (PCT), and total bilirubin (TBil) in the diagnosis and prognosis evaluation of patients with trauma complicated with sepsis.Methods:The clinical data of 151 patients with severe trauma admitted to the Department of Emergency Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2019 to August 2023 were analyzed retrospectively. The patients were divided into the sepsis group (72 cases) and non-sepsis group (79 cases) according to the diagnosis. They were further divided into the death group (37 cases) and non-death group (114 cases) based on clinical outcomes. Clinical data were compared between groups. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the above indicators, and Spearman correlation analysis was applied to evaluate the correlation between the indicators.Results:The levels of BLA, PCT, TBil, and Sequential Organ Failure Assessment (SOFA) score in the sepsis group were higher than those in the non-sepsis group (all P<0.05). The mortality rate of the sepsis group was significantly higher than that of the non-sepsis group, with a statistically significant difference [26/72(36.11%) vs 11/79(13.92%), χ 2=10.024, P=0.002]. The levels of BLA, PCT, TBil, and SOFA score in the death group were higher than those in the non-death group (all P<0.05). ROC curve analysis showed that the areas under the curve (AUC) of BLA, PCT, TBil, and their combination for diagnosing sepsis were 0.745, 0.826, 0.753, and 0.889 respectively; the sensitivity and specificity of the combined diagnosis of sepsis were 87.5% and 72.2%. The AUCs of BLA, PCT, TBil, and their combination for predicting the prognosis of sepsis were 0.644, 0.697, 0.614, and 0.713 respectively; the sensitivity and specificity of the combined prediction of sepsis prognosis were 64.9% and 71.1%. Among the 151 patients, the levels of BLA, PCT, TBil were positively correlated with SOFA score, with statistically significant differences ( r=0.3871, 0.4399, 0.4851, all P<0.001). Conclusions:BLA, PCT, and TBil levels have certain value in the early diagnosis and prognosis evaluation of patients with sepsis. The combined evaluation has the best efficacy and high guiding value in clinical practice.

Objective: To prospectively evaluate the feasibility, accuracy, and safety of multiparameter MRI-guided percutaneous biopsy using a 1T open MRI scanner for evaluating suspicious centrally located lung lesions with associated post-obstructive atelectasis. Materials and Methods: In this single-center study, MRI-guided percutaneous coaxial cutting biopsy was performed for 107 suspicious central lung lesions with associated post-obstructive atelectasis in 107 patients between July 2015 and December 2020. A fast T2-weighted imaging (T2WI)-turbo spin echo (TSE) sequence and an enhanced fast T1-weighted imaging (T1WI)-TSE sequence were used to identify, localize, and biopsy lung lesions, and diffusion-weighted imaging (DWI) was used as a supplementary sequence for identifying the lesion location. The final diagnosis was confirmed by surgical histopathology or clinical follow-up for a minimum of 24 months. The sensitivity, specificity, and accuracy for diagnosing lung malignancies were calculated, and the complications were recorded for each case. Results: Using multiparameter MRI, central lung lesions could be clearly distinguished from post-obstructive atelectasis in 96 patients (89.7%). The sensitivity, specificity, and accuracy of MRI-guided percutaneous biopsy for diagnosing lung malignancy was 97.0% (98/101), 100% (6/6), and 97.2% (104/107), respectively. Self-limited hemoptysis occurred in three patients. Pneumothorax occurred in five patients, of which none required pleural drainage. No serious procedure-related complications were observed. Conclusion As a technology that does not involve ionizing radiation, multiparameter MRI-guided percutaneous coaxial cutting biopsy is a safe and accurate diagnostic technique for evaluating centrally located lung lesions associated with post-obstructive atelectasis.