ObjectiveTo investigate the effect of SU056， an azo-podophyllotoxin derivative， on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group， model group （CCl₄+normal saline）， and treatment group （CCl₄+SU056）， with 4 mice in each group. Mice were given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and during the middle stage of modeling， the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury， collagen deposition， and liver function were assessed based on HE staining， Masson staining， Sirius Red staining， the content of hydroxyproline in liver tissue， and the serum levels of alanine aminotransferase and aspartate aminotransferase， and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α （α-SMA）， collagen type Ⅰ， and Y-box binding protein 1 （YB1）. The human hepatic stellate cell （HSC） line LX-2 and primary mouse HSC were used， and CCK-8 assay was used to measure cell proliferation； Transwell assay was used to observe cell migration； quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ， collagen type Ⅲ， YB1， phosphorylated mammalian target of rapamycin （mTOR）， and phosphorylated S6K， so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the mouse model of liver fibrosis induced by CCl₄， compared with the model group， the treatment group had significant alleviation of inflammatory cell infiltration， collagen deposition， and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue （all P<0.01）. Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA， collagen type I， and YB1 in liver tissue （all P<0.01）. In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells （P<0.01）， the migration of LX-2 cells （P<0.05）， and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ （all P<0.05） in a dose-dependent manner， and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1， phosphorylated mTOR， and phosphorylated S6K in LX-2 cells， and treatment with SU056 （10 and 20 µmol/L） could downregulate the protein expression levels of collagen type I， YB1， phosphorylated mTOR， and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice （P<0.01）. ConclusionSU056 can effectively inhibit HSC activation， proliferation， migration， and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis， by disrupting the YB1/mTOR positive feedback signaling axis.

BackgroundObstructive sleep apnea （OSA） represents a prevalent sleep disordered breathing condition characterized by complex pathophysiology. The arousal threshold （ArTH）， a core non-anatomical contributor to OSA pathogenesis， is intimately tied to the disease severity and clinical phenotypes. To date， research regarding factors associated with ArTH has yielded inconsistent findings， and ArTH profiles and disparities across populations with different genetic backgrounds are not fully elucidated. ObjectiveTo explore the differences of ArTH in OSA patients with different genetic backgrounds and analyze the key factors affecting ArTH， thereby providing evidence for understanding OSA pathophysiology and formulating targeted treatment regimens. MethodsA total of 285 patients who met the diagnostic criteria for OSA， as defined by the Multidisciplinary Diagnosis and Treatment Guidelines for Adult Obstructive Sleep Apnea， were retrospectively enrolled in this study. All participants underwent overnight polysomnography （PSG） at the Sleep Medicine Center of Inner Mongolia Mental Health Center from December 2022 to May 2024. Based on the study design， the cohort was stratified into two distinct genetic background subgroups （group A and group B）. Demographic and clinical characteristics， the Epworth Sleepiness Scale （ESS） score， and overnight PSG data were collected. The apnea hypopnea index （AHI）， the lowest pulse oxygen saturation （LSpO₂）， and fraction of hypopneas （F_Hypopneas） were utilized as surrogate indicators to estimate ArTH in OSA patients. The influencing factors of low ArTH were tested by binary Logistic regression analysis. ResultsAmong the 285 OSA patients， there were 227 cases （79.65%） in group A and 58 cases （20.35%） in group B. Comparisons between the two genetic background subgroups revealed no statistically significant differences in the proportion of low ArTH， ESS score， PSG parameters， and the three markers for low ArTH （AHI<30 events/h， LSpO₂>82.5%， F_Hypopneas>58.3%） （P>0.05）. Binary Logistic regression analysis identified sex （OR=2.421， 95% CI： 1.070–5.478）， BMI （OR=0.847， 95% CI： 0.770–0.932）， N1 sleep duration （OR=0.974， 95% CI： 0.963–0.985）， and hypertension （OR=0.348， 95% CI： 0.143–0.848） as independent factors associated with low ArTH in the total cohort. Stratified analysis by genetic backgrounds revealed that sex（OR=3.799， 95% CI： 1.389–10.392）， BMI（OR=0.819， 95% CI：0.723–0.929）， and N1 sleep duration（OR=0.973， 95% CI： 0.961–0.986） were independent factors of low ArTH in group A. In contrast， only N1 sleep duration （OR=0.951， 95% CI： 0.911–0.993） remained a significant factor in group B. ConclusionArthur may have conservative characteristics in patients with OSA with different genetic backgrounds， but the pathophysiological mechanism of OSA may have population heterogeneity. ［Funded by Inner Mongolia Autonomous Region Natural Science Fundation Project （number， 2024QN08050）； Intra-institutional Scientific Research Project of Inner Mongolia Mental Health Center （number， 2022QNWN0010）］

Tangye Jingfa Tu is an important content in the ancient book Fuxingjue from Dunhuang， implying the fundamental principles of formula compatibility in traditional Chinese medicine （TCM）. Our research group has delved into nearly 200 formulas （both classical and contemporary formulas） recorded in the Fangjixue under the theoretical framework of the deficiency or excess syndrome of five Zang-organs together with the reinforcing and reducing effects of Chinese medicinal materials of five flavors. We have initially elucidated the essential principles of the correspondence between formulas and syndromes， revealing the deep-level logic of medicinal material selection and compatibility， thus enriching the understanding about the core characteristics and essence of the diseases and syndromes targeted by formulas. The lunar year of 2024 is Jia Chen year. The formula recorded in Sanyin Jiyi Bingzheng Fanglun for treating the epidemic diseases characterized by excessive earth， prevalent dampness and wetness， and invasion of pathogenic factors into the kidney water in Jia Chen year is Fuzi Shanzhuyutang. Therefore， elucidating the compatibility principle of Fuzi Shanzhuyutang is of great significance for clinical prescription and medication modification in Jia Chen year. According to the Tangye Jingfa Tu theory on the deficiency or excess of syndrome of five Zang-organs and the reinforcing and reducing effects of Chinese medicinal materials of five flavors， this article dissects Fuzi Shanzhuyutang regarding the etiology and pathogenesis of the main indications， as well as the five-element properties and efficacy characteristics of Chinese medicinal materials constituting this formula. It explains the compatibility principles of Fuzi Shanzhuyutang and puts forward suggestions for modifying the formula to address different indications， providing a reference for guiding clinical syndrome differentiation and treatment.

Tangye Jingfa Tu is an important content in the ancient book Fuxingjue from Dunhuang， implying the fundamental principles of formula compatibility in traditional Chinese medicine （TCM）. Our research group has delved into nearly 200 formulas （both classical and contemporary formulas） recorded in the Fangjixue under the theoretical framework of the deficiency or excess syndrome of five Zang-organs together with the reinforcing and reducing effects of Chinese medicinal materials of five flavors. We have initially elucidated the essential principles of the correspondence between formulas and syndromes， revealing the deep-level logic of medicinal material selection and compatibility， thus enriching the understanding about the core characteristics and essence of the diseases and syndromes targeted by formulas. The lunar year of 2024 is Jia Chen year. The formula recorded in Sanyin Jiyi Bingzheng Fanglun for treating the epidemic diseases characterized by excessive earth， prevalent dampness and wetness， and invasion of pathogenic factors into the kidney water in Jia Chen year is Fuzi Shanzhuyutang. Therefore， elucidating the compatibility principle of Fuzi Shanzhuyutang is of great significance for clinical prescription and medication modification in Jia Chen year. According to the Tangye Jingfa Tu theory on the deficiency or excess of syndrome of five Zang-organs and the reinforcing and reducing effects of Chinese medicinal materials of five flavors， this article dissects Fuzi Shanzhuyutang regarding the etiology and pathogenesis of the main indications， as well as the five-element properties and efficacy characteristics of Chinese medicinal materials constituting this formula. It explains the compatibility principles of Fuzi Shanzhuyutang and puts forward suggestions for modifying the formula to address different indications， providing a reference for guiding clinical syndrome differentiation and treatment.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Radiogenomics, an extension of radiomics, explores the relationship between imaging features and underlying gene expression patterns. This field is instrumental in providing reliable imaging surrogates, thus potentially representing an alternative to genetic testing. The rapidly growing area of radiogenomics that utilizes ultrasound (US) imaging seeks to elucidate the connections between US image characteristics and genomic data. In this review, the authors outline the radiogenomics workflow and summarize the applications of US-based radiogenomics. These include the prediction of gene variations, molecular subtypes, and other biological characteristics, as well as the exploration of the relationships between US phenotypes and cancer gene profiles. Although the field faces various challenges, US-based radiogenomics offers promising prospects and avenues for future research.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

OBJECTIVES: Prolonged invasive mechanical ventilation is associated with increased risks of severe complications such as retinopathy of prematurity and bronchopulmonary dysplasia. Although neonatal intensive care unit (NICU) follow the principle of early extubation, extubation failure rates remain high, and reintubation may further increase the risk of adverse outcomes. This study aims to identify risk factors and short-term prognosis associated with first extubation failure in neonates, to provide evidence for effective clinical intervention strategies. METHODS: Clinical data of neonates who received invasive ventilation in the NICU of Children's Hospital of Nanjing Medical University from January 1, 2019, to December 31, 2021, were retrospectively collected. Neonates were divided into a successful extubation group and a failed extubation group based on whether reintubation occurred within 72 hours after the first extubation. Risk factors and short-term outcomes related to extubation failure were analyzed. RESULTS: A total of 337 infants were included, with 218 males (64.69%). Initial extubation failed in 34 (10.09%) infants. Compared with the successful extubation group, the failed extubation group had significantly lower gestational age [(31.37±5.14) weeks vs (34.44±4.07) weeks], age [2.5 (1.00, 8.25) h vs 5 (1.00, 22.00) h], birth weight [(1 818.97±1128.80) g vs (2 432.18±928.94) g], 1-minute Apgar score (6.91±1.90 vs 7.68±2.03), and the proportion of using mask oxygenation after extubation (21% vs 46%) (all P<0.05). Conversely, compared with the successful extubation group, the failed extubation group had significantly higher rates of vaginal delivery (59% vs 32%), caffeine use during mechanical ventilation (71% vs 38%), dexamethasone use at extubation (44% vs 17%), the highest positive end-expiratory pressure level within 72 hours post-extubation [6(5.00, 6.00) cmH₂O vs 5 (0.00, 6.00) cmH₂O] (1 cmH₂O=0.098 kPa), the highest FiO₂ within 72 hours post-extubation [(34.35±5.95)% vs (30.22±3.58)%], and duration of noninvasive intermittent positive pressure ventilation after extubation [0.5 (0.00, 42.00) hours vs 0 (0, 0) hours] (all P<0.05). Multivariate analysis identified gestational age <28 weeks (OR=5.570, 95% CI 1.866 to 16.430), age at NICU admission (OR=0.959, 95% CI 0.918 to 0.989), and a maximum FiO₂≥35% within 72 hours post-extubation (OR=4.541, 95% CI 1.849 to 10.980) as independent risk factors for extubation failure (all P<0.05). Additionally, the failed extubation group exhibited significantly higher incidences of necrotizing enterocolitis grade II or above, moderate-to-severe bronchopulmonary dysplasia, severe bronchopulmonary dysplasia, retinopathy of prematurity, treatment abandonment due to poor prognosis, and discharge on home oxygen therapy (all P<0.05). Total hospital length of stay and total hospitalization costs were also significantly increased in the failed extubation group (all P<0.05). CONCLUSIONS Gestational age <28 weeks, younger age at NICU admission, and FiO₂≥35% after extubation are high-risk factors for first extubation failure in neonates. Extubation failure markedly increases the risk of adverse clinical outcomes.
Humans ; Infant, Newborn ; Male ; Female ; Airway Extubation/adverse effects* ; Risk Factors ; Retrospective Studies ; Respiration, Artificial/methods* ; Intensive Care Units, Neonatal ; Prognosis ; Gestational Age ; Bronchopulmonary Dysplasia ; Infant, Premature ; Treatment Failure ; Intubation, Intratracheal

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.