Liver fibrosis is caused by various factors such as viral infection， alcohol intake， and metabolism-related damage， leading to the replacement of normal tissue by fibrous scars. As a regulatory factor for cell proliferation， insulin-like growth factor 1 （IGF-1） participates in the regulation of cell cycle， the promotion of cell proliferation and differentiation， and the inhibition of cell apoptosis by binding to its receptor insulin-like growth factor-1 receptor （IGF-1R）. Studies have shown that the IGF-1/IGF-1R signaling pathway can regulate the process of liver fibrosis by affecting the senescence and apoptosis of hepatocytes， the activation and proliferation of hepatic stellate cells， and the dysfunction of endothelial cells. In addition， the IGF-1/IGF-1R signaling system can also regulate multiple mechanisms such as DNA damage repair， cell proliferation， lipid metabolism， cell senescence， and oxidative stress， thereby providing new strategies and potential targets for the prevention and treatment of liver fibrosis. This article summarizes the mechanism of action of IGF-1/IGF-1R and its signal transduction system in mediating liver fibrosis by regulating DNA damage repair in different cells， in order to provide a theoretical basis for the treatment of liver fibrosis.

Hemorrhoids are common anorectal diseases with complex pathogenesis, and there is still a lack of ideal experimental animal models for research on their prevention and treatment. In this paper, Chinese and English databases are searched with the keywords "hemorrhoids" and "animal model", and 36 relevant studies are finally included. The shortcomings of existing hemorrhoid animal models in integrating the clinical disease and syndrome characteristics of traditional Chinese and Western medicine are systematically analyzed, and the consistency of various models with clinical practice is evaluated. The studies are divided into four categories according to modeling methods: chemical modeling, physical modeling, biological modeling, and combined modeling. The clinical consistency of modeling is evaluated in combination with the diagnostic points of hemorrhoids in traditional Chinese and Western medicine. The results show that there are significant differences in the reproduction of clinical indicators by different modeling methods. According to clinical consistency, the models can be divided into three grades: high-consistency models are mainly based on combined modeling methods (such as induction by carrageenan combined with norepinephrine hydrochloride), which can more comprehensively simulate core pathological changes such as venous congestion and local inflammation; moderate-consistency models adopt single chemical or physical intervention (such as local inflammation induced by croton oil or vein ligation), which can only reproduce part of the pathological process; low-consistency models mostly adopt direct stimulation, with limited research value for pathological characteristics. Existing animal models have obvious advantages in replicating Western medical structural lesions of hemorrhoids, but they still have obvious defects in simulating the chronic disease course and stably reproducing the characteristics of traditional Chinese medicine syndromes, and a unified standard has not yet been formed for the traditional Chinese medicine evaluation system of models. In conclusion, it is still necessary to further explore the construction of high-quality integrated disease and syndrome animal models for hemorrhoids in traditional Chinese and Western medicine. Future research should integrate the theories of traditional Chinese and Western medicine, adopt multi-factor chronic modeling strategies, and establish a standardized comprehensive evaluation system covering macroscopic signs and microscopic indicators. This paper provides a reference for constructing standardized integrated disease and syndrome animal models of hemorrhoids that conform to the pathological changes of Western medicine and take into account the characteristics of traditional Chinese medicine syndromes, with the aim of providing more effective experimental tools for research on the pathogenesis of hemorrhoids and their integrated prevention and treatment with traditional Chinese and Western medicine.

Metabolic associated fatty liver disease （MAFLD） is a highly prevalent chronic liver disease worldwide， and the mechanism underlying its progression to metabolic associated steatohepatitis and liver fibrosis remain unclear. Endoplasmic reticulum stress （ERS） and ferroptosis （Fer） are deeply involved in the pathological evolution of MAFLD. This article systematically reviews the core regulatory mechanisms of ERS and its role in regulating lipid metabolism， inflammation response， and cell apoptosis in MAFLD. It also analyzes the core mechanism of Fer and discusses the predisposing factors for Fer in the pathological microenvironment of MAFLD， as well as the role of Fer in exacerbating hepatocyte death and activating the progression of liver fibrosis. This article proposes that the crosstalk between ERS and Fer is a key driver for the progression of MAFLD， which provides new references and ideas for the clinical intervention of MAFLD.

Objective To investigate the effects of artesunate(Art)on the proliferation,apoptosis,and autophagy of nephroblastoma cell line(SK-NEP-1).Methods SK-NEP-1 cells were intervened with different concentrations of Art(0,10,20,40 and 80 μmol/L),and MTT method was applied to calculate the cell proliferation inhibition rate to screen the optimal intervention concentration;SK-NEP-1 cells were separated into control group,Art group,3-MA group(Art+autophagy inhibitor,3-methyladenine),and Rapa group(Art+autophagy activator rapamycin).EdU and flow cytometry were applied to detect cell proliferation and apoptosis,respectively;MDC staining was applied to detect autophagy in cells;the level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescent probe;the expression of proliferating cell nuclear antigen(PCNA),anti apoptotic factor B cell lym-phomatoma-2(Bcl-2),Bcl-2 associated X protein(Bax),microtubule junction protein 1 light chain 3 Ⅱ/3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ),selective autophagy junction protein 1(p62),and benzyl chloride 1(Beclin-1)proteins in cells were detected by Western blot.Results Compared with 0 μmol/L Art,the proliferation inhibition rate of SK-NEP-1 cells was gradually increased after 10,20,40 and 80 μmol/L Art treatment(P＜0.05),and the IC50 value was 46.881 μmol/L,so 40 μmol/L Art was selected for follow-up experiments.Compared with the control group,the apoptosis rate,relative autophagy fluorescence intensity,ROS level,Bax,LC3 Ⅱ/LC3 Ⅰ,Beclin-1,PINK1,and Parkin protein expression levels of SK-NEP-1 cells in the Art group were obviously increased,the EdU positive cell rate,PCNA,Bcl-2,and P62 protein expression levels were obviously reduced(P＜0.05);The auto-phagy inhibitor 3-MA inhibited the promoting effect of Art on apoptosis and autophagy of nephroblastoma cells and inhibit proliferation(P＜0.05).Conclusions Art inhibits the proliferation of nephroblastoma cell line SK-NEP-1,and promotes autophagy and apoptosis.

Hepatocellular carcinoma （HCC）， as the sixth most common malignant tumor worldwide， poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota （GM） homeostasis in the development and progression of HCC， in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis， intestinal leakage， microbial-associated molecular pattern， bacterial translocation， and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape， thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC， deeply analyzes the mechanism of action of GM in the development and progression of HCC， investigates the role of bile acid-related metabolites， short-chain fatty acid-related metabolites， and other metabolites in HCC， and explores the strategies for targeting GM in the treatment of HCC， including probiotics， prebiotics， antibiotics， Toll-like receptor 4 antagonists， and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC， which provides a direction for developing new diagnosis and treatment strategies.

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

OBJECTIVES: A stable, reliable, and easily implementable clinical diagnostic method for marginal velopharyngeal insufficiency (MVPI) was established on the basis of the subjective hearing judgement of hypernasality and objective examination of velopharyngeal closure to address the lack of unified diagnostic criteria for MVPI. METHODS: Nasopharyngeal fiberscopy and speech assessment results were collected from postoperative patients with cleft palate. These results were used to analyze the differences in the distribution of nasal resonance in patients with different velopharyngeal closure ratios and the correlation between velopharyngeal closure ratios and nasal resonance status. Mild-to-moderate hypernasality with its corresponding elopharyngeal closure ratio was employed to establish the diagnostic criteria of MVPI. The reproducibility of the criteria and whether the patients with MVPI diagnosed by using the criteria exhibited significantly different speech characteristics compared with other patients were verified. RESULTS: A strong correlation was found between velopharyngeal closure ratios and nasal resonance (P<0.001). Mild-to-moderate hypernasality mainly corresponded to velopharyngeal closure ratios ranging from 90% to 99%, and the combination of the two characteristics as the diagnostic criteria for MVPI demonstrated good consistency (Kappa value=0.789, P<0.001). Moreover, under the diagnostic criteria, significant differences in nasal resonance (P<0.001), nasal emission (P=0.007), and misarticulation (P<0.001) were found between patients with velopharyngeal insufficiency and those with MVPI. CONCLUSIONS Combining the subjective hearing judgement of mild-to-moderate hypernasality with velopharyngeal closure ratios over 90% under nasopharyngeal fiberscopy provides a reliable and effective clinical method for diagnosing MVPI.
Humans ; Velopharyngeal Insufficiency/physiopathology* ; Reproducibility of Results ; Cleft Palate/surgery* ; Male ; Female ; Child

Objective:To explore the risk factors of pulmonary infection in patients with non-small cell lung cancer (NSCLC) after thoracoscopic lobectomy and evaluate their predictive value.Methods:A retrospective analysis was conducted on the clinical data of 152 NSCLC patients who underwent thoracoscopic lobectomy at the Central Hospital of Tongchuan Mining Bureau in Shaanxi Province from May 2021 to May 2024. Among them, 45 cases were diagnosed with pulmonary infection by postoperative lung CT examination (postoperative infection group), while the remaining 107 cases did not develop pulmonary infection (non infection group). The levels of serum procalcitonin, serum amyloid A (SAA), and soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) between two groups of patients before and after surgery were compared, and conduct a multivariate logistic regression analysis on the risk factors of pulmonary infection in NSCLC patients undergoing thoracoscopic lobectomy was conducted to evaluate the predictive value of each indicator for pulmonary infection in NSCLC patients after thoracoscopic lobectomy. The normally distributed quantitative data was represented by xˉ± s. Independent sample t-test was used for comparison between two groups, and paired t-test was used for comparison before and after treatment; The count data was presented as an example (%), and the comparison between groups was conducted using the chi square test. The risk factors for postoperative pulmonary infection in NSCLC patients were analyzed using multiple logistic regression analysis. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of each indicator for pulmonary infection after thoracoscopic lobectomy. Results:No difference were found in the levels of serum procalcitonin, SAA, and sTREM-1 between two groups of patients before surgery(all P>0.05); 24 hours after surgery, the levels of serum procalcitonin, SAA, and sTREM-1 in both groups of patients were higher than before surgery [Postoperative infection group: (1.16±0.29) μg/L compared to (0.34±0.09) μg/L, (10.2±1.8) mg/L compared to (7.3±0.9) mg/L, (20.3±4.8) ng/L compared to (8.0±1.2) ng/L, t-values were 20.70, 9.70, and 16.89, respectively, all P<0.001; The uninfected group (0.84±0.14) μg/L compared to (0.32±0.08) μg/L, (8.2±1.1) mg/L compared to (7.4±0.9) mg/L, and (13.5±6.3) ng/L compared to (8.1±1.2) ng/L, with t-values of 33.36, 6.13, and 8.73, respectively, all P<0.001, and the infected group was higher than the uninfected group ( t-values of 9.18, 8.32, and 6.52, respectively, all P<0.001). The results of multivariate logistic regression analysis showed that serum procalcitonin, SAA, and sTREM-1 levels at 24 hours after surgery were all risk factors for pulmonary infection in NSCLC patients undergoing thoracoscopic lobectomy (odds ratios of 2.40, 1.61, 1.60, 95% confidence intervals: 1.14~5.04, 1.09~2.38, 1.13~2.26, P values of 0.021, 0.017, 0.009, respectively). The area under curve(AUC) of serum procalcitonin, SAA, and sTREM-1 predicting pulmonary infection after thoracoscopic lobectomy in NSCLC patients 24 hours after surgery were 0.84, 0.74, and 0.79, respectively, with cutoff values of 1.03 μg/L, 9.74 mg/L, and 16.85 ng/L, respectively. Conclusions:The levels of serum procalcitonin, SAA, and sTREM-1 24 hours after surgery are all risk factors for pulmonary infection in NSCLC patients undergoing thoracoscopic lobectomy, and all three had a high predictive value for postoperative pulmonary infection.

Objective:To establish and assess the quality control and improvement system for metabolic and bariatric surgery in Beijing.Methods:Based on relevant documents from the National Health Commission and the Beijing Municipal Health Commission,and referencing the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) by the American Society for Metabolic and Bariatric Surgery,a quality control system was developed under the Beijing Quality Control and Improvement Center of Metabolic and Bariatric Surgery. The system incorporated on-site evaluations,data registration,and specialized training. From May to December 2023,on-site assessments were conducted at 21 hospitals in Beijing performing bariatric surgery,evaluating personnel qualifications,infrastructure,clinical workflows,and postoperative follow-up. A quality control database was created to collect real-time surgical data,and training was provided for data entry and professional skills. Assessment results were classified as excellent,qualified,or needing improvement,with rectification suggestions offered and follow-up visits conducted to track progress.Results:All 21 hospitals achieved a 100% compliance rate for surgical indications, 16 (76.2%) met standardized surgical operation criteria,and 14 (66.7%) had standardized postoperative management. However,only 5 (23.8%) achieved a 12-month postoperative follow-up rate of ≥60%,and 4 (19.1%) had established specialized databases. Key challenges included insufficient specialized staffing (19.1%), lack of multidisciplinary collaboration (47.6%), inadequate equipment (57.1%), and low follow-up rates (57.1%). The database collected data from over 2 000 patients across 111 fields. After rectification, specialized database coverage rose to 61.9% (13 hospitals). Multi-level training programs developed backbone physicians and specialized nurses,significantly addressing the shortage of specialized personnel.Conclusion:The quality control system established in this study,through the integration of on-site evaluation,data registration,and specialized training,effectively enhances the standardization of surgical practices and data management capabilities.

To address the limitations of convolutional neural networks in global context modeling and the complexity of secondary computation in Transformer's self attention mechanism,an improved multi-direction-MambaUNet(MD-MambaUNet)based on MambaUNet is proposed.This network integrates with multi directional selective scanning module to extract spatial features from multiple directions of CT images,significantly improving the global context modeling capability.By introducing partial convolution and constructing a lightweight hybrid convolution module,the model's parameter count is significantly reduced,enabling the processing of large-scale medical image data at lower computational costs while maintaining high-level performance.Experiments are conducted on the LiTS2017 and 3DIRCADB public datasets.Compared with MambaUNet on the LiTS2017 dataset,MD-MambaUNet improves the Dice similarity coefficient for liver and tumor segmentation by 3.32%and 4.77%,reaching 95.36%and 76.93%,and increases intersection over union by 4.18%and 4.92%,reaching 91.43%and 69.74%,respectively.Compared with MambaUNet on the 3DIRCADB dataset,MD-MambaUNet improves the Dice similarity coefficient for liver and tumor segmentation by 2.08%and 2.21%,reaching 93.81%and 64.68%,and increases intersection over union by 0.79%and 3.13%,reaching 87.23%and 57.65%,respectively.Meanwhile,the parameter count is 13.71 M less than MambaUNet,making it possible for the model to be deployed in clinical scenarios.