Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Objective To investigate the effects and mechanisms of silica dust on the apoptosis of alveolar epithelial cell (AEC) through in vitro and animal experiments. Methods i) In vitro experiment. A549 cells were stimulated with 100 mg/L silica suspension for 0, 12, 24 and 48 hours. The cell apoptosis rate was detected by flow cytometry. ii) Animal experiment. Specific pathogen-free male C57BL/6 mice were randomly divided into control, 14-day, 28-day, and 56-day groups, with five mice in each group. The mice in the control group were sacrificed at 56 days after being treated with 40.0 μL 0.9% sodium chloride solution, and the mice in the last three groups were sacrificed at 14, 28 and 56 days after being treated with 40.0 μL silica suspension with a mass concentration of 125 g/L via tracheal exposure method. The lung tissues of mice were collected to measure lung organ coefficients. Masson staining was used to detect the degree of pulmonary fibrosis, and Ashcroft scores were evaluated. The apoptosis of AEC in mice was observed by TUNEL immunofluorescence assay. iii) The mRNA relative expression of apoptosis-related genes in A549 cells and mouse lung tissue was detected using reverse transcription and real-time fluorescence quantitative polymerase chain reaction. Results i) In vitro experiment. The apoptosis rate of A549 cells increased with longer silica exposure (all P<0.05). The relative expression of B cell lymphoma-2 (BCL-2) mRNA in A549 cells in 24 h group and 48 h group decreased (both P<0.05), and the relative expression of BCL-2 associated X protein (BAX) mRNA increased (both P<0.05), compared with 0 h group. The mRNA relative expression of caspase (CASP) -3 and CASP-9 in A549 cells increased with longer silica exposure (all P<0.05). ii) Animal experiment. The lung organ coefficients and Ashcroft score in mice progressively increased (all P<0.05), the degree of pulmonary fibrosis was gradually aggravated, and TUNEL positive cells in lung tissue were gradually increased, while Bax, Casp-3 and Casp-9 mRNA relative expression increased with longer silica exposure (all P<0.05). Conclusion Silica dust may cause pulmonary fibrosis by inducing apoptosis of AEC, with a time-dependent effect. The mechanism may be related to the effect of silica dust on mitochondrial apoptosis through Bcl-2/Bax/Caspase-3 signaling pathway.

Objective To explore the mechanism of the gut-lung axis in paraquat-induced lung injury in mice, with a focus on analyzing the changes in intestinal gene expression and their potential roles. Methods Specific pathogen-free C57BL/6 wild-type mice were randomly divided into control, low-dose, and high-dose groups, with 10 mice in each group. Mice in the three groups received a single intragastric administration of paraquat solution at doses of 0, 25, or 50 mg/kg body weight. The mice were euthanized on day 21. Lung histopathological changes were assessed, and the differentially expressed genes (DEGs) in the intestinal tissues of mice in these two groups were analyzed through transcriptomics. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore potential mechanisms of the gut-lung axis in paraquat-induced lung injury and fibrosis. Results Paraquat exposure induced dose-dependent pulmonary injury and fibrosis in the mice. The Ashcroft score of lung tissue was higher in the mice of low-dose group than that in the control group (P<0.05). Both the lung organ coefficient and Ashcroft score of lung tissues in the mice of high-dose group were higher than those in the control group and the low-dose group (all P<0.05). The result of transcriptomic analysis showed 146 DEGs, including 91 upregulated and 55 downregulated genes, in intestinal tissues of mice in the low-dose group, and 57 DEGs, including 47 upregulated and 10 downregulated genes in the high-dose group, compared with the control group. Notably, 19 DEGs were commonly altered in both low- and high-dose groups. The result of GO enrichment analysis showed that the DEGs were primarily involved in biological processes including "immune response", "oxidative stress" and "cell differentiation". The result of KEGG enrichment analyses showed that DEGs were primarily involved in key processes including "oxidative stress response path way", "immune response path way" and "digestion and absorption path way". Conclusion Paraquat exposure alters intestinal gene expression, particularly in genes in biological processes related to immune responses and oxidative stress. These changes may mediate inflammatory signaling via the gut-lung axis and contribute to the development of paraquat-induced pulmonary fibrosis.

[摘 要] 目的：探究包被蛋白复合体β1亚基（COPB1）在食管鳞状细胞癌（ESCC）中的表达，及其对ESCC细胞恶性生物学行为的影响、作用机制及临床意义。方法：采用2014～2018年间在河北医科大学第四医院生物样本库中82例ESCC组织及癌旁组织，常规培养正常食管鳞状上皮细胞HEEC和食管癌细胞KYSE-150、KYSE-170、Eca109、TE1、KYSE-30、KYSE-450，用转染试剂将pcDNA3.1-vector（空载体）、pcDNA3.1-COPB1载体，si-NC和si-COPB1转染至KYSE-150、TE1细胞中，记为NC、COPB1-OE、si-NC和si-COPB1组。用数据库数据分析COPB1 mRNA在泛癌组织中的表达及其表达与免疫细胞浸润的关系，qPCR法检测ESCC组织和细胞中COPB1、PIK3CB、CD68、CD163、CD206、ARG1、IL-10 mRNA水平表达情况，WB法检测ESCC组织和各组细胞中的COPB1、PI3K、CD68、CD163、CD206、p-AKT蛋白表达，克隆形成实验和MTS实验检测各组细胞的增殖能力，划痕愈合实验和Transwell实验检测各组细胞的迁移和侵袭能力，免疫组织化学染色（IHC）法检测ESCC组织中COPB1和CD206蛋白表达。以人单核细胞白血病细胞（THP-1）构建巨噬细胞模型，用佛波酯（PMA）和IL-3和IL-4和ESCC细胞上清液诱导巨噬细胞转型，用qPCR和WB法检测CD68和CD206m RNA和蛋白的表达。结果：COPB1在泛癌组织和ESCC组织中均呈高表达且与淋巴结转移和TNM分期有关联（均P < 0.01），COPB1高表达的ESCC患者总生存期短（P < 0.05），COPB1是潜在的ESCC的诊断标志物。COPB1在KYSE-150和TE1细胞中也呈高表达（均P < 0.05），过表达或敲减COPB1可明显抑制或促进KYSE-150和TE1细胞的增殖能力、迁移和侵袭能力（均P < 0.05）。COPB1表达变化诱导的差异表达基因主要富集于PI3K/AKT通路（均P < 0.001）, COPB1可促进PI3K/AKT通路的活化（P < 0.05），COPB1高表达可导致M2型巨噬细胞浸润增加（P < 0.05），COPB1高表达促进TAM/M2极化（P < 0.05）。结论：COPB1在ESCC组织中呈高表达，其可激活PI3K/AKT通路及调控肿瘤免疫微环境促进 ESCC发生发展，COPB1有望成为ESCC诊断和预后的生物标志物及治疗靶点。

Objective: To explore the influencing factors and pathways of suicidal ideation among children and adolescents with severe autism spectrum disorder (ASD), so as to provide references for clarifying the impact intensity and pathways of various factors on suicidal ideation in the population. Methods: A cross sectional study was conducted from June 17, 2024, to January 12, 2025, involving 96 severely affected ASD children and adolescents aged 8-18 years from Tianjin. Participants were assessed using the Puberty Development Scale (PDS), Children s Alexithymia Measure (CAM), Strengths and Difficulties Questionnaire (SDQ), and Positive and Negative Suicide Ideation (PANSI). The random forest Boruta algorithm was employed to screen core variables, and a Bayesian network model was constructed to analyze the influencing factors of suicidal ideation in children and adolescents with severe ASD. Results: Through the screening using the Boruta algorithm, the SDQ scale score, conduct problems, hyperactivity, peer relationship problems and prosocial behavior were identified as the key predictors of suicidal ideation. A Bayesian network model was established with hyperactivity as the central mediating node. The impact of hyperactivity on suicidal ideation exhibited a non linear relationship: compared to the normal state (31.6%, 68.4%), the borderline state of hyperactivity was associated with a higher probability of low risk suicidal ideation (47.1%) and a lower probability of high risk suicidal ideation (52.9%). Suicidal ideation among children and adolescents with severe ASD was closely related to hyperactivity. In the state of hyperactivity, the abnormal peer relationship (95.2%) and the abnormal prosocial behavior (77.0%) were aggravated. Conclusions Suicide ideation among children and adolescents with severe ASD is strongly associated with hyperactivity traits. It is necessary to establish a prevention and control system centered on hyperactivity intervention to reduce this risk.

Objective:To compare the curative effect of modified lateral approach and caudal approach in laparoscopic radical operation for colon cancer.Methods:A total of 100 patients undergoing colon cancer surgery in the Suihua City First Hospital from January 2020 to January 2023 were retrospectively selected as the study objects, and they were divided into two groups according to different surgical methods, 49 patients undergoing laparoscopic radical resection by caudal approach were in the control group, and 51 patients undergoing laparoscopic radical resection by modified lateral approach were in the study group. The levels of clinical related surgical indexes, tumor markers, gastrointestinal function indexes and stress response indexes were compared between the two groups, and the incidence of complications was compared between the two groups.Results:The operation time, intraoperative blood loss, number of lymph node dissection and hospital stay in the study group were lower than those in the control group: (175.48 ± 16.87) min vs. (203.12 ± 15.41) min, (104.63 ± 13.47) ml vs. (118.07 ± 15.98) ml, (18.72 ± 1.67) nodes vs. (19.96 ± 2.01) nodes, (9.13 ± 1.64) d vs. (13.48 ± 2.19) d, there were statistical differences ( P<0.05). After operation, the levels of cancer antigen 19-9 (CA199) and carcinoembryonic antigen (CEA) in the study group were lower than those in the control group: (37.16 ± 9.24) kU/L vs. (42.14 ± 10.23) kU/L, (18.27 ± 6.76) μg/L vs. (22.45 ± 8.45) μg/L, there were statistical differences ( P<0.05). The postoperative exhaust time, feeding time and bowel sound recovery time in the study group were shorter than those in the control group: (40.47 ± 5.03) h vs. (59.73 ± 6.16) h, (70.58 ± 8.24) h vs. (94.57 ± 10.42) h, (21.79 ± 3.68) h vs. (35.06 ± 4.27) h, there were statistical differences ( P<0.05). After operation, the levels of adrenocorticotropin (ACTH), aldosterone (ALD) and cortisol (Cor) in the study group were lower than those in the control group: (16.95 ± 1.91) ng/L vs. (21.52 ± 2.53) ng/L, (135.00 ± 15.24) ng/L vs. (151.80 ± 15.72) ng/L, (220.03 ± 21.40) μg/L vs. (239.94 ± 24.37) μg/L, there were statistical differences ( P<0.05). The incidence of surgical complications in the study group was lower than that in the control group: 5.88%(3/51) vs. 22.45%(11/49), there was statistical difference ( χ2 = 11.60, P<0.05). Conclusions:The therapeutic effect of modified transverse approach radical laparoscopy is higher than that of caudal approach radical laparoscopy.

Objective:To investigate the application effect of situational simulation combined with the Debriefing-GAS method in the teaching of prenatal genetic counseling.Methods:A total of 30 medical students of the five- and eight-year programs in the classes of 2017 and 2018 who received genetic counseling training in The First Affiliated Hospital of Sun Yat-sen University from May 2021 to May 2022 were selected as research subjects, and situational simulation combined with the debriefing-GAS method was used for the teaching of prenatal genetic counseling. Assessment was performed by the teacher to evaluate the change in genetic counseling abilities during the teaching process, and a questionnaire survey was conducted to investigate the degree of satisfaction with teaching among the students. SPSS 26.0 software was used for data analysis; normally distributed continuous data were expressed as mean±standard deviation, non-normally distributed continuous data were expressed as M d(P 25,P75), and categorical data were expressed as frequency and rate; the paired samples t-test was used for comparison of assessment scores before and after teaching. Results:After teaching, there were significant increases in the assessment scores of genetic counseling [(74.5±18.6) points vs. (87.2±14.5) points, t=4.10, P<0.001] and comprehensive abilities such as clinical ability [(35.4±9.6) points vs. (41.1±6.9) points, t=3.72, P=0.001], doctor-patient communication [(17.5±4.6) points vs. (20.8±3.8) points, t=4.34, P<0.001], professional literacy [(11.0±2.5) points vs. (12.5±2.3) points, t=2.89, P=0.007], teamwork [(3.5±1.0) points vs. (4.2±0.8) points, t=3.67, P=0.001], and organizational effectiveness [(7.1±2.0) points vs. (8.3±1.7) points, t=2.94, P=0.006]. The questionnaire survey showed that the degree of satisfaction among students was rated above satisfaction for the reasonability of the implementation process and links of genetic counseling teaching [3.0 (3.0, 4.0) points], teaching quality [3.5 (3.0, 4.0) points], whether the teaching model could effectively increase the interest and initiative in learning [4.0 (3.0, 4.0) points], the improvement in theoretical knowledge [4.0 (3.0, 4.0) points], communication skills in genetic counseling [3.0 (3.0, 4.0) points], and the understanding of related techniques and application prospect [3.0 (3.0, 4.0) points]. However, two students (6.7%) thought that this teaching model could not efficiently reach teaching objectives, since the teaching process was slightly complicated. Conclusions:Situational simulation combined with the debriefing-GAS method has achieved a good effect in the teaching of prenatal genetic counseling and can help undergraduates to master the theoretical knowledge of prenatal genetic counseling and improve their comprehensive clinical abilities, with a relatively high degree of satisfaction, and therefore, it holds promise for clinical application.

Objective To explore the accuracy and clinical application value of artificial intelligence(AI)-based coronary computed tomography angiography(CCTA)in the evaluation of coronary artery stenosis in patients with acute coronary syndrome(ACS).Methods Fifty-four patients with suspected ACS who underwent CCTA examination and invasive coronary angiography(ICA)within 72 h were retrospectively selected.The CCTA images of all patients were processed by AI(AI group)and manual post-pro-cessing(manual group),respectively.The image quality,work efficiency and detection rate of coronary artery stenosis were compared between AI group and manual group.With ICA results as the gold standard,the sensitivity,specificity,positive predictive value,negative predictive value and accuracy of AI in the diagnosis of ACS patients with coronary artery stenosis(≥50％)in CCTA were analyzed,and the consistency of AI and ICA examination results was tested.Results The image quality of CCTA in AI group(grade Ⅰ 27.8％)was better than that in manual group(grade Ⅰ 14.8％),but there was no statistical difference between the two groups(X2=2.707,P＞0.05).The average diagnosis time of AI group(89.67 s±33.21 s)was significantlyshorter than that of manual group(813.33 s±301.84 s)and the difference was statistically significant(t=-17.512,P＜0.001),and the average time gain rate was 88.97％.There was no statistical difference in the detection rate of coronary artery stenosis(≥50％)between AI group and manual group(x2=0.003,P＞0.05).The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of AI in diagnosis of ACS were 87.60％,96.44％,80.30％,97.92％,and 95.19％,respectively,which were significantly consistent with the results of ICA examina-tion(Kappa=0.810,P＜0.05).Conclusion AI-assisted diagnosis can correctly identify the coronary artery tree with better image,significantly shorten the diagnosis time of CCTA in ACS patients with high accuracy,and can provide a strong basis for the early treat-ment of patients with acute chest pain.

Objective To investigate the relationship between systemic immune-inflammation index (SII)and lower extremity vascular disease in patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional study was conducted on 390 T2DM patients admitted in our department from January 2013 to January 2024.According to the diagnostic criteria for lower extremity vascular disease in T2DM patients,they were divided into a lower extremity vascular disease group (n=158)and a control group (n=232).General data and results of laboratory tests were compared between the 2 groups.Spearman correlation analysis was used to identify the related factors for lower extremity vascular diseases in T2DM patients.The correlation between SII and lower extremity vascular diseases in T2DM patients was analyzed using the Row Mean Scores and Cochran-Armitage Trend analysis.Multivariate logistic regression analysis was applied to identify the risk factors for lower limb vascular lesions in T2DM patients.Receiver operating characteristic (ROC)curve was plotted to evaluate the diagnostic efficacy of SII for lower extremity vascular disease in the patients.Results Compared with T2DMpatients without lower extremity vascular disease,those with lower extremity vascular disease were older,had higher levels of total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),SII,larger proportion of carotid vascular lesions,and increased proportion of no-taking statins.The lower extremity vascular disease in T2DM patients was positively correlated with SII/100 (r=0.429,P<0.001),age (r=0.517,P<0.001),TC (r=0.161,P=0.001),LDL-C (r=0.117,P=0.021),carotid artery lesions (r=0.101,P=0.047),no-taking statins (r=0.266,P<0.001).Logistic regression analysis showed that SII,age,LDL-C,and no-taking statins were the risk factors for lower extremity vascular lesions in T2DM patients (P<0.01).The area under the curve (AUC)value of SII combined with age,LDL-C,and no-taking statins in predicting lower extremity vascular disease in T2DM patients was 0.896.Conclusion SII is not only a risk factor,but also a simple marker for lower extremity vascular disease in T2DM patients,suggesting that inflammatory response plays an important role in the occurrence and development of lower extremity vascular disease in T2DM.

Gastric cancer （GC） is one of the most common cancers in the world， with hidden symptoms， complex pathogenesis， high morbidity， high mortality， and poor prognosis. As one of the classical apoptosis pathways， mitochondrial apoptosis has been widely described in the apoptosis escape by GC cells. Mitochondrial apoptosis can regulate the proliferation， invasion， and metastasis of GC cells via oxidative stress， cell cycle， mitochondrial membrane potential， mitochondrial translocation and other mechanisms， and it is one of the potential targets of traditional Chinese medicine （TCM） intervention to restore the mitochondrial function in GC. The theory of spleen-mitochondria in correlation explains that spleen deficiency and cancer toxin are the root causes of mitochondrial apoptosis. Accordingly， the TCM treatment should follow the basic principle of invigorating spleen to restore healthy Qi and removing cancer toxin to eliminate the root cause. Mitochondrial apoptosis can be promoted by inhibiting oxidative stress， promoting cell cycle arrest， and reducing mitochondrial membrane potential. This therapy can improve the energy metabolism， restore the mitochondrial structure and function， and prevent the occurrence and development of GC， with mild side effects and low drug resistance. However， the mechanism of mitochondrial apoptosis in GC and the target of TCM intervention in GC have not been systematically reviewed. Therefore， this paper systematically summarized the effects of mitochondrial apoptosis on the occurrence and development of GC and the role of TCM in the treatment of GC by intervening in mitochondrial apoptosis， aiming to provide a theoretical reference for the treatment and further research of GC.