Nowadays, gastric cancer has become a significant issue in the global cancer burden, and its impact cannot be ignored. The rapid development of artificial intelligence technology is attempting to address this situation, aiming to change the clinical management landscape of gastric cancer fundamentally. In this transformative change, machine learning and deep learning, as two core technologies, play a pivotal role, bringing unprecedented innovations and breakthroughs in the diagnosis, treatment, and prognosis evaluation of gastric cancer. This article comprehensively reviews the latest research status and application of artificial intelligence algorithms in gastric cancer, covering multiple dimensions such as image recognition, pathological analysis, personalized treatment, and prognosis risk assessment. These applications not only significantly improve the sensitivity of gastric cancer risk monitoring, the accuracy of diagnosis, and the precision of survival prognosis but also provide robust data support and a scientific basis for clinical decision-making. The integration of artificial intelligence, from optimizing the diagnosis process and enhancing diagnostic efficiency to promoting the practice of precision medicine, demonstrates its promising prospects for reshaping the treatment model of gastric cancer. Although most of the current AI-based models have not been widely used in clinical practice, with the continuous deepening and expansion of precision medicine, we have reason to believe that a new era of AI-driven gastric cancer care is approaching.
Chronic atrophic gastritis(CAG) represents a critical precancerous stage in gastric carcinogenesis, and its pathogenesis involves circadian rhythm disruption, chronic inflammation, and lipid metabolism reprogramming. Employing an integrative Chinese-western medical approach, this study systematically elucidated the molecular mechanisms whereby the core circadian clock gene BMAL1 promotes "inflammation to cancer" transformation through modulating the HIF-1α-FABP axis, driving lipid metabolism reprogramming, exacerbating oxidative stress, and disrupting immune homeostasis. The study revealed that compound traditional Chinese medicine(TCM) formulas(including Huangqi Jianzhong Tang, Xianglian Huazhuo Fang, and Lizhong Tang) intervened in the BMAL1-mediated "circadian-metabolic-immune" network, significantly ameliorated pathological damage to the gastric mucosa, suppressed inflammatory responses, alleviated lipid metabolism disorder, and reversed the "inflammation to cancer" transformation through multi-target effects. The TCM concept of "Taiyin disease resolution period"(21:00-03:00) gave insights into the link between spleen and stomach functions and circadian rhythms, with its therapeutic time window exhibiting remarkable synchronization with BMAL1 expression rhythms. Clinical studies further demonstrated that chronotherapy strategies based on chronopharmacological principles can significantly enhance the therapeutic efficacy of TCM. Based on these findings, the theory of "Taiyin disease resolution period" provides guidance for chronotherapeutic intervention in CAG management. Through innovative integration of modern chronobiology and traditional temporal medicine principles, the study illuminates the central role of the circadian clock gene in the CAG "inflammation to cancer" transformation and emphasizes the potential of the circadian clock and chronotherapy in reversing the "inflammation to cancer" transformation, offering both mechanistic insights and clinically actionable strategies for CAG treatment via chronobiology.
Inhibition of malignant transformation from the precancerous stage has important clinical value for the prevention of gastric cancer. Here, we report a strategy to inhibit precancerous gastric conditions by Luteolin (Lut). Lut treatment resulted in remarkable resistance to oxyntic atrophy, spasmolytic polypeptide-expressing metaplasia (SPEM), and gastric mucosal injury in tamoxifen (TAM)-treated mice, chenodeoxycholic acid-treated rats, and human organoids. Mechanism study suggested that LCN2 expression was upregulated in the SPEM mucosa and downregulated after Lut treatment. LCN2 blocking suppressed TAM-induced oxyntic atrophy and metaplasia and partially counteracted the effect of Lut. Quantitative chemoproteomics identified that Lut bound to STAT3 and inhibited its phosphorylation. Functional experiments using STAT3 inhibitors and epithelial cell-specific Stat3 deficient mice showed that STAT3 inhibition and deletion attenuated the beneficial effects of Lut. Our data supported that Lut might be a therapeutic candidate for the treatment of gastric mucosal injury by binding to STAT3 and thereby inhibiting the STAT3/LCN2 axis.
Endoplasmic reticulum (ER) stress plays a key role in the pathogenesis of several organ damages. Studies show that excessive ER stress (ERS) can destroy cellular homeostasis, causing cell damage and physiological dysfunction in various organs. In recent years, Sirtuin1 (SIRT1) has become a research hotspot on ERS. Increasing evidence suggests that SIRT1 plays a positive role in various ERS-induced organ damage via multiple mechanisms, including inhibiting cellular apoptosis and promoting autophagy. SIRT1 can also alleviate liver, heart, lung, kidney, and intestinal damage by inhibiting ERS. We discuss the possible mechanism of SIRT1, explore potential therapeutic targets of diseases, and provide a theoretical basis for treating ERS-related diseases.
目的 观察葛根芩连汤对幽门螺杆菌(Hp)感染人正常胃黏膜上皮(GES-1)细胞增殖与凋亡的影响及相关机制.方法 按照葛根芩连汤干预剂量的不同、是否有Hp感染将人GES-1 细胞分为空白对照组、模型组、葛根芩连汤低剂量组(10 μmol/L)、葛根芩连汤中剂量组(20 μmol/L)、葛根芩连汤高剂量组(40 μmol/L)及阳性药对照组(阿莫西林5 μmol/L).培养结束后,采用细胞增值检测分析法(CCK-8 法)检测细胞存活率,酶联免疫吸附法(ELISA)检测上清液肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和IL-6 水平,流式细胞术检测细胞凋亡率,实时荧光定量聚合酶链式反应(RT-qPCR)检测细胞p38、丝裂原活化蛋白激酶2(MK2)mRNA表达,蛋白免疫印迹(Western bloting)法检测细胞p38、MK2 蛋白表达.结果 与空白对照组比较,模型组人GES-1 细胞存活率降低(P<0.05);与模型组比较,葛根芩连汤各剂量组与阳性药对照组人GES-1 细胞存活率均升高(P<0.05),且葛根芩连汤各剂量组效应呈剂量依赖性(P<0.05);阳性药对照组与葛根芩连汤高剂量组人GES-1 细胞存活率比较差异无统计学意义(P>0.05).与空白对照组比较,模型组TNF-α、IL-1β和IL-6 均升高(P<0.05);与模型组比较,葛根芩连汤各剂量组与阳性药对照组TNF-α、IL-1β和IL-6 均降低(P<0.05),且葛根芩连汤各剂量组效应呈剂量依赖性(P<0.05);阳性药对照组与葛根芩连汤高剂量组TNF-α、IL-1β和IL-6 比较差异均无统计学意义(P>0.05).与空白对照组比较,模型组人GES-1细胞凋亡率升高(P<0.05);与模型组比较,葛根芩连汤各剂量组和阳性药对照组人GES-1 细胞凋亡率降低(P<0.05),且葛根芩连汤各剂量组效应呈剂量依赖性(P<0.05);阳性药对照组和葛根芩连汤高剂量组人GES-1 细胞凋亡率比较差异无统计学意义(P>0.05).与空白对照组比较,模型组人GES-1 细胞p38、MK2 mRNA和蛋白表达水平均升高(P<0.05);与模型组比较,葛根芩连汤各剂量组和阳性药对照组人GES-1 细胞p38、MK2 mRNA和蛋白表达水平均降低(P<0.05),且葛根芩连汤各剂量组效应呈剂量依赖性(P<0.05);阳性药对照组和葛根芩连汤高剂量组人GES-1 细胞p38、MK2 mRNA和蛋白表达比较差异均无统计学意义(P>0.05).结论 葛根芩连汤可有效提高Hp感染后人GES-1 细胞增殖率,同时降低细胞凋亡水平,其机制可能与抑制p38/MK2 信号通路、降低细胞炎性反应有关.
Colon polyps are closely related to the occurrence of colon cancer. With the change of living environment,the incidence rate of the disease increases year by year. At present, endoscopic resection is the main treatment of colonic polyps in western medicine, but there is a certain probability of recurrence. The author followed professor LI Dian-gui, a master of traditional Chinese medicine, to analyze and summarize professor LI Dian-gui’s ideas on the treatment of colon polyps. Professor LI Dian-gui believes that the key pathogenesis of colonic polyps is the accumulation of turbid toxin. In the clinical treatment, the treatment method is to remove turbid toxin. According to the patient’s symptoms, signs and pathological results of enteroscopy,combined with the treatment methods of strengthening the spleen, regulating qi, eliminating phlegm and dispersing blood stasis,it has achieved good clinical efficacy. And the case demonstrates professor LI Dian-gui’s clinical thinking and medication characteristics of treating colonic polyps based on turbid toxin theory.
Background: Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and premalignant lesion of gastric cancer. As an antimicrobial peptide, hepcidin can maintain iron metabolic balance and is susceptible to inflammation. Objectives: The objective of this study was to clarify whether hepcidin is involved in abnormal iron metabolism and ferroptosis during CAG pathogenesis. Methods: Non-atrophic gastritis (NAG) and chronic atrophic gastritis (CAG) patient pathology slides were collected, and related protein expression was detected by immunohistochemical staining. The CAG rat model was established using MNNG combined with an irregular diet. Results: CAG patients and rats exhibited iron deposition in gastric tissue. CAG-induced ferroptosis in the stomach was characterized by decreased GPX4 and FTH levels and increased 4-HNE levels. Hepcidin, which is mainly located in parietal cells, was elevated in CAG gastric tissue. The high gastric level of hepcidin inhibited iron absorption in the duodenum by decreasing the protein expression of DMT1 and FPN1. In addition, the IL-6/STAT3 signaling pathway induced hepcidin production in gastric tissue. Conclusion: Our results showed that the high level of gastric hepcidin induced ferroptosis in the stomach but also inhibited iron absorption in the intestines. Inhibiting hepcidin might be a new strategy for the prevention of CAG in the future.
BACKGROUND:Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine.METHODS:PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data.RESULTS:Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient.CONCLUSIONS:PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment.
目的 通过隐结构模型方法 诠释名老中医"调肝守恒"治疗慢性胃炎经验,运用网络药理学探讨"调肝守恒"核心组方治疗慢性胃炎的潜在靶标及作用机制.方法 利用TCMSP数据库筛选组方具有成药可能性较大以及口服吸收较佳的候选活性成分;通过GeneCards数据库筛选获得慢性胃炎相关预测靶点,并与潜在活性成分的作用靶点进行交集分析,获得组方治疗慢性胃炎的靶点;采用Cytoscape软件,构建"药物-活性成分-作用靶点"网络图;借助String数据库平台构建蛋白质相互作用网络,筛选核心靶点;利用Cytoscape软件中的ClueGO插件对共同作用靶蛋白进行GO生物功能注释与KEGG富集分析.结果 发现组方中包含的59个候选成分可能作用于疾病的101个靶点,候选成分中槲皮素、木犀草素、山柰酚可能是组方发挥作用的关键成分,生物学功能涉及凋亡、增殖、炎症反应等多方面,交集基因富集于MAPK信号通路、PI3K/AKT信号通路等经典炎症-肿瘤信号通路.结论 隐结构模型方法 诠释名老中医遣方用药以"调肝守恒"为路法,提供临床实践用药范式与借鉴.组方治疗慢性胃炎是多靶点、多成分、多通路的复杂过程,其可能是通过调节以上关键蛋白表达及信号通路,来发挥改善慢性胃炎相关症状,延缓、阻断炎-癌转化的作用.
前不久我在门诊收治了一位患者张先生,他因工作的事情生闷气,导致胃胀、恶心、食欲不振,还伴有失眠.此前他去别的医院看过,用了些"疏肝理气"的药,但症状改善不明显,依然吃不好、睡不好.结合他的情况,我给他开了越鞠保和丸.
Background: Infection with Helicobacter pylori (H. pylori) can cause chronic gastritis and other digestive tract diseases, and represents a public health concern. Current anti-H. pylori treatment can result in antibiotic resistance and other adverse reactions. Huangqi Jianzhong decoction (HQJZD) is a prescription form of traditional Chinese medicine for chronic gastritis that increases probiotics and inhibits H. pylori. In this study, its anti-bacterial activity against H. pylori receives a preliminary evaluation, and a pharmacology analysis is performed to predict its underlying mechanisms. Methods: Human GES-1 cells are divided into a blank control group, a model group, a HQJZD low-dose (2.08 mg·mL−1), a high-dose group (4.16 mg·mL−1), and a positive control group (amoxicillin, 5 μg·mL−1). After culture, the CCK-8 method is used to detect cell viability; flow cytometry is used to detect cell apoptosis rate; and RT-qPCR is used to detect the expression of mRNA virulence factors, including HpPrtC, OPiA, IceA1, and BabA2. Network pharmacology analysis and molecular docking were performed to explore the mechanisms of HQJZD in treating H. pylori gastritis, based on its anti-H. pylori infection effect. Results: We noted lower cell survival rates in the model group, but higher apoptosis rates and mRNA expressions of HpPrtC, OPiA, IceA1, and BabA2 than in the control group (p < 0.05). Compared to the model group, the cell survival rate of each dosage group of Huangqi Jianzhong decoction and the positive control group increased significantly, while the apoptosis rate and the mRNA expressions of HpPrtC, OPiA, IceA1, and BabA2 were decreased significantly. The effect in each HQJZD group was dose-dependent (p < 0.05). Network pharmacological analysis involving 159 signaling pathways was used to screen 6 key active components of HQJZD and 102 potential target proteins for the treatment of H. pylori-related gastritis. The molecular docking results revealed that the 6 active compounds had a strong binding ability with the target proteins of ALB, IL-6, AKT1, IL-1B, and JUN. Conclusion: HQJZD effectively increases the proliferation rate of human GES-1 cells after infection, while reducing the level of apoptosis. The mechanism may be related to multiple components, multiple targets and pathways, which provides a scientific basis for further elucidating the mechanism of action, the pharmacodynamic material basis, and the clinical application of HQJZD against H. pylori infection.
Gastroscopic image detection is mainly used to diagnose common diseases. Relying on clinicians’ manual identification methods is time-consuming and prone to missing and misdiagnosis. Therefore, for gastroscopic image detection (GID), we propose a novel identification method (GidCNN-SVM) that fuses convolutional neural networks (CNN) with support vector machines (SVM).Firstly, a convolutional neural network (CNN) is used for feature extraction of gastroscopy images to obtain deeper semantic features of gastroscopy images; Secondly, the SVM classifier is used to build the recognition model, so that the SVM based on structural risk minimization will improve the generalization ability and recognition accuracy of the model. Finally, the application of actual gastroscopy images shows that the recognition accuracy of GidCNN-SVM proposed in this paper is as high as 98.2% and the overall AUC value is 98.4%. In gastric cancer and chronic atrophic gastritis, the sensitivity is 93.3% and 95.0%, and the F1 is 98.4% and 98.2%, which is better than that of GoogleNet, AlexNet, LeNet and their methods fused with SVM, and has a wide range of application.
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years of precancerous lesions of gastric cancer (PLGC) stages before progressing to gastric malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven effective in treating PLGC. Classical TCM formulas and chemical components isolated from some Chinese herbal medicines have been administered to treat PLGC, and the main advantage is their comprehensive intervention with multiple approaches and multiple targets. In this review, we focus on recent studies using TCM treatment for PLGC, including clinical observations and experimental research, with a focus on targets and mechanisms of drugs. This review provides some ideas and a theoretical basis for applying TCM to treat PLGC and prevent GC.
相传古时有一位郎中,巧遇一户人家正在办理丧事,众人抬着装有死者的棺材往墓地走.郎中仔细一观察,发现地上有滴滴鲜血的痕迹,便随棺而行,直至墓地.询问后方知,棺中是一成年女子,因崩漏出血不止而死.郎中说:"鲜血淋漓,从棺而出,或许还有一线生机,能否开棺治疗?"死者家属听说还有救治希望,大喜,立即开棺.郎中即用一种无名小草,浓浓地煎了一锅,滤汁给病人缓缓灌入,不到一个时辰,病人苏醒,出血停止,再经一段时间治疗后渐趋康复.
目的:观察"三字经流派"小儿推拿联合复方甘草片治疗成人痰热郁肺证慢性咳嗽的临床疗效.方法:将60例符合纳入标准的慢性咳嗽患者随机分为对照组和试验组各30例,对照组给予复方甘草片口服,3片/次,3次/天;试验组在对照组的治疗基础上辨证施治,采用以掐揉小横纹为主的三字经流派小儿推拿法治疗,每天1次,两组均连续治疗7天.采用痰热郁肺证中医症状分级量化和临床有效率比较治疗效果.结果:治疗后,两组均可以降低慢性咳嗽的主要临床症状积分(P<0.05),且试验组对咳嗽频率、痰的质地、咳痰困难度和排痰量等单项指标的效果优于对照组(P<0.05);试验组总有效率86.7%高于对照组66.7%,差异有统计学意义(P<0.05).结论:三字经流派小儿推拿联合复方甘草片对于成人慢性咳嗽的相关症状改善和临床有效率,比单纯使用复方甘草片的效果更优.
目的 探讨益胃化浊解毒方联合维酶素片治疗慢性萎缩性胃炎胃癌前病变疗效及对Ki-67蛋白表达的影响.方法 将2017年2月—2018年3月河北省中医院诊治的102例慢性萎缩性胃炎胃癌前病变患者随机分为观察组和对照组,每组51例.对照组采用维酶素片治疗,观察组在对照组治疗基础上加用益胃化浊解毒方治疗,2组均连续治疗3个月.观察2组治疗前后消化不良症状评分、病理组织学变量积分、胃黏膜Ki-67蛋白表达阳性率及SF-36生活质量评分,比较2组患者临床疗效.结果 治疗后,2组患者消化不良症状评分、病理组织学变量积分、胃黏膜Ki-67蛋白表达阳性率均明显降低(P均<0.05),SF-36生活质量评分均明显升高(P均<0.05),且观察组上述各指标改善情况均明显优于对照组(P<0.05).观察组的总有效率为94.1%(48/51),对照组为80.4%(41/51),观察组明显高于对照组(P<0.05).结论 益胃化浊解毒方联合维酶素片能有效改善慢性萎缩性胃炎胃癌前病变患者临床症状及病理组织学病变状态,降低胃黏膜Ki-67蛋白表达阳性率,提高患者生活质量.
目的 基于当代京津冀名老中医药专家经验,分析慢性萎缩性胃炎的病因病机及证素分布规律,梳理、阐述该病病因病机.方法 基于河北省中医院《当代名老中医药专家脾胃病数据库(1911-2018年)》以及《学术期刊脾胃病数据库(1989-2018年)》,整合、建立河北省中医院《国家中医临床研究基地当代名老中医药专家诊治慢性萎缩性胃炎文献数据库》,利用Microsoft Excel 2013和SPSS 23.0统计软件进行分析.结果 慢性萎缩性胃炎主要病因(1158条)有浊毒内蕴、阴虚内热、情志不畅、脉络瘀阻、久病年老、脾胃素虚、饮食伤胃、外邪犯胃.病机以浊毒内蕴、暗耗胃阴、气滞血瘀、胃气阻滞、肝气犯胃、胃失和降、不通则痛、不荣则萎居多.病理性质以寒、热、虚、实、浊毒、痰等为主,病位主要在脾、胃,涉及肝、肾、心.病理因素证素多为浊毒、阴虚、气滞、血瘀、寒凝、气虚、湿阻、热郁、食积、痰饮.单一病性证素以浊毒、阴虚、气滞、血瘀较为多见,病位主要在脾、胃,与肝、心、肾关系密切.二病性证素以浊毒+阴虚、气滞+血瘀、气虚+湿阻.三病性证素以浊毒+阴虚+血瘀、气滞+寒凝+血瘀常见,二、三病性证素组合病位主要在脾、胃,与肝、肾、心关系密切.结论 当代名老中医药专家对慢性萎缩性胃炎病因病机认识较前人认识增加了络病、浊毒等认识,在肝胃气滞、胃络瘀阻、脾胃虚弱等方面有了更深层次的认识,一定程度上丰富、充实了中医基础理论,并有待于进一步规范、总结.
目的 验证化浊解毒方对溃疡性结肠炎大鼠肠黏膜的保护作用.方法 将Wistar大鼠随机分为正常组、模型组、美沙拉嗪组及化浊解毒方高、低剂量组,每组10只,2,4,6-三硝基苯磺酸/乙醇法建立溃疡性结肠炎大鼠动物模型,造模成功后化浊解毒方高、低剂量组分别予41.6、20.8 g/kg化浊解毒方灌胃,美沙拉嗪组给予0.3 g/kg美沙拉嗪灌胃,模型组及正常组以蒸馏水10 mL/kg灌胃,连续14 d,观察各组大鼠疾病活动指数(DAI)评分、组织病理学、结肠上皮细胞Bax、caspase-9蛋白表达变化.结果 化浊解毒方可降低大鼠DAI评分,改善结肠组织病理形态,下调Bax、caspase 9蛋白表达,以化浊解毒方高剂量组最明显,与美沙拉嗪组效果相当.结论 化浊解毒方能下调溃疡性结肠炎大鼠结肠上皮细胞Bax、caspase-9蛋白表达,进而抑制细胞过度凋亡,恢复肠黏膜屏障功能,进一步促进溃疡愈合.
目的 验证基于快速区域卷积神经网络萎缩性胃炎-胃癌胃镜图像自动识别系统,并探讨其临床应用价值.方法 回顾性收集80例萎缩性胃炎-胃癌患者的640张胃镜图像序列,将所有图像序列作为训练组输入卷积神经网络系统,建立图像自动识别模型,通过读取图像进行验证,记录识别准确率,绘制精确回归曲线.结果 模型训练损失在12轮训练后基本趋于0,准确率在第29轮达到最大值98%,在42轮以后也基本稳定在最大值.结论 卷积神经网络系统能够帮助消化科医师对萎缩性胃炎-胃癌进行诊断,具有一定的临床应用价值.
前前不久,门诊来了一位女性患者,年龄50岁,自述最近半年睡觉爱出汗,且情绪易烦躁,在其他医院被诊断为更年期综合征,使用过激素调节等药物治疗,效果一直不好.经辨证之后,医生给她开了 10剂知柏地黄汤加减,连续用药后,患者症状大为缓解.