Gastric cancer is one of the most common malignant tumors in the digestive tract, which has the characteristics of high morbidity and mortality. However, gastric cancer is not achieved overnight but is gradually developing through the interaction of many factors. Therefore, actively delaying or blocking the "inflammation-cancer" transformation in gastric mucosa is the key to treatment. Nod-like receptor protein 3(NLRP3) inflammasome is a multi-protein signal complex and one of the important innate immune signal receptors. Inflammation plays an important role in the occurrence and development of gastric cancer, and continuous inflammation mediation will trigger the transformation from inflammation to cancer. Therefore, the significance of NLRP3 inflammasome to gastric mucosa lies in the transformation between inflammation and cancer. Traditional Chinese medicine(TCM) has the functions of multi-components, multi-targets, and few adverse reactions. A large number of studies show that TCM and related monomers have significant effects in treating liver, kidney, and immune diseases through mediating NLRP3 inflammasome, but there is less research on the "inflammation-cancer" transformation in gastric mucosa. By combing the NLRP3-related nuclear factor-κB transcription factor(NF-κB), hypoxia inducible factor-1α(HIF-1α), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), and other signal pathways, this paper clarified their mechanisms in the "inflammation-cancer" transformation in gastric mucosa, delayed the process of "inflammation-cancer" transformation in gastric mucosa through four aspects: energy metabolism, pyroptosis, immune response, and vascular endothelial growth factor, and prevented and treated "inflammation-cancer" transformation in gastric mucosa from three aspects: TCM monomer, TCM compound prescription, and other therapies, so as to provide ideas for the subsequent treatment of "inflammation-cancer" transformation in gastric mucosa with TCM.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/pathology* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Inflammation/drug therapy* ; Signal Transduction/drug effects*

This study aimed to investigate the effects of Zhiwei Fuwei Pills on mitochondrial apoptosis in the rat model of precancerous lesions of gastric cancer(PLGC) based on the microRNA-21(miRNA-21)/B-cell lymphoma-2(Bcl-2) signaling pathway. Eighty-five 5-week-old male SPF-grade SD rats were selected, of which 75 were fed with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) for multifactorial modeling, and the PLGC model was established after 26 weeks. The rats were randomly grouped as follows: model, folic acid(0.002 g·kg~(-1)), low-dose(0.42 g·kg~(-1)) Zhiwei Fuwei Pills, medium-dose(0.84 g·kg~(-1)) Zhiwei Fuwei Pills, and high-dose(1.67 g·kg~(-1)) Zhiwei Fuwei Pills, with 15 rats in each group. Additionally, 10 rats were assigned to a blank group and administrated with an equivalent volume of normal saline by gavage. After four weeks of continuous drug administration, the gastric mucosal tissue was collected. Hematoxylin-eosin(HE) staining was performed to reveal the pathological changes in the gastric mucosa. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) was employed to detect apoptosis in gastric mucosal epithelial cells. RT-PCR was adopted to determine the mRNA levels of miRNA-21, phosphatase and tensin homolog(PTEN), Bcl-2, Bcl-2-associated X protein(Bax), and cysteinyl aspartate-specific protease 3(caspase-3). Western blot was employed to determine the protein levels of PTEN, Bcl-2, Bax, and caspase-3. Immunohistochemistry(IHC) was used to detect the positive expression of PTEN, Bcl-2, and Bax in the gastric mucosal tissue. Transmission electron microscopy(TEM) was employed to observe the morphological and structural changes in mitochondria. The results showed that compared with model group, the drug administration groups showed alleviated pathological changes, with increased apoptotic cells, down-regulated mRNA levels of miRNA-21 and Bcl-2, up-regulated mRNA and protein levels of PTEN, Bax, and caspase-3, and down-regulated protein level of Bcl-2. In addition, the drug administration groups exhibited mitochondrial swelling and rupture and reduction of cristae, which indicated mitochondrial apoptosis. These findings suggest that Zhiwei Fuwei Pills can effectively improve mitochondrial apoptosis in PLGC cells by regulating the miRNA-21/Bcl-2 signaling pathway.
Animals ; MicroRNAs/metabolism* ; Male ; Apoptosis/drug effects* ; Stomach Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Rats ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Mitochondria/genetics* ; Signal Transduction/drug effects* ; Precancerous Conditions/drug therapy* ; Humans ; PTEN Phosphohydrolase/genetics*

Gastric cancer (GC) is a highly prevalent malignant tumor of the digestive system, with high incidences and mortality rates worldwide, posing a serious threat to human health. Studies have shown that tumor-associated neutrophils (TAN) are closely related to adverse biological behaviors of GC, such as initiation, invasion and metastasis, immune evasion, and resistance to treatment, playing a pivotal role in the pathological progression of GC. This article aims to summarize the role of neutrophils in the onset and development of GC and explore their potential applications in GC treatment by reviewing relevant literature in recent years, in order to provide reference for clinicians and basic research.
Humans ; Stomach Neoplasms/therapy* ; Neutrophils/pathology* ; Animals

OBJECTIVES: To investigate the effect of Scleromitrion diffusum on gastric mucosal epithelial-mesenchymal transition (EMT) in rats with gastric precancerous lesion. METHODS: Fifty SD rats were randomly divided into blank control group (n=11), model control group (n=13), Scleromitrion diffusum (SD) group (n=13) and vitase group (n=13). Gastric precancerous lesion animal model was prepared by 1-methyl-3-nitro-1-nitrosoguanidine complex polyfactor method, and the drugs were administrated by gavage once a day for 6 weeks. The pathological changes of gastric mucosa were observed with hematoxylin and eosin staining, the expression of EMT marker proteins were detected with immunohistochemical staining and Western blotting. RESULTS: Compared with the model control group, the gastric mucosal injury was significantly attenuated in the Scleromitrion diffusum group, the mucosal tissue structure gradually recovered, the saccular expansion area was reduced, and the inflammatory infiltration was ameliorated. The expression of epithelial cadherin was higher, and the expression of neural cadherin and vimentin in the Scleromitrion diffusum group were lower than those of model control group (all P<0.05). CONCLUSIONS Scleromitrion diffusum can ameliorate gastric mucosal injury in rats with gastric precancerous lesion by reversing the EMT.
Animals ; Rats ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition/drug effects* ; Precancerous Conditions/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/drug therapy* ; Male ; Cadherins/metabolism*

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

OBJECTIVES: To evaluate the value of ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT imaging in staging and treatment decision for gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). METHODS: This retrospective analysis was conducted in 49 patients with GEP-NEN undergoing ¹⁸F-FDG and ⁶⁸Ga-DOTATATE PET/CT imaging at our hospital from August, 2020 to March, 2023, including 34 newly diagnosed patients and 15 patients with recurrence or metastasis after treatment. GEP-NEN were classified into G1, G2, and G3 neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC) based on pathological typing. The detection efficiency were classified into 4 patterns based on the number of positive tumor lesions detected by the two tracers: ⁶⁸Ga-DOTATATE>¹⁸F-FDG (A); ⁶⁸Ga-DOTATATE=¹⁸F-FDG (B); ⁶⁸Ga-DOTATATE<¹⁸F-FDG (C); and complementation (D). The value of dual-modality imaging in staging and treatment decision were evaluated by visual analysis. RESULTS: In the 49 patients with GEP-NEN, ⁶⁸Ga-DOTATATE PET/CT was superior to ¹⁸F-FDG PET/CT for detecting systemic tumor lesions (P<0.001) and more sensitive for detecting primary/recurrent lesions, lymph node metastasis, liver metastasis, and bone metastasis (P<0.05), while ¹⁸F-FDG PET/CT had higher detection rates for lung metastasis and peritoneal metastasis (P<0.05). In terms of the detection efficiency, Pattern A was found in 46.9% (23/49) patients, Pattern B in 38.8% (19/49), Pattern C in 12.2% (6/49), and Pattern D in 2.0% (1/49). The complementary value of ¹⁸F-FDG PET/CT to ⁶⁸Ga-DOTATATE PET/CT was 0% in G1 NET patients (0/13), 8.3% in G2 NET patients (2/24), 50% in G3 NET patients (3/6), and 33.3% in NEC patients (2/6). 12.2% (6/49) of the patients had their staging confirmed or changed due to additional lesions detected by ¹⁸F-FDG PET/CT imaging, resulting subsequently in establishment or adjustment of their treatment plans. CONCLUSIONS ⁶⁸Ga-DOTATATE PET/CT imaging should be the primary choice for GEP-NEN patients. Additional ¹⁸F-FDG PET/CT imaging can potentially improve precision of staging and treatment decision-making for G2, G3 and NEC patients but provides virtually no clinical benefits for G1 NET patients.
Humans ; Positron Emission Tomography Computed Tomography/methods* ; Neuroendocrine Tumors/therapy* ; Pancreatic Neoplasms/therapy* ; Retrospective Studies ; Organometallic Compounds ; Stomach Neoplasms/therapy* ; Neoplasm Staging ; Fluorodeoxyglucose F18 ; Intestinal Neoplasms/therapy* ; Female ; Male ; Middle Aged ; Aged ; Adult

OBJECTIVES: To analyze the differences in the prognosis of gastric signet ring cell carcinoma (SRCC) among different races using the US Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. METHODS: We analyzed the data of patients with gastric SRCC from the SEER database from 2000 to 2020, and divided the patients into cohorts of whites, blacks, Asians or Pacific Islanders, American Indians/Alaska Natives according to their race. The prognosis and treatment of the cohorts were evaluated using baseline demographic analysis, Kamplan-Meier survival curve, and nomogram analysis. RESULTS: We analyzed the data of a total of 2058 patients, including 8.6% blacks, 72.4% whites, 16.6% Asians or Pacific Islanders, 1.0% American Indians/Alaska Natives, and 1.4% other races. The tumor grade varied among different races, and the prevalence and survival rates of patients differed significantly across races. The differences in the white cohort were the most prominent, and all the differences were statistically significant (P<0.05). Racial differences were also noted in patient management and prognosis. CONCLUSIONS There are racial differences in tumor grades and prognosis of gastric SRCC, and these differences provide evidence for optimizing clinical diagnosis and treatment strategies for this malignancy.
Aged ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Signet Ring Cell/therapy* ; Databases, Factual ; Prognosis ; Racial Groups ; SEER Program ; Stomach Neoplasms/therapy* ; Survival Rate ; United States/epidemiology* ; White ; Asian American Native Hawaiian and Pacific Islander ; American Indian or Alaska Native ; Black or African American

OBJECTIVE: To observe the effects of thumbtack-needle embedding therapy of auricular acupuncture on gastrointestinal function and intestinal microflora in the patients with gastric cancer after operation, and to explore its mechanism. METHODS: A total of 80 patients with gastric cancer after radical operation were randomly divided into an observation group (40 cases, 3 cases discontinued) and a control group (40 cases, 3 cases discontinued). The patients of both groups received the perioperative care for accelerating recovery. Additionally, in the observation group, the thumbtack-needle embedding therapy of auricular acupuncture was delivered at the auricular points of unilateral side, including Wei (CO₄), Pi (CO₁₃), Dachang (CO₇), Xiaochang (CO₆), Yuanzhong (AT_2,3,4i), Erzhong (HX₁), Sanjiao (CO₁₇) and Jiaowozhong (TF₃), and the needles were embedded and retained for 72 h. The postoperative recovery time of gastrointestinal function (the postoperative bowel sound recovery time, the first exhaust time, the first defecation time), the postoperative hospital stay and pain visual analogue scale (VAS) score were observed in the two groups. Before operation and on day 5 after operation, the serum gastrin level was detected in the two groups. The third-generation 16S rRNA sequencing technology was used to detect the composition and relative abundance of intestinal flora in the two groups before and after operation. RESULTS: Compared with the control group, the postoperative bowel sound recovery time, the first exhaust time and the first defecation time were shortened in the observation group (P<0.05). In the observation group, the VAS scores at 24 h, 48 h, and 72 h after surgery were lower than those of the control group, respectively (P<0.05). There was no significant differences in postoperative hospital stay and serum gastrin level between the two groups (P>0.05). The alpha diversity analysis showed that the differences in Shannon index, Simpson index, Pielou_J index and Pd_fath index were not significant statistically after intervention between the two groups (P>0.05). After intervention, the community structure of the fecal sample was similar at each taxonomic level between the two groups, and although the proportion between species was various, the difference was not significant (P>0.05). After intervention, there were 55 species with the differences between the two groups, 17 species of them presented significant difference in relative abundance in the observation group and 38 species in the control group. Regarding the level of genus, the levels of Klebsiell and Enterobacter increased (P<0.05) and the level of Streptococcus decreased (P<0.05) in the observation group. The main microbial groups that played an important role were Coprobacillaceae, Sutterellaceae and Yersiniaceae in the observation group. KEGG function prediction indicated that the function of intestinal microflora was mainly associated with the cofactor and vitamin metabolism, carbohydrate metabolism, and amino acid metabolism. CONCLUSION The thumbtack-needle embedding therapy of auricular acupuncture improves the postoperative gastrointestinal function of the patients with gastric cancer probably through regulating the structure and relative abundance of intestinal microflora and affecting the energy metabolism.
Humans ; Male ; Female ; Middle Aged ; Acupuncture, Ear/instrumentation* ; Gastrointestinal Microbiome ; Aged ; Stomach Neoplasms/therapy* ; Adult ; Acupuncture Points ; Gastrointestinal Tract/microbiology* ; Intestines/physiopathology* ; Postoperative Period ; Acupuncture Therapy

OBJECTIVE: To observe the effect of electroacupuncture combined with enhanced recovery after surgery (ERAS) protocol on promoting intestinal function in patients after gastric cancer surgery. METHODS: Forty-four patients who underwent radical gastrectomy for gastric cancer were randomly divided into an experimental group (22 cases, 3 cases were excluded) and a control group (22 cases, 4 cases were excluded). Both groups received treatment under ERAS protocol, the experimental group was given electroacupuncture at bilateral Neiguan (PC6), Hegu (LI4), Zusanli (ST36) and Quchi (LI11), disperse-dense wave was selected, with frequency of 2 Hz/100 Hz. The control group received placebo electroacupuncture intervention, with the same acupoints as the experimental group, electrode pads were placed on the acupoints without electrical stimulation. Each session lasted 30 min, starting from 1 h after surgery, once every 24 h, until the patient resumed anal flatus. The intestinal sound rate of both groups was observed 24 h before surgery and 24, 48 h after surgery. The bowel sound recovery time (BSRT), time to first anal flatus, time to first defecation, and tolerance to oral enteral nutrition suspension were compared between the two groups. The levels of serum C-reactive protein (CRP), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured 24 h before surgery and 24 h after surgery in both groups. RESULTS: The intestinal sound rate 24 h after surgery was decreased compared with that 24 h before surgery in the two groups (P<0.05), the intestinal sound rate 24, 48 h after surgery in the experimental group was higher than that in the control group (P<0.05). The BSRT in the experimental group was earlier than that in the control group (P<0.05) .The levels of serum CRP, IL-6, IL-10 24 h after surgery in the experimental group were higher than those 24 h before surgery (P<0.05), while the levels of serum CRP, IL-4, IL-6, IL-10, IFN-γ in the control group were higher than those 24 h before surgery (P<0.05); the levels of serum CRP、IL-4、IFN-γ 24 h after surgery in the experimental group were lower than those in the control group (P<0.05) .The tolerance rate of oral enteral nutrition suspension in the experimental group was 84.2% (16/19), which was higher than 50.0% (9/18) in the control group (P<0.05). CONCLUSION Electroacupuncture combined with ERAS protocol can improve the intestinal motility, shorten the BSRT, enhance the tolerance of oral intake, and reduce inflammatory response in patients after gastric cancer surgery.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Acupuncture Points ; C-Reactive Protein/metabolism* ; Electroacupuncture ; Gastrectomy ; Interleukin-10 ; Interleukin-6 ; Intestines/physiopathology* ; Stomach Neoplasms/therapy*

OBJECTIVE: To observe the clinical efficacy of herb-spreading moxibustion as an adjuvant treatment for chemotherapy-induced nausea and vomiting (CINV) of spleen and stomach deficiency cold in gastric cancer. METHODS: Seventy-six patients with CINV of spleen and stomach deficiency cold in gastric cancer were randomly divided into an observation group (38 cases, 1 case was discontinued, 1 case dropped out) and a control group (38 cases, 1 case was discontinued). The patients in both groups were treated with cisplatin+tigio regimen chemotherapy, and were treated with basic anti-nausea drugs on the 1st to 3rd day of chemotherapy. The observation group was treated with herb-spreading moxibustion at Zhongwan (CV12) acupoint area (covering from Shangwan [CV13] to Shenque [CV8] of the conception vessel, and from both sides to the kidney meridian of foot-shaoyin). The herb was selected as Fuzi Lizhong decoction, once a day, about 50 min each time, with 3 consecutive days as one treatment course, with an interval of 1 day between each course, for a total of 3 treatment courses. The grading of nausea and vomiting degree in the two groups were recorded on the 1st, 3rd, 7th and 14th days of chemotherapy. Karnofsky performance status (KPS) score in the two groups was observed before treatment and on the 1st, 3rd, 7th and 14th days of chemotherapy. The TCM symptom grading and TCM syndrome score of the two groups before and after treatment were compared, and the clinical efficacy and safety of the two groups were evaluated. RESULTS: On the 7th and 14th days of chemotherapy, the grading of nausea degree in the observation group was lower than that in the control group (P<0.05). On the 3rd, 7th and 14th days of chemotherapy, the grading of vomiting degree in the observation group was lower than that in the control group (P<0.05, P<0.01). Compared before treatment, the KPS scores of the two groups on the 1st day of chemotherapy and the control group on the 7th day of chemotherapy were decreased (P<0.05, P<0.01), and the KPS scores of the observation group on the 7th day of chemotherapy and the two groups on the 14th day of chemotherapy were increased (P<0.01). On the 7th and 14th days of chemotherapy, the KPS scores of the observation group were higher than those of the control group (P<0.01). After treatment, the each item grading of TCM symptom in the two groups was better than that before treatment (P<0.01), except for loose stool, the each item grading of TCM symptom in the observation group was better than that in the control group (P<0.05, P<0.01). After treatment, the scores of TCM syndrome in the two groups were lower than those before treatment (P<0.01), and the score in the observation group was lower than that in the control group (P<0.01). The obvious effective rate of the observation group was 58.3% (21/36), which was higher than 24.3% (9/37) of the control group (P<0.01). No adverse events occurred in both groups. CONCLUSION Herb-spreading moxibustion as an adjuvant treatment for CINV of spleen and stomach deficiency cold in gastric cancer can effectively relieve nausea and vomiting, and improve the symptoms of TCM, and improve the quality of life of patients. The clinical efficacy is satisfactory and the safety is good.
Humans ; Moxibustion ; Male ; Female ; Middle Aged ; Stomach Neoplasms/drug therapy* ; Nausea/physiopathology* ; Vomiting/physiopathology* ; Aged ; Adult ; Acupuncture Points ; Antineoplastic Agents/therapeutic use* ; Drugs, Chinese Herbal/administration & dosage* ; Spleen/drug effects* ; Stomach/drug effects*