The lncRNA-MALAT1/miR-330-3p Axis Promotes Growth and Metastasis of Gastric Cancer Through Regulation of Vascular Endothelial Growth Factor A: A Genetic and Cell Evaluation Study

SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.

Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.

Infección por Helicobacter pylori y factores asociados en adultos de la sierra norte del Perú / Helicobacter pylori infection and associated factors in adults from the northern highlands of Peru

INTRODUCCIÓN: Helicobacter pylori afecta a más de 50% de la población mundial, siendo más prevalente en poblaciones de nivel socioeconómico bajo; esta bacteria constituye la principal causa de cáncer gástrico a nivel global. OBJETIVO: Determinar la frecuencia y los factores asociados a la infección por H. pylori en personas adultas que viven en el centro histórico de la ciudad de Cajamarca, en el norte del Perú. MATERIAL Y MÉTODO: Estudio descriptivo que incluyó 124 personas encuestadas mediante un cuestionario y evaluadas mediante endoscopía y cultivo de biopsia gástrica. Una biopsia por persona fue sometida a prueba de ureasa y los cultivos se confirmaron por reacción de polimerasa en cadena (RPC). RESULTADOS: La frecuencia de infección fue de 60,5 % (IC 95% 51,3 - 69,2). El análisis univariado demostró asociación significativa entre la infección y la edad (p = 0,002), y entre la infección y el antecedente de patología gástrica (p = 0,015). El análisis multivariado reveló dos factores asociados: edad (OR = 0,94; IC95% 0,90-0,97) y antecedente de infección por H. pylori (OR = 0,23; IC95% 0,08 - 0,67). CONCLUSIONES: Existe alta frecuencia de infección por H. pylori en esta población; la edad y el antecedente de infección constituyen factores asociados que deben evaluarse con mayor profundidad.

BACKGROUND: Helicobacter pylori affects more than 50% of the world's population, being more prevalent in populations of low socioeconomic status. H. pylori is the main cause of gastric cancer globally. AIM: To establish the frequency and factors associated with H. pylori infection in adults living in the historic center of Cajamarca City, in northern Peru. METHODS: This was a descriptive study that included 124 individuals surveyed through a questionnaire and evaluated through endoscopy and gastric biopsy culture. One biopsy per person underwent the urease test, and the cultures were confirmed by PCR. RESULTS: The frequency of infection was 60.5% (95% CI 51.3 - 69.2). In the univariate analysis, there was a significant association between the infection and age (p = 0.002), and between the infection and a history of gastric pathology (p = 0.015). The multivariate analysis revealed two associated factors: age (OR = 0.94; 95% CI 0.90 - 0.97), and history of H. pylori infection (OR = 0.23; 95% CI 0.08 - 0.67). CONCLUSIONS: There is a high frequency of H. pylori infection in this population, and the age and history of H. pylori infection are factors that should be further evaluated.

Terapia de conversión en cáncer gástrico: experiencia del Instituto Nacional de Cancerología de Colombia / Conversion therapy in gastric cancer: experience at Instituto Nacional de Cancerología de Colombia

RESUMEN Antecedentes: el cáncer gástrico (CG) representa un problema de salud pública en Colombia y el mundo. Dado que la mayoría de los pacientes se encuentran en estadios avanzados en el momento del diagnóstico. desarrollar estrategias de manejo. como la terapia de conversión (TC). es una necesidad cada vez mayor en su tratamiento. Objetivo: estimar los resultados con la TC en el tratamiento de pacientes con CG avanzado en el Instituto Nacional de Cancerología de Colombia (INC). Material y métodos: serie de casos de pacientes con adenocarcinoma gástrico incurable llevados a quimioterapia de inducción y cirugía con intención curativa. entre los años 2010 y 2021. Se revisaron de forma retrospectiva los datos clínico-patológicos y de supervivencia. La supervivencia global (SG) se calculó desde la fecha de la primera quimioterapia hasta la muerte. Las funciones de supervivencia se estimaron con tablas de vida y por el método de Kaplan-Meier y se realizaron curvas de supervivencia a 3 y 5 años. Resultados: se analizaron los datos de 23 pacientes con edad promedio de 56 años. 17 (74%) fueron varones. El criterio de irresecabilidad más frecuente fue un tumor T4b en 13 casos (56.5%). Todos recibieron TC. La mediana de seguimiento fue de 28 meses. Se documentaron 11 recurrencias (52%). La mediana de supervivencia fue de 41.2 meses y la SG a 3 y 5 años de 57.7% y 38.5%. respectivamente. Conclusiones: la TC permitió obtener una SG aceptable de pacientes seleccionados con CG avanzado incurable. Esta estrategia requiere una cuidadosa selección y manejo multidisciplinario en centros oncológicos de referencia.

ABSTRACT Background: Gastric cancer (GC) represents a public health problem in Colombia and worldwide. Since most patients are at advanced stages at the time of diagnosis. it is necessary to develop management strategies as conversion therapy (CT). Objective: The aim of this study was to estimate the results of CT for treating patients with advanced and GC at Instituto Nacional de Cancerología de Colombia (INC). Material and methods: We included patients with incurable gastric cancer who underwent induction chemotherapy and intended curative surgery between 2010 and 2021. The clinical and pathological data and survival of the patients included were retrospectively reviewed. Overall survival (OS) was calculated from the time of initiation of chemotherapy until the date of death. Survival functions were estimated using the life table and Kaplan-Meier methods. and survival curves at 3 and 5 years were constructed. Results: 23 patients were analyzed; mean age was 56 years. and 17 (74%) were men. The most common criterion indicating unresectability was a T4b tumor in 13 cases (56.5%). All the patients underwent CT. Median follow-up was 28 months. Eleven patients developed disease recurrence (52%). Median survival was 41.2 months. and 3- and 5-year OS was 57.7% and 38.5%. respectively. Conclusions: CT provided an acceptable OS rate for selected patients with incurable advanced GC. This strategy requires an adequate selection of patients and multidisciplinary management in reference oncology centers.

Cáncer Gástrico Bifocal con Linfonodos Negativos en un Paciente con Cirrosis Hepática / Bifocal Gastric Cancer with Negative Lymph Nodes in a Hepatic Cirrhosis Patient

El cáncer gástrico (CG), es la primera causa de muerte por cáncer, en hombres, y la tercera en mujeres, en Chile. No obstante ello, el CG bifocal (CGB) es una situación poco frecuente. El objetivo de este manuscrito fue reportar un caso de CGB, con linfonodos negativos en un paciente con cirrosis hepática, que fue intervenido quirúrgicamente; y revisar la evidencia existente respecto de sus características morfológicas, terapéuticas y pronósticas. Caso clínico: Hombre de 74 años diabético, hipertenso, insuficiente cardíaco y cirrótico; portador de CGB (subcardial y antro-pilórico), diagnosticado por endoscopia y con confirmación histológica de ambas lesiones; operado en Clínica RedSalud Mayor Temuco en septiembre de 2023. En el intraoperatorio se verificó además la coexistencia de una lesión de aspecto metastásico en el segmento III del hígado, y adhesión de la región antro-pilórica a la vesícula biliar. Se realizó gastrectomía total, linfadenectomía D2, esófago-yeyuno anastomosis término-lateral, resección segmentaria hepática (segmento III) y colecistectomía. El paciente permaneció 6 días en la UCI debido a que desarrolló insuficiencia hepática (encefalopatía leve y ascitis). Se alimentó vía enteral por sonda naso-yeyunal. Posteriormente inició alimentación oral progresiva, la que fue bien tolerada. Completó 11 días de hospitalización en servicio médico-quirúrgico, donde mejoró actividad neurológica, hasta su alta domiciliaria. Actualmente, lleva dos meses desde su operación, se encuentra en buenas condiciones generales, y el Comité Oncológico decidió no dar quimioterapia adyuvante. Se presenta un caso inusual de CG de tipo bifocal, respecto de lo cual hay escasa información disponible. Se logró realizar cirugía con intención curativa en un paciente de alto riesgo, con un resultado exitoso.

SUMMARY: Gastric cancer (GC) is the first cause of death from cancer in men, and the third one in women, in Chile. However, a bifocal GC (BGC) is uncommon. The aim of this study was to report a case of CGB, with negative-lymph nodes in a patient with liver cirrhosis, who underwent surgery; and review the existing evidence regarding its morphological, therapeutic and prognostic characteristics. Clinical case: A 74-year-old male patient with a medical history of diabetes, hypertension, congestive heart failure, and cirrhosis underwent surgical intervention for GC located in subcardial and antro- pyloric regions. The diagnosis was established via endoscopy and confirmed histologically. Surgery was performed at the RedSalud Mayor Temuco Clinic in September 2023. During intraoperative assessment, the coexistence of a lesion with metastatic-like characteristics in segment III of the liver was also verified, along with adhesions between the antro-pyloric region and the gallbladder. Surgical approach encompassed total gastrectomy, D2 lymphadenectomy, esophago-jejunostomy, segmental hepatic resection, and cholecystectomy. Subsequently, the patient required a six-day stay in ICU due to the development of hepatic insufficiency, characterized by mild encephalopathy and ascites. Enteral nutrition was administered via a naso-jejunal tube, followed by a gradual transition to oral feeding, which was well-tolerated. The patient completed an 11-day hospitalization period in the medical-surgical ward, during which his neurological function improved significantly, resulting in his discharge. At present, 2 months post-surgery, the patient remains in satisfactory general health, and the Oncology Committee decided not to proceed with adjuvant chemotherapy. This case represents a rare instance of bifocal GC, for which there is limited available literature. Surgical intervention with curative intent was successfully carried out in a high-risk patient, yielding a positive outcome.

Transcription Factor E2F7 Activates PKMYT1 to Partially Suppress Adriamycin Sensitivity in Gastric Cancer Through the MAPK Signaling Pathway

ABSTRACT Background: Adriamycin (ADM) resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer. Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot. Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells. Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.

Reducción de la infección por Helicobacter pylori en pacientes derivados a endoscopia digestiva alta en Santiago de Chile entre 2010-2020 / Reduction in Helicobacter pylori infection among patients referred for upper gastrointestinal endoscopy in Santiago, Chile, between 2010-2020

RESUMEN Latinoamérica presenta una alta prevalencia de infección por Helicobacter pylori (Hp). Entre 1996-2003 la prevalencia en Santiago de Chile fue del 70%; estudios recientes presentan una disminución en esta infección. Actualizar la frecuencia de Hp es fundamental debido a su impacto en la salud asociado. Objetivo: Nuestro objetivo fue describir la tendencia de la infección por Hp en pacientes que asisten a endoscopía digestiva alta (EDA) ambulatoria en una población chilena. Materiales y métodos: Se realizó un estudio observacional retrospectivo de pacientes mayores de 18 años que asistieron a una primera EDA con test rápido de ureasa entre 2010-2020. La tendencia en el tiempo fue descrita mediante análisis de series de tiempo. Se construyó un modelo Poisson para estimar el riesgo de infección, ajustado por edad y sexo. Resultados: Se incluyeron 11 355 pacientes [66,9% mujeres; edad media 52 años; Hp 41,6%]. El sexo masculino presentó una mayor frecuencia de infección por Hp [RR 1,13; (IC95%:1,08-1,18)]. La frecuencia de Hp disminuyó significativamente desde 45,1% en 2010 hasta 29% en 2020, con 36% menor probabilidad de presentar infección por Hp en 2020 con respecto al 2010 [RR 0,64; (IC95%:0,55-0,74)]. Se proyectó un descenso progresivo en la tendencia de infección por Hp hasta valores cercanos al 25% para el año 2025. Conclusión: Se observó una reducción significativa en la infección por Hp entre los años 2010-2020. Esta disminución pudiese ser explicada mediante la incorporación de políticas públicas de salud en la última década asociadas a cambios sociosanitarios.

ABSTRACT Latin America presents a high prevalence of Helicobacter pylori (Hp) infection. Between 1996-2003, the prevalence in Santiago, Chile, was 70%; recent studies indicate a decrease in this infection. Updating the frequency of Hp is crucial due to its associated health impact. Objective: Our objective was to describe the trend in Hp infection in patients undergoing ambulatory esophagogastroduodenoscopy (EGD) in a Chilean population. Materials and methods: A retrospective observational study was conducted on patients over 18 years old who attended a first EGD with a rapid urease test between 2010-2020. Time trends were described through time series analysis. A Poisson model was constructed to estimate the risk of infection, adjusted for age and gender. Results: 11,355 patients were included [66.9% females; mean age 52 years; Hp 41.6%]. Male gender presented a higher frequency of Hp infection [RR 1.13; (95% CI: 1.08-1.18)]. Hp frequency infection decreased significantly from 45.1% in 2010 to 29% in 2020, with a 36% lower probability of Hp infection in 2020 compared to 2010 [RR 0.64; (95% CI: 0.55-0.74)]. A progressive decline in Hp infection trend was projected, reaching values close to 25% by year 2025. Conclusion: A significant reduction in Hp infection was observed between 2010-2020. This decrease could be explained by the implementation of public health policies in the last decade associated with socio-sanitary changes.

Research progress on the mechanism of metachronous gastric cancer after endoscopic submucosal dissection and Helicobacter pylori eradication in early gastric cancer / 解放军医学杂志

Helicobacter pylori(HP)infection is a Class Ⅰ carcinogen in gastric cancer,closely related to the occurrence of gastric cancer.Many studies have shown that HP eradication has a preventive effect on gastric cancer.However,2.7%-6.1%of patients with early gastric cancer who have been eradicated after endoscopic submucosal dissection(ESD)can still develop metachronous gastric cancer(MGC),and the mechanism of its occurrence is still unclear.In this review,the atrophy of gastric mucosa and intestinal metaplasia cannot be completely reversed after HP eradication,the excessive proliferation of gastric mucosa epithelial cells,the accumulation of genetic abnormalities,the homeostasis imbalance of the epigenetic group,changes in immune microenvironment,the abnormality of stem cells in gastric mucosa,chromatin accessibility,and changes in chromosome remodeling were discussed in the mechanism of carcinogenesis caused by the above molecular changes after ESD and HP eradication in early gastric cancer.

Analysis of risk factors of postoperative venous thromboembolism in patients with gastric cancer and establishment of prediction model / 临床外科杂志

Objective To explore the related risk factors of postoperative venous thromboembolism(VTE)in patients with gastric cancer,establish a prediction model and verify the predictive value of the model.Methods 160 gastric cancer patients who underwent radical surgery at the First Affiliated Hospital of Hainan Medical College from January 2019 to June 2021 were included as the modeling group,167 cases as validation group.Their clinicopathological data were collected.All modeling group patients were divided into VTE group and N-VTE group according to the occurrence of VTE within 6 months after operation.The clinicopathological factors of the two groups were analyzed by univariate analysis.Then,the statistically significant indexes in the univariate analysis were substituted into the multivariate logistic regression model for multivariate analysis to obtain the independent risk factors affecting the postoperative VTE of patients with gastric cancer.The independent risk factors obtained based on the results of multivariate analysis were combined p Value,assign scores to independent risk factors according to the principle of nomogram,construct the nomogram model,draw the nomogram with R software,internal and external validation of nomogram model with Bootstrap method and calibration curve,calculate the discrimination evaluation Index C index,and evaluate the calibration ability of the prediction model through goodness of fit(H-L).Results 160 modeling group patients with gastric cancer underwent radical gastrectomy.According to the occurrence of VTE within 6 months after operation,they were divided into VTE group(23 cases)(14.38％)and N-VTE group(137 cases)(85.62％).Multivariate analysis showed that the age of 60 years old,the diameter of the lesion was more than 5 cm,the stage of diabetes,the TNM/T stage was 3-4,and the lymph node metastasis was the independent risk factors affecting the postoperative VTE of patients with gastric cancer(P＜0.05).Construct nomogram:P=1/(1+e-x),X=1.885 × Age(≥ 60 years=1,＜60 years=0)+2.051 × Diabetes mellitus(=1,no=0)+2.646 × Lesion diameter(≥ 5 cm=1,＜5 cm=0)+2.952 × TNM/T stage(stage 1-2=0,stage 3-4=1)+0.694 × Lymph node metastasis(yes=1,no=0)-0.436.The C index of nomogram model was 847(95％CI:0.784-0.932)and 0.832(95％CI:0.772-0.910).H-L test showed that the predicted value of postoperative VTE in patients with gastric cancer was in good agreement with the actual value(P＞0.05).Conclusion A nomogram model for predicting the risk of postoperative VTE in patients with gastric cancer was established.It was verified that the model can accurately predict the risk of postoperative VTE in patients with gastric cancer.

Research and clinical progress of immunotherapy for gastric cancer / 临床外科杂志

Due to the limited treatment options of advanced gastric cancer and prone to chemoresistance,there is an urgent need for novel treatment methods to improve the prognosis of these patients.At present,immunotherapy including immune checkpoint inhibitor,adoptive cell therapy,tumor vaccine,nonspecific immune enhancer and cytokine therapy has shown good curative effect on gastric cancer.Additionally,carrier drugs and 3D printing technology have also achieved curative effects in preclinical experiments.Clinical trials used immunooncology monotherapy or combined immunochemotherapy to improve the overall survival time and objective response rate of patients with gastric cancer.Based on the preliminary evidence,we believe that immunotherapy can positively affect the natural history and improve the prognosis of patients with gastric cancer.

Clinicopathological features of gastric fundus mucosal adenocarcinoma:report of four cases / 临床与实验病理学杂志

Purpose To observe the clinicopathological changes of gastric adenocarcinoma of fundic-gland mucosa type(GA-FGM).Methods The clinicopathological data of 4 cases of GA-FGM was analyzed retrospectively.The expression of MUC5AC and MUC6 was detected by immunohistochemical method,and review relevant literature.Results The tumor dif-ferentiated into gastric foveal epithelium and gastric fundus gland.The differentiated part of the pits consists of high colum-nar neoplastic epithelium with low atypia,which can be papilla-ry,villous or tubular morphology.Immunohistochemical staining showed MUC5AC expression.The gastric fundus gland differen-tiated into cervical mucous cells,main cells and parietal cells,and was positive for MUC6 immunohistochemistry.Conclusion Gastric adenocarcinoma of fundic-gland mucosa type has u-nique pathologic characteristics,which is very difficult to diag-nose in biopsy,and the morphology of GA-FGM overlaps with that of gastric fundus adenocarcinoma,so we need to strengthen our understanding.Immunohistochemistry plays an important role in differential diagnosis.

Progress of research on m6A demethylases in gastric cancer / 上海交通大学学报（医学版）

Gastric cancer(GC)is one of the most common malignancies in the digestive system.Many patients are found in advanced stage and have a poor prognosis.Surgery and chemotherapy remain the main treatments for gastric cancer.N6-methyladenosine(m6A)is a hot topic in tumor research in recent years.As the most common form of RNA modification in eukaryotes,m6A can regulate various stages of the RNA cycle,including RNA splicing,processing,degradation,and translation,thereby regulating RNA expression and function,playing a critical role in various pathways such as cell differentiation,development,and metabolism.The m6A demethylase can remove methyl groups on RNA,ensuring that m6A methylation is a dynamic and reversible process.As a key enzyme in the m6A methylation process,the imbalance of m6A demethylases fat mass and obesity-associated protein(FTO),AlkB homolog 5(ALKBH5)and ALKBH3 regulate the progression of gastric cancer through various mechanisms,which is closely related to the occurrence and development of gastric cancer.These m6A demethylases regulate the signaling pathway,alter the proliferation and invasion ability of gastric cancer cells,affect its resistance to chemotherapy drugs,participate in regulating the immune response and mitochondrial metabolism of gastric cancer,and affect the growth of gastric cancer cells.They are expected to become a novel therapeutic target.This article comprehensively summarizes the molecular mechanism of m6A demethylase involved in the occurrence and development of gastric cancer,and the relationship between its expression and function,and biological characteristics of m6A demethylase were reviewed,aiming to provide new research ideas for early diagnosis and targeted treatment of gastric cancer.

Correlation between CYP3A5*3 Gene Polymorphism and Adverse Reactions of Apatinib Monotherapy in Patients with Advanced Gastric Cancer / 现代检验医学杂志

Objective To investigate the relationship between cytochrome P450 3A5*3(CYP3A5*3)gene polymorphism and adverse reactions of apatinib monotherapy in advanced gastric cancer patients.Methods A total of 86 patients with advanced gastric cancer who received apatinib monotherapy at Nanjing First Hospital from January 2020 to June 2022 were selected,and 2 ml of peripheral venous blood from patients was collected.The genotype of CYP3A5*3 was identified using PCR-RFLP combined sequencing method,and its correlation with adverse reactions was analyzed by apatinib.Results Among the 86 patients,there were 29 cases of mutant heterozygous genotype(AG genotype)and 51 cases of mutant homozygous genotype(GG genotype),with a mutation type accounting for 93.02％.The incidence of hypertension and leukopenia in patients with the CYP3A5*3 GG genotype was significantly higher than in patients with the AA+AG genotype(χ2=6.154,6.947,P=0.043,0.027).Other adverse reactions related to apatinib treatment were not found to be associated with the CYP3A5*3 genotype(P＞0.05).In addition,no correlation was found between severe adverse reactions and the CYP3A5*3 genotype(P＞0.05).Conclusion The CYP3A5*3 GG genotype significantly increased the risk of hypertension and leukopenia caused by apatinib monotherapy,and no correlation was found with the risk of serious adverse reactions.

Study on Preoperative Serum Exosomes miR-193a and miR-208b Levels Expression and Their Prognostic Predictive Value in Patients Undergoing Radical Gastrectomy for Gastric Cancer / 现代检验医学杂志

Objective To investigate the expression levels and prognostic value of preoperative serum exosomes micro RNA(miR)-193a and micro RNA(miR)-208b in patients with gastric cancer(GC).Methods A total of 132 patients who underwent GC radical gastrectomy in the First Affiliated Hospital of Xinjiang Medical University from March 2018 to March 2020 were regarded as the GC group,while 132 healthy individuals who underwent physical examination were selected as the control group.Their clinical and pathological data were collected and compared.The relative expression levels of miR-193a and miR-208b in serum exosomes were detected using quantitative real-time polymerase chain reaction(qRT-PCR)method.Pearson method was used to analyze the correlation between miR-193a and miR-208b.The correlation between the expression of miR-193a and miR-208b in preoperative serum exosomes of GC patients and postoperative prognosis was analyzed using Kaplan-Meier method.Univariate and multivariate COX regression were applied to analyze the influencing factors of prognosis.Results The expression level of miR-208b in the serum exosomes of the GC group was higher than that of the control group(1.77±0.14 vs 1.02±0.01),while the expression level of miR-193a was lower than that of the control group(0.52±0.06 vs 1.01±0.01),and the differences were statistically significant(t=92.551,61.392,all P<0.05).The expression levels of miR-193a and miR-208b in GC patients before surgery were negatively correlated(r=-0.409,P<0.05).The low expression rate of miR-193a and high expression rate of miR-208b in patients with TNM stage Ⅰ+Ⅱ,no lymph node metastasis,and no distant metastasis were lower than those in patients with TNM stage Ⅲ+Ⅳ,lymph node metastasis,and distant metastasis,and the differences were statistically significant(χ2=5.008,4.397;7.142,4.688;4.407,5.189,all P<0.05).The 3-year cumulative survival rate of patients with low expression of miR-193a(30.43%)was lower than that of patients with high expression(60.32%)(χ2=17.861,P<0.001),while the 3-year cumulative survival rate of patients with high expression of miR-208b(27.14%)was lower than that of patients with low expression(64.52%)(χ2=16.340,P<0.001).The independent prognostic factors included serum levels of exosomes miR-193a(HR=0.493,95%CI:0.323～0.753)and miR-208b(HR=2.697,95%CI:1.382～5.262)(all P<0.05).Conclusion The preoperative serum miR-193a level in the exosomes was decreased and miR-208b level was increased,and their expression levels were related to the prognosis of patients undergoing GC radical gastrectomy.

Effect of the explain-simulate-practice-communication-support nursing mode on perioperative stress and postoperative rehabilitation of patients undergoing laparoscopic radical gastrectomy for gastric cancer / 中国实用护理杂志

Objective:To investigate the effect of the explain-simulate-practice-communication-support (ESPCS) nursing model on perioperative stress and postoperative rehabilitation in patients undergoing laparoscopic radical gastrectomy for gastric cancer. Provide a basis for the application of ESPCS nursing model in patients undergoing radical gastrectomy for gastric cancer.Methods:This was a quasi-experimental study. A total of 212 patients who underwent laparoscopic radical gastrectomy for gastric cancer in the First Affiliated Hospital of China Medical University from May 2019 to May 2023 were selected by convenience sampling and divided into the observation group and the control group by random digital table method, with 106 patients in each group. The control group received routine nursing intervention, while the observation group received ESPCS nursing intervention for 3 months. The perioperative stress hormones (serum cortisol and epinephrine), Self-rating Depression Scale (SDS) score, Self-rating Anxiety Scale (SAS) score, gastrointestinal function indicators, and the 36-item Short Form Health Survey Questionnaire (SF-36) score were compared between the two groups.Results:Two groups of patients were lost to follow-up, with a total of 104 patients in each group. The control group consisted of 65 males and 39 females, aged (61.59 ± 3.42) years old, while the observation group consisted of 61 males and 43 females, aged (60.78 ± 3.63) years old. Six days after operation, serum cortisol and epinephrine levels in the observation group were (221.46 ± 24.15) nmol/L and (28.11 ± 3.47) pmol/L, respectively, which were lower than those in the control group (261.84 ± 27.91) nmol/L and (31.49 ± 3.86) pmol/L, respectively, and the differences were statistically significant ( t=11.16, 6.64, both P<0.05). After 1 week of operation, the SDS and SAS scores in the observation group were (41.39 ± 2.21), (39.62 ± 2.31) points, respectively, which were lower than those in the control group (45.27 ± 2.34), (44.35 ± 2.37) points, and the differences were statistically significant ( t=12.29, 14.58, both P<0.05). The time of first exhaust, first defecation, intestinal ringing and first solid eating in the observation group were (55.38 ± 6.23), (68.84 ± 7.92), (38.73 ± 4.31), (62.31 ± 7.67) h, respectively, which were lower than those in the control group (67.51 ± 8.39), (84.17 ± 9.25), (48.43 ± 5.79), (75.65 ± 8.52) h, the differences were statistically significant ( t values were 11.84-13.71, all P<0.05). After intervention, the scores of physiological function, role physical, general health, mental health, social function and the total score of SF-36 in the observation group were (82.17 ± 4.12), (83.21 ± 3.67), (75.27 ± 3.64), (80.63 ± 4.31), (77.58 ± 4.13), (73.89 ± 4.86) points, respectively, which were higher than those in the control group (75.61 ± 4.39), (74.24 ± 3.88), (69.45 ± 4.38), (71.28 ± 4.05), (72.35 ± 3.84), (68.81 ± 5.14) points, the differences were statistically significant ( t values were 7.32-17.13, all P<0.05). Conclusions:The ESPCS nursing model can effectively alleviate the perioperative stress reaction of gastric cancer patients undergoing laparoscopic radical gastrectomy, promote the recovery of gastrointestinal function and improve the quality of life.

The mechanism of emodin inhibiting YAP1 and FOXD1 in gastric cancer AGS cells and its related study / 实用医学杂志

Objective To explore the possible mechanism of emodin in inhibiting proliferation,migration,and invasion of AGS cells and in suppressing the expressions of YAP1 and FOXD1.Methods Normal gastric cell GES-1 and gastric cancer cell AGS were cultured with different concentrations of emodin.CCK8 test,scratch test and Transwell assay were used to verify changes in the biological phenotype of AGS cells.TCGA database was applied to analyze expressions of HK2,YAP1 and FOXD1 in gastric cancer tissues and normal gastric tissues.Western blotting method was used to detect the impacts of emodin on HK2,YAP1 and FOXD1 proteins in AGS cells.Exogenous pyruvic acid was added to verify the changes in YAP1 and FOXD1.Results The IC50 of emodin was significantly higher in GES-1 cells than in AGS cells(P<0.05).CCK8 proliferation test,scratch test,and Transwell assay showed that emodin significantly inhibited the biological abilities of AGS(P<0.05 for comparisons).Analysis on the TCGA bioinformatics database found that the expression of key enzymes HK2 in the glycolysis pathway and oncogenes YAP1 and FOXD1 was significantly higher in gastric cancer tissues than in normal gastric tissues(P<0.05 for comparisons).Emodin significantly inhibited the protein expressions of key glycolytic enzymes HK2 and oncogenes YAP1 and FOXD1(P<0.05 for comparisons).With supplement of exogenous glycolytic metabolite pyruvate,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased(P<0.05 for comparisons).Conclusions Emodin has a significant pharmacological inhibitory effect on gastric cancer AGS cells,markedly suppressing their biological phenotype.Emodin not only significantly inhibits the key enzyme HK2 in glycolysis metabolism,but also the protein expressions of oncogenes YAP1 and FOXD1.With the addition of exogenous pyruvate to enhance the glycolytic metabolic pathway,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased.The above results suggest a close association of YAP1 and FOXD1 with glycolytic metabolism.Emodin may inhibit oncogenes YAP1 and FOXD1 through the glycolytic metabolism of gastric cancer AGS cells.

Expression of CENPF and miR-1-3p in the serum of patients with advanced gastric cancer and their correla-tion with prognosis / 实用医学杂志

Objective To investigate the expression of centromeric protein F(CENPF)and microribonucleic acid 1-3p(miR-1-3p)in the serum of patients with advanced gastric cancer and their correlation with prognosis.Methods Sixty patients with advanced gastric cancer admitted to our hospital from March 2019 to March 2020 were collected as the study group,while 60 healthy volunteers who underwent physical examinations at our hospital's physical examination center during the same period were collected as the control group.Real-time fluorescence quantitative PCR(qRT-PCR)method was applied to detect the expression levels of serum CENPF and miR-1-3p in each group;Pearson method was applied to analyze the correlation between serum levels of CENPF and miR-1-3p;Kaplan-Meier method was applied to analyze the relationship between the expression of CENPF,miR-1-3p,and prognosis in patients with advanced gastric cancer;and COX regression was applied to analyze risk factors affecting the prognosis of patients with advanced gastric cancer.Results Compared with the control group,the CENPF level in the study group was obviously increased,while the miR-1-3p level was obviously reduced(P＜0.05).The correlation analysis results showed that there was a negative correlation between serum CENPF and miR-1-3p levels in patients with advanced gastric cancer(r =-0.650,P＜0.001).There were obvious differences in CENPF and miR-1-3p levels among different TNM stages and lymph node metastasis status(P＜0.05).The 3-year survival rate of patients in the high expression group of CENPF was 19/30(63.33%),which was obviously lower than that in the low expression group,28/30(93.33%)(χ2 = 7.954,P＜0.001);the 3-year survival rate of patients in high expression group of miR-1-3p was 29/30(96.67%),which was obviously higher than that in the low expression group,18/30(60.00%)(χ2 = 11.882,P = 0.001).Multivariate COX regression analysis showed that TNM staging,lymph node metastasis,CENPF,and miR-1-3p expression were risk factors affecting the prognosis of patients with advanced gastric cancer(P＜0.05).Conclusion The serum CENPF level in patients with advanced gastric cancer obviously increase,while miR-1-3p level obviously decrease,both of which are related to prognosis.

LncRNA GNAS-AS1 participates in the proliferation and migration of gastric cancer cells by regulating the miR-449a/Notch1 axis / 实用医学杂志

Objective To explore the impacts of long non-coding RNA(LncRNA)GNAS antisense RNA1(GNAS-AS1)on the proliferation and migration of gastric cancer(GC)cells by regulating the miR-449a/Notch1 axis.Method Tumor tissue and adjacent tissue samples were collected from 30 patients diagnosed with GC at Sichuan Provincial People's Hospital from September 2013 to September 2017;GC cells AGS were randomly divided into Control group,si-NC group,si-GNAS-AS1 group,si-GNAS-AS1+inhibitor NC group,and si-GNAS-AS1+miR-449a inhibitor group.Real-time fluorescence quantitative PCR method was applied to detect the expres-sion of GNAS-AS1,miR-449a,and Notch1 mRNA;MTT experiments and plate cloning experiments were applied to detect the proliferation;wound healing test was applied to detect cell migration;Transwell experiment was applied to detect cell invasion.Western Blot was applied to detect the expression of Notch1,E-cadherin,Vimentin,and N-cadherin proteins.Double Luciferase reporter gene experiment was applied to verify the relationship between GNAS-AS1 and miR-449a,between miR-449a and Notch1,respectively.Results Compared with adjacent tissues,the expression of GNAS-AS1 and Notch1 mRNA in tumor tissue was increased,the expression of miR-449a was reduced(P<0.05).Compared with the Control group and si-NC group,the expression of GNAS-AS1,OD490 value,number of clones formed,scratch healing rate,number of cell invasions,and the expression of Notch1,Vimentin,and N-cadherin proteins in AGS cells in the si-GNAS-AS1 group reduced,the expression of miR-449a and E-cadherin protein increased(P<0.05).Compared with the si-GNAS-AS1 group and the si-GNAS-AS1+inhibitor NC group,the OD490 value,scratch healing rate,number of cell invasions,Notch1,Vimentin,and N-cadherin expression in the si-GNAS-AS1+miR-449a inhibitor group increased,the expression of miR-449a and E-cadherin protein reduced(P<0.05).GNAS-AS1 targeted and negatively regulated miR-449a expression,while miR-449a targeted and negatively regulated Notch1 expression.Conclusion Silencing GNAS-AS1 may inhibit the expression of Notch1 protein by up-regulating miR-449a,thereby inhibiting the proliferation,migration,and invasion pro-cesses of GC cells.

Research on establishing gastric cancer lymph node metastasis prediction model based on machine learning and routine laboratory indicators / 实用医学杂志

Objective To establish a prediction model for lymph node metastasis(LNM)of gastric cancer based on routine laboratory indicators using machine learning algorithms.Methods This study collected data of 741 gastric cancer patients at Affiliated Hospital of Nantong University between January 2020 and January 2022 for model training and testing.Additionally,data of 102 gastric cancer patients between January 2023 and October 2023 were collected for model validation.XGBoost algorithm was used to calculate the importance of indicators and filter out a set of important indicators from 66 indicators.Five machine learning algorithms,including K-Nearest Neighbor,Support Vector Machine,Multilayer Perceptron,Random Forest and Adaboost,were constructed and trained for comparative analysis.Furthermore,the stability and accuracy of the model were further validated on the validation set.Results This study selected a set of important indicators composed of 9 routine laboratory indicators and trained the gastric cancer LNM prediction model,named V9.Additionally,through comparative experiments,it was found that the Adaboost algorithm based on the boosting strategy had the best performance,with evaluation metrics such as area under the curve,F1 score,accuracy,sensitivity,and specificity ranging from 0.833 to 0.968.The accuracy of the predictions on the validation set was 94.12%.Conclusion V9 was a gastric cancer LNM prediction model that has auxiliary clinical diagnostic value.It can be used to assess the risk of patients accurately and provide a basis for clinical decision-making.

Research progress of exosomes in distant metastasis and drug resistance of gastric cancer / 实用医学杂志

Gastric cancer(GC)is one of the most common tumors and the fourth leading cause of cancer-related death worldwide.Due to the lack of specific signs in early GC,most cases are diagnosed at an advanced stage,often accompanied by infiltration and distant metastasis.Although chemotherapy is the most commonly used treatment for gastric cancer,due to the emergence of drug resistance,many patients will still relapse after chemo-therapy,resulting in poor prognosis.Exosome(EXOs)in the Tumor micro environment(TME)can participate in intercellular communication and play an important role in GC distant metastasis and drug resistance.At present,the detailed mechanism of GC distant metastasis and drug resistance is still unclear.Identifying the exosome-induced mechanism involved in GC distant metastasis and drug resistance can help us find more reliable treatment methods for GC metastasis and drug resistance.This article reviews the mechanism of exosome in GC distant metastasis and drug resistance,in order to provide help for the diagnosis,treatment and research of GC.

EUS Combined with LCI/BLI-ME in Determination of Infiltration Depth of Early Gastric Cancer after Helicobacter pylori Eradication / 华中科技大学学报(医学版)

Objective To explore the value of endoscopic ultrasonography combined with linked color imaging/blue laser imaging technology combined with magnifying endoscopy(LCI/BLI-ME)in determining the depth of infiltration in early gastric cancer after eradication of Helicobacter pylori(H.pylori),as well as the influencing factors affecting the accuracy of the judg-ment,so as to explore its clinical application value.Methods Clinical data of 91 patients with early gastric cancer after H.pylori eradication were collected from October 2017 to June 2023 in Wuhan No.1 Hospital.Based on the pathological diag-nosis,the endoscopic manifestations of gastric mucosa and early gastric cancer after eradication of H.pylori were summa-rized.The accuracy of endoscopic ultrasonography combined with LCI/BLI-ME in determining the infiltrating depth of early gastric cancer and the related factors affecting the accuracy were evaluated.Sensitivity,specificity,and accuracy were used to in-dicate the effectiveness of endoscopic diagnosis.Chi-square test was used to compare the difference between endoscopic diagnosis and pathological diagnosis.Logistic regression analysis was used to determine the factors affecting the diagnostic accuracy of en-doscopy.Results The overall accuracy of endoscopic ultrasonography combined with LCI/BLI-ME in determining the infiltra-tion depth of early gastric cancer after H.pylorieradication was 77.08％,and the accuracies of uT1a and uT1b stages were 82.86％and 61.53％,respectively.There were 12 under-diagnosed cases(17.14％)and 10 over-diagnosed cases(38.46％).The sensitivity,specificity,positive predictive value and negative predictive value of endoscopic ultrasonography combined with LCI/BLI-ME in the diagnosis of mucosal lesions were 85.29％,57.14％,82.86％and 61.5％,respectively.The results of univariate and multivariate logistic regression analysis showed that the maximum diameter of the lesion and the degree of tissue differentia-tion were the factors affecting the diagnostic accuracy,but not the location and shape of the lesion.The accuracy of endoscopy in judging the infiltration depth of early gastric cancer was decreased with the increase of lesion or the reduction of tissue differen-tiation degree.Conclusion Endoscopic ultrasonography combined with LCI/BLI-ME has good clinical application value in deter-mining the infiltration depth of early gastric cancer T1a after H.pylori eradication.The lesion size and the degree of tissue dif-ferentiation affect the accuracy of the judgment.