Over-expression of gastrin inhibits apoptosis of gastric cancer cells via reactive oxygen species and annexin A2-mediated mitochondrial dysfunction / La sobreexpresión de gastrina inhibe la apoptosis de las células de cáncer gástrico a través de especies reactivas de oxígeno y disfunción mitocondrial mediada por anexina A2

SUMMARY: Gastrin plays a vital role in the development and progression of gastric cancer (GC). Its expression is up-regulated in GC tissues and several GC cell lines. Yet, the underlying mechanism remains to be investigated. Here, we aim to investigate the role and mechanism of gastrin in GC proliferation. Gastrin-overexpressing GC cell model was constructed using SGC7901 cells. Then the differentially expressed proteins were identified by iTRAQ analysis. Next, we use flow cytometry and immunofluorescence to study the effect of gastrin on the mitochondrial potential and mitochondria-derived ROS production. Finally, we studied the underlying mechanism of gastrin regulating mitochondrial function using Co-IP, mass spectrometry and immunofluorescence. Overexpression of gastrin promoted GC cell proliferation in vitro and in vivo. A total of 173 proteins were expressed differently between the controls and gastrin- overexpression cells and most of these proteins were involved in tumorigenesis and cell proliferation. Among them, Cox17, Cox5B and ATP5J that were all localized to the mitochondrial respiratory chain were down-regulated in gastrin-overexpression cells. Furthermore, gastrin overexpression led to mitochondrial potential decrease and mitochondria-derived ROS increase. Additionally, gastrin-induced ROS generation resulted in the inhibition of cell apoptosis via activating NF-kB, inhibiting Bax expression and promoting Bcl-2 expression. Finally, we found gastrin interacted with mitochondrial membrane protein Annexin A2 using Co-IP and mass spectrometry. Overexpr ession of gastrin inhibits GC cell apoptosis by inducing mitochondrial dysfunction through interacting with mitochondrial protein Annexin A2, then up-regulating ROS production to activate NF-kB and further leading to Bax/Bcl-2 ratio decrease.

La gastrina juega un papel vital en el desarrollo y progresión del cáncer gástrico (CG). Su expresión está regulada al alza en tejidos de CG y en varias líneas celulares de CG. Sin embargo, el mecanismo subyacente aun no se ha investigado. El objetivo de este estudio fue investigar el papel y el mecanismo de la gastrina en la proliferación de CG. El modelo de células CG que sobre expresan gastrina se construyó usando células SGC7901. Luego, las proteínas expresadas diferencialmente se identificaron mediante análisis iTRAQ. A continuación, utilizamos la citometría de flujo y la inmunofluorescencia para estudiar el efecto de la gastrina en el potencial mitocondrial y la producción de ROS derivada de las mitocondrias. Finalmente, estudiamos el mecanismo subyacente de la gastrina que regula la función mitocondrial utilizando Co-IP, espectrometría de masas e inmunofluorescencia. La sobreexpresión de gastrina promovió la proliferación de células CG in vitro e in vivo. Un total de 173 proteínas se expresaron de manera diferente entre los controles y las células con sobreexpresión de gastrina y la mayoría de estas proteínas estaban implicadas en la tumorigenesis y la proliferación celular. Entre estas, Cox17, Cox5B y ATP5J, todas localizadas en la cadena respiratoria mitocondrial, estaban reguladas a la baja en las células con sobreexpresión de gastrina. Además, la sobreexpresión de gastrina provocó una disminución del potencial mitocondrial y un aumento de las ROS derivadas de las mitocondrias. Por otra parte, la generación de ROS inducida por gastrina resultó en la inhibición de la apoptosis celular mediante la activación de NF-kB, inhibiendo la expresión de Bax y promoviendo la expresión de Bcl-2. Finalmente, encontramos que la gastrina interactuaba con la proteína de membrana mitocondrial Anexina A2 usando Co-IP y espectrometría de masas. La sobreexpresión de gastrina inhibe la apoptosis de las células CG al inducir la disfunción mitocondrial a través de la interacción con la proteína mitocondrial Anexina A2, luego regula el aumento de la producción de ROS para activar NF-kB y conduce aún más a la disminución de la relación Bax/Bcl-2.

Application values of progastrin-releasing peptide, neuron-specific enolase, cytokeratin 19 fragment antigen 21-1, squamous cell carcinoma antigen and human epididymis protein 4 in the diagnosis of lung cancer / 肿瘤研究与临床

Objective:To investigate the clinical values of progastrin-releasing peptide (Pro-GRP), neuron-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), squamous cell carcinoma antigen (SCCA) and human human epididymis protein 4 (HE4) detections in the diagnosis of lung cancer patients.Methods:The clinical data of 200 lung cancer patients who were admitted to the Second Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2021 were retrospectively analyzed. According to the pathological type, the patients were divided into lung adenocarcinoma group (80 cases), lung squamous cell carcinoma group (75 cases) and small cell lung cancer group (45 cases). Fifty patients with benign lung diseases and 50 healthy physical examiners who were admitted to the hospital during the same period were selected. All the subjects were tested for the levels of Pro-GRP, NSE, CYFRA21-1, SCCA and HE4, and the differences of each index level in the subjects of different subgroups were compared. The receiver operating characteristic (ROC) curve was drawn, and using pathological diagnosis result as the gold standard, the diagnostic efficacy of each index alone and in combination for lung cancer was compared.Results:The serum levels of Pro-GRP, NSE, CYFRA21-1, SCCA and HE4 in lung cancer group were higher than those in the benign lung diseases group and the healthy control group (all P < 0.001). There were no statistical differences in the levels of serum Pro-GRP, NSE, CYFRA21-1, SCCA and HE4 between the benign lung diseases group and the healthy control group (all P > 0.05). The levels of Pro-GRP, NSE and HE4 in the small cell lung cancer group were higher than those in the lung adenocarcinoma group and the lung squamous cell carcinoma group (all P < 0.05). NSE and HE4 levels in the lung adenocarcinoma group were higher than those in the lung squamous carcinoma group (both P < 0.05), while CYFRA21-1 and SCCA levels were lower than those in the lung squamous carcinoma group (both P < 0.05). The AUC of lung cancer diagnosed by HE4 was the largest (0.813), the AUC of lung adenocarcinoma diagnosed by HE4 was the largest (0.824), the AUC of lung squamous carcinoma diagnosed by CYFRA21-1 was the largest (0.884), and the AUC of small cell lung cancer diagnosed by NSE was the largest (0.959). The AUC of lung cancer diagnosed by combined detection of 5 indicators was 0.951, the AUC of lung adenocarcinoma and small cell lung cancer diagnosed by combined detection of 5 indicators was 0.975 and 0.996, and the AUC of lung squamous cell carcinoma diagnosed by combined detection of CYFRA21-1, SCCA and HE4 was 0.967. Conclusions:The levels of Pro-GRP, NSE, CYFRA21-1, SCCA, HE4 and other indicators have certain clinical values in the diagnosis of lung cancer and its pathological types, and the combined detection of each index is more valuable than a single index.

Correlation of serum pro-gastrin-releasing peptide, sugar chain antigen 242, procalcitonin levels in patients with chronic atrophic gastritis with intestinal metaplasia and Helicobacter pylori infection and prognosis / 中国医师进修杂志

Objective:To investigate the correlation of serum pro-gastrin-releasing peptide (ProGRP), sugar chain antigen 242(CA242), procalcitonin(PCT) levels in patients with chronic atrophic gastritis (CAG) with intestinal metaplasia and Helicobacter pylori(Hp) infection and prognosis.Methods:One hundred patients with CAG intestinal metaplasia in Emergency General Hospital were selected as the research objects, and they were divided into infection group (75 cases) and non-infected group (25 cases) according to whether they had Hp infection. The clinical data, levels of serum ProGRP, CA242, and PCT were compared between the two groups, and the diagnostic value of the combination of serum indicators in the diagnosis of Hp infection in CAG intestinal metaplasia patients and their correlation with prognosis were analyzed.Results:The degree of atrophy and intestinal metaplasia in the infected group were higher than those in the non-infected group ( P<0.05). The levels of serum ProGRP, CA242 and PCT in the infected group were higher than those in the non-infected group: (159.41 ± 42.38) ng/L vs. (105.84 ± 18.29) ng/L, (7.24 ± 2.28) kU/L vs. (4.12 ± 1.30) kU/L, (3.84 ± 1.12)μg/L vs. (2.57 ± 0.82) μg/L, there were statistical differences ( P<0.05). The results of Spearman analysis showed that the levels of ProGRP, CA242, PCT had positive correlation with atrophy degree ( r = 0.614, 0.629, 0.672, P<0.05), and had positive correlation with intestinal metaplasia degree ( r = 0.574, 0.591, 0.603, P<0.05). The area under the curve (AUC) for the combined diagnosis of Hp infection in patients with CAG intestinal metaplasia by serum ProGRP, CA242, and PCT was 0.874 (95% CI 0.793 - 0.932), the diagnostic sensitivity and specificity were 76.00% and 92.00%, respectively. The incidence of gastric neoplasms in patients with Hp positive combined diagnosis of serum ProGRP, CA242, and PCT within 2 years (11.86%) was higher than that of negative patients (0), but the difference was not statistically significant ( P>0.05). Conclusions:The levels of serum ProGRP, CA242 and PCT in patients with CAG intestinal metaplasia are closely related to Hp infection. The combination of various indicators has high application value in the diagnosis of Hp infection.

Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Correlation of serum miRNA-21 and miRNA-335-5p expression with pepsinogen and gastrin-17 in patients with gastric cancer / 中国基层医药

Objective:To correlate the expression of microRNA (miRNA)-21 and miRNA-335-5p with pepsinogen and gastrin-17 in patients with gastric cancer.Methods:Sixty-one patients with gastric cancer who received treatment in Linhai Second People's Hospital between January 2019 and January 2021 were included in the patient group. An additional 60 healthy patients who concurrently received physical examination were included in the control group. Serum pepsinogen I, pepsinogen II and gastrin-17 levels were determined by latex-enhanced immunoturbidimetry. miRNA-21 and miRNA-335-5p expression were determined by quantitative reverse transcription-polymerase chain reaction. Serum pepsinogen I, pepsinogen II and gastrin-17 levels and miRNA-21 and miRNA-335-5p expression were compared between the two groups. The sensitivity and specificity of miRNA-21 and miRNA-335-5p in the diagnosis of gastric cancer were analyzed. The correlation between miRNA-21 and miRNA-335-5p expression and pepsinogen I, pepsinogen II and gastrin-17 levels was analyzed.Results:Serum pepsinogen I and gastrin-17 levels in the patient group were (54.36 ± 9.89) μg/L and (13.74 ± 1.89) pg/mL, respectively, which were significantly lower than those in the control group [(112.31 ± 23.24) μg/L, (18.75 ± 2.36) pg/mL, t = 17.89, 12.90, both P < 0.05]. Serum pepsinogen II level in the patient group was significantly higher than that in the control group [(24.35 ± 4.53) μg/L vs. (20.37 ± 3.28) μg/L, t = 5.52, P < 0.05]. The relative mRNA expression of miRNA-21 in the patient group was significantly higher than that in the control group [(3.42 ± 0.61) vs. (0.53 ± 0.12), t = 30.01, P < 0.05]. The relative mRNA expression of miRNA-335-5p in the patient group was significantly lower than that in the control group [(0.32 ± 0.17) vs. (1.65 ± 0.35), t = 26.65, P < 0.05]. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of miRNA-21 in the diagnosis of gastric cancer were 74.36% and 68.18%, respectively, and they were 79.49% and 60.90% for miRNA-335-5p, respectively. There was a negative linear correlation between miRNA-21 and pepsinogen I and gastrin-17 levels ( r = -0.82, -0.74), but there was a positive linear correlation between miRNA-21 and pepsinogen II levels ( r = 0.76). There was a positive linear correlation between miRNA-335-5p and pepsinogen I and gastrin-17 ( r = 0.79, 0.72), but there was a negative linear correlation between miRNA-335-5p and pepsinogen II levels ( r = -0.70). Conclusion:miRNA-21 is highly expressed in patients with gastric cancer, while miRNA-335-5p is lowly expressed. miRNA-21 and miRNA-335-5p are highly correlated with pepsinogen and gastrin-17 levels. miRNA-21 and miRNA-335-5p can be used as effective indices for diagnosis of gastric cancer. Findings of this study are highly innovative and scientific.

Interdomain Disulfide Bond Enhances the Stability of Single-chain Antibody Against Pro-gastrin-releasing Peptide / 中国生物化学与分子生物学报

Pro-gastrin-releasing peptide (ProGRP) is a specific marker of small cell lung cancer.

Value of serum pepsinogen Ⅰ, Ⅱ and gastrin-17 in screening precancerous lesions of gastric cancer in physical examination population / 中国医师进修杂志

Objective:To evaluate the value of serum pepsinogen Ⅰ and Ⅱ combined with gastrin-17 in screening precancerous lesions of gastric cancer in physical examination population.Methods:Serum pepsinogen, gastrin-17 and Helicobacter pylori (Hp) antibody were detected in 18 354 physical examination people from July to December 2017 in Wenrong Hospital, Hengdian, Dongyang. The patients were divided into youth group (18 to 39 years old), middle-aged group (40 to 59 years old) and elderly group (≥60 years old) according to their ages. The correlation between the serological level of the above indexes and age was analyzed; according to the new ABC method, the test results were divided into groups A, B, C and D. The patients in group C and D were examined by gastroscopy. The differences of gastric mucosal atrophy or intestinal metaplasia and other precancerous lesions detected by gastroscopy in different age groups were compared.Results:Finally, 18 354 cases were enrolled, including 9 614 males and 8 740 females. With the increase of age, the proportion of group C and D increased gradually. In group C, 181 cases underwent gastroscopy, including 39 cases of atrophic gastritis, 29 cases of intestinal metaplasia and 3 cases of dysplasia/intraepithelial neoplasia, the detection rate of precancerous lesions was 39.23%; in group D, 94 cases underwent gastroscopy, including 22 cases of atrophic gastritis and 13 cases of intestinal metaplasia, the detection rate of precancerous lesions was 37.23%. The proportion of gastric precancerous lesions in group C and D was 29.63% in the young group, 69.70% in the middle-aged group and 71.58% in the old group, respectively. There was significant difference compared with the young group ( P<0.01); atypical hyperplasia occurred in 2.02% and 9.47% of the middle-aged group and the elderly group. Conclusions:The combined detection of serum pepsinogen Ⅰ and Ⅱ and gastrin-17 levels is of great value in the screening of precancerous lesions of gastric cancer; when this method used for early gastric cancer screening in healthy population, it is necessary to consider the influence of age for the risk stratification of gastric cancer.

Changes and clinical significance of gastrin 17 in diabetic nephropathy / 中国医师进修杂志

Objective:To investigate the changes and clinical significance of gastrin 17 (G-17) in patients with diabetic nephropathy (DN).Methods:One hundred and twenty-four DN patients admitted to Hefei Second People′s Hospital from July 2018 to December 2020 were selected as the DN group, and divided into Ⅰ-Ⅱstage subgroup (68 cases) and Ⅲ-Ⅴ stage subgroup (56 cases) according to the stage of DN.Inaddition, 100 cases of type 2 diabetes mellitus(T2DM) patients without DN were selected as the T2DM group, and 100 healthy subjects who examined during the same period were selected as the control group. The levels of G-17, serum creatinine (SCr), evaluated glomerular filtration rate (eGFR) and other index in each group were detected. The normal level of G-17 was 1-7 pmol/L. G-17>7 pmol/L and ≤ 15 pmol/L was as marginal rising, and G-17>15 pmol/L was as rising.Results:The marginal rising rate of G-17 in the DN group was higher than that in the T2DM group: 43.5%(54/124) vs. 23.0%(23/100); the rising rate of G-17 in the DN group was higher than that in the T2DM group and the control group: 21.0%(26/124) vs. 7.0%(7/100), 4.0%(4/100), and the differences were statistically significant ( P<0.05). The marginal rising rate and rising rate of G-17 in Ⅲ-Ⅴstage subgroup were both higher than those in the Ⅰ-Ⅱ stage subgroup and the T2DM group: 58.9%(33/56) vs. 30.9%(21/68), 23.0%(23/100); 32.1%(18/56) vs. 11.8%(8/68), 7.0%(7/100), and the differences were statistically significant ( P<0.05). The marginal rising rate and rising rate of G-17 in DN patients with a disease course of ≥3 years was higher than that in patients with a disease course of <3 years and the T2DM group: 53.0%(44/83) vs. 24.4%(10/41), 23.0%(23/100); 27.7%(23/83) vs. 7.3%(3/41), 7.0%(7/100), and the differences were statistically significant ( P<0.05). Correlation analysis showed that G-17 was positively correlated with SCr ( r = 0.367, P<0.001) and negatively correlated with eGFR ( r = -0.619, P<0.001) in DN patients. Conclusions:The level of G-17 in ND patients is significantly increased, which is closely related to DN staging and can provide an auxiliary indicator for screening renal function in patients with T2DM.

Clinical study on the treatment of Helicobacter pylori positive chronic superficial gastritis with modified Liqi-Hewei Decoction combined with conventional western medicine therapy / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of modified Liqi-Hewei Decoction combined with conventional western medicine therapy in the treatment of Hp-positive chronic superficial gastritis (CSG). Methods:A total of 96 patients with Hp-positive CSG in the First People’s Hospital of Lianyungang and Changshu No.1 People’s Hospital who met the inclusion criteria between January 2017 and January 2019 were divided into two groups according to the random number table method, with 48 in each group. The control group was treated with conventional western medicine, and study group was additionally given modified Liqi-Hewei Decoction on the basis of control group. Both groups were treated for 8 weeks and followed up for 12 weeks. The TCM symptom score, gastric mucosa and pathological grading were scored before and after treatment. Levels of motilin, gastrin and somatostatin were detected by immunoturbidimetry, and levels of CD3 +, CD4 + and CD8 + were detected by automatic flow cytometry and the ratio of CD4 +/CD8 + was calculated. The Hp negative conversion rate was observed, the adverse reactions were recorded, the clinical efficacy was evaluated and the recurrence rate was statistically analyzed. Results:The Hp negative conversion rate was 89.6% (43/48) in study group and was 72.9% (35/48) in control group, where the difference was statistically significant ( χ2=4.376, P=0.036). The total effective rate was 95.8% (46/48) in study group and was 83.3% (40/48) in control group ( χ2=5.031, P=0.025). After treatment, the scores of epigastric pain, upper abdominal fullness, acid reflux, belching and poor appetite in the study group were significantly lower than those in control group ( t=8.919, 3.971, 7.949, 8.171, 9.865, all Ps<0.01). The scores of gastric mucosa and pathological grading were significantly lower than those in control group ( t=13.705, 15.495, all Ps<0.001). After treatment, the levels of gastrin [(126.15 ± 14.36) ng/L vs. (152.38 ± 17.51) ng/L, t=8.025], motilin [(93.59 ± 11.87) ng/L vs. (102.48 ± 14.68) ng/L, t=3.263] and somatostatin [(36.76 ± 8.97) ng/L vs. (40.84 ± 10.68) ng/L, t=2.027] in the study group were significantly lower than those in the control group ( P<0.01 or P<0.05). The levels of CD3 +, CD4 + and CD4 +/CD8 + were significantly higher than those in the control group ( t=6.883, 6.720, 4.306, all Ps<0.001). The recurrence rate was 4.3% (2/46) in the study group and was 17.5% (7/40) in the control group ( χ2=3.950, P=0.046). During treatment, the incidence rate of adverse reactions was 8.3% (4/48) in the study group and was 12.5% (6/48) in the control group ( χ2=0.446, P=0.504). Conclusion:Modified Liqi-Hewei Decoction combined with conventional western medicine therapy can effectively improve the levels of gastrointestinal hormones and clinical symptoms, enhance the immunity and Hp negative conversion rate, and reduce the recurrence rate of patients with Hp-positive CSG.

Correlations of OLGIM Stage With Gastric Mucosal Serology and Helicobacter pylori Infection in Patients With Chronic Gastritis / 胃肠病学

Background: The OLGIM (operative link on gastric intestinal metaplasia assessment) staging system is important for the prediction of gastric cancer risk in patients with chronic gastritis. However, there are few studies focusing on the correlations of OLGIM stage with gastric mucosal serology and Helicobacter pylori ( Hp) infection. Aims: To investigate the correlations between OLGIM stage and serum pepsinogens (PGs) , gastrin-17 (G-17) , and Hp infection in patients with chronic gastritis. Methods: Individuals undergoing health examination and upper GI endoscopy in the Affiliated Provincial Hospital of Anhui Medical University from May 2015 to December 2017 were enrolled consecutively in this retrospective study. Information on demography, gastric mucosal serology, endoscopy, biopsy pathology and Hp infection was collected. The severity, topography and extension of intestinal metaplasia were assessed by OLGIM staging system. The clinical features of chronic gastritis patients with different OLGIM stages were compared; the risk factors for OLGIM stage HI-IV and the predictive performance of PG I to PG II ratio (PGR) for OLGIM stage HI -TV were analyzed. Results: A total of 1 112 health examination subjects were included in this study. The Hp infection rate was 49. 1%. The serum levels of PG I , PGII , and G-17 were higher, whereas the PGR was lower in Hp-positive subjects than those in Hp-negative ones (all P <0. 05). With the increasing of OLGIM stage, the serum levels of PG II and G-17 were increased, and the PGR was decreased ( all P < 0. 05 ). Meanwhile, the Hp infection rate and the proportion of family history of GI tumors were increased in patients with higher OLGIM stages (all P < 0. 05). In multivariate Logistic regression analysis, age was identified as the independent risk factor for OLGIM stage IH -IV ( OR = 1. 032 , 95% CI: 1. 002-1. 063 , P = 0. 035 ) , while higher PGR was a protective factor ( OR = 0. 837, 95% CI: 0. 754-0. 928 , P = 0. 001) . The optimal cut-off value of PGR for predicting OLGIM stage HI -IV was 8. 065 , with the sensitivity and specificity of 73. 8% and 69. 4% , respectively. Conclusions: Older age and lower PGR are independent risk factors for OLGIM stage HI-IV- PGR can be used as an indicator for screening OLGIM stage HI -IV individuals.

Clinical efficacy and action mechanism of mild moxibustion combined with salt-separated moxibustion for gastrointestinal response in breast-cancer chemotherapy patients / 中国针灸

OBJECTIVE@#To evaluate the clinical efficacy and partial action mechanism of mild moxibustion combined with salt-separated moxibustion for gastrointestinal discomfort caused by chemotherapy for breast cancer.@*METHODS@#A total of 48 patients were randomly divided into an observation group and a control group, 24 cases in each group. The patients in the control group were treated with intravenous infusion of tropisetron hydrochloride (5 mg), once a day for three days; the patients in the observation group were additionally treated with mild moxibustion at Zusanli (ST 36), Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6) and salt-separated moxibustion at Shenque (CV 8), 15 min per treatment, once a day for 7 days. Before treatment and on the 7th day of chemotherapy, the levels of pepsinogenⅠ(PGⅠ), pepsinogenⅡ (PGⅡ), the ratio of PGⅠto PGⅡ (PGR) and gastrin 17 (G-17) in serum were measured. Before treatment and on the 3rd, 5th, 7th day of chemotherapy, the gastrointestinal reactions (nausea, vomiting, constipation, diarrhea) were compared between the two groups.@*RESULTS@#On the 7th day of chemotherapy, the serum levels of PGⅠ, PGⅡand G-17 in the observation group were lower than those in the control group (0.05). The total scores of nausea, vomiting and constipation during chemotherapy in the observation group were significantly lower than those in the control group (all <0.05).@*CONCLUSION@#The mild moxibustion combined with salt-separated moxibustion could effectively improve the symptoms of nausea, vomiting and constipation caused by chemotherapy in patients with breast cancer, and its mechanism may be related to the down-regulation of the levels of PGⅠ, PGⅡ and G-17 in serum.

Chronic use of proton pump inhibitors and the quantity of g, d, and ecl cells in the stomach / Uso crônico de inibidores de bomba de prótons e a quantidade de células g, d e ecl no estômago

ABSTRACT Background: Acid inhibition from chronic proton pump inhibitor use and a possible increase in gastrin can lead to changes in the regulation of hydrochloric acid production. However, it has not known whether such chronic use changes the presence of gastrin, delta, and enterochromaffin-like cells in the stomach or the relationship between gastrin and delta cells. Aim: To analyze the number of gastrin-producing gastrin cells, somatostatin-producing cells, and histamine-producing cells in patients who were chronic users of proton pump inhibitor, with or without related Helicobacter pylori infection. Methods: Biopsies from 105 patients, including 81 chronic proton pump inhibitor users (experimental group) and 24 controls, were processed immunohistochemically and subjected to counting of gastrin, delta, and enterochromaffin-like cells in high-magnification microscopic fields and in 10 glands. Results: Gastrin cell, delta cell, and enterochromaffin-like cells counts were similar across the groups and appeared to be unaffected by Helicobacter pylori infection. The ratio between gastrin cells and delta cells was higher in the chronic users of proton pump inhibitor group than in controls. Conclusion: Chronic users of proton pump inhibitor does not affect gastrin cell, delta cell, and enterochromaffin-like cell counts significantly, but may alter the ratio between gastrin cells and delta cells.

RESUMO Racional: A inibição ácida pelo uso crônico de inibidores de bomba de prótons e o possível aumento da gastrina podem ser seguidos de alterações na regulação da produção do ácido clorídrico. Ainda não está definido se o uso crônico altera a quantidade de células G, D e ECL no estômago ou a razão células G/D. Objetivo: Avaliar o número de células G - produtoras de gastrina -, células D - produtoras de somatostatina - e células ECL - produtoras de histamina -, em pacientes com uso crônico de inibidores de bomba de prótons, com ou sem infecção pelo Helicobacter pylori. Método: Trata-se de estudo retrospectivo avaliando 105 pacientes, 81 usadores crônicos de inibidores de bomba de prótons e 24 controles, através de biópsias com contagem das células G, D e ECL por estudo imunoistoquímico, de forma quantitativa onde havia maior número de células positivas por campo microscópico de grande aumento e em 10 glândulas. Resultados: Não houve diferença estatística comparando-se o número de células G, D e ECL. A razão entre as células G e D foi maior nos pacientes usadores crônicos de inibidores de bomba de prótons. Conclusão: O uso crônico de inibidores de prótons parece não interferir na contagem das células G, D e ECL, porém, interfere na razão entre as células G e D.

Glucagon-like peptide-1 and gastrin synergistically promote the differentiation of insulin-producing cells / 中华内分泌代谢杂志

Objective@#Glucagon-like peptide-1(GLP-1) and gastrin synergistically promote the differentiation of insulin-producing cells which differentiated from rat bone marrow mesenchymal stem cells (BMSCs).@*Methods@#(1)Prepare IPCs model: pancreatic duodenal homeobox 1 (Pdx-1), neurogenin 3 (Ngn3) combined with V-type tendon fibrosarcoma oncogene homolog A (MafA) co-transfected BMSCs differentiation into IPCs; (2)IPCs were divided into 4 groups: Group A(uninduced group), group B(GLP-1 induction group), group C(gastrin induction group), and group D(GLP-1 combined with gastrin induction group). Cultured in high glucose medium for 7 days, the expression levels of insulin2, Pdx-1, GK, nestin, and glucagon mRNA were detected by RT-PCR. The insulin secretion of each group was detected by ELISA.@*Results@#After cultured for 7 days under high glucose conditions, the morphology of IPCs in each induction group changed significantly, gradually aggregated and formed scattered cell masses, and the combined induction group formed large cell masses. The staining of disulfide brown was reddish brown; The levels of insulin secretion increased gradually on the 0, 3rd, 5th, 7th, and 9th day after induction, and the increase was the most significant in the combined induction group (P<0.05). Compared with group A, the expression of insulin2 and GK in group B and D was significantly up-regulated, the expression of glucagon was down-regulated in group D, the expression of Pdx-1 was down-regulated in group C, and the expression of glucagon was up-regulated (P<0.05). Compared with group B, The expression of insulin2 was down-regulated in group C, and the expression level of glucagon was up-regulated. The expression levels of Pdx-1 and Insulin2 were significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05). Compared with group C, the expression level of Pdx-1, insulin2 and GK was significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05).@*Conclusion@#GLP-1 and gastrin synergistically promote the differentiation of IPCs into islet β cells by up-regulating GK and insulin2 and down-regulating glucagon.

Effect of herb-partitioned moxibustion at point on plasma motilin and serum gastrin in patients of diabetic gastroparesis / 中国针灸

OBJECTIVE@#To explore the clinical therapeutic effect of herb-partitioned moxibustion at point in patients of diabetic gastroparesis differentiated as spleen and stomach deficiency and retention of turbid dampness as well as its effect mechanism.@*METHODS@#A total of 134 patients with diabetic gastroparesis were randomized into an observation group and a control group, 67 cases in each one. In the observation group, herb-partitioned moxibustion at point was adopted, 40 min each time, once a day for 5 times a week. In the control group, itopride hydrochloride tablets were prescribed for oral administration, 50 mg each time, three times a day. A total of 6 weeks of treatment was required in the two groups. Before and after treatment, the gastroparesis cardinal symptom index (GCSI) scores, 4-hour gastric emptying rate, TCM symptom score, as well as the levels of plasma motilin and serum gastrin were observed in the patients of the two groups. Additionally, the clinical therapeutic effect was evaluated in the two groups.@*RESULTS@#After treatment, the score of every item of GCSI, TCM symptom scores and the levels of plasma motilin and serum gastrin were all reduced as compared with those before treatment in the patients of the two groups (<0.05), and those in the observation group were lower than the control group (<0.05). Regarding 4-hour gastric emptying rates, which were increased as compared with those before treatment in the two group (<0.05), and the rate in the observation group was higher remarkably than that in the control group (<0.05). The total effective rate was 92.5% (62/67) in the observation group, higher than 74.6% (50/67) in the control group (<0.05).@*CONCLUSION@#Herb-partitioned moxibustion at point relieves the clinical symptoms in the patients with diabetic gastroparesis and increases the gastric emptying rate, which is probably related to the regulation of the levels of plasma motilin and serum gastrin.

Application of New Gastric Cancer Screening Scoring System in Early Gastric Cancer Screening: A Preliminary Community-based Study / 胃肠病学

Background: Gastric cancer is one of the common gastrointestinal malignancies. Early diagnosis can reduce the mortality rate significantly. In the Chinese consensus published in 2017, the New Gastric Cancer Screening Scoring System was recommended to be used for risk stratification of gastric cancer. Aims: To preliminarily explore the value of the New Gastric Cancer Screening Scoring System in early gastric cancer screening in asymptomatic community population. Methods: At several communities in Suzhou City Xiangcheng District, a questionnaire survey was conducted in asymptomatic community residents willing to accept voluntary serum tests to collect information on high risk factors of gastric cancer. Serum pepsinogen (PG), PGⅡ, gastrin 17 (G-17) and Helicobacter pylori (Hp) IgG were tested simultaneously. Risk stratification of gastric cancer was carried out in accordance with the New Gastric Cancer Screening Scoring System. Gastroscopy was recommended for moderate to high risk individuals. Results: A total of 540 asymptomatic individuals completed the study, of which 11 were categorized as high risk (2.0%), 168 as moderate risk (31.1%), and 361 as low risk (66.9%). Sixty-four moderate to high risk individuals completed the gastroscopy with a response rate of 35.8%. Four precancerous lesions were detected (6.2%), including 3 gastric low-grade intraepithelial neoplasia and 1 duodenal adenoma. No gastric cancer was detected. Conclusions: The New Gastric Cancer Screening Scoring System is useful for risk stratification of gastric cancer in asymptomatic population and may provide a basis for further endoscopic examination. However, the value of this scoring system in low risk areas of gastric cancer needs to be further verified.

Occurrence of gastric ulcers and serum gastrin levels in jumping horses / Ocorrência de úlceras gástricas e níveis séricos de gastrina em cavalos de hipismo

The aim of this study was to determine the occurrence of EGUS and to quantify serum gastrin levels in jumping horses during competition season and interseason period. Forty jumping horses, competing at high level were randomly allocated into two groups, the Training Group: twenty jumping horses undergoing intense training and participating in competitions, and the Rest Group: twenty jumping horses in the interseason (resting period). The gastroscopic examinations and blood samples of the horses in the training group were performed 1-2 days following the competition while in the horses of the rest group, following 4 weeks of rest. The serum gastrin levels were measured at two different times: pre-feeding and two hours after feeding the horses (postprandial) by ELISA kit. Gastric lesion score data were compared by the Mann-Whitney U test (α= 0.05) and the mean gastrin values were compared between the groups and between the two moments by the paired tet tests, respectively (α= 0, 05). Squamous gastric ulcers were detected in 42.5% of all jumping horses examined independent of the period, competition season or interseason. Serum gastrin levels were significantly higher in the Training Group with no difference between pre-feeding and postprandial values.(AU)

O objetivo deste estudo foi determinar a ocorrência de EGUS e quantificar os níveis séricos de gastrina em cavalos de hipismo durante a época de competições e o período de férias. Quarenta cavalos de hipismo de alta performance foram aleatoriamente distribuídos em dois grupos, grupo treinamento: vinte cavalos de hipismo submetidos a treinamento intenso e participando de competições, e grupo descanso: vinte cavalos de hipismo em férias (período de descanso). As avaliações gastroscópicas e as coletas de sangue dos cavalos em treinamento foram realizadas um ou dois dias após as competições, enquanto nos cavalos do grupo descanso foram realizadas após quatro semanas de repouso. Os níveis séricos de gastrina foram mensurados por kit de ELISA, em dois momentos: antes da alimentação e duas horas após. Os dados de escore das lesões gástricas foram comparados pela prova U de Mann-Whitney (α= 0,05) e os valores médios de gastrina foram comparados entre os grupos e entre os dois momentos pelos testes t e t pareado, respectivamente (α= 0,05). Foram encontradas úlceras gástricas em 42,5% de todos os cavalos examinados, independentemente do período de competições ou repouso. Os níveis séricos de gastrina foram significativamente maiores no grupo treinamento, sem diferença entre os períodos pré e pós-alimentação.(AU)

Comparison of different serological methods in screening early gastric cancer / 中华内科杂志

Objective To compare the consistency and detection rate of early gastric cancer (EGC) of three different methods including anti-Helicobacter pylori (Hp) antibody combined with pepsinogen (PG) (ABC method),serum PG combined with gastrin-17 (G-17) (new ABC method) and the new scoring system.Methods Serological tests were performed in Zhejiang population,which divided the subjects into low risk,intermediate risk and high risk groups.High risk subjects were examined by endoscopic and pathological examination.SPSS19.0 were used to evaluate the consistency of three methods.According to the receiver operating characteristic (ROC) curve,the ratio of G-17 to PG (PGR) was calculated for the optimal diagnostic cut-off value of EGC.Results A total of 30 126 subjects were recruited.Based on the data of ABC method,the proportions of low risk,intermediate risk and high risk group were 15 368 (51.01％),13 246 (43.97％),and 1 512 (5.02％),respectively.These proportions by the new ABC method were 20 584 (68.32％),8 990 (29.84％),552 cases (1.83％),respectively.By new scoring system,these were 20 810 (69.08％),8 059 (26.75％),and 1 257 (4.17％),respectively.Among them,1 263 subjects underwent endoscopy and 22 cases (1.74％) were finally diagnosed as gastric cancer including 19 EGC (86.4％).There were 1 case (0.35％),14 cases (1.84％),and 7 cases (3.21％) with gastric cancer in low risk,intermediate risk,and high risk groups by ABC methods,respectively.Gastric cancer patients were 7 (1.68％),10 (1.38％),and 5 (4.10％) in three groups respectively by new ABC methods.Via new scoring system,gastric cancer were detected in 5 (0.66％),9 (2.22％),and 8 (7.84％) patients of three risk groups respectively.The consistency of three screening methods was poor.The detection rate of gastric cancer in high risk group was higher than that in the other two (P＜0.05).The area under the curve (AUC) for diagnosis of gastric cancer by G-17 and PGR was 0.588 and 0.729,respectively.According to the PGR cut-off value determined by the fitted model,the incidence of gastric cancer in the low,intermediate and high risk groups was 0.94％,1.97％,and 6.31％,respectively.When the cut-off value is PGR＜4.135,the sensitivity is 0.855 and the specificity is 0.545.Conclusion The new scoring system has a better predictive value in EGC screening.The detection rate of EGC in high risk group is higher than that in low and intermediate risk groups.

Risk Factors of Multiple Gastric Polyps according to the Histologic Classification: Prospective Observational Cohort Study / 대한소화기학회지

BACKGROUND/AIMS: The aim of this study was to determine the risk factors of multiple gastric polyps according to the histological classification of gastric polyps. METHODS: Subjects with multiple gastric polyps (at least three) during endoscopy were enrolled prospectively. They were assigned to a fundic gland polyp (FGP) group and hyperplastic polyp (HP) group based on a histological classification of gastric polyps. Helicobacter pylori (H. pylori) was confirmed by its histology. Serum gastrin was measured using the radioimmunoassay method. A questionnaire was taken regarding the intake of proton pump inhibitor and nonsteroidal anti-inflammatory drugs, alcohol, smoking history, and diet. RESULTS: Among the 60 subjects enrolled from 2015 to 2018 at Seoul National University Bungdang Hospital, 47 and 13 subjects were assigned to the FGP and HP groups, respectively. The H. pylori infection rate was 12.8% in the FGP group, which is lower than that in the HP group (69.2%, p<0.001). The gastrin level was higher in the HP group (194.7 pg/dL, range 50.6–387.8 pg/dL) than in the FGP group (57.4 pg/dL, range 24.8–79.0 pg/dL) (p=0.007). Histologically, neutrophil infiltration in the antrum and body of the stomach were higher in the HP group than in the FGP group (p=0.022 and p=0.030, respectively). In contrast, monocyte infiltration in the antrum and body of the stomach were higher in the FGP group than in the HP group (p=0.018 and p<0.001, respectively). CONCLUSIONS: HPs arise from inflammation caused by H. pylori. On the other hand, the FGP was not associated with H. pylori or environmental factors.

Risk Factors of Multiple Gastric Polyps according to the Histologic Classification: Prospective Observational Cohort Study / 대한소화기학회지

BACKGROUND/AIMS: The aim of this study was to determine the risk factors of multiple gastric polyps according to the histological classification of gastric polyps.METHODS: Subjects with multiple gastric polyps (at least three) during endoscopy were enrolled prospectively. They were assigned to a fundic gland polyp (FGP) group and hyperplastic polyp (HP) group based on a histological classification of gastric polyps. Helicobacter pylori (H. pylori) was confirmed by its histology. Serum gastrin was measured using the radioimmunoassay method. A questionnaire was taken regarding the intake of proton pump inhibitor and nonsteroidal anti-inflammatory drugs, alcohol, smoking history, and diet.RESULTS: Among the 60 subjects enrolled from 2015 to 2018 at Seoul National University Bungdang Hospital, 47 and 13 subjects were assigned to the FGP and HP groups, respectively. The H. pylori infection rate was 12.8% in the FGP group, which is lower than that in the HP group (69.2%, p<0.001). The gastrin level was higher in the HP group (194.7 pg/dL, range 50.6–387.8 pg/dL) than in the FGP group (57.4 pg/dL, range 24.8–79.0 pg/dL) (p=0.007). Histologically, neutrophil infiltration in the antrum and body of the stomach were higher in the HP group than in the FGP group (p=0.022 and p=0.030, respectively). In contrast, monocyte infiltration in the antrum and body of the stomach were higher in the FGP group than in the HP group (p=0.018 and p<0.001, respectively).CONCLUSIONS: HPs arise from inflammation caused by H. pylori. On the other hand, the FGP was not associated with H. pylori or environmental factors.

Comparison of effects of Hedysari Radix and Hedysari Radix Praeparata Cum Melle on Buzhong Yiqi and differential analysis of its chemical compositions / 中草药

Objective: To compare the effects of Hedysari Radix and Hedysari Radix Praeparata Cum Melle in Buzhong Yiqi and its chemical composition, and preliminarily reveal the mechanism of Hedysari Radix processed with honey. Methods: A rat model of spleen qideficiency was established. The rats were treated with different doses of water extracts of Hedysari Radix and Hedysari Radix Praeparata Cum Melle and the content of serum D-xylose, GAS, IL-2, TNF-α were used as indicators to study the differences in the efficacy of Hedysari Radix and Hedysari Radix Praeparata Cum Melle in Buzhong Yiqi. Based on HPLC techniques, the different components in methanol extract of Hedysari Radix and Hedysari Radix Praeparata Cum Melle were analyzed. Results: Compared with the blank group, the serum xylose, gastrin content in the model group were significantly decreased. Compared with the model group, except for the low dose group of Hedysari Radix, the serum xylose, and gastrin content of the rats in each administration group were significantly increased (P < 0.01), and the results in the middle dose group of Hedysari Radix were significantly higher than those in the middle dose group of Hedysari Radix Praeparata Cum Melle (P < 0.05, P < 0.01). Compared with the blank group, the serum IL-2 and TNF-α levels in the model group were significantly increased (P < 0.01). Compared with the model group, the serum IL-2 and TNF-α levels in the rats in each drug group were significantly decreased (P < 0.05, P < 0.01); Compared with the medium dose group of Hedysari Radix, the serum IL-2 and TNF-α levels in the medium dose group of honey-processing Hedysari Radix were significantly decreased (P < 0.05, P < 0.01). There were differences in the chromatographic peaks in the fingerprints of Hedysari Radix and Hedysari Radix Praeparata Cum Melle. Conclusion: Both Hedysari Radix and Hedysari Radix Praeparata Cum Melle can significantly intervene and improve the syndrome of spleen qi deficiency in rats and the pharmacodynamics effect of Hedysari Radix Praeparata Cum Melle is better than that of Hedysari Radix. There are differences in the components of Hedysari Radix and Hedysari Radix Praeparata Cum Melle and these differences may be the active substances that cause differences in the efficacy.