Clinical analysis of 368 cases of superficial esophageal cancer treated by endoscopic submucosal dissection / 中华消化杂志

Objective:To observe the clinical efficacy of endoscopic submucosal dissection (ESD) in the treatment of superficial esophageal cancer (SEC), and to explore the application value of ESD in the treatment of SEC.Methods:From January 2016 to December 2019, at The First Affiliated Hospital With Nanjing Medical University, the clinical data of 368 patients with SEC and receiving ESD treatment were retrospectively analyzed, induding the general condition, the circumferential proportion of lesions, effectiveness of ESD treatment (en bloc resection rate, complete resection rate, curative resection rate, operation time and resected lesion area), incidence of complications and follow-up. 368 patients were divided into stenosis group (94 cases) and non-stenosis group (274 cases) according to the occurrence of esophageal stenosis after ESD. The circumferential proportion of lesions, operation time and resected lesion area were compared between stenosis group and non-stenosis group, and the independent risk factors of esophageal stenosis after ESD were analyzed. Independent sample t test, chi-square test and binary logistic regression analysis were used for statistical analysis. Results:Among 368 patients, 270(73.4%) were male and 98 (26.6%) were female; the age was (64.4±7.6) years old. The circumferential proportion of lesions of 231 cases (62.8%) was <1/2 circle, 49 cases (13.3%) was 1/2 to <2/3 circle, and 88 cases (23.9%) was ≥2/3 circle. The en bloc resection rate of the lesion was 98.6%(363/368), the complete resection rate and curative resection rate were both 97.8% (360/368). The operation time was (89.4±47.9) min. The area of resected lesion was (12.5±8.9) cm 2. The incidence of perforation during operation, delayed bleeding and stenosis was 0.3% (1/368), 0.5% (2/368) and 25.5% (94/368), respectively. The followed-up period was 8 to 53 months, and the median follow-up period was 25 months. During the follow-up period, no recurrence or new lesion was found, and no lymph node or distant metastasis occurred. The circumferential proportion of lesions of 38 cases (40.4%) of stenosis group and 193 cases (70.4%) of non-stenosis group was <1/2 circle, respectively, the circumferential proportion of lesions of 9 cases (9.6%) and 40 cases (14.6%) was 1/2 to <2/3 circle, respectively, the circumferential proportion of lesions of 47 cases (50.0%) and 41 cases (15.0%) was ≥2/3 circle, respectively, and the difference was statistically significant ( χ2=47.30, P<0.01). The operation time of stenosis group was longer than that of non-stenosis group, the resected lesion area was larger than that of non-stenosis group ((126.1±56.3) min vs. (76.8±37.2) min, (17.5±10.7) cm 2 vs. (10.8±7.4) cm 2), and the differences were statistically significant ( t=9.57 and 5.41, both P<0.01). The results of binary logistic regression analysis showed that circumferential proportion of lesions ≥2/3 circle, operation time and the resected lesion area were independent risk factors for the occurrence of esophageal stenosis after ESD (odds ratio=0.253, 1.018 and 1.041, 95% confidence interval 0.116 to 0.551, 1.011 to 1.025, 1.007 to 1.076, all P<0.05). Conclusions:ESD is a safe and effective way to treat SEC, with low local recurrence rate and few complications, which is worthy of further clinical promotion.

Correlation between long-term use of proton pump inhibitors and micro-structure of bone in older men / 中华消化内镜杂志

To explore the effect of proton pump inhibitors (PPI) on the micro-structure of bone in older men. A retrospective study was conducted on data of patients over the age of 60 who were admitted to the Geriatric Department of Jiangsu People′s Hospital from June 2018 to January 2019. Patients were divided into control group (taking PPI for less than 1 week, 50 cases) and PPI treatment group (taking PPI for more than 3 months, 30 cases). Biochemical indexes, bone mineral density (BMD)and trabecular bone score (TBS) were analyzed. Compared with control group, the weight and albumin level in the PPI treatment group were lower, and the thyrotropin level was higher ( P<0.05). There was no statistical difference in the BMD of femur or lumbar vertebrae between the two groups ( P>0.05), but the TBS of lumbar vertebrae in the PPI treatment group was significantly decreased ( P<0.05). Correlation analysis found that TBS was positively correlated with alkaline phosphatase (ALP) ( r=0.45, P=0.002) and body mass index ( r=0.164, P=0.045), and negatively correlated with age ( r=-0.291, P=0.025). Multiple linear regression model analysis showed that there was still a positive correlation between TBS and ALP ( β=0.437, P=0.023). In the elderly men, the use of PPI for more than 3 months can significantly affect the bone micro-structure, and the bone micro-structure can better reflect the adverse effect of PPI on bone than BMD.

High Expression of GADD45B Induced by Acid and Bile Acid is A Potential Prognostic Marker for Barrett's Esophagus-associated Adenocarcinoma / 胃肠病学

Background: Esophageal mucosal injury induced by gastroesophageal reflux is a key link to the development of Barrett's esophagus-associated adenocarcinoma. However, the molecular mechanism is still not elucidated. Aims: To investigate the role of differentially expressed genes (DEGs) after stimulating esophageal cells with acid and bile acid in the development of esophageal adenocarcinoma (EAC). Methods: The DEGs were obtained through bioinformatics methods after stimulating esophageal cells with low pH and deoxycholic acid, and GO, KEGG enrichment analysis were performed. Protein-protein interaction (PPI) network was performed to screen the hub genes, and their relationships with prognosis and tumor stage of EAC patients were analyzed. The role of co-expressed genes of GADD45B in EAC was also analyzed. Results: Thirty-one overlapping DEGs were obtained after stimulating esophageal cells with low pH and deoxycholic acid, which mainly enriched in the cytokine-cytokine receptor interaction, transcription factors activity, and regulation of cell proliferation and apoptotic process. High expression of GADD45B was correlated with the survival prognosis and tumor stage of EAC patients. GADD45B and its co-expressed genes were involved in the production of tumor necrosis factor. Conclusions: The high expression of GADD45B induced by acid and bile acid is correlated with the prognosis and tumor stage of EAC patients, and is a potential diagnosis and treatment target for Barrett's esophagus-associated adenocarcinoma.

Effect and Underlying Mechanism of Harmine on Proliferation and Apoptosis of Gastric Cancer Cells / 胃肠病学

Background:Previous study has found that harmine inhibited the proliferation of gastric cancer cells by down-regulating cyclooxygenase-2(COX-2)expression. However,its molecular mechanism is not fully clear. Aims:To investigate the effect of harmine on proliferation and apoptosis of gastric cancer cells,and explore the role of PTEN/Akt/MDM2 signaling pathway in this process. Methods:Human gastric adenocarcinoma cell line SGC-7901 and MKN-45 were treated with harmine at different concentrations(2,4,8,16,32 μg/mL)for 24,48,and 72 hours. The cell proliferation and apoptosis were detected by MTT assay and Hoechst staining,respectively. The expressions of PTEN,COX-2, phosphorylated Akt(p-Akt)and p-MDM2 were measured by Western blotting. Results:Harmine dose- and time-dependently inhibited proliferation and induced apoptosis of SGC-7901 and MKN-45 cells. Also,harmine dose-dependently increased PTEN expression,and inhibited p-Akt,p-MDM2 and COX-2 expressions in SGC-7901 and MKN-45 cells. Conclusions:Harmine may inhibit proliferation and induce apoptosis of gastric cancer cells via down-regulating COX-2 expression through PTEN/Akt/MDM2 signaling pathway.

Relationship of the preoperative neutrophil-lymphocyte ratio with clinicopathological features and prognosis of colorectal cancer in middle-aged and elderly patients / 中华老年医学杂志

Objective To evaluate the relationship of preoperative neutrophil-lymphocyte ratio (NLR) with clinicopathological features and prognosis of colorectal cancer in middle-aged and elderly patients.Methods A retrospective analysis was performed in 212 patients with colorectal cancer in the First Affiliated Hospital of Nanjing Medical University from January 2011 to June 2013.All patients were divided into middle-aged group (46-65 year old,n=130) and old-aged group (66-89 year old,n=82),The optimal cut-off point of NLR was identified by the area under receiver operating characteristic curve,while NLR ＞ 3.13 and NLR≤3.13 were classified as high and low NLR group.The clinicopathological features and prognosis between the two groups were compared.Results There was no difference in gender,tumor growth site,depth of invasion,tumor embolus,lymphatic metastasis,distant metastasis,TNM stage between low and high NLR group (allP＞ 0.05).However,the difference between high NLR group and low NLR group in old-aged group with diabetes mellitus was statistically significant (P＜0.05).The 1-,2-,and 3-year survival rate of the overall 212 patients were 96.2％ (204/212),87.7％ (186/212) and 74.5％ (158/212) In middle-aged group,the 1-,2-,and 3-year survival rates were 98.8％ (85/86),90.7％ (78/86) and 84.9％ (73/86) respectively in low NLR group,but 95.5％ (42/44),84.1％ (37/44) and 72.7％ (32/44) respectively in high NLR group,(allP＜0.05).In old-aged group,the 1-,2-,and 3-year survival rates were 95.7％ (44/46),89.1％ (41/46) and 73.9％ (34/46) respectively in low NLR group,but 91.7％ (33/ 36),83.3％ (30/36) and 52.8％ (19/36) respectively in high NLR group (all P＜0.05).Cox regression showed that TNM stage and NLR were independent risk factors for the prognosis of the middle-aged and elderly patients with colorectal cancer (P＜0.05 or P＜0.01).Conclusions Preoperative NLR ＞ 3.13 suggest that the prognosis is poor in middle-aged and elderly patients with colorectal cancer.

Ursolic Acid Inhibits Gastric Cancer Cells Proliferation through AMPK/STAT3/COX-2 Signaling Pathway / 胃肠病学

Background: Previous study has found that ursolic acid (UA) inhibited the proliferation of gastric cancer cells by the down-regulation of cyclooxygenase-2 (COX-2) expression.However,its molecular mechanism is not fully clear.Aims: To investigate the role of adenosine monophosphate-activated protein kinase (AMPK)/signal transducer and activator of transcription 3 (STAT3)/COX-2 signaling pathway in UA-mediated inhibition of gastric cancer cells proliferation.Methods: AMPK-pLVX,AMPK-shRNA,STAT3-pLVX,STAT3-shRNA plasmids were constructed,and then were transfected into human gastric cancer cell lines SGC-7901 and MKN-45,respectively.Gastric cancer cells were cultured with different concentrations of UA for different times.The expressions of phosphorylated AMPK (p-AMPK),phosphorylated STAT3 (p-STAT3) and COX-2 were measured by Western blotting,and cell proliferation was detected by CCK-8 assay.Results: UA dose-and time-dependently increased p-AMPK expression,inhibited p-STAT3 and COX-2 expressions in SGC-7901 and MKN-45 cells.Knockdown of AMPK blocked UA-induced inhibition of STAT3 phosphorylation and COX-2 expression.Overexpression of STAT3 blocked UA-induced down-regulation of COX-2 expression.Knockdown of AMPK and overexpression of STAT3 blocked UA-induced inhibition of proliferation of gastric cancer cells.Conclusions: UA may inhibit the proliferation of gastric cancer cells via down-regulation of COX-2 expression through AMPK/STAT3 pathway.

Signal transduction pathway of ursolic acid inhibiting COX-2 expression in gastric cancer cells / 中国药理学通报

Aim Our previous study has found that ur-solic acid( UA) increased intracellular reactive oxygen species ( ROS ) production and adenosine monophos-phate-activated protein kinase ( AMPK ) phosphoryla-tion, inhibited signal transducer and activator of tran-scription 3 ( STAT3 ) phosphorylation and cyclooxygen-ase-2 ( COX-2 ) expression in gastric cancer cells . However , the molecular mechanism by which UA in-hibits COX-2 expression in gastric cancer cells has not been fully clarified .In this study we aimed to further clarify the signal transduction pathways involved in the UA-mediated inhibition of COX-2 expression in gastric cancer cells .Methods Human gastric cancer cell lines SGC-7901 and MKN-45 were routinely cultured in RPMI-1640 medium supplemented with 10% heat-in-activated fetal calf serum .Sub-confluent cell cultures were pre-treated with antioxidant N-acetylcysteine ( NAC) , AMPK activator 5-amino-4-imida-zolecarbox-amide-riboside ( AICAR ) , AMPK inhibitor compound C, or STAT3 inhibitor WP1066 and then treated with or without UA for 24 h.The expression of AMPK and phosphorylated AMPK ( p-AMPK ) , STAT3 and phos-phorylated STAT3 ( p-STAT3 ) , as well as COX-2 was detected by Western blot analysis .Results Antioxi-dant NAC and AMPK inhibitor compound C blocked UA-induced inhibition of STAT 3 phosphorylation and down-regulation of COX-2 expression in gastric cancer cells.Both AMPK activator AICAR and UA inhibited STAT3 phosphorylation and COX-2 expression; the combination of two drugs resulted in further reduction . STAT3 inhibitor WP1066 did not affect UA-induced AMPK phosphorylation , whereas it inhibited STAT3 phosphorylation and COX-2 expression .The inhibitory effects on the STAT3 phosphorylation and COX-2 ex-pression were significantly enhanced when SGC-7901 and MKN-45 cells were treated simultaneously with WP1066 plus UA.Conclusion UA inhibits COX-2 expression in gastric cancer cells , which may be medi-ated through ROS/AMPK/STAT3 signal transduction pathway .

Clinical Trials on Zhenjujiangya Tablets Combined with Long-acting Antihypertensive Drugs in the Treat-ment of Hypertension / 中国药师

To determine the efficacy and safety of Zhenjujiangya tablets combined with long-acting antihypertensive drugs in the patients with hypertension. Methods:A controlled study was carried out among 220 patients meeting the inclusion / ex-clusion criteria. All the patients were randomly divided into the experimental group and the control group. Both groups were treated with long-acting antihypertensive drugs as usual. The 110 patients in the experimental group were orally treated with Zhenjujiangya tab-lets ( bid) , while the other 110 patients in the control group were orally treated with Zhenjujiangya simulated tablets ( bid) , and the treatment course was 4 weeks. The efficacy was assessed using the reduction range of blood pressure, the clinical symptom score of hy-pertension and the indicators of ambulatory blood pressure monitoring as the indices, and the safety was assessed by the symptoms, signs and laboratory tests. Results:After the four-week treatment, the systolic blood pressure, diastolic blood pressure and hyperten-sion clinical symptom score were significantly decreased in the two groups, and the changes in the experimental group were more signifi-cant than those in the control group (P0. 05). After the treatment, the changes in average systolic blood pres-sure in 24h and daytime in the experimental group showed statistically significant difference (P0. 05), and the number of abnormal blood pressure in 24h and daytime in the experimental group exhibited reduction trend. There were no significant difference in the incidence of adverse events between the two groups (P>0. 05). Conclusion:Long-acting antihypertensive drugs combined with Zhenjujiangya tablets can further improve the antihypertensive efficacy without significant adverse reactions, which is suitable for clinical application.