1.Clinical Study on Role of Serum Homocysteine Level in Gastric Cancer and Precancerous Diseases
Songmiao CHAN ; Weihao SUN ; Xiaobing ZHU ; Xilong OU
Chinese Journal of Gastroenterology 2016;(1):52-54
Background:Recent studies have showed that high homocysteine(Hcy)level can increase the risk of gastric cancer, but no related studies have been reported on role of Hcy in gastric precancerous diseases. Aims:To investigate the role of serum Hcy,folic acid and vitamin B12 in patients with gastric cancer and precancerous diseases. Methods:Eighty-six normal controls,46 atrophic gastritis,46 gastric ulcer,31 gastric polyp,52 gastric cancer patients diagnosed by gastroscopy and pathology were enrolled. Serum levels of Hcy,folic acid and vitamin B12 were determined,and their correlations with clinicopathological features in gastric cancer were analyzed. Results:Compared with normal controls, serum Hcy level in patients with atrophic gastritis and gastric cancer was significantly increased(P < 0. 05);serum folic acid and vitamin B12 levels in patients with gastric ulcer,gastric polyp and gastric cancer were significantly decreased(P <0. 05). Serum Hcy level in patients with gastric cancer was positively correlated with depth of tumor infiltration,TNM staging and lymph node metastasis(P < 0. 05),however,serum folic acid and vitamin B12 levels had no correlation with clinicopathological features. Conclusions:Hcy level is increased in chronic atrophic gastritis,gastric cancer;levels of folic acid and vitamin B12 are decreased in gastric ulcer,gastric polyp and gastric cancer. High level of Hcy is involved in infiltration and metastasis of gastric cancer. Intervention in patients with high level of Hcy,low levels of folic acid and vitamin B12 might be an effective strategy for the prevention and treatment of gastric cancer and precancerous diseases.
2.Signal transduction pathway of ursolic acid inhibiting COX-2 expression in gastric cancer cells
Yue ZHU ; Yichan ZHOU ; Guoqin ZHU ; Jianping LI ; Zheng JIAO ; Xiaolin LI ; Yun SHAO ; Weihao SUN
Chinese Pharmacological Bulletin 2016;32(7):925-931,932
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 .
3.Relationship of the preoperative neutrophil-lymphocyte ratio with clinicopathological features and prognosis of colorectal cancer in middle-aged and elderly patients
Ping YANG ; Zhenguo LUO ; Xiaopu HE ; Guoqin ZHU ; Xiaolin LI ; Weihao SUN ; Yun SHAO
Chinese Journal of Geriatrics 2017;36(9):975-978
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.
4.Analysis of influencing factors of nonalcoholic fatty liver disease in healthy people: Based on nested case control study
Zhenzhen HAN ; Weihao YANG ; Mingliang LI ; Guanhui MA ; Chao ZHU ; Guobao XIA ; Ying ZHOU ; Feng LIU
Clinical Medicine of China 2021;37(2):141-147
Objective:Based on the occupational cohort of Beijing Medical Examination Center, to explored the relevant factors of nonalcoholic fatty liver disease (NAFLD), and to provide scientific basis for screening and early diagnosis of NAFLD in high-risk population.Methods:Based on the cohort of occupational population who underwent physical examination in Beijing physical examination center from January to December 2009, the physical examination indexes were collected, and a retrospective survival cohort with a follow-up period of 3 years was established.According to the idea of nested case-control study, each case was randomly matched with the same gender, age and physical examination time in the same month by using the method of random sampling without putting back.Conditional logistic regression model was established by using the matched data.The diagnostic value of related indicators for NAFLD was analyzed by receiver operating characteristic curve (ROC).Results:A total of 1 194 subjects were included, including 684 males (57.3%, 684/1 194) and 510 females (42.7%, 510/1 194). The age was (50.8±11.6) years.The age ranged from 24.0 to 88.0 years.There were 597 patients with NAFLD, including 342 males and 255 females.Logistic regression analysis showed that body mass index, high density lipoprotein cholesterol, hemoglobin, platelet count, uric acid and urea nitrogen were statistically significant in male model (all P<0.05). Body mass index( OR=1.242, 95% CI 1.143-1.349, P<0.001), hemoglobin( OR=1.034, 95% CI 1.015-1.053, P<0.001), platelet( OR=1.005, 95% CI 1.002-1.009, P=0.005), uric acid( OR=1.004, 95% CI 1.001-1.006, P=0.004), high density lipoprotein cholesterol( OR=0.377, 95% CI 0.184-0.775, P=0.008) and urea nitrogen( OR=0.807, 95% CI 0.693-0.938, P=0.005) were protective factors for NAFLD in male patients..Body mass index( OR=1.552, 95% CI 1.366-1.762, P<0.001), triglyceride ( OR=2.606, 95% CI 1.616-4.204, P<0.001), blood glucose( OR=2.199, 95% CI 1.332-3.631, P=0.002), uric acid( OR=1.005, 95% CI 1.001-1.010, P=0.024) in female model were statistically significant ( P<0.05), and were risk factors for NAFLD in female patients. Conclusion:The incidence rate of NAFLD was different among different gender and age, body mass index, high density lipoprotein cholesterol, hemoglobin, platelet count, uric acid, urea nitrogen, triglyceride and blood glucose were closely related to the incidence of NAFLD.
5.Ursolic Acid Inhibits Gastric Cancer Cells Proliferation through AMPK/STAT3/COX-2 Signaling Pathway
Zheng JIAO ; Guoqin ZHU ; Yichan ZHOU ; Xian XU ; Xiaolin LI ; Jianping LI ; Xiaopu HE ; Wei XU ; Yun SHAO ; Weihao SUN
Chinese Journal of Gastroenterology 2017;22(4):208-213
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.
6.Effects of cyclooxygenase-2 inhibitors on gastric epithelial cell proliferating and gastric healing following hydrochloric acid-induced injury in rats
Weihao SUN ; Xilong OU ; Qian YU ; Dazhong CAO ; Hong CHEN ; Ting YU ; Hua SHAO ; Feng ZHU ; Yunliang SUN
Chinese Journal of Pathophysiology 2000;0(11):-
AIM: To clarify the effects of specific and non-specific cyclooxygenase-2 (COX-2) inhibitors on gastric epithelial cell proliferating and gastric healing following acid-induced damage. METHODS: Male Sprague-Dawley rats were given 1 mL of 0.6 mol/L hydrochloric acid (HCl) into the stomach. Ten minutes after the administration of the acid,the animals were given NS-398 (COX-2 inhibitor) or indomethacin. Levels of COX-1 and COX-2 in the gastric mucosa before and after HCl-administration were analyzed using western blotting and immunohistochemical staining. Proliferating cell nuclear antigen (PCNA) was detected using immunohistochemistry for epithelial cell proliferation. Gastric lesion index (LI) was assessed using planimetry. RESULTS: Expression of COX-2 was enhanced mainly in surface epithelial cells and neck cells following HCl-administration. At 24 h following acid administration,PCNA labeling index (PCNA-LI) was (22.72?4.33) % and (21.98?5.18) % in the groups treated with 40 mg/kg of NS-398 and indomethacin respectively,which was significantly lower than that in the control group [ (34.46?3.61) %,P
7.Effects of gastrin on expression of cyclooxygenase and growth factors in rat gastric mucosa
Weihao SUN ; Dazhong CAO ; Qian YU ; Xilong OU ; Hong SHEN ; Ting YU ; Feng ZHU ; Yunliang SUN ; Xiling FU
Chinese Journal of Pathophysiology 1986;0(02):-
AIM: To clarify the effects of gastrin on t he expression of cyclooxygenase (COX) and several growth factors in rat gastric mu cosa. METHODS: Male Sprague Dawley rats were fasted for 24 hours and s ubcutaneously injected with saline or gastrin 17 at doses of 1 ?g/kg, 10 ?g/kg and 100 ?g/kg, respectively. The expression of COX-1, COX-2, heparin-binding e p idermal growth factor-like growth factor (HB-EGF) and hepatocyte growth factor ( HGF) in the gastric mucosa were examined using Western blotting and immunohistoc hemical staining. Effects of a potent gastrin receptor antagonist YM022 on the e xpression of COX-1, COX-2, HB-EGF and HGF in gastric mucosa were also evaluated. RESULTS: Gastrin dose-dependently increased the expression of C OX-2 and HB-EGF in rat gastric mucosa while the expression of COX-1 and HGF did not change significantly after treatment with gastrin. However, pretreatment wit h YM022 dose-dependently abolished the up-regulation of COX-2 and HB-EGF express ion induced by gastrin. CONCLUSIONS: This study demonstrates that gastrin up-regulates C OX-2 and HB-EGF expression in rat gastric mucosa, indicating that COX-2 and HB-E GF are involved in pathogenesis of the gastrin-related gastric mucosal hyperplas ia and carcinoma of stomach.
8.Quickly investigating the absorption ingredients of Gentianae Radix et Rhizoma by SEMAC.
Bei SONG ; Jingjing ZHU ; Weihao WANG ; Guang HU ; Xiaomei SONG ; Zhimin WANG
China Journal of Chinese Materia Medica 2012;37(7):969-973
OBJECTIVETo establish a method for quickly investigating the absorption ingredients which could be used as the index of quality control of Gentianae Radix et Rhizoma.
METHODThe absorption ingredients of Gentianae Radix et Rhizoma were investigated by using the model of in vitro everted intestinal sac (VEIS). The intestinal sac liquors of jejunum and ileum were collected at 6 intervals (15, 30, 45, 60, 90, 120 min) and gentiopicroside, loganin acid, swertiamarin and sweroside were detected by HPLC as the representative marker. The accumulative absorption quantity of gentiopicroside, loganin acid, swertiamarin and sweroside were calculated, respectively.
RESULTSix components could be detected in intestinal sac. In different concentrations of Gentianae Radix et Rhizoma, gentiopicroside and swertiamarin in various intestinal sections were the linear absorption (R2 > 0.9), conformed to zero order absorption rate. In jejunum the constant of absorption rate (Ka) of gentiopicroside and swertiamarin increased with the raised dosage of Gentianae Radix et Rhizoma (P < 0.05), which indicated a passive absorption manner, and the value of Ka of high and middle dosage of those in ileum were higher than that of low dosage, and the difference of Ka between high and middle dosage were not significant, which indicated a positive absorption manner. The Ka of high and middle dosage of sweroside in ileum and jejunum were higher than that of low dosage (P < 0.05), and the difference of Ka between high and middle dosage were not significant, which indicated a positive absorption manner. The Ka of loganin acid in jejunum and ileum increased along with the raised dosage of Gentianae Radix et Rhizoma (P < 0.05), which indicated a passive absorption manner.
CONCLUSIONSEMAC could be used as a tool to investigate the absorption ingredients of Gentianae Radix et Rhizoma. Drug in intestine sac was selective, and the absorption part of intestine was also different.
Absorption ; Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Gentiana ; chemistry ; Ileum ; metabolism ; Iridoid Glucosides ; pharmacokinetics ; Jejunum ; metabolism ; Male ; Pyrones ; pharmacokinetics ; Rats ; Rats, Wistar
9.Analysis of the effect of home quarantine on blood lipid and glucose of healthy adults during the COVID-19 epidemic times based on the data of physical examination
Feng LIU ; Junming HAN ; Weihao YANG ; Mingliang LI ; Chao ZHU ; Guobao XIA ; Ying ZHOU ; Guanhui MA ; Jingbo ZHANG
Chinese Journal of Health Management 2021;15(2):134-137
Objective:To analyze the effect of home quarantine on blood glucose and lipids in healthy adults during the COVID-19 epidemic times.Method:From April 7, 2020 to May 1, 2020, 512 adults wereexamined in Beijing physical examination center, of which 87 adults aged olderthan 18, received community closed management or home quarantine from January 23, 2020 to March 30, 2020, and theadultshad physical examination in Beijing physical examination center in the same month of 2018 and 2019 were selected as controls. The change trend of blood glucose and blood lipid acrossthe three years was analyzed by one-way repeated measurement of variance, and the difference of blood lipid and blood glucose between two years of physical examination was further analyzed by Bonferroni method. Datawereanalyzed by gender.Result:Among the 87 subjects, 36 (41.4%) were male and 51(58.6%) were female. The average age was (46.3±13.2) years and ranged from 24 to 74. The difference of high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and fasting blood glucose (FBG) among 2018, 2019 and 2020 was statistically significant (all P<0.05), while differences in LDL-C, TC and FBG were statistically significant for males (all P<0.05) and HDL-C, LDL-C, TC and FBG were statistically significant for females (all P<0.05). HDL-C in 2018and 2020were significantly lower than that in 2019 [(1.27±0.29), (1.30±0.31) vs. (1.36±0.34) mmol/L], LDL-C in 2020was significantly higher than that in 2018and 2019 [(3.11±0.88) vs. (2.81±0.77), (2.84±0.71) mmol/L], TG in 2020 was significantly higher than that in 2019[(1.54±1.17) vs. (1.32±0.80) mmol/L], TC in 2019and 2020were significantly higher than that in 2018 [(4.88±0.94), (5.10±0.99) vs. (4.63±0.90) mmol/L], and the FBG in 2019and 2020were significantly lower than that in 2018 [(5.34±1.17), (5.44±1.58) vs. (5.84±1.70) mmol/L] (all P<0.05). The comparative analysis of men and women showed that the means of LDL-C, TG, TC and FBG of men were higher than those of women while the mean of HDL-C was lower than that of women in each year; compared with 2019, the increase of LDL-C and TC of men was obvious while the decrease of HDL-C of women was obvious (all P<0.05) in 2020. Conclusion:During the epidemic period of COVID-19, the home quarantine has adverse effects on blood glucose and lipid.
10.Quick finding of absorption ingredients of Paeoniae Radix Alba by SEMAC.
Qin TAN ; Weihao WANG ; Bei SONG ; Liangmian CHEN ; Jingjing ZHU ; Zhimin WANG ; Jiucheng CUI
China Journal of Chinese Materia Medica 2011;36(6):687-690
OBJECTIVETo establish a method for quick finding of the absorption ingredients of Paeoniae Radix Alba in order to select the index of quality control.
METHODThe absorption ingredients of three concentration of Paeoniae Radix Alba were investigated with the in vitro-everted intestinal sac (VEIS) model. The intestinal sac fluids of jejunum and ileum were collected in different time and detected by HPLC. The accumulative absorption quantity of albiflorin and paeoniflorin were calculated, respectively.
RESULTFive ingredients could be detected. In different concentrations of Paeoniae Radix Alba, albiflorin and paeoniflorin in various intestinal sections were the linear absorption (R2 > 0.9), conformed to the zero order absorption rate. The values of Ka in the jejunum and ileum were increased along with the raised dosage of the Paeoniae Radix Alba (P < 0.05), indicating a passive absorption manner.
CONCLUSIONSEMAC could be used as a tool to find the absorption ingredients of Paeoniae Radix Alba. Compared with the jejunum, the ileum could provide the more absorption information. It was showed that the optimal detecting time was 60 min.
Animals ; Intestinal Absorption ; Male ; Paeonia ; Rats ; Rats, Wistar