[Interaction of polymorphisms of PPAR-γ2 gene -C34G and NADPH oxidase subunit p22phox gene -C242T with Helicobacter pylori infection in esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the interaction of polymorphisms of PPAR-γ2 gene -C34G and NADPH oxidase subunit p22phox gene -C242T with helicobacter pylori (H. pylori) infection in esophageal squamous cell carcinoma (ESCC) . METHODS: A total of 200 cases of LSCC of Broder grade I, 200 of Broder grade II and of grade III were enrolled in this study with 200 healthy individuals as the control group. The genetic polymorphisms of PPAR-γ2 gene -C34G and NADPH oxidase subunit p22phox gene -C242T were analyzed using PCR-RFLP in peripheral blood leukocytes. 14C-urea breath test (14C-UBT) was used to test 14C disntegration per minute (DPM) for evaluating the infection status of H. pylori. An unconditional logistic regression model was used to analyze the interaction of nucleotide polymorphisms and H. pylori infection. RESULTS: The risk of ESCC significantly increased in subjects with -C34G (CG), -C34G(GG), -C242T (CT), and -C242T (TT) genotypes. Combined analysis of the polymorphisms showed that the subjects carrying -C34G (GG)/ -C242T (TT) had a high risk of ESCC, and a positive interaction was found between -C34G (GG) and -C242T (TT) in increasing the risk of ESCC. Positive interactions in the pathogenesis of ESCC were also found between -C34G (CG) and -C242T (TT), between -C34G (CG) and -C242T (CT), and between -C34G (GG) and -C242T (CT) (γ>1). The risk of ESCC significantly increased in subjects with H. pylori infection, which showed positive interactions with -C34G (CG), -C34G (GG), -C242T (CT) and -C242T (TT) in increasing the risk of ESCC (γ>1). CONCLUSION: Individuals carrying -C34G(CG), -C34G(GG), -C242T (CT) and -C242T (TT) genotypes have a high risk of developing ESCC, and these genotypes interact with H. pylori infection in the pathogenesis of LSCC, suggesting the importance of eradicating H. pylori for prevention of ESCC.

Association of polymorphisms of adiponectin gene promoter-11377C/G, glutathione peroxidase-1 gene C594T, and cigarette smoking in nonalcoholic fatty liver disease.

BACKGROUND: The number of studies on adiponectin, GPx-1 gene polymorphisms, and nonalcoholic fatty liver disease (NAFLD) susceptibility is increasing, but none have investigated the effect of cigarette smoking in combination with the gene polymorphisms on the susceptibility to NAFLD. In order to understand the distribution of adiponectin and GPx-1 in the local population, to explore the possible association of cigarette smoking with adiponectin and GPx-1 gene polymorphisms in the pathogenesis of NAFLD, we conducted this research, examining the distribution of polymorphisms of adiponectin and GPx-1 in NAFLD patients and healthy controls, analyzing the association between these polymorphisms and cigarette smoking. METHODS: Two hundred nonalcoholic simple fatty liver (NAFL), 200 nonalcoholic steatohepatitis (NASH), and 200 nonalcoholic fatty hepatic cirrhosis (NAFHC) cases from the First Affiliated Hospital of Xinxiang Medical College in China from February 2011 to November 2014 were selected for this study, and 200 healthy individuals as a control group. No significant difference among the four groups in age, sex, ethnicity, and birthplace was observed. The genetic polymorphisms of adiponectin gene promoter-11377C/G and GPx-1 gene C594T were analyzed using polymerase chain reaction-restriction fragment length polymorphisms in peripheral blood leukocytes of the above-mentioned cases. The interaction between the two mutants and the gene-environment association of the genotypes with cigarette smoking were analyzed. RESULTS: The frequencies of adiponectin gene promoter-11377C/G(CG), -11377C/G (GG), GPx-1 gene C594T (CT) and C594T (TT) were 24.50%, 26.00%, 24.00%, and 25.50% in the NAFL group, 34.50%, 37.00%, 35.00%, and 36.00% in the NASH group, 42.00%, 46.00%, 43.50%, and 45.50% in the NAFHC group, and 14.00%, 14.50%, 13.00%, and 14.00% in the control group, respectively. Statistical tests showed a significant difference in the frequencies among each group (p < 0.01). The risk of NAFLD significantly increased in patients with adiponectin gene promoter-11377C/G (CG) genotype [odds ratio (OR)NAFL = 2.5278; ORNASH = 6.1823; ORNAFHC = 17.8570), in those with -11377C/G (GG) genotype (ORNAFL = 2.5900; ORNASH = 6.4017; ORNAFHC = 18.9023), in those with GPx-1 gene C594T (CT) genotype (ORNAFL = 2.6687; ORNASH = 6.7772; ORNAFHC = 22.2063), and in those with C594T (TT) genotype (ORNAFL = 2.6330; ORNASH = 6.4729; ORNAFHC = 21.5682). Combined analysis of the polymorphisms showed that percentages of adiponectin gene promoter -11377C/G (GG)/GPx-1 gene C594T (TT) in the NAFL, the NASH, NAFHC, and control groups was 7.00%, 13.50%, 21.00%, and 2.00%, respectively (p < 0.01). The people who carried the adiponectin gene promoter -11377C/G (GG)/GPx-1 gene C594T (TT) had a high risk of NAFLD (ORNAFL = 7.2800; ORNASH = 41.2941; ORNAFHC = 363.9724), and statistical analysis suggested a positive association between -11377C/G (GG) and C594T (TT) in increasing the risk of NAFLD (γ2NAFL = 2.2071, γ4 NAFL = 2.0773; γ2 NASH = 2.1084; γ4NASH = 2.0543; γ2 NAFHC = 2.1387; γ4NAFHC = 2.0004). Likewise, there were also positive association in the pathogenesis of NAFLD between -11377C/G (CG) and C594T (TT), -11377C/G (CG) and C594T (CT), -11377C/G (GG), and C594T (TT) (CT).The frequencies of smoking index (SI) ≤ 400 and SI > 400 were 22.50% and 26.50% in the NAFL group, 29.00% and 40.50% in the NASH group, 34.00% and 51.50% in the NAFHC group, and 15.50% and 12.00% in the control group, respectively. Statistical tests showed a significant difference in the frequencies among each group (all p < 0.01). The risk of NAFLD significantly increased in patients with SI ≤ 400 (ORNAFL = 2.0636; ORNASH = 4.4474; ORNAFH C = 10.9677) and in those with SI > 400 (ORNAFL = 3.1393; ORNASH = 8.0225; ORNAFHC = 21.4583), and statistical analysis suggested a positive association between cigarette smoking and -11377C/G (CG), -11377C/G (GG), C594T (CT), and C594T (TT) in increasing the risk of NAFLD (all γ > 1). CONCLUSION: Adiponectin gene promoter -11377C/G (CG), -11377C/G (GG), GPx-1 gene C594T (CT), C594T (TT), and cigarette smoking are risk factors in NAFLD, and the significant association between genetic polymorphisms of -11377C/G, C594T, and cigarette smoking amplify the risk of NAFLD.

Interaction of Polymorphisms of Resistin Gene Promoter -420C/G, Glutathione Peroxidase -1 Gene Pro198Leu and Cigarette Smoking in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Many studies have suggested that cigarette smoking and polymorphisms of resistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, examined the distribution of polymorphisms in GPx-1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status. METHODS: Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes. Interactions between the two mutants and the gene-environment interaction with cigarette smoking were also analyzed. RESULTS: Genotype frequencies of -420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56% and 50.11%, respectively) compared with healthy controls (23.67% and 24.22%, respectively) (P = 0.0069; P = 0.0072). Moreover, the risk of NAFLD with -420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685, 95% confidence interval (CI) =1.9366-5.2073). Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR = 3.1424, 95% CI = 1.7951-5.2367). Combined analysis of the polymorphisms showed that the -420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44% vs. 12.78%, respectively, P = 0.0054), while individuals with -420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR = 5.0357, 95% CI = 3.1852-7.8106). Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR = 1.8990, P = 0.0083 in the smoking index (SI) ≤400 subgroup; OR = 5.0937, P = 0.0051 in the SI >400 subgroup), and statistical analysis suggested a positive interaction between cigarette smoking and -420C/G (GG) (γ = 5.6018 in the SI ≤400 subgroup; γ = 4.4770 in the SI >400 subgroup) and Pro198Leu (LL) (γ = 5.7715 in the SI ≤400 subgroup; γ = 4.5985 in the SI >400 subgroup) in increasing the risk of NAFLD. CONCLUSION: NAFLD risk factors include -420C/G (GG), Pro198Leu (LL) and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.

Dalitong granule combined with electroacupuncture in the treatment of functional dyspepsia: A randomized controlled trial.

OBJECTIVE: To explore clinical short and long-term effect of combining dalitong granule (DG) and electroacupuncture group (EA) in the treatment of functional dyspepsia. METHODS: Totally 640 patients with confirmed functional dyspepsia were randomly divided into 4 groups using a randomized digital table: the DG group, the EA group, the combined group and the control group, 160 cases in each group. The DG group was treated with 6 g DG 3 times daily; the EA group was treated with puncture of points Zusanli (ST36), Zhongwan (CV12), Neiguan (PC6), Taichong (LR3) and Gongsun (SP4) twice daily; the combined group with above-mentioned DG and EA; and the control group with 5 mg mosapride 3 times, 20 mg pantoprazole and 25 mg amitriptylines twice daily. The treatment course was 4 weeks for all groups. The symptom score, quality of life score by Short Form 36 Health Survey Questionnaires (SF-36), plasma motilin by radioimmunoassay, electrogastrographic frequencies by electrogastrogram (EGG) and gastric emptying by B-sonography were examined, and adverse reactions were observed before, at the end of treatment and 60 weeks post-treatment. RESULTS: In the DG group 1 case dropped out for not taking medicine strictly and 1 case was lost to follow-up, while 1 case in the EA group and 2 cases in the combined therapy group were lost to follow-up. Compared with pre-treatment, quality of life score, plasma motilin, electrogastrographic frequencies and gastric emptying were all increased significantly, while symptom score was decreased significantly at the end of treatment in each group (P<0.01); in the combined group quality of life score, plasma motilin, electrogastrographic frequencies and gastric emptying were all significantly higher than those in the other groups, while symptom score was significantly lower than in the other groups (P<0.05). Compared with at the end of treatment, these indices changed insignificantly in the combined group and the EA group 60 weeks post-treatment (P>0.05), but the 4 increased indices were all decreased significantly, and symptom score was increased significantly in the DG and the control groups (P>0.05). The short and long-term total effective rates in the combined group were all significantly higher than those in the other treatment groups (P<0.05 or P<0.01). No serious adverse reaction occurred in the four groups. CONCLUSION: Combined treatment of DG and EA could increase both plasma motilin and electrogastrographic frequencies, promote gastric emptying, alleviate the symptom of dyspepsia so as to increase quality of life, with better safety and long-term effect.

Interaction between the polymorphisms of cyclooxygenase-2-1195G/A,MnSOD9Ala/val genes and the high-fat diets and its correlation with ulcerative colitis.

OBJECTIVE: To investigate the interaction of the polymorphisms of cyclooxygenase-2-1195G/A (COX-2-1195G/A) and manganese superoxide dismutase 9Ala/Val (MnSOD9Ala/Val) genes and the high-fat diets and its potential correlation with ulcerative colitis (UC). METHODS: The genetic polymorphisms of COX-2-1195G/A and MnSOD9Ala/Val were analyzed by polymorphism-polymerase chain reaction (PCR) in peripheral blood leukocytes obtained from 750 UC patients (UC group) and 750 healthy subjects (control group). RESULTS: The frequencies of COX-2-1195G/A(A/A) and MnSOD9Ala/Val(V/V) were 49.07% and 50.13% in UC group and 21.20% and 22.40% in control group, respectively (P<0.01). The risk of UC significantly increased in subjects with COX-2-1195G/A(A/A) genotype (OR=3.5808,95%CI=1.8062-5.3478) and in those with MnSOD9Ala/Val(V/V) genotype(OR=3.4828,95%CI=1.9137-5.5496). Pooled analysis of the polymorphisms showed that distribution frequency of COX-2-1195G/A(A/A)/MnSOD9Ala/Val (V/V) was 40.67% in UC group and 8.40% in control group (P<0.01). Subjects with COX-2-1195G/A(A/A)/MnSOD9Ala/Val(V/V) had a significantly higher risk of UC (OR=7.5655,95% CI=4.1849-11.2037). The rate of high-fat diets was significantly higher in the UC group than in the control group(49.73 vs.20.13%,P<0.01),and statistic analysis suggested an interaction between high-fat diet and COX-2-1195G/A(A/A)(Γ=11.81821)and MnSOD9Ala/Val (V/V)(Γ=9.0107), which increase risk of UC. CONCLUSIONS: COX-2-1195G/A(A/A),MnSOD9Ala/Val (V/V), and high-fat diet are the risk factors of UC. The interaction between the genetic polymorphisms of COX-2-1195G/A and MnSOD9Ala/Val and the high-fat diet increases the risk of UC.

Correlations between polymorphisms of extracellular superoxide dismutase, aldehyde dehydrogenase-2 genes, as well as drinking behavior and pancreatic cancer.

OBJECTIVE: To investigate the correlation between drinking behavior combined with polymorphisms of extracellular superoxide dismutase (EC-SOD) and aldehyde dehydrogenase-2 (ALDH2) genes and pancreatic cancer. METHODS: The genetic polymorphisms of EC-SOD and ALDH2 were analyzed by polymerase chain reaction restriction fragment length polymorphism in the peripheral blood leukocytes obtained from 680 pancreatic cancer cases and 680 non-cancer controls. Subsequently the frequency of genotype was compared between the pancreatic cancer patients and the healthy controls.The relationship of drinking with pancreatic cancer was analyzed. RESULTS: The frequencies of EC-SOD (C/G) and ALDH2 variant genotypes were 37.35% and 68.82% respectively in the pancreatic cancer cases, and were significantly higher than those in the healthy controls (21.03% and 44.56%, all P<0.01). People who carried EC-SOD (C/G) (OR=2.24, 95% CI= 1.81-4.03, P<0.01) or ALDH2 variant genotypes (OR=2.75, 95% CI=1.92-4.47, P<0.01) had a high risk to develop pancreatic cancer. Those who carried EC-SOD (C/G) genotype combined with ALDH2 variant genotype had a high risk for pancreatic cancer (29.56% vs. 6.76%, OR=7.69, 95% CI=3.58-10.51, P<0.01). The drinking rate of the pancreatic cancer group (64.12%) was significantly higher than that of the control group (40.15%; OR=2.66, 95% CI=1.30-4.42, P<0.01). An interaction between drinking and EC-SOD (C/G)/ALDH2 variant genotypes increased the risk of occurrence of pancreatic cancer (OR=25.00, 95% CI= 11.87-35.64, P<0.01). CONCLUSION: EC-SOD (C/G), ALDH2 variant genotypes and drinking might be the risk factors of pancreatic cancer.

Association of genetic polymorphisms of aldehyde dehydrogenase-2 and cytochrome P450 2E1-RsaI and alcohol consumption with oral squamous cell carcinoma.

OBJECTIVE: To investigate the association of the polymorphisms of aldehyde dehydrogenase-2(ALDH2) and CYP2E1-RsaI genes and alcohol consumption with oral squamous cell carcinoma (OSCC). METHODS: The genetic polymorphisms of ALDH2 and CYP2E1-RsaI were determined by polymorphism-polymerase chain reaction (PCR) technique in the peripheral blood leukocytes of 320 OSCC patients and 320 non-cancer controls. RESULTS: The frequencies of ALDH2 variant genotypes and CYP2E1-RsaI (c2/c2) were 70.94% and 39.06% in the OSCC group and 43.44% and 20.62% in the control group (both P<0.01). The risk of OSCC with ALDH2 variant genotypes was significantly higher than that in control group (OR=3.178, 95% CI=1.917-4.749), whereas the subjects carried with CYP2E1-RsaI (c2/c2) also had a high risk of OSCC (OR=2.467, 95%CI=1.783-4.045). Combined analysis of the polymorphisms showed that percentage of ALDH2 variant genotypes/CYP2E1-RsaI (c2/c2) in OSCC group and control group was 32.19% and 6.25%, respectively (P<0.01). Carriers of ALDH2 variant genotypes/CYP2E1-RsaI (c2/c2) had a high risk of OSCC (OR=9.792, 95%CI=3.583-12.472). The percentage of alcohol consumption was significantly higher in OSCC group than in the control group (OR=2.861, 95% CI=1.541-4.781, P<0.01), and ALDH2 variant genotypes and CYP2E1-RsaI (c2/c2) showed synergic effects with alcohol consumption for the increased risk of OSCC (OR=41.152, 95%CI=19.903-67.551). CONCLUSION: The polymorphisms of ALDH2 and CYP2E1-RsaI genes and alcohol consumption, independently and synergically, increase the risk of OSCC.

[Acupuncture combined with Chinese herbal medicine Plantain and Senna Granule in treatment of functional constipation: a randomized, controlled trial].

BACKGROUND: Functional constipation is one of the most common gastrointestinal diseases. Currently, there is no effective Western medical therapy for functional constipation and it significantly impacts the quality of life of the patients. Integrated traditional Chinese and Western medicine therapies were reported to have better therapeutic effects than routine Western medicine therapies. OBJECTIVE: To explore the efficacy of acupuncture combined with Chinese herbal medicine Plantain and Senna Granule in the treatment of functional constipation. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 390 patients with confirmed functional constipation enrolled from the Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical College in China from February 2008 to January 2010 were randomly divided into three groups, with 130 cases in each group. Acupuncture group was treated with puncture of point Tianshu (ST25), Shangjuxu (ST37), Zusanli (ST36), Dachangyu (BL25) and Zhigou (SJ6) twice daily for four weeks, while Plantain and Senna Granule group was treated with 5 g of Plantain and Senna Granule once daily, and the combination group was given above-mentioned acupuncture and Plantain and Senna Granule. MAIN OUTCOME MEASURES: The defecation cycle, stool property, constipation symptom, accompanying symptoms, gastrointestinal transit time, including total gastrointestinal transit time, mouth-intestine transit time, colonic transit time, right colonic transit time, left colonic transit time and rectosigmoid colonic transit time, and adverse reactions of the three groups were evaluated before treatment, at the end of treatment and 64 weeks after treatment, respectively. RESULTS: Compared with before treatment, the scores of defecation cycle, stool property, constipation symptoms and accompanying symptoms, and gastrointestinal transit time all decreased significantly at the end of treatment in each group (P<0.01), and the combination group showed better results than the other groups (P<0.05). Compared with the end of treatment, the above-mentioned indexes recurred insignificantly in the combination group and acupuncture group after 64 weeks of follow-up (P>0.05), but all recurred significantly in the Plantain and Senna Granule group (P>0.05). Both short- and long-term total response rates of the combination group showed significant differences compared with those of the other two groups (P<0.05 or P<0.01). No serious adverse reactions occurred in all the three groups. CONCLUSION: Acupuncture plus Plantain and Senna Granule can significantly decrease gastrointestinal transit time and defecation cycle in patients with functional constipation; it can also change stool property and alleviate constipation symptom and accompanying symptoms, with good security and tolerance.

[Long-term efficacy and safety research on functional dyspepsia treated with electroacupuncture and Zhizhu Kuanzhong capsule].

OBJECTIVE: To observe the long-term efficacy and safety on functional dyspepsia treated with electroacupuncture and Zhizhu Kuanzhong capsule and explore the therapeutic mechanism. METHODS: Three hundreds and twenty patients with confirmed diagnosis as functional dyspepsia were randomly divided into 4 groups: an electroacupuncture group, a Zhizhu Kuanzhong capsule group, a combined therapy group and a western medication group, 80 cases in each group. In electroacupuncture group, acupuncture was applied to Zusanli (ST 36), Zhongwan (CV 12), Neiguan (PC 6), Taichong (LR 3) and Gongsun (SP 4), twice per day, continuously for 5 days each week. In Zhizhu Kuanzhong capsule group, Zhizhu Kuanzhong capsule, 1.29 g was administered for oral application, three times each day. In combined therapy group, the therapeutic programs in the above-mentioned groups were applied in combination. In western medication group, Mosapride 5 mg, three times per day; Omeprazole 20 mg, twice per day and Amitriptyline 25 mg, twice per day were administered for oral application. Six weeks treatment was required in each group. The symptoms score, the Nepean Dyspepsia Symptom Index (NDSI), the Nepean Dyspepsia Life Quality Index (NDLQI), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), electrogastrography, plasma motilin, gastric emptying by B-sonography and adverse reactions were observed before and after treatment, as well as 4 weeks after treatment separately. RESULTS: Compared with those before treatment, the symptom score and NDSI decreased apparently after treatment (all P < 0.01), NDLQI, SF-36, electrogastrographic frequency, plasma motilin and gastric emptying were up-regulated apparently (all P < 0.01) after treatment in each group. The results of the above-mentioned indices in combined therapy group were superior to the other groups (all P < 0.05). As compared with the condition at the end of treatment, in 4 weeks after treatment, the above indices were not rebound apparently in electroacupuncture group and combined therapy group (all P > 0.05). But they were rebound obviously in Zhizhu Kuanzhong capsule group and western medication group (all P < 0.05). The short-term and long-term efficacies in combined therapy group were significantly higher than the total effective rates in the other groups (P < 0.05, P < 0.01). No serious adverse reaction was reported in each group. CONCLUSION: Electroacupuncture and Zhizhu Kuanzhong capsule all up-regulate plasma motilin and electrogastrographic frequency, promote gastric emptying, alleviate the symptom of functional dyspepsia and improve NDLQI. But the combined medication achieves much better efficacy and presents better safety and long-term therapeutic effect.