Modified Sequential Therapy Regimen versus Conventional Triple Therapy for Helicobacter Pylori Eradication in Duodenal Ulcer Patients in China: A Multicenter Clinical Comparative Study.

Objective. Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. To observe the effect of eradicating Helicobacter pylori (H. pylori) and the treatment of duodenal ulcer by 2 kinds of modified sequential therapy through comparing with that of 10-day standard triple therapy. Methods. A total of 210 patients who were confirmed in duodenal ulcer active or heal period by gastroscopy and H. pylori positive confirmed by rapid urease test, serum anti-H. pylori antibody (ELASE), or histological examination enrolled in the study. All the patients were randomly divided into three groups: group A (70 cases) and group B (70 cases) were provided 10-day modified sequential therapy; group C (70 cases) was provided 10-day standard triple therapy. Patients of group A received 20 mg of Esomeprazole, 500 mg of Clarithromycin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group B received 20 mg of Esomeprazole, 1000 mg of Amoxicillin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group C received 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for standard 10-day therapy. All drugs were given twice daily. H. pylori eradication rate was checked four to eight weeks after taking the medicine by using a (13)C urea breath test. In the first, second, third, seventh, twenty-first, thirty-fifth days respectively, the symptoms of patients such as epigastric gnawing, burning pain, and acidity were evaluated simultaneously. Results. Overall, 210 patients accomplished all therapy schemes, 9 case patients were excluded. The examination result indicated that the H. pylori eradication rate of each group was as follows: group A 92.5% (62/67), group B 86.8% (59/68), and group C 78.8% (52/66). The H. pylori eradication rate of group A was slightly higher than group B (P < 0.05) and both of them were obviously higher than group C (P < 0.05). Modified sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (80%/67% versus 31%; P = 0.02). Symptoms improvement: all the three groups could improve the symptoms such as epigastric gnawing, burning pain, and acidity since the first day. There was no significant difference in total score descending of symptoms between each group (P > 0.05). Conclusions. All the three therapy schemes could alleviate symptoms of duodenal ulcer patients in China efficiently. But as far as eradicating H. pylori is concerned, the modified sequential therapy was better than standard triple therapy, especially the therapy scheme used in group A.

The eradicating Helicobacter pylori infection in duodenal ulcer patients by three short-term triple therapies in China: a multicenter clinical comparative study.

BACKGROUND/AIMS: This study aimed to compare the 7d triple therapy with 3d and 5d triple therapies, to observe the effect of eradicating Helicobacter pylori (Hp) on treating duodenal ulcers. METHODOLOGY: One hundred and sixteen patients who were confirmed duodenal ulcer active period and Hp positive were enrolled in the study. All the patients were divided into three groups: 3d group (n=39), 5d group (n=37) and 7d control group (n=40). All three groups were provided triple therapy first: rabeprazole, 10mg + furazolidone, 100mg + clarithromycin 250mg, twice a day for three days, five days and seven days, respectively. Then rabeprazole 10mg was provided once a day. Following the treatment, 13C urea breath test was performed to observe the Hp eradication rate. The symptoms of patients such as epigastralgia, burning pain and acidity were evaluated. RESULTS: The Hp eradication rate was: 3d group 76% (28/37), 5d 89% (31/35) and 7d 91% (32/35). There was no significant difference between 5d and 7d group (p>0.05). But the rate of groups 5d and 7d was significantly higher than group 3d (p<0.05). All the three groups showed an improvement in symptoms such as epigastralgia, burning pain and acidity. CONCLUSIONS: All three therapy schemes could alleviate symptoms of duodenal ulcer patients efficiently. But as far as eradicating Hp concerned, 5d and 7d therapies were better than 3d.

Cyclopamine blocked the growth of colorectal cancer SW116 cells by modulating some target genes of Gli1 in vitro.

BACKGROUND/AIMS: Hedgehog (Hh) pathway has been considered as a therapy target for various cancer entities. However, its mechanism in colorectal cancer is still unclear. METHODOLOGY: We analyzed the expression of Hh pathway members in colorectal adenomas and cancer cell lines and then studied its relationship with survival of colorectal cancer cells through inhibiting Hh pathway by cyclopamine. Moreover, we studied the regulation of Gli1 on insulin-like growth factor binding protein 6 (IGFBP6) and B-cell CLL/lymphoma 2 (Bcl-2) genes at the level of transcription by XChIP and cyclopamine inhibition assay. RESULTS: Sonic hedgehog (Shh), Smoothened (Smo), patched (Ptch) and Gli1 genes mRNA were expressed in SW116 cells. Gli1 bound to promoter regions of Bcl-2 and IGFBP6 genes, cyclopamine inhibited proliferation and induced apoptosis through inhibiting the transcriptions of IGFBP6 (p=0.003), proliferating cell nuclear antigen (PCNA) (p=0.014) and Bcl-2 (p=0.013), and increasing that of BCL2-associated X protein (Bax) and BCL2-antagonist/killer 1 (Bak1) (p=0.003 and 0.001, respectively) in SW116 cells. CONCLUSIONS: Hh pathway is aberrant activation in part colorectal carcinomas cell lines and its inhibitor may be an effectual agent for colorectal cancer chemoprevention. It may be one of the mechanisms that Gli1 maintained cell survival by binding the promoter regions and facilitating transcription of IGFBP6 and Bcl-2 genes.

[Study on patients with benign prostate hyperplasia treated by the therapeutic regimen of watchful waiting during a twenty-four-month follow-up period].

OBJECTIVE: To analyze the changes of the main clinic parameters in patients with benign prostate hyperplasia (BPH) treated by watchful waiting and to find out the risk factors contributing the progress of BPH. METHODS: According to the inclusion and exclusion criteria,61 patients diagnosed as BPH were recruited in the group of watchful waiting. Data on IPSS, prostate volume, prostate specific antigen (PSA), maximum flow rate, average flow rate and residual urine volume during follow-up period of 24 months, were recorded. RESULTS: At 0, 12, 24 months, the IPSS, prostate volume (ml), PSA(ng/ml), maximum flow rate (ml/s) were 7 +/- 4, 4 +/- 3, 4 +/- 3; 33.0 +/- 9.0, 33.8 +/- 7.6, 30.9 +/- 6.8; 1.53 +/- 1.35, 1.43 +/- 0.95, 1.22 +/- 0.99; 17.1 +/- 5.0, 17.2 +/- 6.1, 19.2 +/- 8.0, respectively. At the end of the 24-months follow-up, all observed parameters had a little improvement except the average prostate volume in this group. Of the 61 patients, 42 (62%) progressed slowly or became better when comparing with baseline data of the study. Moreover, the difference between at 24-month and at baseline period, IPSS showed statistical significance (P < 0.0001) in t test. In the study of BPH progression risk factors by logistic regression analysis, prostate volume (P = 0.0910) and residual urine volume (P = 0.0780) showed a trend of becoming the risk factors. CONCLUSION: Our study showed that patients treated with watchful waiting had slow progression and majority of these patients did not need to alter their treatment options. Through data analysis, we noticed that the changes of data watchful waiting patients could help us to choose more precise and reasonable treatment option in clinical practice.

[Data analysis of the objective observation parameters of benign prostatic hyperplasia patients accepting different treatment regimens].

OBJECTIVE: To observe different objective observation parameters of the benign prostatic hyperplasia (BPH) patients accepting different treatment strategies, and to further analyze the relationship of these factors with the treatment option. METHODS: Three hundred and twenty-nine BPH patients, aged 50-80, were assigned into 3 groups jointly decided by the physicians and patients based on the individual conditions and the patients' willingness: watchful waiting group (n=61), aged (63 +/- 8), drug treatment group (n=179), aged (68 +/- 7), and operation group (n=89), aged (71 +/- 6). The data of prostate volume, prostate specific antigen (PSA), maximum flow rate (Qmax), average flow rate, urinating volume, and residual urine volume before treatment were recorded. RESULTS: The prostate volume of the watchful waiting group was 33.0 ml, significantly smaller then those of the drug treatment and operation groups (40.1 and 65.5 ml respectively, both P < 0.01); the Qmax of the watchful waiting group was 17.1 ml/s, significantly higher than those of the drug treatment and operation groups (12.4 and 9.1 ml/s respectively, both P < 0.01), and the urinating volume of the watchful waiting group was 332 ml, significantly more than those of the drug treatment and operation groups (247 and 188 ml respectively, both P < 0.01). The serum PSA of the operation group was 5.44 ng/ml, significantly higher than those of the watchful waiting and drug treatment groups (1.53 and 1.99 ng/ml respectively, both P < 0.01); and the residual urine volume of the operation group was 208 ml, significantly higher than those of the watchful waiting and drug treatment groups (21 and 45 ml respectively, both P < 0.01). There were no significant differences in the serum PSA and residual urine volume between the drug treatment and watchful waiting groups. CONCLUSIONS: Prostate volume, PSA, Qmax, average flow rate, urinating volume, and residual urine volume are important influential factors influencing the treatment option of BPH. Data analysis of the objective observation parameters will be helpful in clinical decision making.

PCR-SSCP-DNA sequencing method in detecting PTEN gene mutation and its significance in human gastric cancer.

AIM: To discuss the possible effect of PTEN gene mutations on occurrence and development of gastric cancer. METHODS: Fifty-three gastric cancer specimens were selected to probe PTEN gene mutations in genome of gastric cancer and paracancerous tissues using PCR-SSCP-DNA sequencing method based on microdissection and to observe the protein expression by immunohistochemistry technique. RESULTS: PCR-SSCP-DNA sequencing indicated that 4 kinds of mutation sites were found in 5 of 53 gastric cancer specimens. One kind of mutation was found in exons. AA-TCC mutation was located at 40 bp upstream of 3' lateral exon 7 (115946 AA-TCC). Such mutations led to terminator formation in the 297th codon of the PTEN gene. The other 3 kinds of mutation were found in introns, including a G-C point mutation at 91 bp upstream of 5' lateral exon 5(90896 G-C), a T-G point mutation at 24 bp upstream of 5' lateral exon 5 (90963 T-G), and a single base A mutation at 7 bp upstream of 5' lateral exon 5 (90980 A del). The PTEN protein expression in gastric cancer and paracancerous tissues detected using immunohistochemistry technique indicated that the total positive rate of PTEN protein expression was 66% in gastric cancer tissue, which was significantly lower than that (100%) in paracancerous tissues (P < 0.005). CONCLUSION: PTEN gene mutation and expression may play an important role in the occurrence and development of gastric cancer.

Effects of endothelin-1 on hepatic stellate cell proliferation, collagen synthesis and secretion, intracellular free calcium concentration.

AIM: To explore the effects of endothelin-1(ET-1) on hepatic stellate cells (HSCs) DNA uptake, DNA synthesis, collagen synthesis and secretion, inward whole-cell calcium concentration ([Ca2+]i) as well as the blocking effect of verapamil on ET-1-stimulated release of inward calcium (Ca2+) of HSC in vitro. METHODS: Rat hepatic stellate cells (HSCs) were isolated and cultivated. 3H-TdR and 3H-proline incorporation used for testing DNA uptake and synthesis, collagen synthesis and secretion of HSCs cultured in vitro; Fluorescent calcium indicator Fura-2/AM was used to measure [Ca2+]i inward HSCs. RESULTS: ET-1 at the concentration of 5X10(-8) mol/L, caused significant increase both in HSC DNA synthesis (2,247+/-344 cpm, P<0.05) and DNA uptake (P<0.05) when compared with the control group. ET-1 could also increase collagen synthesis (P<0.05 vs control group) and collagen secretion (P<0.05 vs control group). Besides, inward HSC [Ca2+]i reached a peak concentration (422+/-98 mol/L, P<0.001) at 2 min and then went down slowly to 165+/-51 mol/L (P<0.01) at 25 min from resting state (39+/-4 mol/L) after treated with ET-1. Verapamil (5 mol/L) blocked ET-1-activated [Ca2+]i inward HSCs compared with control group (P<0.05). Fura-2/AM loaded HSC was suspended in no Ca2+ buffer containing 1 mol/L EGTA, 5 min later, 10(-8) mol/L of ET-1 was added, [Ca2+]i inward HSCs rose from resting state to peak 399+/-123 mol/L, then began to come down by the time of 20 min. It could also raise [Ca2+]i inward HSCs even without Ca2+ in extracellular fluid, and had a remarkable dose-effect relationship(P<0.05). Meanwhile, verapamil could restrain the action of ET-1(P<0.05). CONCLUSION: Actions of ET-1 on collagen metabolism of HSCs may depend on the transportation of inward whole-cell calcium.

Clinical evaluation of four one-week triple therapy regimens in eradicating Helicobacter pylori infection.

AIM: To evaluate clinical efficacy of four one-week triple therapies in eradicating Helicobacter pylori infection. METHODS: In this clinical trial, 132 patients with duodenal ulcer and chronic gastritis were randomly divided into four groups, and received treatment with OAC (omeprazole 20 mg + amoxicillin 1 000 mg + clarithromycin 250 mg), OFC (omeprazole 20 mg + furazolidone 100 mg + clarithromycin 250 mg), OFA (omeprazole 20 mg + furazolidone 100 mg + amoxicillin 1 000 mg) and OMC (omeprazole 20 mg + metronidazole 200 mg + clarithromycin 250 mg), respectively. Each drug was taken twice daily for one week. The (13)C urea breath test was carried out 4-8 weeks after treatment to determine the success of H pylori eradication. RESULTS: A total of 127 patients completed the treatment. The eradication rate for H pylori infection was 90.3%, 90.9%, 70.9% and 65.6%, respectively in OAC, OFC OMC and OFA groups. CONCLUSION: A high eradication rate can be achieved with one-week OAC or OFC triple therapy. Thus, one-week triple therapies with OAC and OFC are recommended for Chinese patients with duodenal ulcers and chronic gastritis.