PHF21A expression as a biomarker of hepatocellular carcinoma progression and prognosis.

Previous studies have shown that PHF21A is associated with the initiation and progression of various tumors. However, its role in hepatocellular carcinoma (HCC) is still unclear. Thus, this study aimed to determine the expression and clinical significance of PHF21A in HCC. PHF21A expression in 201 liver cancer samples and 129 adjacent normal tissues was detected by immunohistochemistry. The correlation between PHF21A expression and the clinicopathological features and prognosis of HCC was verified in 70 other liver tissue microarray samples. The relationship between PHF21A expression and HCC immune cell infiltration was explored via the Tumor Immune Estimation Resource (TIMER). The mechanism underlying the effect of PHF21A on HCC progression was analyzed by gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network analysis. Immunohistochemical staining showed that PHF21A expression in HCC tissue was significantly lower than that in adjacent nontumor liver tissue and was associated with patient sex, tumor size, metastasis, and Edmondson grade (p<0.05). Kaplan-Meier analysis demonstrated that low PHF21A expression was associated with a poor prognosis, and Cox regression analysis showed that PHF21A was an independent predictor of prognosis. TIMER analysis showed that PHF21A is positively correlated with tumor immune cell infiltration levels. Functional annotation indicated that PHF21A is involved in important pathways, including transcriptional deregulation pathways in cancer. Finally, in vitro experiments confirmed the low expression of PHF21A in HCC cells. PHF21A affects the progression and prognosis of HCC, suggesting that PHF21A may play an important role in monitoring and preventing the development of HCC.

[A transcriptional study of SDF-1alpha expression in PBL and the correlation between SDF-1alpha transcription and HIV-1 infection].

OBJECTIVE: To determine the transcription of SDF-1alpha in peripheral blood lymphocytes (PBL) and analysis the correlation between SDF-1alpha transcription and HIV infection. METHODS: Three groups of study subjects were recruited: (1) 97 HIV negative healthy donors, (2) 92 HIV patients of A1 to A3 stages and (3) 146 HIV patients of B1 to C3 stages. Total RNA was extracted from PBL. Reverse transcription (RT)-PCR and quantification PCR were developed for the SDF-1alpha transcriptional study. R1 value was calculated based on the ratio of SDF-1alpha copies to beta-globin copies. RESULTS: SDF-1alpha transcription is heterogeneous among the three study groups. The SDF-1alpha transcription was significantly up-regulated during late stage of HIV infection than the healthy donors. Correlation analysis indicated that R1 value was negatively correlated to CD4+ T cells counts (P = 0.002); and positively correlated to virus load (P = 0.001). The result demonstrated an association between SDF-1alpha transcription and disease progression. CONCLUSION: SDF-1alpha transcription was significantly up-regulated during late stage of HIV infection. It would be worthwhile to determine the mechnism of HIV affecting on SDF-1alpha genes transcription and the up-regulated SDF-1alpha expression on the disease progression.

Effects of proton-pump inhibitors on functional dyspepsia: a meta-analysis of randomized placebo-controlled trials.

BACKGROUND & AIMS: The aim of this study was to assess systematically the efficacy of proton pump inhibitors (PPIs) in the treatment of functional dyspepsia compared with placebo and to determine if any difference in the response exists between symptom subgroups of functional dyspepsia. METHODS: A literature search was performed through September 2005 in PubMed, Medline, Embase, CINAHL, and Cochrane databases to include randomized, double-blind, placebo-controlled trials evaluating the efficacy of PPIs for the treatment of functional dyspepsia. Relative risk (RR) and relative risk reduction (RRR) and 95% confidence intervals (CI) were calculated under a random-effects model. RESULTS: Seven studies with a total of 3725 patients were identified. PPIs were found to be more effective than placebo for reducing symptoms in patients with functional dyspepsia (RRR, 10.3%; 95% CI, 2.7%-17.3%). The estimated number needed to treat is 14.6 (95% CI, 8.7-57.1). When stratified analyses were performed, a significant difference in the efficacy was observed only in patients with ulcer-like (RRR, 12.8%; 95% CI, 7.2%-18.1%) and reflux-like dyspepsia (RRR, 19.7%; 95% CI, 1.8%-34.3%), but not in those with dysmotility-like (RRR, 5.1%; 95% CI, -10.9% to 18.7%) and unspecified dyspepsia (RRR, -8.0%; 95% CI, -23.7% to 5.6%). The effect of H pylori on the efficacy of PPIs remains unclear. Significant heterogeneity among studies was found for the overall analysis, dysmotility-like dyspepsia, H pylori-negative subgroup, and different dose subgroups. CONCLUSIONS: PPIs are more effective than placebo for the management of patients with ulcer-like and reflux-like functional dyspepsia.

Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: a meta-analysis.

AIM: To systematically evaluate the efficacy of H(2)-receptor antagonists (H(2)RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H(2)RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H(2)RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H(2)RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H(2)RAs of all doses across all grades of esophagitis, including patients refractory to H(2)RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H(2)RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H(2)RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.

Is proton pump inhibitor testing an effective approach to diagnose gastroesophageal reflux disease in patients with noncardiac chest pain?: a meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is common in patients with noncardiac chest pain (NCCP). Results of studies evaluating the accuracy of a proton pump inhibitor (PPI) treatment as a diagnostic test for GERD-related NCCP have varied. We evaluated the overall accuracy of this modality. METHODS: We searched the PubMed, MEDLINE, EMBASE, CINAHL, and Cochrane databases to May 2004 and included randomized, placebo-controlled studies evaluating the accuracy of findings from PPI testing in the diagnosis of GERD in patients with NCCP. The GERD diagnosis was confirmed by results of endoscopy and/or 24-hour esophageal pH monitoring. A summary diagnostic odds ratio and summary receiver operating characteristic curve analysis were used to estimate the overall accuracy and to explore any contributing factors. RESULTS: Six studies met the inclusion criteria. The overall sensitivity and specificity of a PPI test were 80% (95% confidence interval [CI], 71%-87%) and 74% (95% CI, 64%-83%), respectively, compared with 19% (95% CI, 12%-29%) and 77% (95% CI, 62%-87%), respectively, in the placebo group. The PPI test showed a significant higher discriminative power, with a summary diagnostic odds ratio of 19.35 (95% CI, 8.54-43.84) compared with 0.61 (95% CI, 0.20-1.86) in the placebo group. The impact of the prevalence of GERD and treatment duration on the accuracy of the test could not be determined because of the lack of an adequate number of studies. CONCLUSION: The use of PPI treatment as a diagnostic test for detecting GERD in patients with NCCP has an acceptable sensitivity and specificity and could be used as an initial approach by primary care physicians to detect GERD in selected patients with NCCP.

Do patients with non-ulcer dyspepsia respond differently to Helicobacter pylori eradication treatments from those with peptic ulcer disease? A systematic review.

AIM: It is controversial whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H pylori) eradication treatment than those with peptic ulcer disease (PUD). To review the evidence for any difference in H pylori eradication rates between PUD and NUD patients. METHODS: A literature search for full articles and meeting abstracts to July 2004 was conducted. We included studies evaluating the efficacy of a proton pump inhibitor (P) or ranitidine bismuth citrate (RBC) plus two antibiotics of clarithromycin (C), amoxicillin (A), metronidazole (M), or P-based quadruple therapies for eradicating the infection. RESULTS: Twenty-two studies met the criteria. No significant difference in eradication rates was found between PUD and NUD patients when treated with 7-d RBCCA, 10-d PCA or P-based quadruple therapies. When the 7-d PCA was used, the pooled H pylori eradication rate was 82.1% (431/525) and 72.6% (448/617) for PUD and NUD patients, respectively, yielding a RR of 1.15 (95%CI 1.01-1.29). However, the statistically significant difference was seen only in meeting abstracts, but not in full publications. CONCLUSION: There is no convincing evidence to suggest that NUD patients respond to H pylori eradication treatments differently from those with PUD, although a trend exists with the 7-d PCA therapy.

Assessing heterogeneity in meta-analyses of Helicobacter pylori infection-related clinical studies: a critical appraisal.

OBJECTIVE: To critically assess the meta-analyses of Helicobacter pylori infection-related clinical studies, particularly the handling of between-study heterogeneity. METHODS: A qualitative, all-language, systematic literature search was performed in Medline, PubMed, BioMed Central and Embase up to February 2003, supplemented by a manual search of major relevant journals. Assessment was according to modified criteria for literature searching, eligibility criteria, validity assessment, data extraction and presentation. Five parameters were used to assess the quality of the meta-analyses in handling between-study heterogeneity. RESULTS: Of 84 potentially relevant citations, 47 were systematic reviews and of them 38 were meta-analyses. Of these 38 studies, 15 (39.5%) had conducted a literature search of multiple databases and 34 (89.5%) had conducted a supplementary manual search. The eligibility criteria were clearly presented in 81.6% of studies, but the quality of the primary studies was assessed in only 26.3%. The process and strategy for data extraction was reported in 57.9% of all studies; 19 (50%) studies planned statistical tests of between-study homogeneity and the results were reported in 18, but the level of statistical significance was reported in only 11 (57.9%). The selection of and justification for a statistical model was presented in 39.5% and 26.3% of studies, respectively. Among the 11 meta-analyses in which statistical between-study heterogeneity was reported, 54.5% ignored the statistical findings and proceeded to pool the study results. The implications of between-study heterogeneity were discussed in only 8 studies. CONCLUSIONS: Many methodological flaws were identified in the meta-analyses of H. pylori-related clinical studies, particularly for assessing, reporting and interpreting between-study heterogeneity. This warrants consistent and urgent adherence by reviewers and journal editors to the methodological guidelines for meta-analyses.

Pathophysiology of gastroesophageal reflux diseases in Chinese--role of transient lower esophageal sphincter relaxation and esophageal motor dysfunction.

BACKGROUND AND AIMS: Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism for gastroesophageal reflux in the Western population. The major reflux mechanism in Chinese patients with GERD has not been studied before. METHODS: Fifty-four patients with GERD and 28 controls underwent stationary baseline manometry and the 24-h ambulatory esophageal pH monitoring. TLESRs were measured before and after an 850 kcal meal in the supine position. Primary peristalsis, secondary peristalsis, and esophageal acid clearance were measured by esophageal manometry. RESULTS: Total time esophageal pH

Population based study of noncardiac chest pain in southern Chinese: prevalence, psychosocial factors and health care utilization.

AIM: Population-based assessment of noncardiac chest pain (NCCP) is lacking. The aim of this study was to evaluate the prevalence, psychosocial factors and health seeking behaviour of NCCP in southern Chinese. METHODS: A total of 2 209 ethnic Hong Kong Chinese households were recruited to participate in a telephone survey to study the epidemiology of NCCP using the Rose angina questionnaire, a validated gastroesophageal reflux disease (GERD) questionnaire and the hospital anxiety-depression scale. NCCP was defined as non-exertional chest pain according to the Rose angina questionnaire and had not been diagnosed as ischaemic heart diseases by a physician. RESULTS: Chest pain over the past year was present in 454 subjects (20.6%, 95% CI 19-22), while NCCP was present in 307 subjects (13.9%, 95% CI 13-15). GERD was present in 51% of subjects with NCCP and 34% had consulted a physician for chest pain. Subjects with NCCP had a significantly higher anxiety (P<0.001) and depression score (P=0.007), and required more days off (P=0.021) than subjects with no chest pain. By multiple logistic regression analysis, female gender (OR 1.9, 95% CI 1.1-3.2), presence of GERD (OR 2.8, 95% CI 1.6-4.8), and social life being affected by NCCP (OR 6.9, 95% CI 3.3-15.9) were independent factors associated with health seeking behaviour in southern Chinese with NCCP. CONCLUSION: NCCP is a common problem in southern Chinese and associated with anxiety and depression. Female gender, GERD and social life affected by chest pain were associated with health care utilization in subjects with NCCP.

Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The relationship between the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, and the risk of gastric cancer has not been well studied. We performed a systematic review and meta-analysis of published studies to evaluate the association between use of this class of drugs and the risk of gastric cancer. METHODS: A fully recursive literature search to January 2003 was conducted in MEDLINE, PubMed, and CANCERLIT to identify potentially relevant case-control or cohort studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under a random-effects model. RESULTS: Nine studies (eight case-control and one cohort) with a total of 2831 gastric cancer case patients were identified. NSAID use was associated with a reduced risk of gastric cancer, with a summary odds ratio of 0.78 (95% CI = 0.69 to 0.87). Users of aspirin (OR = 0.73, 95% CI = 0.63 to 0.86) and non-aspirin NSAIDs (OR = 0.74, 95% CI = 0.55 to 1.00) experienced similar magnitudes of risk reduction. Regular users of NSAIDs (OR = 0.57, 95% CI = 0.44 to 0.74) experienced a lower risk of gastric cancer relative to nonusers than did irregular users (OR = 0.76, 95% CI = 0.62 to 0.94; P =.09 versus regular users). A stratified analysis showed that NSAID use was associated with a statistically significant reduction in risk of noncardia gastric cancer (OR = 0.72, 95% CI = 0.58 to 0.89), but not of gastric cancer at the cardia (OR = 0.80, 95% CI = 0.53 to 1.20). There was no evidence that study design or type of control subject substantially influenced the estimate of effects. CONCLUSION: NSAID use was associated with a decreased risk of gastric cancer in a dose-dependent manner. This finding warrants proper clinical trials in populations with high risk of gastric cancer.

The evolving epidemiology of Helicobacter pylori infection and gastric cancer.

The relationship between Helicobacter pylori infection and the risk of gastric cancer has been well established in the last decade. Four meta-analyses have found that the infection increases the risk of noncardia gastric cancer by 2- to 6-fold compared with noninfected control populations. However, the role of cagA strains of H pylori in relation to gastric cancer has not been evaluated systematically. We undertook a meta-analysis of epidemiological studies examining the relationship between infection with cagA-positive strains of H pylori and the risk of gastric cancer, and found that patients who are seropositive for cagA strains of H pylori are at an increased risk for developing noncardia gastric cancer compared with those with H pylori infection alone. Therefore, searching for cagA-positive strains of H pylori may help identify populations at a greater risk for developing gastric cancer.

Meta-analysis of the relationship between cagA seropositivity and gastric cancer.

BACKGROUND & AIMS: Reports in the literature regarding the relationship of infection with cagA -positive strains of Helicobacter pylori to gastric cancer over and above H. pylori infection alone are conflicting. The aim of this study was to estimate the magnitude of the risk for gastric cancer associated with cagA seropositivity and to identify any sources of heterogeneity between studies. METHODS: A meta-analysis of case-control studies with age- and sex-matched controls, which provided raw data on the infection rates with H. pylori and cagA strains of H. pylori as detected by serology or polymerase chain reaction DNA, was performed. RESULTS: A comprehensive literature search identified 16 qualified studies with 2284 cases and 2770 controls. H. pylori and cagA seropositivity significantly increased the risk for gastric cancer by 2.28- and 2.87-fold, respectively. Among H. pylori -infected populations, infection with cagA -positive strains further increased the risk for gastric cancer by 1.64-fold (95% confidence interval [CI], 1.21-2.24) overall and by 2.01-fold (95% CI, 1.21-3.32) for noncardiac gastric cancer. Gastric cancer at the cardia is not associated with H. pylori infection or cagA -positive strains of H. pylori. Patient age and site of gastric cancer contributed to the heterogeneity between studies. CONCLUSIONS: Infection with cagA -positive strains of H. pylori increases the risk for gastric cancer over the risk associated with H. pylori infection alone. Searching for cagA status over H. pylori infection may confer additional benefit in identifying populations at greater risk for gastric cancer.

Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis.

BACKGROUND: The relation between H pylori infection and use of non-steroidal anti-inflammatory drugs (NSAIDs) in the pathogenesis of peptic-ulcer disease is controversial. We undertook a meta-analysis to address this issue. METHODS: By computer and manually we sought observational studies on the prevalence of peptic-ulcer disease in adult NSAID takers or the prevalence of H pylori infection and NSAID use in patients with peptic-ulcer bleeding. Summary odds ratios were calculated from the raw data. Tests for homogeneity were done. FINDINGS: Of 463 citations identified, 25 studies met inclusion criteria. In 16 studies of 1625 NSAID takers, uncomplicated peptic-ulcer disease was significantly more common in patients positive than in those negative for H pylori (341/817 [41.7%] vs 209/808 [25.9%]; odds ratio 2.12 [95% CI 1.68-2.67]). In five controlled studies, peptic-ulcer disease was significantly more common in NSAID takers (138/385 [35.8%]) than in controls (23/276 [8.3%]), irrespective of H pylori infection. Compared with H pylori negative individuals not taking NSAIDs, the risk of ulcer in H pylori infected NSAID takers was 61.1 (9.98-373). H pylori infection increased the risk of peptic-ulcer disease in NSAID takers 3.53-fold in addition to the risk associated with NSAID use (odds ratio 19.4). Similarly, in the presence of risk of peptic-ulcer disease associated with H pylori infection (18.1), use of NSAIDs increased the risk of peptic-ulcer disease 3.55-fold. H pylori infection and NSAID use increased the risk of ulcer bleeding 1.79-fold and 4.85-fold, respectively. However, the risk of ulcer bleeding increased to 6.13 when both factors were present. INTERPRETATION: Both H pylori infection and NSAID use independently and significantly increase the risk of peptic ulcer and ulcer bleeding. There is synergism for the development of peptic ulcer and ulcer bleeding between H pylori infection and NSAID use. Peptic-ulcer disease is rare in H pylori negative non-NSAID takers.