Helicobacter pylori Infection Maybe a Risk Factor for Cardiac Syndrome X.

Purpose: Cardiac syndrome X (CSX) is a condition with normal coronary angiography but angina pectoris. Chronic inflammation caused by Helicobacter pylori (H. pylori) infection may play a pathogenic role in CSX. Therefore, we conducted a meta-analysis to explore the relationship between H. pylori infection and risk of CSX. Methods: A systematic search in the Web of Science, Medline, Embase and Chinese databases (CNKI and Wanfang) was conducted up to October 2021. Articles on the association between H. pylori infection and the risk of CSX were included and were analyzed by R software (version 4.1.0). Results: Ten case-control studies involving 703 CSX patients and 731 healthy controls were included. H. pylori infection was associated with an increased risk of CSX (OR: 8.29, 95% CI: 4.64-14.82). We also found a significant association in those 25-40 years of age (OR: 1.34, 95% CI: 1.04-1.72), those 40-50 years of age (OR: 11.27, 95% CI: 4.29-29.61), those over 50 years of age (OR: 7.18, 95% CI: 3.59-14.36), those in developing countries [Iran (OR: 12.99, 95% CI: 8.61-19.60) and China (OR: 5.14, 95% CI: 3.09-8.56)]. However, this association was not apparent in a developed country [Italy (OR: 0.93, 95% CI: 0.37-2.33)]. Conclusions: Our study suggested a possible association between H. pylori infection and the risk of CSX. Its pathogenicity is stronger in middle-aged individuals and some developing countries. However, more studies are needed to further investigate whether early eradication of H. pylori can reduce the incidence rate of CSX, especially in middle-aged individuals and some developing countries.

Long-Chain Non-Coding RNA SNHG3 Promotes the Growth of Ovarian Cancer Cells by Targeting miR-339-5p/TRPC3 Axis.

BACKGROUND: Long-chain non-coding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) is reportedly overexpressed in malignant tumors, but its regulatory role in human ovarian cancer (OC) is not fully understood. METHODS: A qRT-PCR assay was carried out to detect the level of SNHG3 in OC tissues, serum and cells, a CCK-8 assay to measure the proliferation of OC cells, a transwell assay to measure the invasion and migration of OC cells, and a flow cytometry to detect the cell cycle distribution and apoptosis rate of OC cells. In addition, in vivo experiment was also conducted to determine the effect of SNHG3 on the growth of OC cells. RESULTS: SNHG3 was overexpressed in OC tissues, serum, and cells, and the overexpression in serum indicated a poor prognosis of patients. It was also found that knockdown of SNHG3 could inhibit the malignant phenotypes of OC cells, cause G1/G0 cell cycle arrest, and intensify apoptosis. Furthermore, in in vitro experiments, the growth ability of OC cells was inhibited under knockdown of SNHG3. Assays for relationship verification showed that SNHG3 regulated the expression of miR-339-5p and the canonical transient receptor potential 3 (TRPC3), and the rescue experiment revealed that co-transfection of si-SNHG3+miR-339-5p-inhibitor or si-SNHG3+pcDNA3.1-TRPC3 could reverse the effects of knockdown of SNHG3 on the biological behavior of OC cells. CONCLUSION: SNHG3 can be adopted as a marker for diagnosis and prognosis evaluation of OC and it plays a role in the progression of OC by enabling the miR-339-5p sponge to regulate TRPC3 expression.

Osthole sensitizes with radiotherapy to suppress tumorigenesis of human nasopharyngeal carcinoma in vitro and in vivo.

BACKGROUND: Radiotherapy is one of the most comment and useful treatment for nasopharyngeal carcinoma (NPC), but the radioresistance remains a major obstacle. Osthole, a natural coumarin derivative, has been shown to have anti-tumor and anti-inflammatory activity. However, the relationship between osthole and NPC treatment, especially for radiotherapy, is still elusive. METHODS: Osthole with or without X ray radiotherapy treated with CNE2 cells, a human EC cell line. Cell viability, proliferation, migration and apoptosis were measured by MTT, colony formation, Annexin V/PI double staining, Transwell assay, respectively. NPC tumor models were established on BALB/c nude mice by subcutaneously injection of CNE2 cells and the effect of osthole and radiotherapy on tumor growth in vivo was studied. RESULTS: We found that in a dose-dependent manner, osthole could individually, and synergistically with radiotherapy, reduce NPC cell (CNE2) viability, proliferation, migration, and invasion, and induce apoptosis, respectively. This effect of anti-tumor growth and induction of apoptosis was further confirmed in mice induced by subcutaneously injection with CNE2 cells and following treated with osthole or/and radiation. CONCLUSION: Osthole increases the effect of radiotherapy on anti-human nasopharyngeal cancer.

DNA methylation of human telomerase reverse transcriptase associated with leukocyte telomere length shortening in hyperhomocysteinemia-type hypertension in humans and in a rat model.

BACKGROUND: Elevated homocysteine (Hcy) levels might play a role in the development of essential hypertension (EH). Telomere dynamics provide valuable insight into the pathogenesis of age-related diseases. The contribution of Hcy to leukocyte telomere length (LTL) shortening in EH and the underlying mechanism was examined. METHODS AND RESULTS: LTL (ratio of the copy number of telomere [T] repeats to that of a single [S] gene, T/S ratio) was inversely associated with age in patients with EH (n=258) and healthy controls (n=137), but significantly decreased with the Hcy level only in patients with hypertension after adjustment for age and sex. Age, hypertension and levels of Hcy and low-density lipoprotein combined contributed to LTL shortening; an increased serum folate level could reverse the Hcy effect seen on multivariate regression analysis. In addition, qPCR and methylation-specific PCR assay revealed that LTL shortening and mRNA expression and the methylation ratio of human telomerase reverse transcriptase (hTERT) were lower in patients with EH than in controls, and gradually decreased with increasing Hcy level, but not with blood pressure, in EH patients (Ptrend<0.0001, 0.004 and 0.012, respectively). Furthermore, Hyperhomocysteinemia, but not hypertension, promoted telomerase reverse transcriptase DNA hypomethylation and reduced mRNA levels, which contributed to shortened LTL in the hypertension rat model. CONCLUSIONS: Elevated Hcy but not hypertension was related to hTERT DNA hypomethylation and reduced mRNA level, thus contributing to the shortening of LTL hypertension.

High-risk human papillomavirus infection associated with telomere elongation in patients with esophageal squamous cell carcinoma with poor prognosis.

BACKGROUND: Telomere maintenance is crucial in carcinogenesis and tumor progression. The results of a previous study from the authors indicated that infection with high-risk human papillomavirus (HR-HPV) types 16, 18, and 58 was a risk factor for esophageal squamous cell carcinoma (ESCC) in the Shantou region of China. In the current study, the authors explored the association between HR-HPV infection, telomere length (TL), and DNA methylation and their significance in the prognosis of patients with ESCC. METHODS: TL and DNA methylation were analyzed by real-time polymerase chain reaction and methylation-specific polymerase chain reaction in 70 cases of ESCC tumor (T) and paired nontumor (NT) tissues and 50 cases of normal esophagus (NE). The prognostic value of TL and DNA methylation in ESCC was analyzed. RESULTS: TL gradually decreased from NE to NT to T tissue. TL in tumor tissue (T-TL) was found to be longer in tissue that was positive for HR-HPV compared with negative tissue and was found to be positively associated with viral load (Spearman correlation, 0.410; P = .037) and integration (represented by the ratio of HR-HPV E2 to E6/E7 genes; P = .01). The DNA methylation ratio of human telomerase reverse transcriptase was more prevalent with long (≥ 0.7) compared with short (< 0.7) T-TL and was positively correlated with T-TL (Spearman correlation, 0.318; P = .007) and HR-HPV integration (P = .036). Furthermore, Cox proportional hazards modeling revealed a high ratio of T-TL to NT-TL (≥ 0.80) as a factor of poor prognosis, independent of other clinicopathologic variables. CONCLUSIONS: HR-HPV infection and integration related to telomere elongation and DNA methylation of human telomerase reverse transcriptase may be a potential biomarker of prognosis in patients with ESCC.

Status and significance of CpG island methylator phenotype in endometrial cancer.

BACKGROUND: Endometrial cancer is a common gynecologic malignant disease, but patients with advanced disease have a poor prognosis. The CpG island methylator phenotype (CIMP) involves hypermethylation targeted toward the promoters of multiple genes. OBJECTIVE: To investigate the role of epigenetic aberration of tumor-related genes in endometrial cancer. METHODS: The promoter methylation status of 5 genes was examined in 35 endometrial cancer tissues, 15 matched adjacent normal endometrial tissues (NET) from the same cancer patients, and 22 benign endometria from unaffected patients by methylation-specific PCR. CIMP positivity (CIMP+) was defined as concordant methylation of ≥3 genes. RESULTS: The methylation frequency of promoters for the 5 genes in the cancer tissues ranged from 37% for P16 to 57% for P14. Cancer and benign endometria, but not cancer and adjacent NET, significantly differed in methylation of P14, P16, ER, COX-2 and RASSF1A (p < 0.05). CIMP+ was frequent in cancer and adjacent NET (46 and 47%, respectively; p > 0.05), but absent in benign endometria. Moreover, CIMP+ was significantly correlated with methylation of P16 and COX-2 (r = 0.673 and 0.662, respectively; p < 0.001). CONCLUSION: CIMP+ is an important and frequent epigenetic event in endometrial cancer or adjacent NET, and may be a biomarker for predicting early carcinogenesis. COX-2 is a good representative gene of CIMP+ in this cancer.

Prevalence and association of human papillomavirus 16, Epstein-Barr virus, herpes simplex virus-1 and cytomegalovirus infection with human esophageal carcinoma: a case-control study.

Recent research shows esophageal carcinoma (EC) as the ninth most common malignancy in the world. The association of viral infection and EC has been reported in the last 30 years. However, geographic variation in infection rates and the key mechanisms of the viral action have yet to be resolved. This study aimed to determine the prevalence and association of human papillomavirus 16 (HPV-16), herpes simplex virus 1 (HSV-1), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection in the etiology of EC in the area of Shantou, Guangdong, China. Nested PCR was used to detect viral DNA in the mucosa of 70 cases of EC and in paracancerous tissues, as well as 100 cases of normal esophagus mucosa. Data were analyzed by χ2 test, Fisher's exact test and bivariate correlation analysis. The infection rates of HPV-16, HSV-1 and EBV were 40.0, 30.0 and 30.0%, respectively, in EC mucosa, and were significantly higher than those in normal mucosa. However, no CMV DNA was detected in either EC or normal mucosa. HPV-16 or EBV infection was mainly detected in EC patients 48-58 years old, and the infection rate was positively associated with pathological grade of EC (P<0.05). Tobacco smoking and alcohol consuption were high risk factors for HPV-16 infection for male patients [odds ratio (OR), 5.9; 95% confidence interval (CI), 1.4-24.6; OR = 3.8; 95% CI, 1.1-13.8]. Rates of infection with a mixture of these 3 viruses were all more than 10.0% in cancerous mucosa and closely related to the pathological grade of EC (P = 0.001). Infection with HPV-16, HSV-1 or EBV may be an important etiological factor in EC.

Infection and integration of human papillomavirus in esophageal carcinoma.

Infection with human papillomavirus (HPV) could be a suspected or potential modifiable risk factor in esophageal carcinoma (EC) but findings have not been consistent. We therefore investigated the epidemiology of HPV infection and integration in the pathogenesis of esophageal carcinoma (EC) in the Shantou region, China. This was a retrospective study involving nested PCR to evaluate HPV presence, HPV genotyping, and analyzing HPV-16 integration status in esophageal tumor tissues (n=106) and paired tumor-adjacent normal tissues, as well as normal esophagus tissue from control subjects (n=100). The detection rates of HPV DNA in EC and tumor-adjacent tissue were significantly higher than that in normal controls (77.4% and 80.2% vs. 33.0%). HPV infection was mainly found in adults, ages 35-47 years old, and the infection rate was negatively associated with the age of EC patients (P-trend<0.05). In addition, the HPV infection rates in patients who smoked was 3.27 times higher than in non-smoking patients (84.9% vs. 67.4%, P<0.05) but was not associated with gender, alcohol consumption, tumor grade or lymph-node metastasis of EC patients. The distribution of HPV genotypes in patients from high to low proportion was HPV-16, -58, -18, -33, -31 and -11. Infection with multiple HPV genotypes mainly included HPV-16/-18 and HPV-16/-33. The integration rate of HPV-16 in EC tissue was higher than that in tumor-adjacent and control tissues (93.4% vs. 50.9% and 45.5%). Our findings indicate that infection with HPV, especially the high-risk HPV, and their integration suggest an association in malignant transformation of EC in the high-incidence EC region in Shantou, China.

[Incidence and causes of nonresponse to cardiac resynchronization therapy in patients with congestive heart failure].

OBJECTIVE: To observe the incidence and explore the potential factors of nonresponse to cardiac resynchronization therapy(CRT)in patients with severe chronic congestive heart failure. METHOD: CRT was performed in 119 patients with NYHA function class III-IV and left ventricular ejection fraction ≤ 35% [96 men and 23 women, age (60.5 ± 11.3) years]. RESULTS: Seven patients died for different reasons between 1 - 6 months post CRT and clinical and echocardiographic (Echo) data at 6 months post CRT were analyzed from the remaining 112 patients. The incidence of nonresponse to CRT was 28.57%. Compared to the response group, complete right bundle branch block, longer course of congestive heart failure, higher pulmonary systolic pressure and serum creatinine level and non-optimal target vessels positioning of the left ventricle lead (the great cardiac vein and the middle cardiac vein) were the independent predictors for nonresponse after CRT (all P < 0.05). Compared with nonresponse group, the dosages of digoxin and diuretics used for heart failure were significantly reduced in response group (P < 0.01). CONCLUSIONS: The incidence of nonresponse after CRT was 28.57% in this patient cohort. Higher pulmonary systolic pressure and serum creatinine level and non-optimal target vessels positioning of the left ventricle lead (the great cardiac vein and the middle cardiac vein) were the independent predictors for nonresponse after CRT.

Factors influencing intercellular spaces in the rat esophageal epithelium.

AIM: To evaluate the effect of acute stress, hydrochloric acid, ethanol, aspirin, and prednisolone on the intercellular spaces of the esophageal epithelium. METHODS: Part I, male Sprague-Dawley rats were randomly divided into eight groups and treated with the damaging or control factors. The esophagus of each rat was macroscopically inspected. Histological changes in mucosal biopsies were examined by light microscopy, and the widths of intercellular spaces were determined by transmission electron microscopy (TEM). Part II, in part I, we found that acute stress and aspirin induced dilated intercellular spaces (DIS) of the esophageal epithelium. Therefore, the effect of acid suppression pretreatment with esomeprazole on esophageal epithelial DIS induced by water immersion and restraint stress (WRS) and aspirin was further investigated to determine the association of DIS with acid reflux. After administration of 0.9% sodium chloride solution or esomeprazole solution orally for five days, rats underwent WRS or intragastric administration of aspirin solution. Esophageal epithelial intercellular spaces were investigated by TEM. RESULTS: (1) The five damaging factors produced no lesions or inflammation in esophageal mucosa of rats under either gross or routine histological inspections. Esophageal epithelial intercellular space diameters in stress and aspirin groups were significantly greater, nearly three or two-fold respectively, than those in their corresponding control groups (stress model: 0.38 + or - 0.05 microm vs 0.13 + or - 0.02 microm, P < 0.01; aspirin model: 0.32 + or - 0.12 microm vs 0.19 + or - 0.05 microm, P < 0.01). Neither intragastric administration of hydrochloric acid or ethanol, nor hypodermic injection of prednisolone produced DIS compared with their corresponding control groups (hydrochloric acid model: 0.24 + or - 0.03 microm vs 0.19 + or - 0.05 microm, P > 0.05; ethanol model: 0.25 + or - 0.10 microm vs 0.19 + or - 0.05 microm, P > 0.05; prednisolone model: 0.20 + or - 0.03 microm vs 0.14 + or - 0.03 microm, P > 0.05); and (2) No significant difference in the intercellular space diameters was observed between the group pretreated with esomeprazole and the control group, in both the stress and aspirin models (stress model: 0.35 + or - 0.05 microm vs 0.37 + or - 0.05 microm, P > 0.05; aspirin model: 0.24 + or - 0.02 microm vs 0.27 + or - 0.03 microm, P > 0.05). CONCLUSION: Acute stress and aspirin can induce DIS of the esophageal epithelium in rats, and it is not correlated with acid reflux.

Recent changes in the prevalence of Helicobacter pylori infection among children and adults in high- or low-incidence regions of gastric cancer in China.

BACKGROUND: The prevalence of Helicobacter pylori (H. pylori) infection varies by geographic locations. Studies indicate that the infection rate of H. pylori was previously high in China but that rates had been declining worldwide over recent decades. THE AIMS OF OUR STUDY WERE: (1) to determine the current prevalence of H. pylori infection among children and adults residing in areas with high (Muping County, Shandong) and low (Yanqing County, Beijing) incidences of gastric cancer in China, and (2) to compare the prevalence for 2006 with the prevalence for the early 1990s. METHODS: Using Warthin-Starry silver staining of gastric mucosal biopsy specimens and H. pylori stool antigen tests (HpSA), we tested a total of 2065 asymptomatic children aged 8 - 15 years and adults aged 40 - 79 years in the above two regions from May to July 2006. We evaluated 520 children and 526 adults from Muping, and 516 children and 503 adults from Yanqing. Subjects were selected randomly and H. pylori status was determined by HpSA in children and either HpSA or histology of gastric biopsies in adults. Data obtained in the early 1990s in the same two areas of China were also collected and studied. RESULTS: For children, the prevalence of H. pylori infection was significantly higher in Muping (37.69%) than it was in Yanqing (25.58%, P < 0.001). In both regions, the prevalence of H. pylori increased with age but was not related to gender. A significant difference was observed between 8 - 9-years old and 10 - 11-years old (P < 0.05), but not between other adjoining age groups (P > 0.05). From 1991 to 2006 H. pylori prevalence among 8 - 10-year-old children decreased in Muping (60.00% vs 32.07%, P < 0.001), but not Yanqing (24.06% vs 19.10%, P > 0.05). In the adult group, H. pylori prevalence was 50.95% in Muping, which was significantly higher than the 41.35% positive rate in Yanqing (P < 0.01). But there were no statistically significant differences between different age groups of 40 - 49, 50 - 59, and 60 - 79 years, or between males and females. A significant decrease in H. pylori prevalence in both regions was observed when the results of 2006 were compared with the data obtained in 1990 in Muping (50.95% vs 73.78%, P < 0.001) and in 1992 in Yanqing (41.35% vs 55.35%, P < 0.01). CONCLUSIONS: After fifteen years, the prevalence of H. pylori infection among both children and adults remained significantly higher in areas with a high incidence of gastric cancer in China compared with that in areas with a low incidence of gastric cancer. H. pylori infection rates have decreased in the general Chinese population during recent years.

[Epidemiology of Helicobacter pylori infection in Shandong and Beijing areas.].

OBJECTIVES: To study the current prevalence and recent epidemiological changes of Helicobacter pylori (H. pylori) infection among children and adults residing in regions with high (Muping, Shandong) and low (Yanqing, Beijing) incidence of gastric cancer in China. METHODS: A total of 2065 asymptomatic children aged 8 - 15 years and adults aged 40 - 79 years in the above two regions were examined from May to July 2006. The data obtained in early 1990s in the same two areas and those of 11 656 patients undergoing endoscopy in our hospital in 1991 and 2006 were also collected and studied. RESULTS: The prevalence of H. pylori infection in Muping was significantly higher than that in Yanqing among both children (37.69% vs 25.58%, P < 0.001) and adults (50.95% vs 41.35%, P < 0.01). From 1991 to 2006 H. pylori prevalence among children aged 8 - 10 years decreased in Muping (60.00% vs 32.07%, P < 0.001), but not in Yanqing (24.06% vs 19.10%, P > 0.05). A significant decrease in H. pylori prevalence among adults in both regions was observed when the results of 2006 were compared with the data obtained in 1990 in Muping (50.95% vs 73.78%, P < 0.001) and in 1992 in Yanqing (41.35% vs 55.35%, P < 0.01). The detected rate of H. pylori infection in patients undergoing endoscopy in our hospital decreased from 51.88% in 1991 to 33.59% in 2006 (P < 0.001). CONCLUSIONS: The prevalence of H. pylori infection is significantly higher in areas with a high incidence of gastric cancer in China as compared with that in areas with a low incidence of gastric cancer among both children and adults. H. pylori infection may be a risk factor in gastric carcinogenesis. In the past decade or more, H. pylori infection rates have decreased in Chinese population.

[The risk factors of reflux esophagitis in Shandong farmers].

OBJECTIVE: To investigate the risk factors of reflux esophagitis (RE) in farmers of Shandong province. METHODS: Five hundred and fifty six peasants (aged from 34 to 90 years old) were randomly selected from the rural general population in Yantai area, Shandong province. All participants received a face to face interview for relating clinical symptoms. Upper gastrointestinal endoscopic and histopathologic examination were carried out. RESULTS: 101 (18.2%) patients were diagnosed endoscopically as RE. According to Los Angeles Classification system, the distribution of types was as follows: A: 36.6% (37/101), B: 56.4% (57/101), C: 3.0% (3/101), D: 4.0% (4/101). The gender (P < 0.001), age (P = 0.041), time engaged in farming (P = 0.040) of the subjects and the length from Z line to fore-tooth (P = 0.001) were correlated with the occurrence of RE. Smoking (OR 1.894, 95% CI 1.207 - 2.974), drinking strong tea (OR 2.900, 95% CI 1.651 - 5.092), using non-steroidal anti-inflammatory drugs (NSAIDs) (OR 2.159, 95% CI 1.166 - 3.997) and loose cardia (OR 13.630, 95% CI 7.37 - 25.19) were risk factors of RE. But there was no relationship between RE and the height, body weight, abdominal circumference, body mass index (BMI), alcohol drinking, special food habit and the history of diabetes, previous abdominal operation, peptic ulcer and atrophic gastritis of the subjects. H.pylori infection rate in the population was 51.3% (273/532). 37.1% (36/97) of RE patients and 54.5% (237/435) of non-RE patients were H.pylori positive (P = 0.002), OR 0.492 (95% CI 0.313 - 0.776). CONCLUSIONS: Male gender, aging, shorter length from Z line to fore tooth, loose cardia and absence of H.pylori infection were correlated with RE. Smoking, drinking strong tea, NSAIDs and long time engaged in farming were risk factors of RE.