MKLN1-AS promotes pancreatic cancer progression as a crucial downstream mediator of HIF-1α through miR-185-5p/TEAD1 pathway.

In pancreatic ductal adenocarcinomas (PDAC), profound hypoxia plays key roles in regulating cancer cell behavior, including proliferation, migration, and resistance to therapies. The initial part of this research highlights the important role played by long noncoding RNA (lncRNA) MKLN1-AS, which is controlled by hypoxia-inducible factor-1 alpha (HIF-1α), in the progression of PDAC. Human samples of PDAC showed a notable increase in MKLN1-AS expression, which was linked to a worse outcome. Forced expression of MKLN1-AS greatly reduced the inhibitory impact on the growth and spread of PDAC cells caused by HIF-1α depletion. Experiments on mechanisms showed that HIF-1α influences the expression of MKLN1-AS by directly attaching to a hypoxia response element in the promoter region of MKLN1-AS.MKLN1-AS acts as a competitive endogenous RNA (ceRNA) by binding to miR-185-5p, resulting in the regulation of TEAD1 expression and promoting cell proliferation, migration, and tumor growth. TEAD1 subsequently enhances the development of PDAC. Our study results suggest that MKLN1-AS could serve as a promising target for treatment and a valuable indicator for predicting outcomes in PDAC. PDAC is associated with low oxygen levels, and the long non-coding RNA MKLN1-AS interacts with TEAD1 in this context.

Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention.

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.

Identification of potential diagnostic biomarkers in MMPs for pancreatic carcinoma.

ABSTRACT: Pancreatic cancer (PC) is a malignant tumor which ranks fourth in cancer-related death. However, the specificity and sensitivity of traditional biomarkers such as carbohydrate antigen 19-9 no longer meet the clinical requirements.Tools as ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA) were used to analyze the differential expression of matrix metalloproteinases (MMPs) in PC and adjacent tissues. For further analysis, we adopted database for annotation, visualization and integrated discovery (DAVID 6.8), transcriptional regulatory relationships unraveled by sentence-based text (TRRUST) and other tools. We also identified drugs targeted the selected MMPs.Eight MMPs (MMP1, MMP2, MMP7, MMP9, MMP11, MMP12, MMP14, and MMP28) were differentially expressed in PC and adjacent tissue. MMP1 (P = .0189), MMP7 (P = .000216), MMP11 (P = .0209), MMP14 (P = .00611) were correlated with the pathological stages of PC. Patients with higher expression of MMP1 (P = .0011), MMP2 (P = .011), MMP7 (P = .0081), MMP9 (P = .046), MMP11 (P = .0019), MMP12 (P = .0011), MMP14 (P = .0011), and MMP28 (P = 6.3e-06) showed poor prognosis. Ten transcription factors were associated with the up-regulation of selected MMPs. Marimastat (DB00786) was found to target selected MMPs.Our research revealed that selected MMPs played an important role in the early diagnosis and prognosis of PC.

Metal Versus Plastic Stents for Pancreatic Fluid Collection Drainage: A Systematic Review and Meta-analysis.

OBJECTIVES: The therapeutic efficacy of metal stents (MSs) for pancreatic fluid collections (PFCs) is invariably controversial. Here, we conducted a meta-analysis to summarize the results of efficacy of MSs and plastic stents (PSs) in PFC drainage. SUBJECTS AND METHODS: We performed a literature search of PubMed/MEDLINE, EMBASE, and COCHRANE for all of the published studies regarding the use of MSs and PSs for endoscopic transmural drainage of PFCs from January, 1 2015 to June 1, 2020. We extracted data from 9 studies (1359 patients) that met the inclusion criteria. The main outcome measures were the rates of treatment success, including technique success and clinical success (CS), adverse events, recurrence, procedure time, and length of hospital stay (LOS). RESULTS: There was no difference in overall technique success between patients treated with MSs and PSs for PFCs. However, MSs showed a higher CS rate 92% versus 82% (P<0.01) and a lower overall adverse event rate 20% versus 31% (P<0.01) than PSs. The recurrence rate of PFCs using MSs also had significant advantages over PSs 3% versus 10% (P<0.01) and MSs needed a shorter procedure time than PSs (26.73 vs. 45.40 min, P<0.01). In comparing direct endoscopic necrosectomy use and LOS, there was no difference between MSs and PSs. CONCLUSIONS: Bringing together the results of the current study, endoscopic ultrasound-guided drainage of PFCs using MSs may be superior to PSs in terms of CS, adverse events rates and recurrence rate, with similar LOS and direct endoscopic necrosectomy use.

Helicobacter pylori Infection and Serum Pepsinogen Level With the Risk of Gastric Precancerous Conditions: A Cross-sectional Study of High-risk Gastric Cancer Population in China.

BACKGROUND AND AIM: Gastric precancerous conditions are generally considered to play an essential role in the gastric carcinogenesis cascade. This study identified risk factors of gastric precancerous conditions in a nationwide multicenter cross-sectional study. METHODS: Individuals who made their visit to 115 hospitals in China for gastric cancer screening were recruited. Lifestyle habits and personal information were collected through a series of questionnaires. Serum biomarker test (pepsinogen I, pepsinogen II, gastrin-17, and anti-Helicobacter pylori immunoglobulin G antibody) and endoscopy were then performed. Risk factors for gastric precancerous conditions were identified by univariate and multivariate analyses. RESULTS: Of 14,929 subjects eligible for analysis, 4477 (30.0%) developed gastric precancerous conditions and 405 (2.71%) developed gastric cancer. In multiple logistic regression, precancerous conditions were associated with advanced age [odds ratio (OR)=1.027; 95% confidence interval (Cl), 1.023-1.032; P<0.001], male gender (OR=1.303; 95% Cl, 1.188-1.429; P<0.001), H. pylori infection (OR=1.377; 95% Cl, 1.272-1.490, P<0.001), and smoking (OR=1.142; 95% Cl, 1.005-1.298, P=0.004), whereas they were inversely correlated with white meat intake (OR=0.731; 95% Cl, 0.673-0.794; P<0.001) and pepsinogen I level (30 to 70 subgroup OR=1.536; 95% Cl, 1.163-2.028; P=0.002; <30 subgroup OR=1.354; 95% Cl, 1.206-1.520; P<0.001). Also, the authors observed a statistically lower prevalence of reflux esophagitis (2.8% vs. 4.7%) and of gastric polyps (11.0% vs. 13.7%) in H. pylori-infected population. CONCLUSIONS: Patients with H. pylori have a 1.4-fold higher risk of having gastric precancerous conditions. Besides, precancerous conditions were associated with advanced age, male gender, H. pylori infection, and smoking in a large population. However, regular white meat intake and higher pepsinogen I level were associated with reduced risk of having precancerous lesions.

Awareness and attitudes regarding Helicobacter pylori infection in Chinese physicians and public population: A national cross-sectional survey.

BACKGROUND: There is a lack of reports on the awareness of Helicobacter pylori (H pylori) prevention and treatment in the general Chinese population. And whether the knowledge level will affect their action toward screening was unknown. This study aimed to conduct a national survey on the knowledge, attitudes, and practice regarding H pylori infection in Chinese physicians and the public. METHODS: This was an Internet-based survey of the general Chinese population and Chinese physicians from different specialties, carried out from January to February 2019. Both surveys (general population's and physicians') included questions to assess the knowledge and attitudes toward H pylori and its action. RESULTS: A total of 3211 people and 546 physicians were enrolled. In the population, the proportion of subjects who answered correctly to all questions about H pylori's infectivity was only 16%, and that for H pylori's harmfulness and that for H pylori preventive measures were 35% and 43.6%, respectively. In general, physicians had a better understanding of H pylori's harmfulness (83.9%) than the other population. The vast majority of the surveyed population (87.0%) and physicians (82.2%) supported a national H pylori screening plan to prevent gastric cancer. The support ratio paralleled with the overall knowledge level. Unexpectedly, gastroenterologists tend to have a relatively low support rate for H pylori screening than non-gastroenterologists (58.2% vs 84.2%, P < .001), which may be related to consideration of heavy medical burden (67.3%). CONCLUSIONS: The general population in China has relatively insufficient awareness of H pylori, which is incompatible with the highly infectious status. More works on health education are needed to improve the knowledge of this gastric pathogen.