Biological Clock Genes are Crucial and Promising Biomarkers for the Therapeutic Targets and Prognostic Assessment in Gastric Cancer.

BACKGROUND: Gastric cancer is one of the major public health problems worldwide. Circadian rhythm disturbances driven by circadian clock genes play a role in the development of cancer. However, whether circadian clock genes can serve as potential therapeutic targets and prognostic biomarkers for gastric cancer remains elusive. METHODS: In this study, we comprehensively analyzed the potential relationship between circadian clock genes and gastric cancer using online bioinformatics databases such as GEPIA, cBioPortal, STRING, GeneMANIA, Metascape, TIMER, TRRUST, and GEDS. RESULTS: Biological clock genes are expressed differently in human tumors. Compared with normal tissues, only PER1, CLOCK, and TIMELESS expression differences were statistically significant in gastric cancer (p < 0.05). PER1 (p = 0.0169) and CLOCK (p = 0.0414) were associated with gastric cancer pathological stage (p < 0.05). Gastric cancer patients with high expression of PER1 (p = 0.0028) and NR1D1 (p = 0.016) had longer overall survival, while those with high expression of PER1 (p = 0.042) and NR1D1 (p = 0.016) had longer disease-free survival. The main function of the biological clock gene is related to the circadian rhythms and melatonin metabolism and effects. CLOCK, NPAS2, and KAT2B were key transcription factors for circadian clock genes. In addition, we also found important correlations between circadian clock genes and various immune cells in the gastric cancer microenvironment. CONCLUSIONS: This study may establish a new gastric cancer prognostic indicator based on the biological clock gene and develop new drugs for the treatment of gastric cancer using biological clock gene targets.

Post-infection functional gastrointestinal disorders following coronavirus disease-19: a prospective follow-up cohort study.

BACKGROUND: Acute gastrointestinal infections can lead to post-infectious irritable bowel syndrome (PI-IBS). Moreover, coronavirus disease (COVID-19) is related to long-term gastrointestinal sequelae. In this study, the frequency, disease spectrum, and risk factors for post-infection functional gastrointestinal disease (PI-FGID) in COVID-19 patients and healthy controls were prospectively examined. METHODS: Validated Rome III and Rome IV questionnaires and limited objective assessment were used to assess the incidence of PI-FGID in 190 COVID-19 patients, and 160 healthy controls prospectively followed for 1, 3, and 6 months. RESULTS: Six(3.2%), 1(0.5%), 3(1.6%), 5(2.6%), 6(3.2%)COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at 1 month, respectively, while 4(2.1%), 1(0.5%), 4(2.1%), 4(2.1%), and 6(3.2%)COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at three months, respectively. Furthermore, 2(1.3%), 4(2.5%), and 3(1.9%)healthy controls developed constipation, dyspepsia, and their overlap at one month, respectively (P = 0.193), while 2(1.3%), 4(2.5%), and 2(1.3%)healthy controls developed constipation, dyspepsia and their overlap at three months, respectively (P = 0.286). FGIDs incidence was higher among COVID-19 patients(8.9%) than in healthy controls(3.1%) at 6-month follow-up (P = 0.025). Moreover, 7 (3.7%), 5 (2.6%), 3 (1.6%), and 2 (1.1%) COVID-19 patients developed IBS, functional dyspepsia(FD), functional diarrhea(FDr), functional constipation(FC)at six months, respectively, while only 2 (1.3%) and 3 (1.9%) healthy controls developed IBS and FD at six months, respectively. Notably, gastrointestinal(GI)symptoms at onset were the independent risk factors for post-COVID-19 FGIDs at six months. CONCLUSIONS: COVID-19 increases new-onset PI-FGID at six months compared with healthy controls. GI symptom at the onset of COVID-19 is an independent risk factor for post-COVID-19 FGIDs.

CYP2C19 gene polymorphism in Ningxia.

BACKGROUND: Poor metabolizer (PM) status of CYP2C19 can be a predisposing factor for developing gastric cancer in H. pylori-infected patients. It is unclear whether PM status of CYP2C19 can also be a potential factor for H.pylori infection in healthy people. METHODS: We used high-throughput sequencing to detect single nucleotide polymorphisms (SNPs) at just three loci, rs4244285 (CYP2C19*2), rs4986893 (CYP2C19*3) and rs12248560 (CYP2C19*17), to identify the exact CYP2C19 alleles corresponding to the mutated sites. We determined CYP2C19 genotypes of 1050 subjects from 5 cities of Ningxia from September 2019 to September 2020 and evaluated the potential correlation between H.pylori and CYP2C19 gene polymorphisms. Clinical data were analyzed using χ2 tests. RESULTS: The frequency of CYP2C19*17 in Hui (3.7%) was higher as compared to Han (1.4%) in Ningxia (p = 0.001). The frequency of CYP2C19*1/*17 of Hui (4.7%) was higher as compared to Han (1.6%) in Ningxia (p = 0.004). The frequency of CYP2C19*3/*17 of Hui (1%) was higher as compared to Han (0%) in Ningxia (p = 0.023). The frequencies of alleles (p = 0.142) and genotypes (p = 0.928) were not found to be significantly different among the different BMI groups. The frequencies of four alleles between H. pylori positive and negative groups were not found to be statistically different (p = 0.794). The frequencies of the different genotypes between H. pylori positive and negative groups were not statistically different (p = 0.974), and no statistical difference was observed between the different metabolic phenotypes (p = 0.494). CONCLUSION: There were regional differences observed in CYP2C19*17 distribution in Ningxia. The frequency of CYP2C19*17 in Hui was higher than in Han of Ningxia. No significant relationship was found between CYP2C19 gene polymorphism and susceptibility to H. pylori infection.

Comparison of the Dual Therapy of Ilaprazole-Amoxicillin and the Bismuth Quadruple Therapy of Ilaprazole-Amoxicillin-Furazolidone-Bismuth Glycyrrhizinate for Eradication of Helicobacter pylori.

Objective: The present study aims to compare the safety and efficacy of an amoxicillin/ilaprazole regimen with a bismuth quadruple regimen as the first-line treatment for eradicating Helicobacter pylori (H. pylori) infection. Methods: This was an open-label, randomized, single-center study involving 450 patients with untreated H. pylori infection who were randomly assigned to an Ilaprazole-amoxicillin-furazolidone-bismuth glycyrrhizinate (IAFB) quadruple therapy group for 14 days, a bismuth quadruple therapy group for 10 days, or Ilaprazole-amoxicillin (IA) dual therapy group for 14 days. The 13C urea breath test determined that H. pylori had been eliminated 4-6 weeks after treatment. For patients who failed the first treatment, mucosal tissues (two gastric antrum and one gastric body) were taken under gastroscope for the culture of H. pylori, drug sensitivity, the CYP2C19 gene, and globular degeneration. Results: In the intention-to-treat analysis, the eradication rates of H. pylori in the IAFB-14-day group, the IAFB-10-day group, and the IA-14-day group were 84.0, 79.3, and 88.0%, respectively. In the per-protocol analysis, the eradication rates in the three groups were 94.7, 87.5, and 93.0%, respectively. The resistance rates of patients who failed H. pylori eradication were 68.9% (22/32) for amoxicillin, 90.6% (29/32) for clarithromycin, 68.9% (22/32) for metronidazole, and 87.5% (28/32) for levofloxacin, and the extensive metabolizers of CYP2C19 polymorphism were 59.3% (19/32), the intermediate metabolizers were 34.4% (11/32), and the poor metabolizers were 6.3% (2/32). Conclusion: For newly treated patients with H. pylori infection in China, the efficacy of IA therapy for 14 days was similar to IAFB quadruple therapy for 10 or 14 days with better compliance and less cost. Therefore, these therapies can be considered first-line regimens for empirical treatment. Clinical Trial Registration: [http://www.chictr.org.cn/searchproj.aspx], identifier [ChiCTR2100052308].

Long noncoding RNA NBAT1 suppresses hepatocellular carcinoma progression via competitively associating with IGF2BP1 and decreasing c-Myc expression.

Hepatocellular Carcinoma (HCC) is the second leading cause of cancer-related deaths. Neuroblastoma associated transcript 1 (NBAT1) is a newly identified long noncoding RNA (lncRNA), which has been reported to play an important role in human cancers. However, the functional role and underlying mechanism of NBAT1 in HCC remains unclear. Here, we found that the expression of NBAT1 was decreased in HCC tissues and cells; as well, the decreased expression of NBAT1 was also associated with tumor size and clinical TNM stages. NBAT1 overexpression, both in vitro and in vivo studies, inhibited tumorigenesis through apoptosis augmentation and cell cycle blockade. Mechanistically, NBAT1 bound to IGF2BP1 and inhibited the interaction between IGF2BP1 and c-Myc mRNA, thus suppressing the stability of c-Myc mRNA. Collectively, NBAT1 is associated with HCC tumorigenesis and could be a therapeutic target for HCC treatment.

The relationship between serum hepatitis B virus DNA level and liver histology in patients with chronic HBV infection.

BACKGROUND: There is no consensus regarding the relationship between HBV DNA and liver fibrosis, and the relationship between HBV DNA and the degree of liver cirrhosis has not been reported in patients with chronic HBV infection. METHODS: From January 2011 to December 2016, liver biopsies were performed on 396 patients with chronic hepatitis B and cirrhosis. Assessments of liver fibrosis and cirrhosis were based on the Laennec staging system. RESULTS: Serum levels of HBV DNA were correlated with fibrosis and cirrhosis (KW = 73.946, P<0.001). Serum HBV DNA level was correlated with mild fibrosis, moderate to severe fibrosis and cirrhosis (P = 0.009, P<0.001, and P<0.001, respectively). The HBeAg-positive group and HBeAg-negative group showed significant differences in HBV DNA levels, and the rates of mild fibrosis, severe fibrosis and cirrhosis were significantly different between these two groups (F = 17.585, P<0.001 and F = 6.017, P = 0.003, respectively). The replication status of the serum HBV DNA affected fibrosis formation as well as cirrhosis (χ2 = 53.76, P<0.001). In the HBeAg-positive group, the sensitivity, specificity and AUC values of HBV DNA as a predictor for mild fibrosis and cirrhosis were 64.3%, 78.94% and 0.818, respectively, and 81.0%, 69.2%, and 0.871, respectively. In the HBeAg-negative group, the sensitivity, specificity and AUC values of HBV DNA for liver sclerosis prediction were 48%, 76.8% and 0.697, respectively. CONCLUSIONS: Different HBV DNA levels had different effects on the formation of fibrosis and sclerosis in liver tissues. HBV DNA levels can predict mild fibrosis and cirrhosis in liver tissue, which is enhanced in HBeAg-positive patients.