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Pyroptosis is a type of programmed cell death mediated by gasdermines (GSDMs). The N-terminal domain of GSDMs forms pores in the plasma membrane, causing cell membrane rupture and the release of cell contents, leading to an inflammatory response and mediating pyrodeath. Pyroptosis plays an important role in inflammatory diseases and malignant tumors. With the further study of pyroptosis, an increasing number of studies have shown that the pyroptosis pathway can regulate the tumor microenvironment and antitumor immunity of colorectal cancer and is closely related to the occurrence, development, treatment and prognosis of colorectal cancer. This review aimed to explore the molecular mechanism of pyroptosis and the role of pyroptosis in the occurrence, development, treatment and prognosis of colorectal cancer (CRC) and to provide ideas for the clinical diagnosis and treatment of CRC., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Norwegian scabies (NS) is a serious parasitic skin condition. Although NS is one of the causes of erythroderma, it is frequently overlooked. Therefore, it is essential to raise awareness regarding NS presenting as erythroderma., Case Summary: We present a case of NS that persisted for more than 3 years. After following nonstandard treatment, the patient's rash worsened and gradually progressed into erythroderma. Finally, NS was diagnosed by skin microscopy and pathology., Conclusion: When patients with pruritic dermatosis have high-risk factors such as prolonged bed rest and immunodeficiency, clinicians need to enhance their awareness of NS and ensure prompt diagnosis and treatment., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rapidly increasing, currently affecting approximately 25% of the global population. Liver fibrosis represents a crucial stage in the development of MAFLD, with advanced liver fibrosis elevating the risks of cirrhosis and hepatocellular carcinoma. Simple serum markers are less effective in diagnosing liver fibrosis compared to more complex markers. However, imaging techniques like transient elastography face limitations in clinical application due to equipment and technical constraints. Consequently, it is imperative to identify a straightforward yet effective method for assessing MAFLD-associated liver fibrosis., Aim: To investigate the predictive value of angiopoietin-like protein 8 (ANGPTL8) in MAFLD and its progression., Methods: We analyzed 160 patients who underwent abdominal ultrasonography in the Endocrinology Department, Xiaogan Central Hospital affiliated to Wuhan University of Science and Technology, during September 2021-July 2022. Using abdominal ultrasonography and MAFLD diagnostic criteria, among the 160 patients, 80 patients (50%) were diagnosed with MAFLD. The MAFLD group was divided into the liver fibrosis group ( n = 23) and non-liver fibrosis group ( n = 57) by using a cut-off fibrosis-4 index ≥ 1.45. Logistical regression was used to analyze the risk of MAFLD and the risk factors for its progression. Receiver operating characteristic curves were used to evaluate the predictive value of serum ANGPTL8 in MAFLD and its progression., Results: Compared with non-MAFLD patients, MAFLD patients had higher serum ANGPTL8 and triglyceride-glucose (TyG) index (both P < 0.05). Serum ANGPTL8 ( r = 0.576, P < 0.001) and TyG index ( r = 0.473, P < 0.001) were positively correlated with MAFLD. Serum ANGPTL8 was a risk factor for MAFLD [odds ratio (OR): 1.123, 95% confidence interval (CI): 1.066-1.184, P < 0.001). Serum ANGPTL8 and ANGPTL8 + TyG index predicted MAFLD [area under the curve (AUC): 0.832 and 0.886, respectively; both P < 0.05]. Compared with MAFLD patients without fibrosis, those with fibrosis had higher serum ANGPTL8 and TyG index (both P < 0.05), and both parameters were positively correlated with MAFLD-associated fibrosis. Elevated serum ANGPTL8 (OR: 1.093, 95%CI: 1.044-1.144, P < 0.001) and TyG index (OR: 2.383, 95%CI: 1.199-4.736, P < 0.013) were risk factors for MAFLD-associated fibrosis. Serum ANGPTL8 and ANGPTL8 + TyG index predicted MAFLD-associated fibrosis (AUC: 0.812 and 0.835, respectively; both P < 0.05)., Conclusion: The serum levels of ANGPTL8 are elevated and positively correlated with MAFLD. They can serve as predictors for the risk of MAFLD and liver fibrosis, with the ANGPTL8 + TyG index potentially exhibiting even higher predictive value., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Diabetic kidney disease (DKD), characterized by increased urinary microalbumin levels and decreased renal function, is the primary cause of end-stage renal disease. Its pathological mechanisms are complicated and multifactorial; Therefore, sensitive and specific biomarkers are needed. Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney. The microRNAs (miRNAs) in urinary exosome are remarkably stable and highly tissue-specific for the kidney., Aim: To determine if urinary exosomal miRNAs from diabetic patients can serve as noninvasive biomarkers for early DKD diagnosis., Methods: Type 2 diabetic mellitus (T2DM) patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups: DM, diabetic patients without albuminuria [urinary albumin to creatinine ratio (UACR) < 30 mg/g] and DKD, diabetic patients with albuminuria (UACR ≥ 30 mg/g). Healthy subjects were the normal control (NC) group. Urinary exosomal miR-145-5p, miR-27a-3p, and miR-29c-3p, were detected using real-time quantitative polymerase chain reaction. The correlation between exosomal miRNAs and the clinical indexes was evaluated. The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic (ROC) analysis. Biological functions of miR-145-5p were investigated by performing Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment., Results: Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group (miR-145-5p: 4.54 ± 1.45 vs 1.95 ± 0.93, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.71 ± 0.76, P < 0.05) and the NC group (miR-145-5p: 4.54 ± 1.45 vs 1.55 ± 0.83, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.10 ± 0.51, P < 0.001). The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate. miR-27a-3p was also closely related to blood glucose, glycosylated hemoglobin A1c, and low-density lipoprotein cholesterol. ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88 [95% confidence interval (CI): 0.784-0.985, P < 0.0001] in diagnosing DKD than miR-27a-3p with 0.71 (95%CI: 0.547-0.871, P = 0.0239). Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament, cytoskeleton, and extracellular exosome and were involved in the pathological processes of DKD, including apoptosis, inflammation, and fibrosis., Conclusion: Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Low anterior resection syndrome (LARS) is one of the common postoperative complications in patients with rectal cancer, which seriously affects their postoperative recovery and quality of life (QoL). Electroacupuncture therapy is one of the characteristic therapies of traditional Chinese medicine. There are few reports on the prevention and treatment of LARS by electroacupuncture therapy., Aim: To explore the clinical effectiveness of electroacupuncture in managing rectal cancer patients with postoperative LARS., Methods: A total of 50 patients with LARS after rectal cancer surgery were retrospectively selected as the research subjects. According to the treatment methods, they were divided into an observation group ( n = 25) and a control group ( n = 25). During the four-week treatment period, the control group received standard defecation function training, while the observation group received electroacupuncture care and traditional defecation function training. The anal pressure index (which includes anal resting pressure, anal systolic pressure, and maximum tolerable volume), European Organization of Research and Treatment of Cancer (EORTC) QoL C30 (QLQ-C30) score, LARS Scale (LARSS) score, Wexner anal incontinence scale score, Xu Zhongfa five-item 10-point scale score, and the occurrence of adverse reactions were compared between the two groups before and after treatment., Results: The experimental group showed considerably enhanced LARSS scores compared to those in the control group after four weeks of treatment. In the first week, second week, and fourth week, the LARSS score and Wexner anal incontinence scale score decreased, and the Xu Zhong method five-item 10-point scale score increased, with significant differences ( P < 0.05). The experimental group showed substantial improvements in anal resting pressure, anal systolic pressure, and maximum tolerance volume after undergoing 4 wk of therapy in the untreated group ( P < 0.05). The experimental group's QLQ-C30 score on the EORTC QoL questionnaire was higher than that of the control group during the 1 st , 2 nd , and 4 th wk ( P < 0.05). No significant variation between the groups in the frequency of adverse reactions ( P > 0.05) was observed., Conclusion: Electroacupuncture positively impacted LARS following rectal cancer surgery, effectively improving clinical symptoms and anal pressure indicators and patients' standard of life., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The impact of racial and regional disparity on younger patients with gastric cancer (GC) remains unclear., Aim: To investigate the clinicopathological characteristics, prognostic nomogram, and biological analysis of younger GC patients in China and the United States., Methods: From 2000 to 2018, GC patients aged less than 40 years were enrolled from the China National Cancer Center and the Surveillance Epidemiology and End Results database. Biological analysis was performed based on the Gene Expression Omnibus database. Survival analysis was conducted via Kaplan-Meier estimates and Cox proportional hazards models., Results: A total of 6098 younger GC patients were selected from 2000 to 2018, of which 1159 were enrolled in the China National Cancer Center, and 4939 were collected from the Surveillance Epidemiology and End Results database. Compared with the United States group, younger patients in China revealed better survival outcomes ( P < 0.01). For race/ethnicity, younger Chinese cases also enjoyed a better prognosis than that in White and Black datasets ( P < 0.01). After stratification by pathological Tumor-Node-Metastasis (pTNM) stage, a survival advantage was observed in China with pathological stage I, III, and IV (all P < 0.01), whereas younger GC patients with stage II showed no difference ( P = 0.16). In multivariate analysis, predictors in China involved period of diagnosis, linitis plastica, and pTNM stage, while race, diagnostic period, sex, location, differentiation, linitis plastica, signet ring cell, pTNM stage, surgery, and chemotherapy were confirmed in the United States group. Prognostic nomograms for younger patients were established, with the area under the curve of 0.786 in the China group and of 0.842 in the United States group. Moreover, three gene expression profiles (GSE27342, GSE51105, and GSE38749) were enrolled in further biological analysis, and distinctive molecular characteristics were identified in younger GC patients among different regions., Conclusion: Except for younger cases with pTNM stage II, a survival advantage was observed in the China group with pathological stage I, III, and IV compared to the United States group, which might be partly due to differences in surgical approaches and the improvement of the cancer screening in China. The nomogram model provided an insightful and applicable tool to evaluate the prognosis of younger patients in China and the United States. Furthermore, biological analysis of younger patients was performed among different regions, which might partly explain the histopathological behavior and survival disparity in the subpopulations., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Postoperative gastrointestinal function recovery is critical for rapid rehabilitation of patients with gastrointestinal tumors. Traditional Chinese medicine offers considerable advantages for gastrointestinal disease treatment. However, no study has reported the clinical efficacy of intradermal needle therapy (INT) at the Yuan-source, Luo-connecting, and He-sea points of the corresponding meridian for gastrointestinal function in patients following surgery for gastrointestinal tumors., Aim: To investigate the effect of INT at combined acupoints on patients' gastrointestinal function following surgery for gastrointestinal tumors., Methods: This randomized controlled trial was conducted at the Second Affiliated Hospital of Xi'an Jiaotong University on patients with diagnosed gastrointestinal cancer, no distant metastases or organ failure, and hospitalized for elective radical tumor resection, who did not receive preoperative radiotherapy or chemotherapy. Participants were randomly allocated to either the intervention ( n = 32) or the control ( n = 32) group. Participants in the control group received enhanced recovery care, while those in the intervention group received enhanced recovery care combined with INT at the Yuan-source, Luo-connecting, and He-sea points. After surgery, INT was performed immediately upon the patient's return to the ward, and continued for seven consecutive days. The independent samples t -test, chi-square test, and generalized estimating equations were used for data analysis., Results: The participants' ages ranged from 40 to 80 years (average 63 ± 10.1 years). Most participants underwent surgery for either gastric (43.8%) or colon cancer (39.1%) and had adenocarcinoma (87.5%). Significant differences were noted in time to first postoperative flatus passage (66 ± 27 h vs 103 ± 41 h, P < 0.001), time to first defecation (106 ± 44 h vs 153 ± 50 h, P < 0.001), and time to first oral feeding (73 ± 30 h vs 115 ± 38 h, P < 0.001) between the intervention and control groups. Gastrointestinal symptoms, including abdominal distension, nausea, and fatigue 48 h and 72 h after surgery, were significantly alleviated in the intervention group compared with that observed in the control group ( P < 0.05)., Conclusion: INT at the Yuan-source, Luo-connecting, and He-sea points can promote recovery of gastrointestinal function and ease gastrointestinal symptoms in patients following surgical resection of gastrointestinal tumors., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: O 6 -methylguanine-DNA methyltransferase (MGMT) is a suicide enzyme that repairs the mispairing base O 6 -methyl-guanine induced by environmental and experimental carcinogens. It can transfer the alkyl group to a cysteine residue in its active site and became inactive. The chemical carcinogen N-nitroso compounds (NOCs) can directly bind to the DNA and induce the O 6 -methylguanine adducts, which is an important cause of gene mutation and tumorigenesis. However, the underlying regulatory mechanism of MGMT involved in NOCs-induced tumorigenesis, especially in the initiation phase, remains largely unclear., Aim: To investigate the molecular regulatory mechanism of MGMT in NOCs-induced gastric cell malignant transformation and tumorigenesis., Methods: We established a gastric epithelial cell malignant transformation model induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N-methyl-N-nitroso-urea (MNU) treatment. Cell proliferation, colony formation, soft agar, cell migration, and xenograft assays were used to verify the malignant phenotype. By using quantitative real-time polymerase chain reaction (qPCR) and Western blot analysis, we detected the MGMT expression in malignant transformed cells. We also confirmed the MGMT expression in early stage gastric tumor tissues by qPCR and immunohistochemistry. MGMT gene promoter DNA methylation level was analyzed by methylation-specific PCR and bisulfite sequencing PCR. The role of MGMT in cell malignant transformation was analyzed by colony formation and soft agar assays., Results: We observed a constant increase in MGMT mRNA and protein expression in gastric epithelial cell malignant transformation induced by MNNG or MNU treatment. Moreover, we found a reduction of MGMT gene promoter methylation level by methylation-specific PCR and bisulfite sequencing PCR in MNNG/MNU-treated cells. Inhibition of the MGMT expression by O 6 -benzylguanine promoted the MNNG/MNU-induced malignant phenotypes. Overexpression of MGMT partially reversed the cell malignant transformation process induced by MNNG/MNU. Clinical gastric tissue analysis showed that MGMT was upregulated in the precancerous lesions and metaplasia tissues, but downregulated in the gastric cancer tissues., Conclusion: Our finding indicated that MGMT upregulation is induced via its DNA promoter hypomethylation. The highly expressed MGMT prevents the NOCs-induced cell malignant transformation and tumorigenesis, which suggests a potential novel approach for chemical carcinogenesis intervention by regulating aberrant epigenetic mechanisms., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Recent epidemiological studies have shown that general eye measurement parameters and corneal biomechanical properties can predict the speed of myopic progression in children., Aim: To investigate the correlation between the onset and progression of myopia and corneal biomechanical parameters in children., Methods: The study included 102 cases in the emmetropia group, 207 cases in the myopic group, and 109 cases in the hyperopic group. The correlation between the change in corneal biomechanical indexes and the change in general ocular measurement parameters was analyzed. A one-way ANOVA test compared general ocular measurement and corneal biomechanical parameters. Pearson's correlation coefficient was analyzed to correlate corneal biomechanical and general ocular measurement parameters., Results: The general ophthalmometric parameters: Spherical equivalent (SE), intraocular pressure (IOP), and axial length (AL), differed significantly among subjects in myopia, emmetropia, and hyperopic groups. Children's SE positively correlated with corneal biomechanical parameters: Second velocity of applanation (A2V), peak distance (PD), and deformation amplitude (DA) ( P < 0.05), and second applanation length (A2L) ( P < 0.05). But it was negatively correlated with PD, DA and integral radius (IR) ( P < 0.05). Also, IOP was negatively correlated with A2L and IR ( P < 0.05). AL positively correlated with A2V and negatively correlated with second applanation time (A2T), highest concavity, and PD. Central corneal thickness positively correlated with first applanation length, first applanation time, first applanation deformation amplitude, A2V, A2L, A2T, second applanation deformation amplitude, central curvature radius at highest concavity (HCR), PD, DA, IR, ambrosia relational thickness-horizontal, first applanation stiffness parameter, corvis biomechanical index, topographic and biomechanics index and the first velocity of applanation. The general ocular Km in children positively correlated with corneal biomechanical parameters DA and IR and negatively correlated with A2L, HCR, and PD. There was a positive correlation between the general ocular measurement parameters ΔSE and corneal biomechanical parameters ΔA2V and ΔA2L, and a negative correlation with ΔIR. The increase in general ocular measurement parameter ΔKm positively correlated with changes in corneal biomechanical parameters, ΔDA and ΔIR, and negatively correlated with ΔHCR and ΔPD., Conclusion: Myopia development in children was associated with multiple corneal biomechanical parameters., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Percutaneous transhepatic cholangiography drainage (PTCD) effectively treats biliary obstruction. However, patients must maintain the drainage tube after hospital discharge, which may interfere with daily life and work, potentially causing psychological distress. Postoperative rehabilitation is crucial, and strengthened nursing interventions can shorten recovery time., Aim: The aim was to evaluate an inpatient model to shorten rehabilitation duration and improve quality of life after PTCD., Methods: A total of 118 patients with malignant obstructive jaundice who were admitted to our hospital between May 2018 and January 2021 were included and divided into observational (with therapy) and control (no therapy) groups of 59 each., Results: The observational group had fewer hospitalization days than the control group. The complication, the PTCD fixed-tube prolapse, and tube-related admission rates within 3 mo after PTCD were significantly lower in the observation group than in the control group ( P < 0.05). The fatigue, pain, nausea, vomiting, pruritus, emaciation, and fever scores after PTCD decreased in both groups compared with the scores before PTCD ( P < 0.05). The quality of life scores after the intervention were higher in the observation than in the control group ( P < 0.05)., Conclusion: The model promoted rehabilitation after PTCD, reduced post-PTCD complications, and the tube-related admissions in the 3 mo after the procedure, and improved the quality of life., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicting interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Dysbiosis of the gastric microbiome is involved in the development of gastric cancer (GC). A number of studies have demonstrated an increase in the relative abundance of Lactobacillus in GC. In this review, we present data that support the overgrowth of Lactobacillus in GC from studies on molecular and bacterial culture of the gastric microbiome, discuss the heterogenic effects of Lactobacillus on the health of human stomach, and explore the potential roles of the overgrowth of Lactobacillus in gastric carcinogenesis. Further studies are required to examine the association between Lactobacillus and GC at strain and species levels, which would facilitate to elucidate its role in the carcinogenic process., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Gastric cancer is the fourth leading cause of cancer-related mortality across the globe, with a 5-year survival rate of less than 40%. In recent years, several applications of artificial intelligence (AI) have emerged in the gastric cancer field based on its efficient computational power and learning capacities, such as image-based diagnosis and prognosis prediction. AI-assisted diagnosis includes pathology, endoscopy, and computerized tomography, while researchers in the prognosis circle focus on recurrence, metastasis, and survival prediction. In this review, a comprehensive literature search was performed on articles published up to April 2020 from the databases of PubMed, Embase, Web of Science, and the Cochrane Library. Thereby the current status of AI-applications was systematically summarized in gastric cancer. Moreover, future directions that target this field were also analyzed to overcome the risk of overfitting AI models and enhance their accuracy as well as the applicability in clinical practice., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Lifestyle factors such as body mass index (BMI), alcohol drinking, and cigarette smoking, are likely to impact the prognosis of gastric cancer, but the evidence has been inconsistent., Aim: To investigate the association of lifestyle factors and long-term prognosis of gastric cancer patients in the China National Cancer Center., Methods: Patients with gastric cancer were identified from the China National Cancer Center Gastric Cancer Database 1998-2018. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models., Results: In this study, we reviewed 18441 cases of gastric cancer. Individuals who were overweight or obese were associated with a positive smoking and drinking history ( P = 0.002 and P < 0.001, respectively). Current smokers were more likely to be current alcohol drinkers (61.3% vs 10.1% vs 43.2% for current, never, and former smokers, respectively, P < 0.001). Multivariable results indicated that BMI at diagnosis had no significant effect on prognosis. In gastrectomy patients, factors independently associated with poor survival included older age (HR = 1.20, 95%CI: 1.05-1.38, P = 0.001), any weight loss ( P < 0.001), smoking history of more than 30 years (HR = 1.14, 95%CI: 1.04-1.24, P = 0.004), and increasing pTNM stage ( P < 0.001)., Conclusion: In conclusion, our results contribute to a better understanding of lifestyle factors on the overall burden of gastric cancer and long-term prognosis. In these patients, weight loss (both in the 0 to 10% and > 10% groups) but not BMI at diagnosis was related to survival outcomes. With regard to other factors, smoking history of more than 30 years conferred a worse prognosis only in patients who underwent gastrectomy. Extensive efforts are needed to elucidate mechanisms targeting the complex effects of lifestyle factors., Competing Interests: Conflict-of-interest statement: All authors have no conflict of interest related to the manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Studies have reported that microRNA-30c (miR-30c) has vital functions in the development and progression of multiple cancers., Aim: To investigate the clinical significance and role of miR-30c in pancreatic cancer., Methods: MiR-30c and twinfilin 1 (TWF1) expression levels were analyzed in Gene Expression Omnibus datasets and validated in human pancreatic cancer by quantitative real-time polymerase chain reaction (RT-qPCR). The effects of miR-30c on pancreatic cancer cell growth, apoptosis, and cell cycle were evaluated by CCK-8 and flow cytometry assays. Furthermore, the in vivo effects were investigated using a subcutaneous xenograft experiment. Target gene prediction software and luciferase reporter assays were used to identify TWF1 as a direct target of miR-30c., Results: The expression of miR-30c was significantly decreased in pancreatic cancer tissues and associated with survival. Gain- and loss-of-function assays showed that miR-30c suppressed pancreatic cancer cell proliferation in vitro and in vivo . RT-qPCR, Western blot, and luciferase reporter assays showed that miR-30c directly targeted TWF1. The expression level of miR-30c was negatively correlated with TWF1 expression in pancreatic cancer tissues. Furthermore, the effects of ectopic miR-30c were rescued by TWF1 overexpression., Conclusion: Our results identified the role of the miR-30c/TWF1 axis in pancreatic cancer progression and demonstrated that miR-30c might serve as a prognostic biomarker and therapeutic target for pancreatic cancer., Competing Interests: Conflict-of-interest statement: All authors declare no competing financial interests., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

The incidence of gastrointestinal (GI) tumors is increasing year by year, and its pathogenesis is closely related to the intestinal flora. At present, the use of antibiotics is very common in the clinic. And cancer patients with low immunity are vulnerable to all sorts of infections, such as respiratory tract infections and urinary tract infections. Moreover, cancer patients easily run into fever and neutropenia induced by myelosuppression. Therefore, antibiotics are used extensively and even overused in many conditions. However, because of the special anatomical location of the gastrointestinal tract, the antibiotic usage will bring changes to the intestinal flora. Besides, with the expanding popularity of immunotherapy, various factors affecting the efficacy of immune checkpoint inhibitors (ICIs) have been extensively explored, including cancer-associated inflammation and the local and systemic factors that lead to immunosuppression. Some biomarkers for ICIs, including the expression of PD-L1, tumor mutation load, and microbiota, also have been investigated, and many studies have confirmed that gut microbiota can affect the efficacy of immunotherapy. But further studies on the influence of antibiotics directly on immunotherapy are rare. In this review, we discuss the relationship between GI tumors and antibiotics, the current status of immunotherapy in GI tumors, and the influence of antibiotics on immunotherapy., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors who contributed their efforts in this manuscript.

Background: Acute exacerbation in patients with chronic hepatitis B virus (HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation (HD) and acute-on-chronic liver failure (ACLF) in patients with severe acute exacerbation (SAE) of chronic HBV infection remain unknown., Aim: To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection., Methods: The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation (AE model) and the model for end-stage liver disease (MELD) score in predicting the development of ACLF were evaluated., Results: Among 164 patients with SAE, 83 (50.6%) had compensated liver cirrhosis (LC), 43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase (AST) levels, and low prothrombin activity (PTA). The area under the receiver operating characteristic of the AE model [0.844, 95% confidence interval (CI): 0.779-0.896] was significantly higher than that of MELD score (0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF., Conclusion: In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest in this study.

Background: Diastolic electromechanical couple, a well-described phenomenon in symptomatic heart failure, has not been well studied in healthy people. We hypothesized that ventricular repolarization variables, such as the QT interval, Tpeak-to-Tend (Tpe) interval and Tpe/QT ratio, are associated with cardiac diastolic function in the healthy Chinese population., Aim: To assess the relationship between ventricular repolarization variables and cardiac diastolic function in apparently healthy Chinese individuals., Methods: This was a community-based cross-sectional study conducted in Shenyang, China. A total of 414 healthy subjects aged 35-91 years were enrolled. All subjects underwent standard 12-lead electrocardiography (ECG) and comprehensive echocardiography. ECG enabled the measurement of QT and Tpe intervals and Tpe/QT ratio. echocardiographic parameters, such as the ratio of mitral early diastolic inflow velocity (E) and late diastolic inflow velocity (A), E-wave deceleration time, left atrial volume (LAV) and LAV index, were measured to assess diastolic function. E/A < 0.75 was considered to indicate reduced diastolic function. ECG and echocardiography results were analyzed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations., Results: Ventricular repolarization variables, such as the QTc interval (393.59 ± 26.74 vs 403.86 ± 33.56; P < 0.001), Tpe interval (72.68 ± 12.41 vs 77.26 ± 17.86; P < 0.01), Tpe c interval (76.36 ± 13.53 vs 83.32 ± 21.25; P < 0.001) and Tpe/QT ratio (0.19 ± 0.03 vs 0.20 ± 0.04; P < 0.01), were significantly different between the normal diastolic function group and the reduced diastolic function group. Significant associations were found between repolarization variables and diastolic function. After adjusting for all other possible confounders, the QTc and Tpe c intervals were significantly associated with the E/A ratio ( P = 0.008; P = 0.010). In men, the QTc interval was associated with abnormal diastolic function, and compared to the third QTc tertile, in the second QTc tertile, the odds ratio was 0.257 (95%CI: 0.102-0.649; P = 0.004)., Conclusion: Repolarization variables are associated with cardiac diastolic function even in healthy people. Moderate levels of the QTc interval exert a protective effect on diastolic dysfunction in men., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest.

Aim: To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori ( H. pylori ) infection in a healthy population, and explore factors associated with gastric biomarkers., Methods: Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen (PG) I and II, gastrin-17 (G-17) and H. pylori antibody levels. Analyses were made by Student's t -test, ANOVA, Pearson's correlation and multiple linear regressions., Results: PGII levels were higher in the ≥ 65-years-old age group ( P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group ( P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol (LDL-C) were higher ( P = 0.009) in H. pylori -infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group ( P < 0.05) for H. pylori -infected subjects and 45-64-years-old age group ( P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-IgG level positively correlated with PGI, PGII and G-17 ( P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII ( P < 0.001). Creatinine positively correlated with PGI, PGII and G-17 ( P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose (FBG) positively correlated with PGI/PGII and G-17 ( P < 0.001, P = 0.037). Age positively correlated with PGII and G-17 ( P = 0.005, P = 0.026)., Conclusion: PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report.

Aim: To clarify the mechanisms involved in the critical endoplasmic reticulum (ER) stress initiating unfolded protein response pathway modified by melatonin., Methods: Hepatoma cells, HepG2, were cultured in vitro . Flow cytometry and TUNEL assay were used to measure HepG2 cell apoptosis. Western blotting and quantitative reverse transcription-polymerase chain reaction methods were used to determine the protein and messenger RNA levels of ER stress and apoptosis related genes' expression, respectively. Tissue microarray construction from patients was verified by immunohistochemical analysis., Results: In the present study, we first identified that melatonin selectively blocked activating transcription factor 6 (ATF-6) and then inhibited cyclooxygenase-2 (COX-2) expression, leading to enhanced liver cancer cell apoptosis under ER stress condition. Dramatically increased CCAAT-enhancer-binding protein homologous protein level, suppressed COX-2 and decreased Bcl-2/Bax ratio by melatonin or ATF-6 siRNA contributed the enhanced HepG2 cell apoptosis under tunicamycin (an ER stress inducer) stimulation. In clinical hepatocellular carcinoma patients, the close relationship between ATF-6 and COX-2 was further confirmed., Conclusion: These findings indicate that melatonin as a novel selective ATF-6 inhibitor can sensitize human hepatoma cells to ER stress inducing apoptosis., Competing Interests: Conflict-of-interest statement: No conflicts of interest exist for any of the authors.

Aim: To investigate whether neuron-glial antigen 2 (NG2) could be an effective prognostic marker in hepatocellular carcinoma (HCC)., Methods: NG2 expression was semi-quantitatively scored from the immunohistochemistry (IHC) data based on the number of positive cells and the staining intensity. A total of 132 HCC specimens and 96 adjacent noncancerous tissue samples were analyzed by IHC for NG2 protein expression. To confirm the NG2 expression levels observed by IHC, we measured NG2 expression in 30 randomly selected tumor and adjacent noncancerous tissue samples by quantitative real-time polymerase chain reaction and Western blot. The correlations between NG2 protein expression and the clinicopathological features of HCC patients were analyzed using the χ (2) test. To assess the prognostic value of NG2 for HCC, the association between NG2 expression and survival was analyzed using the Kaplan-Meier method with the log-rank test. To further evaluate the prognostic value of NG2 expression, a Cox multivariate proportional hazards regression analysis was performed with all the variables to derive risk estimates related to disease-free and overall survival and to control for confounders., Results: High NG2 expression was observed in significantly more primary tumor samples (63.6%; 84/132) compared with the adjacent noncancerous tissue samples (28.1%; 27/96) (P < 0.0001). Moreover, high NG2 protein expression was closely associated with tumor differentiation (χ (2) = 9.436, P = 0.0089), recurrence (χ (2) = 5.769, P = 0.0163), tumor-node-metastasis (TNM) stage (χ (2) = 8.976, P = 0.0027), and invasion (χ (2) = 5.476, P = 0.0193). However, no significant relationship was observed between NG2 protein expression in HCC and other parameters, such as age, sex, tumor size, serum alpha fetoprotein (AFP), tumor number, or tumor capsule. The log-rank test indicated a significant difference in the overall survival of HCC patients with high NG2 expression compared with those with low NG2 expression (29.2% vs 9.5%, P < 0.001). Moreover, NG2 expression in HCC tissue significantly correlated with disease-free survival (15.2% vs 6.7%, P < 0.001). Multivariate analysis showed that NG2 expression (HR = 2.035, P = 0.002), serum AFP (HR = 1.903, P = 0.003), TNM stage (HR = 2.039, P = 0.001), and portal vein invasion (HR = 1.938, P = 0.002) were independent prognostic indicators for OS in HCC patients. Furthermore, NG2 expression (HR = 1.974, P = 0.003), serum AFP (HR = 1.767, P = 0.008), TNM stage (HR = 2.078, P = 0.001), tumor capsule (HR = 0.652, P = 0.045), and portal vein invasion (HR = 1.941, P = 0.002) were independent prognostic indicators for DFS in HCC patients., Conclusion: The up-regulation of NG2 is associated with poor prognosis in HCC. Therefore, NG2 could be useful as an additional prognostic marker to increase the resolution of traditional approaches.

Aim: To investigate the relaxant effect of chromane HEF-19 on colonic smooth muscles isolated from rabbits, and the underlying mechanisms., Methods: The relaxant effect and action mechanisms of HEF-19 were investigated using descending colon smooth muscle of the rabbits. Preparations 1 cm long were mounted in 15-mL tissue baths containing Tyrode's solution, maintained at 37 ± 0.5 °C and aerated with a mixture of 5% CO2 in oxygen (Carbogen). The tension and amplitude of the smooth muscle strips were recorded after adding HEF-19 (10(-6), 10(-5) and 10(-4) mol/L). After cumulative administration of four antispasmodic agents, including acetylcholine chloride (Ach) (10(-4) mol/L), histamine (10(-4) mol/L), high-K(+) (60 mmol/L) and BaCl2 (8.2 mmol/L), HEF-19 (3 × 10(-7)-3 × 10(-4) mol/L) was added to investigate the relaxant effect of HEF-19. CaCl2 (10(-4)-2.5 × 10(-3) mol/L) was added cumulatively to the smooth muscle preparations pretreated with and without HEF-19 (1 × 10(-6) or 3 × 10(-6) mol/L) and verapamil (1 × 10(-7) mol/L) to study the mechanisms involved. Finally, phasic contraction was induced with ACh (15 × 10(-6) mol/L), and CaCl2 (4 × 10(-3) mol/L) was added to the smooth muscle preparations pretreated with and without HEF-19 (3 × 10(-6) mol/L or 1 × 10(-5) mol/L) and verapamil (1 × 10(-7) mol/L) in calcium-free medium to further study the underlying mechanisms., Results: HEF-19 (1 × 10(-6), 1 × 10(-5) and 1 × 10(-4) mol/L) suppressed spontaneous contraction of rabbit colonic smooth muscles. HEF-19 (3 × 10(-7)-3 × 10(-4) mol/L) relaxed in a concentration-dependent manner colonic smooth muscle preparations pre-contracted with BaCl2, high-K(+) solution, Ach or histamine with respective EC50 values of 5.15 ± 0.05, 5.12 ± 0.08, 5.58 ± 0.16 and 5.25 ± 0.24, thus showing a spasmolytic activity. HEF-19 (1 × 10(-6) mol/L and 3 × 10(-6) mol/L) shifted the concentration-response curves of CaCl2 to the right and depressed the maximum response to CaCl2. The two components contracted by Ach were attenuated with HEF-19 (3 × 10(-6) mol/L or 10(-5) mol/L) in calcium-free medium., Conclusion: HEF-19 inhibited rabbit colonic smooth muscle contraction, probably through inhibiting opening of voltage-dependent Ca(2+) channels. HEF-19 reduced inflow and intracellular release of Ca(2+) ions.

Aim: To investigate the anti-tumor effects of paeonol in gastric cancer cell proliferation and apoptosis in vitro and in vivo., Methods: Murine gastric cancer cell line mouse forestomach carcinoma (MFC) or human gastric cancer cell line SGC-7901 was cultured in the presence or absence of paeonol. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell cycle and apoptosis by flow cytometry and TUNEL staining. Tumor growth after subcutaneous implantation of MFC cells in mice was monitored, and the effects of treatment with paeonol were determined., Results: In vitro, paeonol caused dose-dependent inhibition on cell proliferation and induced apoptosis. Cell cycle analysis revealed a decreased proportion of cells in G0/G1 phase, with arrest at S. Paeonol treatment in gastric cancer cell line MFC and SGC-790 cells significantly reduced the expression of Bcl-2 and increased the expression of Bax in a concentration-related manner. Administration of paeonol to MFC tumor-bearing mice significantly lowered the tumor growth and caused tumor regression., Conclusion: Paeonol has significantly growth-inhibitory and apoptosis-inducing effects in gastric cancer cells both in vitro and in vivo.

Aim: To investigate whether melatonin has synergistic effects with doxorubicin in the growth-inhibition and apoptosis-induction of human hepatoma cell lines HepG2 and Bel-7402., Methods: The synergism of melatonin and doxorubicin inhibited the cell growth and induced cell apoptosis in human hepatoma cell lines HepG2 and Bel-7402. Cell viability was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using TUNEL method and flow cytometry. Apoptosis-related protein Bax, Bcl-2 and caspase-3 expressions were measured by immunohistochemical staining., Results: Treatment with melatonin (10(-8)-10(-5) mol/L) alone had a dose-related inhibitory effect on cell proliferation but no cytotoxic effect on hepatoma cell lines HepG2 and Bel-7402. Interestingly, when combined with doxorubicin, melatonin significantly increased the effects of cell growth inhibition and cell apoptosis. Furthermore, TUNEL staining and flow cytometry revealed that cooperative apoptosis induction was associated with decreased expression of Bcl-2 as well as increased expression of Bax and Caspase3., Conclusion: The synergism of melatonin and doxorubicin inhibits hepatoma cell growth and induces cell apoptosis.