The role of anoctamin 1 in liver disease.

Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and hepatocellular carcinoma (HCC). Liver disease is now one of the leading causes of disease and death worldwide, which compels us to better understand the mechanisms involved in the development of liver diseases. Anoctamin 1 (ANO1), a calcium-activated chloride channel (CaCC), plays an important role in epithelial cell secretion, proliferation and migration. ANO1 plays a key role in transcriptional regulation as well as in many signalling pathways. It is involved in the genesis, development, progression and/or metastasis of several tumours and other diseases including liver diseases. This paper reviews the role and molecular mechanisms of ANO1 in the development of various liver diseases, aiming to provide a reference for further research on the role of ANO1 in liver diseases and to contribute to the improvement of therapeutic strategies for liver diseases by regulating ANO1.

Pantoprazole suppresses carcinogenesis and growth of hepatocellular carcinoma by inhibiting glycolysis and Na+/H+ exchange.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. The prevention and therapy for this deadly disease remain a global medical challenge. In this study, we investigated the effect of pantoprazole (PPZ) on the carcinogenesis and growth of HCC. Both diethylnitrosamine (DEN) plus CCl4-induced and DEN plus high fat diet (HFD)-induced HCC models in mice were established. Cytokines and cell proliferation-associated gene in the liver tissues of mice and HCC cells were analyzed. Cellular glycolysis and Na+/H+ exchange activity were measured. The preventive administration of pantoprazole (PPZ) at a clinically relevant low dose markedly suppressed HCC carcinogenesis in both DEN plus CCl4-induced and HFD-induced murine HCC models, whereas the therapeutic administration of PPZ at the dose suppressed the growth of HCC. In the liver tissues of PPZ-treated mice, inflammatory cytokines, IL1, CXCL1, CXCL5, CXCL9, CXCL10, CCL2, CCL5, CCL6, CCL7, CCL20, and CCL22, were reduced. The administration of CXCL1, CXCL5, CCL2, or CCL20 all reversed PPZ-suppressed DEN plus CCL4-induced HCC carcinogenesis in mice. PPZ inhibited the expressions of CCNA2, CCNB2, CCNE2, CDC25C, CDCA5, CDK1, CDK2, TOP2A, TTK, AURKA, and BIRC5 in HCC cells. Further results showed that PPZ reduced the production of these inflammatory cytokines and the expression of these cell proliferation-associated genes through the inhibition of glycolysis and Na+/H+ exchange. In conclusion, PPZ suppresses the carcinogenesis and growth of HCC, which is related to inhibiting the production of inflammatory cytokines and the expression of cell proliferation-associated genes in the liver through the inhibition of glycolysis and Na+/H+ exchange.

Endoscopic cyanoacrylate injection therapy for refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy.

OBJECTIVE: To evaluate the efficacy and safety of endoscopic cyanoacrylate injection therapy for refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy. METHODS: 154 patients with refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy at the Affiliated Hospital of Zunyi Medical Univesity and the People's Hospital of Liupanshui City from January 2018 to December 2021were enrolled in this study. Endoscopic intracellular cyanoacrylate injection was first carried out. When failure, perintravascullar injection was carried out. The data were retrospectively collected. RESULTS: Among the 154 patients, 102 patients (66.23%) obtained successful intravascular injection and perivascular injection was performed in 52 patients (33.77%). Immediate hemostatic rate for active bleeding achieved 93.18%. Overall rebleeding rate within 30 days was 12.99% and successful hemostasis rate achieved 87.01%. Immediate hemostatic rate and successful hemostasis rate in intravascular injection patients were markedly superior over perivascular injection. Rebleeding rate in intravascular injection patients was markedly lower than that in perivascular injection patients. 14 patients complicated abdominal pain and no other complication occurred. CONCLUSION: Endoscopic cyanoacrylate injection therapy, especial intravascular injection, was effective and safe, with high successful hemostasis rate for refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy.

Clinical outcomes of clip-assisted endoscopic cyanoacrylate injection versus conventional endoscopic cyanoacrylate injection in treating gastric varices with a gastrorenal shunt.

BACKGROUND AND STUDY AIMS: The optimal treatment for gastric varices (GVs) is a topic that remains definite for this study. This study compared the clinical outcomes of clip-assisted endoscopic cyanoacrylate injection (clip-ECI) to conventional endoscopic cyanoacrylate injection (con-ECI) for the treatment of GVs with a gastrorenal shunt. PATIENTS AND METHODS: Data were collected retrospectively in five medical centers from 2015 to 2020. The patients were treated with con-ECI (n = 126) or clip-ECI (n = 148). Clinical characteristics and procedural outcomes were compared. Patients were followed until death, liver transplantation or 6 months after the treatment. The primary outcome was rebleeding, and the secondary outcome was survival. RESULTS: There were no significant differences in age, sex, etiology, shunt diameter and Child-Pugh classification between the two groups. Fewer GVs obliteration sessions were required in the clip-ECI group than in the con-ECI group (p = 0.015). The cumulative 6-month rebleeding-free rates were 88.6% in the clip-ECI group and 73.7% in the con-ECI group (p = 0.002). The cumulative 6-month survival rates were 97.1% in the clip-ECI group and 94.8% in the con-ECI group (p = 0.378). CONCLUSIONS: Compared with con-ECI, clip-ECI appears more effective for the treatment of GVs with a gastrorenal shunt, which required less sessions and achieved a higher 6-month rebleeding-free rate.

A case of erythrogenic protoporphyria with thyrotoxicosis and liver dysfunction in an adult female. / æˆå¹´å¥³æ€§çº¢ç»†èƒžç”Ÿæˆæ€§åŽŸåŸå•‰ç— åˆå¹¶ç”²çŠ¶è ºåŠŸèƒ½äº¢è¿›ç—‡å’Œè‚åŠŸèƒ½éšœç¢1例.

Erythropoietic protoporphyria (EPP) is an inherited metabolic disease caused by the deficiency in ferrochelatase (FECH) encoded by the FECH gene, and it is inherited in an autosomal recessive manner. EPP usually produces acute pain photosensitivity after exposure to sunlight in infancy or early childhood, and liver failure is the most serious associated complication. This article reported an adult female case of EPP complicated with thyrotoxicosis and liver dysfunction which is a rare condition. The patient's liver function improved after liver protection treatment, her thyroid function returned to normal, and her EPP symptoms improved significantly. Moreover, the c.286C>T gene mutation may be the pathogenic locus of EPP. For patients with abnormal liver function, the possibility of EPP should be considered after the common causes are excluded, and FECH gene detection should be done to confirm the diagnosis in time. When EPP is associated with thyrotoxicosis and liver dysfunction, priority may be given to hepatoprotective therapy.

Diagnosis and treatment of Helicobacter pylori infection by physicians in China: A nationwide cross-sectional study.

BACKGROUND: To investigate the current state of knowledge and practice of Helicobacter pylori (H. pylori) infection management in China. MATERIALS AND METHODS: This nationwide, multicenter, cross-sectional questionnaire survey was conducted between March and April 2021 with respect to the diagnosis and treatment of H. pylori infection in 31 provinces, encompassing over 1000 hospitals in mainland China. General physician information, diagnostic and detection status, eradication treatment, reexamination and follow-up after treatment, and basic knowledge of physicians were collected and compared with the Fifth Chinese National Consensus Report on Management of H. pylori infection and the 2016 Maastricht V/Florence guidelines. The subgroup analysis was also performed. RESULTS: Of the 6873 questionnaire respondents, 48.8% were males, and 51.2% were females. Approximately, 26.5% of respondents indicated that their hospitals had dedicated clinics for managing H. pylori infection. Moreover, 88.0% of respondents prescribed a bismuth-containing quadruple regimen as the initial eradication treatment, and 92.7% deemed the gastric acid suppression critical. Furthermore, 91.0% of respondents routinely recommended a reexamination 1-2 months after eradication therapy, and 95.1% advised patients to stop PPI treatment at least 2 weeks before reexamination. The detail of following (the choice of target population/methods; the choice/availability of drugs/regimens, indications for eradication, factors influencing eradication efficacy/improvement methods and factors influencing adherence, management options/factors influencing relapse; the timing and methods, awareness of reinfection rates/prevention measures, and the approach to continuing education, awareness of guidelines, and acceptance of current core concepts of management) was also described. Subgroup analysis further revealed that significant differences were existed in being gastroenterologist or not, different education level, professional title, years of working, and provincial administrative regions. CONCLUSIONS: Chinese physicians' skills and knowledge about the diagnosis and treatment of H. pylori infection could be improved. More works on education are needed in future.

An extremely dangerous case of acute massive upper gastrointestinal bleeding: a case report.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a severe acute disease of gastroenterology department. Fish bone is the most common food-related foreign body. However, fish bone piercing the esophagus, causing the mediastinal abscess that corroded the left subclavian artery, resulting delayed but high-risk massive upper gastrointestinal bleeding is very rare. CASE PRESENTATION: We report a 54-year-old man who was diagnosed with delayed but high-risk massive upper GI bleeding that was the result of a fish bone piercing the esophagus, causing a mediastinal abscess that corroded the left subclavian artery. He was saved effectively by early and timely multidisciplinary collaboration. CONCLUSION: A fish bone-caused mediastinal abscess that corrodes the left subclavian artery and induces delayed but high-risk massive upper GI bleeding is very rare. In addition to routine consideration of upper GI bleeding, medical history, endoscopy and CT are helpful for achieving a diagnosis. Importantly, early and timely multidisciplinary collaboration can effectively save critically ill patients.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases.

The incidence of gastrointestinal (GI) mucosal diseases, including various types of gastritis, ulcers, inflammatory bowel disease and GI cancer, is increasing. Therefore, it is necessary to identify new therapeutic targets. Ion channels/transporters are located on cell membranes, and tight junctions (TJs) affect acid-base balance, the mucus layer, permeability, the microbiota and mucosal blood flow, which are essential for maintaining GI mucosal integrity. As ion channel/transporter dysfunction results in various GI mucosal diseases, this review focuses on understanding the contribution of ion channels/transporters to protecting the GI mucosal barrier and the relationship between GI mucosal disease and ion channels/transporters, including Cl-/HCO3- exchangers, Cl- channels, aquaporins, Na+/H+ exchangers, and K+ channels. Here, we provide novel prospects for the treatment of GI mucosal diseases.

Ectopic pancreas appearing as a giant gastric cyst mimicking gastric lymphangioma: a case report and a brief review.

BACKGROUND: Ectopic pancreas (EP) is defined as pancreatic tissue that lacks anatomical or vascular communication with the normal body of the pancreas. Despite improvements in diagnostic endoscopy and imaging studies, differentiating ectopic pancreatic tissue from gastric submucosal diseases remains a challenge. CASE PRESENTATION: Here, we present a case of a 44-year-old woman with severe epigastric pain. Initially, gastric lymphangioma was highly suspected due to a well-demarcated protruding mass with a large size that occurred in the submucosal layer of the gastric antrum and appeared as a cystic lesion. The final correct diagnosis of gastric EP was made during surgery. CONCLUSION: Gastric EP with serous oligocystic adenoma appearing as a giant gastric cyst is extremely rare. The difficulty of making an accurate diagnosis and differential diagnosis is highlighted, which may provide additional clinical experience for the diagnosis of EP with serous oligocystic adenoma in the stomach.

Early verrucous cell carcinoma of the esophagus: a case report and endoscopic and histologic features.

BACKGROUND: Verrucous cell carcinoma of the esophagus (VCCE) is an extremely rare tumor and generally detected at advanced stage. Despite of its slow growth and well differentiation, it has very poor prognosis with high mortality. Therefore, early detection is a critical to improve patients' survival. However, no early cases of VCCE have been reported and the endoscopic features of early VCCE are not well described. We herein report the endoscopic and histologic features of an early VCCE. CASE PRESENTATION: A 54-year-old man with a history of excessive alcohol and tobacco use was admitted to our hospital because of chronic persistent swallowing dysfunction for six months. White light endoscopy revealed a flat lesion covered with scattered leukoplakia in the middle esophagus. Magnifying endoscopy with narrow-band imaging showed tiny irregular papillary microsurface structure. The lesion was considered as early esophageal cancer and completely resected with endoscopic submucosal dissection. Histological examination confirmed that the lesion was early VCCE which was limited within the mucosal lamina propria (m2). CONCLUSION: VCCE is rare with poor prognosis. This is a report of early VCCE and description of its endoscopic features which will contribute to early detection of these cancers.

The role of corticotropin-releasing hormone (CRH) family in tumors.

The corticotropin-releasing hormone (CRH) family is widely distributed among the central nervous system and peripheral tissues, such as the digestive, cardiovascular, immune, reproductive, endocrine systems. The CRH family members are widely involved in the regulation of human cell biological processes, immune response, and regulation of inflammatory processes that can affect the occurrence and development of tumors. At present, CRH family members and their receptors can be detected in many tumor tissues, and some people think that members of the CRH family may be potential tumor treatment targets as they can affect cellular processes, such as proliferation, migration, invasion, and apoptosis. However currently, there is no systematic introduction to the relationship between the CRH family and various tumors. This review introduces the molecular regulation of the CRH family in tumor formation and seeks further targeted therapy.

Physiological and pathophysiological role of ion channels and transporters in the colorectum and colorectal cancer.

The incidence of colorectal cancer has increased annually, and the pathogenesis of this disease requires further investigation. In normal colorectal tissues, ion channels and transporters maintain the water-electrolyte balance and acid/base homeostasis. However, dysfunction of these ion channels and transporters leads to the development and progression of colorectal cancer. Therefore, this review focuses on the progress in understanding the roles of ion channels and transporters in the colorectum and in colorectal cancer, including aquaporins (AQPs), Cl- channels, Cl- / HCO3- exchangers, Na+ / HCO3- transporters and Na+ /H+ exchangers. The goal of this review is to promote the identification of new targets for the treatment and prognosis of colorectal cancer.

Function of ion transporters in maintaining acid-base homeostasis of the mammary gland and the pathophysiological role in breast cancer.

The incidence of breast cancer is increasing year by year, and the pathogenesis is still unclear. Studies have shown that the high metabolism of solid tumors leads to an increase in hypoxia, glycolysis, production of lactic acid and carbonic acid, and extracellular acidification; a harsh microenvironment; and ultimately to tumor cell death. Approximately 50% of locally advanced breast cancers exhibit hypoxia and/or local hypoxia, and acid-base regulatory proteins play an important role in regulating milk secretion and maintaining mammary gland physiological function. Therefore, ion transporters have gradually become a hot topic in mammary gland and breast cancer research. This review focuses on the research progress of ion transporters in mammary glands and breast cancer. We hope to provide new targets for the treatment and prognosis of breast cancer.

Pathological role of ion channels and transporters in the development and progression of triple-negative breast cancer.

Breast cancer is a common malignancy in women. Among breast cancer types, triple-negative breast cancer (TNBC) tends to affect younger women, is prone to axillary lymph node, lung, and bone metastases; and has a high recurrence rate. Due to a lack of classic biomarkers, the currently available treatments are surgery and chemotherapy; no targeted standard treatment options are available. Therefore, it is urgent to find a novel and effective therapeutic target. As alteration of ion channels and transporters in normal mammary cells may affect cell growth, resulting in the development and progression of TNBC, ion channels and transporters may be promising new therapeutic targets for TNBC. This review summarizes ion channels and transporters related to TNBC and may provide new tumor biomarkers and help in the development of novel targeted therapies.

EUS in the diagnosis of pathologically undiagnosed esophageal tuberculosis.

BACKGROUND: Esophageal tuberculosis (ET) is relatively rare, and the diagnosis is challenging. The aim of this study was to evaluate the clinical features of ET and highlight the role of endoscopic ultrasonography (EUS) in the diagnosis of pathologically undiagnosed ET. METHODS: We retrospectively analysed the clinical features, radiological performances, conventional endoscopic appearances, EUS features, treatment and outcomes of pathologically undiagnosed ET between January 2011 and December 2018. All 9 patients failed to be diagnosed by at least two repeated biopsies (such as routine biopsy, multipoint or deep biopsy, and even or EUS-guided fine-needle aspiration (EUS-FNA)). RESULTS: Nine patients (66.7% female) with a mean age of 45 years (range 29-59) complained of retrosternal pain or discomfort, or (and) dysphagia. Esophagoscopy demonstrated protruding lesions in the mucosa with central ulcers or erosion in five patients, submucosal bulges with smooth surfaces in one patient, submucosal bulges with diverticula in one patient, ulcers with suspicious fistula formation in one patient, and multiple ulcers in one patient. None of the patients received confirmed histopathological or bacteriological diagnoses by repeated biopsies. However, they were first suspected to have ET based on EUS examination. Because EUS found some characteristic ultrasonographic changes, which were very helpful for the diagnosis of ET when combined with clinical manifestations, the patients subsequently received diagnostic antituberculosis therapy. Finally, the patients recovered or improved with follow-up times ranging from 3 to 10 months. CONCLUSIONS: EUS could help in the diagnosis of ET on basis of EUS features like poorly defined esophageal wall structure, enlarged paraesophageal or mediastinal lymph nodes, hypoechoic lesions of esophageal wall that are linked to the enlarged paraesophageal lymph nodes. However all attempts should be made to obtain histological or microbiological diagnosis.

Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature.

BACKGROUND: Chronic lead poisoning (CLP) is a rare cause of abdominal pain and is common in young children, in whom the incidence is higher than it is in adults. As the symptoms of CLP are nonspecific, misdiagnoses or missed diagnoses often occur, especially in sporadic cases. CASE PRESENTATION: We report a 28-year-old young man who was misdiagnosed with renal colic due to sudden acute abdominal pain. After a detailed medical history and physical examination, other possible causes were excluded, CLP was finally diagnosed, and he recovered after chelation treatment. CONCLUSION: Abdominal pain is a very common clinical symptom in adults, which has many causes. We should be vigilant against chronic poisoning, especially CLP. Detailed diagnosis and physical examination are crucial in early diagnosis and treatment.

Gastric tuberculosis mimicking submucosal tumor: a case series.

BACKGROUND: Gastric tuberculosis mimicking submucosal tumors is extremely rare and often misdiagnosed. CASE PRESENTATION: Three cases of gastric tuberculosis mimicking submucosal tumors were identified among patients admitted to local county hospitals because of upper abdominal discomfort and pain, with gastroscopy showing gastric submucosal tumors. The patients were admitted to our hospital for endoscopic ultrasonography (EUS). As EUS revealed evidence of tuberculosis for the first two patients, we first considered gastric tuberculosis. However, because of atypical characteristics of the miniature ultrasonic probe and EUS, the lesion in the third patient was misdiagnosed as a stromal tumor, and the patient underwent endoscopic submucosal dissection (ESD), and intraoperative characteristics and postoperative pathology confirmed the lesion to be tuberculosis. CONCLUSIONS: EUS is of great value in the diagnosis of gastric tuberculosis, especially gastric tuberculosis mimicking submucosal tumors. Here, we summarize some significant characteristics of gastric tuberculosis by EUS, which will be of substantial value to clinical work.

Estrogen Regulates Duodenal Calcium Absorption Through Differential Role of Estrogen Receptor on Calcium Transport Proteins.

BACKGROUND AND AIMS: Intestinal calcium absorption from the diet plays important role in maintaining calcium homeostasis in the body. Estrogen exerts wide physiological and pathological effects in the human. Previous studies have shown that estrogen is involved in the intestinal calcium absorption. In this study, we made investigation on the mechanism of estrogen action on duodenal calcium absorption. METHODS: The experiments were performed in mice, human, and human duodenal epithelial cells, SCBN cells. Murine duodenal calcium absorption was measured by using single pass perfusion of the duodenum in vivo. The calcium absorption of SCBN cells was evaluated by calcium imaging system. The expression of calcium transport proteins, transient receptor potential cation channel (TRPV6) and plasma membrane calcium pump (PMCA1b), in the duodenum or SCBN cells were analyzed by western blot. RESULTS: The duodenal calcium absorption in ovariectomized mice was significantly decreased, compared with control female mice, which returned to control level after 17ß-estradiol replacement treatment. Estrogen regulated the expressions of TRPV6 and PMCA1b in murine and human duodenal mucosae and SCBN cells. The further results from SCBN cells showed that 17ß-estradiol regulated calcium influx through the respective effects of estrogen receptor (ER) ɑ and ß on TRPV6 and PMCA1b. CONCLUSION: Estrogen regulates duodenal calcium absorption through differential role of ERɑ and ERß on duodenal epithelial cellular TRPV6 and PMCA1b. The study further elucidates the mechanism of estrogen on the regulation of intestinal calcium absorption.

The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma.

The intermediate conductance calcium-activated potassium channel (KCa3.1) plays an important role in maintaining intracellular calcium homeostasis and is involved in the tumorigenesis of many human cancers. However, it is unknown whether KCa3.1 plays a role in the genesis of hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide with a very poor prognosis. In our study, we found that the expression of KCa3.1 was significantly elevated in poorly differentiated HCC tissues compared to adjacent noncancerous tissues. In vitro and in vivo experiments showed that KCa3.1 could promote cell proliferation, migration, and invasion of HCC. Mechanistically, KCa3.1 promoted cell cycle progression and migration and invasion of HCC cells by activating S-phase protein kinase 2 (SKP2) to trigger the degradation of p21 and p27 and targeting Reelin (RELN) to induce epithelial-mesenchymal transition (EMT), respectively. Taken together, our results demonstrate that KCa3.1 plays an important role in the genesis and progression of HCC, implying that it might be a promising therapeutic target in HCC.