Relationship between entero-hepatic bile acid circulation and interdigestive migrating myoelectrical activity in rats

AIM： To investigate the effects of entero-hepatic bile add circulation on the inter-digestive migrating myoelectrical complex （MMC） in rats. METHODS： Thirty-two rats were divided into four groups. Three pairs of bipolar silver electrodes were chronically implanted in the antrum, duodenum and jejunum. Three groups of Uhem were ligatecl around the upper part of common bile duct （CBD）. The experiments were performed in consdous and fasting state. The gastrointestinal myoelectrical activity was recorded. Ursodeoxycholic acid （UDCA） and saline were then perfused into stomachs of two groups with CBD obstruction and the effects of them on the MMC were observed. RESULTS： A typical pattern of MMC was observed in normal fasting rats. MMC of antral and duodenal origin disappeared temporarily in earlier stage of CBD obstruction. While MMC of jejunum origin appeared. increased MMC cycle duration was seen after 4 d in rats with CBD obstruction. The MMC after CBD obstruction was characterized by an increased duration of phase Ⅱ-like activity and decreased duration of phase Ⅰ ＆ Ⅲ activity. Perfusion into stomachs with UDCA resulted in a shorter MMC cycle duration and a longer duration of phase III of duodenal origin compared to the normal group. CONCLUSION： Entero-hepatic bile add drculation initiates inter-digestive MMC of duodenal origin.

Clostridium difficile infection following colon subtotal resection in a patient with gallstones: A case report and review of literature

BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no standardized clinical treatment.CASE SUMMARY A patient experienced recurrent difficulty in bowel movements over the past decade.Recently,symptoms worsened within the last ten days,leading to a clinic visit due to constipation.The patient was subsequently referred to our depart-ment.Preoperatively,the patient was diagnosed with obstructed colon accom-panied by gallstones.Empirical antibiotics were administered both before and after surgery to prevent infection.On the fourth day post-surgery,symptoms of CDI emerged.Stool cultures confirmed the presence of C.difficile DNA.Treatment involved a combination of vancomycin and linezolid,resulting in the patient's successful recovery upon discharge.However,the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.CONCLUSION CDI is the leading cause of nosocomial post-operative care,with limited clinical cases and poor patient prognosis,and comprehensive clinical treatment guidelines are still lacking.This infection can be triggered by a variety of factors,including intestinal hypoxia,inappropriate antibiotic use,and bile acid circulation disorders.In patients with chronic bowel disease and related etiologies,prompt preoperative attention to possible CDI and preoperative bowel preparation is critical.Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.

Liquid biopsies for liquid tumors: emerging potential of circulating free nucleic acid evaluation for the management of hematologic malignancies

Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment.

Changes of gastrointestinal myoelectric activity and bile acid pool size after cholecystectomy in guinea pigs

AIM: To investigate the bile acid pool size after cholecystectomy whether or not correlated to the gastrointestinal migrating myoeiectric complex (MMC) in guinea pigs. METHODS: Gallbladder motilities were assessed before cholecystectomy. Furthermore, we continuously monitored interdigestive gastrointestinal motilities using bipolar electrodes in conscious guinea pigs before and after surgery at 4 wk in standard diet group and high cholesterol diet (cholesterol gallstone) group. Total bile acid pool sizes were measured by isotope dilution method at meantime. RESULTS: After cholecystectomy, there were parallel falls in duration of phase Ⅰ, Ⅱ, Ⅲ and MMC cycle duration but increase in amplitude in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones. However, There were not significantly differences. On the other hand, the bile acid pool was definitely small in the GS guinea pigs compared to normal guinea pigs and became slightly smaller after cholecystectomy. Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased in GS guinea pigs after cholecystectomy, to the same degree as normal. These differences, however, were not significant. CONCLUSION: It is concluded that in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile acids, rather than surgery, which is consistent with changes of the bile acid pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence of postchole cystectomy syndrome.

Circulating cell-free nucleic acids as prognostic and therapy predictive tools for metastatic castrate-resistant prostate cancer

Metastatic castrate-resistant prostate cancer remains a disease hard to cure,and for this reason predictive tools to monitor disease progression and therapy response are an urgent need.In this respect,liquid biopsy on circulating cell-free nucleic acids represents an interesting strategy based on robust data.The low invasiveness and the possibility to target circulating cell-free tumor deoxyribonucleic acid underline the high specificity,sensitivity and clinical usability of the technique.Moreover,it has been observed that the cell-free tumor deoxyribonucleic acid of metastatic castrate-resistant prostate cancer patients can be representative of the tumor heterogeneity.Cell-free tumor deoxyribonucleic acids express the same behaviors as mutations:Variation in gene copy number or the methylation rate of the tumor tissue.Recently,circulating cell-free ribonucleic acid molecules have emerged as interesting markers to stratify the disease.Due to high-throughput technologies,liquid biopsy on circulating cell-free nucleic acids will soon be utilized in the clinical management of metastatic castrate-resistant prostate cancer patients.

Further the liquid biopsy:Gathering pieces of the puzzle of genometastasis theory

Metastasis is the major cause of mortality in cancer disease and still constitutes one of the most controversial mechanism,not yet fully understood.What is almost beyond doubt is that circulatory system is crucial for cancer propagation.Regarding this system,much attention has been recently paid to liquid biopsy.This technique is aimed to detect circulating tumor cells (CTCs) and circulating nucleic acids so it can be used as a tool for diagnostic,prognostic and follow-up of patients.Whereas CTCs tend to be scarce in serum and plasma from cancer patient,abundant circulating nucleic acids can be detected in the same location.This fact,together with the genetic origin of cancer,stands out the relevance of circulating nucleic acids and shed light into the role of nucleic acids as drivers of metastasis,a recently discovered phenomenon called Genometastasis.This innovative theory supports the transfer of oncogenes from cancer cells to normal and susceptible cells located in distant target organs through circulatory system.What is more,many biological processes haven been described to deliver and secrete circulating nucleic acids into the circulation which can allow such horizontal transfer of oncogenes.In this review,we focus not only on these mechanisms but also we demonstrate its putative role in cancer propagation and give insights about possible therapeutic strategies based on this theory.Our objective is to demonstrate how findings about cell-to-cell communications and previous results can agree with this unprecedented theory.

Novel approaches in search for biomarkers of cholangiocarcinoma

Cholangiocarcinoma(CCA)arises from the ductular epithelium of the biliary tree,either within the liver(intrahepatic CCA)or more commonly from the extrahepatic bile ducts(extrahepatic CCA).This disease has a poor prognosis and a growing worldwide prevalence.The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging,especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA,or distal CCA and pancreatic head adenocarcinoma.Most patients present with an advanced disease,unresectable disease,and there is a lack in non-surgical therapeutic modalities.Not least,there is an acute lack of prognostic biomarkers which further complicates disease management.Therefore,there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result,either singlehandedly or combined with other methods.In the"-omics"era,this goal can be attained by various means,as it has been successfully demonstrated in other primary tumors.Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins,metabolites,extracellular vesicles,and ultimately circulating tumor cells.However,given the relatively heterogeneous data,extracting clinical meaning from the inconsequential noise might become a tall task.The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.

Changes of gastrointestinal myoelectric activity and bile acid pool during cholesterol gallstone formation in guinea pig

It has been known that enterohepatic circulation of bile acids is essential for regular cycling of migrating motor complex （MMC）. An important component of the enterohepatic circulation is the active reabsorption of conjugated bile acids in the terminal ileum, with special reference to bile acid pool size that may be defined as the total mass of bile acids in the enterohepatic circulation. However, because of technical difficulties in measuring of bile acid pool size in human being, the role of the bile acid pool has little been investigated, and the exact mechanism of change in bile acid pool size has not yet been clear. Therefore, were there two changes of small intestinal motility and bile acid pool size in cholesterol gallstone patients？ and, if so, was there correlated relationship between both alterations require further investigation？

Circulating microRNAs as a liquid biopsy: a next generation clinical biomarker for diagnosis of gastric cancer

Accumulating evidence has suggested the potential clinical utility of novel body fluid biomarkers,or“liquid biopsy”,using circulating tumor cells and cell-free nucleic acids from cancer patients.Noninvasive and reproducible,liquid biopsy could provide the basis for individualized therapeutic strategies by identifying genetic and epigenetic aberrations that are closely associated with cancer initiation and progression.MicroRNAs(miRNAs)are short noncoding RNAs that post-transcriptionally regulate gene expression.They also play important roles in various physiological and developmental processes as oncogenic or tumor-suppressive regulators.Specific miRNA expression signatures have been identified in a number of human cancers.Circulating miRNAs have been detected in plasma and serum,and this in blood has attracted the attention of researchers for their potential as noninvasive biomarkers.Circulating miRNAs have emerged as tumor-associated biomarkers that reflect not only the existence of cancer,but also the dynamics,malignant potential,and drug resistance of tumors.Herein,we review the recent biological and clinical research on the circulating miRNAs of gastric cancer and discuss future perspectives for their clinical applications as a liquid biopsy.