Association between gut microbiota and seven gastrointestinal diseases: A Mendelian randomized study.

BACKGROUND: Observational research has shed light on the ability of gut microbes to influence the onset and progression of gastrointestinal diseases. The causal relationships between specific gut microbiomes and various gastrointestinal conditions, however, remain unknown. METHODS: We investigated the relationship between gut microbiota and seven specific gastrointestinal disorders using a robust two-sample Mendelian randomization (MR) approach. The inverse variance-weighted (IVW) method was used as the primary analysis tool in our study. Furthermore, we conducted multiple sensitivity analyses to strengthen the robustness of our findings and ensure the reliability of the IVW method. RESULTS: Our research has discovered significant links between the composition of gut microbiota and a variety of gastrointestinal ailments. We found compelling links between 13 gut microbiota and fatty liver, four gut microbiota and cirrhosis, eight gut microbiota and hepatocellular carcinoma, four gut microbiota and cholelithiasis, 12 gut microbiota and acute pancreatitis, eight gut microbiota and chronic pancreatitis, and 11 gut microbiota and pancreatic cancer. These findings shed light on the intricate relationship between gut microbes and the emergence of these specific gastrointestinal conditions. CONCLUSIONS: The findings of this extensive study not only validate the potential role of specific gut microbiota in gastrointestinal diseases, but also fill a critical gap in previous research. The discovery of these specific gut microbiota is a significant step forward because they may serve as novel and promising biomarkers for both the prevention and treatment of gastrointestinal conditions.

Triple gallbladder: radiological review.

Triple gallbladder represents a rare congenital anatomical abnormality that can be a diagnostic challenge in reason to its rarity and consequential difficulties with diagnosis and identification. A systematic review of all published literature between 1958 and 2022 was performed. We identified 20 previous studies that provided 20 cases of triple gallbladder; our case was also included in the analysis, making a total of 21 patients. All patients underwent on diagnostic imaging examinations. After 1985, 9 patients underwent US examination which allowed prompt recognition of triple gallbladder in 2 patients only. CT was performed in 3 patients and allowed the correct diagnosis in a case. In 4 patients, was performed MRCP which allowed the correct diagnosis of triple gallbladder in all patients. Preoperative imaging allows the recognition of triple gallbladder in 9 of 21 patients (43%); in 12 patients (57%) the diagnosis was intraoperative. On patients considered, 16/21 underwent cholecystectomy. In 15 cases, the excised gallbladders were submitted for histopathological characterization with detection of metaplasia of the mucosa in 3 patients, while papillary adenocarcinoma was found in one. Imaging plays a key role in the identification of the anatomical variants of gallbladder, especially triple gallbladder, as modern imaging techniques allow a detailed assessment of the course of the biliary tract for a correct preoperative diagnosis. It is also crucial to be aware of the association between this condition and the metaplasia phenomena with the development of adenocarcinoma, as this may influence the patient's course of treatment.

Surgical treatment of postoperative intractable bile leakage after liver tumor surgery in children.

Aim: To summarize systematically our six-year experience in the surgical treatment of postoperative bile leakage after liver tumor surgery in children, and explore its reoperation approach and treatment effect. Methods: The clinical data of 6 patients with postoperative bile leakage cured by surgery from January 2016 to January 2022 were reviewed retrospectively. Results: Among the six pediatric patients with postoperative bile leakage cured by surgery, four were male (67%) and two were female (33%). All patients underwent complex segmentectomy. The median time to bile leakage was 14 days (range, 10 to 32), and the daily drainage volume was stable from 170 ml to 530 ml per day. After conservative treatment failed, four patients received biliary-enteric anastomosis (patients 1, 3, 4, and 6), and two patients received bilio-cholecyst anastomosis (patients 2 and 5). All six patients were successfully treated with reoperation, and five patients were alive and without recurrence, while one patient was lost to follow-up due to abandoned treatment. Conclusion: Our study suggests that surgery is a reliable and effective treatment for postoperative intractable bile leakage in children undergoing complex segmentectomy. Bilioenteric anastomosis is the most common technique for bile leakage, and bilio-cholecyst anastomosis is a feasible and effective surgical approach. These findings have important implications for the management of postoperative complications in pediatric patients undergoing complex segmentectomy.

An Overview of Ascariasis Involvement in Gallbladder Disease: A Systematic Review of Case Reports.

Ascaris lumbricoides is the most common type of helminth infection in humans. It affects more than one billion of the world's population. Children living in developing nations are prone to ascariasis, presenting with obstructive biliary illnesses. Migration of Ascaris worms through the major duodenal papilla to the hepatobiliary system leads to symptoms of biliary colic and complications along the biliary tree. In April 2022, we performed a systematic review of case reports to identify and examine cases of gallbladder ascariasis worldwide. A methodical search using PubMed, Semantic Scholar, ScienceDirect, and Directory of Open Access Journals yielded 2773 studies. After duplicate removal, title, abstract, and content screening, retrieval, and quality assessment, 13 studies met the criteria for this systematic review of case reports. The cases and results from these 13 studies revealed gallbladder ascariasis in different age groups worldwide. This systematic review discusses ascariasis, explicitly highlighting its presence in the gallbladder, symptomatic presentation, laboratory/imaging findings, complications, and approach to management.

Worldwide distribution, associated factors, and trends of gallbladder cancer: A global country-level analysis.

This study aimed to evaluate the global distribution, associated factors, and epidemiologic trends of gallbladder cancer (GBC) by country, sex, and age groups. The Global Cancer Observatory was interrogated for the disease burden of GBC using age-standardized rates (ASR). The prevalence of different potential risk factors for each country was extracted from Global Health Observatory and their associations with GBC incidence and mortality were examined by linear regression analysis using beta coefficients (ß). The Cancer Incidence in Five Continents I-XI and the WHO Mortality database were searched and Average Annual Percent Change (AAPC) was generated from joinpoint regression analysis. The incidence (ASR = 2.3) and mortality (ASR = 1.7) of GBC varied globally in 2018 and were higher in more developed countries and among females. Countries with higher incidence had higher human development index (ßmale = 0.37; ßfemale = 0.27), gross domestic products (ßmale = 0.13) and higher prevalence of current smoking (ßfemale = 0.05), overweight (ßmale = 0.02), obesity (ßmale = 0.03), and hypercholesterolaemia (ßmale = 0.07). Similar patterns of associations were also observed for mortality with an additional association found for diabetes (ßfemale = 0.07). Although there was an overall decreasing trend in mortality, an increasing trend in incidence was observed among some populations, particularly in males (AAPCs, 8.97 to 1.92) and in younger individuals aged <50 years (AAPCs, 12.02 to 5.66). The incidence of GBC varied between countries and was related to differences in the prevalence of potential risk factors. There was an increasing incidence trend among males and younger individuals. More intensive lifestyle modifications and disease surveillance are recommended for these populations.

Cholecyst-jejunostomy for palliative surgery.

INTRODUCTION AND IMPORTANCE: Many cases of unresectable cancer that cause obstructive jaundice require treatment. Depending on the patient's condition in these cases, surgery may be performed to treat jaundice. The main goal of palliative surgery is to improve the quality of life. Therefore, palliative surgery for obstructive jaundice must be performed safely and quickly. CASE PRESENTATION: This case presents a 45-year-old man with fever and back pain who was diagnosed with pancreatic head cancer and multiple liver metastases. Chemotherapy was initiated; however, during the course of treatment, the patient developed hemorrhage from pancreatic cancer that had invaded the duodenum caused hematemesis and melena. Therefore, the chemotherapy could not be continued. Because the patient also developed obstructive jaundice and cholangitis, a gastrojejunostomy and cholecyst-jejunostomy was performed. The surgery was successful; however, the cancer continued to progress, and patient died 31 days after surgery. CLINICAL DISCUSSION: Biliary reconstruction can be difficult to perform safely and quickly due to many factors. This study shows that cholecyst-jejunostomy is effective for patients with end-stage cancer. In the long term, cholecyst-jejunostomy is not suitable for biliary reconstruction due to the possibility of bile congestion and cholecystitis. However, this easy and quick procedure is well indicated for emergency patients with a short life expectancy. CONCLUSION: As an easy and quick procedure for emergency patients with a short life expectancy, jejunal anastomosis of the gallbladder is an appropriate palliative surgery that is indicated for jaundice treatment.

Study on Network Pharmacology of the Mechanism of Lysimachia christinae in the Treatment of Cholecyst Related Disease / 中国药房

OBJECTIVE： To explore the mechanism of Lysimachia christinae in the treatment of cholecyst related diseases by network pharmacology. METHODS： The active ingredients of L. christinae were screened through TCMSP database with “Lipinski rule” and “Oral bioavailability ＞30％” rules， and their related targets were predicated correspondingly， then compound-target network were constructed by Cytoscape 3.2.1 software. Disease related targets were predicted by searching TTD database， OMIM database， PharmGKB database， DrugBank database and GAD database with “cholelithiasis” “gallstones” “cholecystitis” and “cholangitis” as keywords. Then， the network of disease-target was constructed and merged with active ingredient target to obtain therapeutic target. After pathway enrichment analysis of therapeutic target were performed by utilizing the DAVID database， molecular docking between target and active ingredient was also conducted in order to screen the main active ingredients of L. christinae. RESULTS： Twenty-seven active ingredients with good oral absorption and drug-like properties were screened from L. christinae. Thirty-three targets were attained after constructing and merging the network. Seven pathways， mainly related to cancer pathway and ABC transporter pathway were achieved. Top 4 active ingredients of L. christinae in the list of docking score were kaempferin， acacia， hesperetin and isorhamnetin， which acted on ABCC3， ABCB1， ABCC2， ABCB4 target. CONCLUSIONS： L. christinae treat cholecyst related diseases through ABC transporter pathway.

Effects of a Gluten-Containing Meal on Gastric Emptying and Gallbladder Contraction.

The ingestion of gluten has been associated with gastrointestinal symptoms even in the absence of detectable immune responses. Little is known about the pathophysiological effects of gluten on the upper gastrointestinal tract. We aimed to assess whether the ingestion of gluten leads to an impairment of the physiological mechanisms of gastric emptying, gallbladder contraction and relaxation. A total of 17 healthy subjects underwent ultrasound evaluation of gastric emptying dynamics and gallbladder contractions at baseline and every 30 min after a standard gluten-containing and gluten-free meal (250 kcal, 70% carbohydrates). The pattern of gastric emptying was similar after a standard meal with or without gluten, but differed in terms of the peak of the antral filling curve, which was wider (mean area 5.69, median 4.70, range 3.71‒9.27 cm² vs. mean 4.89, median 4.57, 2.27‒10.22 cm², p = 0.023) after the gluten-containing meal. The pattern of gallbladder contractions was different after the gluten-free meal (p < 0.05), with higher gallbladder volumes in the late refilling phases. The results of this study show that gluten ingestion exerts objective effects on gastric and gallbladder motility. Although the underlying pathophysiological mechanism remains unknown, these results could account for some of the gluten-related symptoms reported by patients with celiac disease and non-celiac gluten sensitivity.

Cross-Linked Cholecyst-Derived Extracellular Matrix for Abdominal Wall Repair.

Abdominal wall repair frequently utilizes either nondegradable or biodegradable meshes, which are found to stimulate undesirable biological tissue responses or which possess suboptimal degradation rate. In this study, a biologic mesh prototype made from carbodiimide cross-linked cholecyst-derived extracellular matrix (EDCxCEM) was compared with small intestinal submucosa (Surgisis®), cross-linked bovine pericardium (Peri-Guard®), and polypropylene (Prolene®) meshes in an in vivo rabbit model. The macroscopic appearance and stereological parameters of the meshes were evaluated. Tailoring the degradation of the EDCxCEM mesh prevents untimely degradation, while allowing cellular infiltration and mesh remodeling to take place in a slower but predictable manner. The results suggest that the cross-linked biodegradable cholecyst-derived biologic mesh results in no seroma formation, low adhesion, and moderate stretching of the mesh. In contrast to Surgisis, Peri-Guard, and Prolene meshes, the EDCxCEM mesh showed a statistically significant increase in the volume fraction (Vv) of collagen (from 34% to 52.1%) in the central fibrous tissue region at both day 28 and 56. The statistically high length density (Lv), of blood vessels for the EDCxCEM mesh at 28 days was reflected also by the higher cellular activity (high Vv of fibroblast and moderate Vv of nuclei) indicating remodeling of this region in the vicinity of a slowly degrading EDCxCEM mesh. The lack of mesh area stretching/shrinkage in the EDCxCEM mesh showed that the remodeled tissue was adequate to prevent hernia formation. The stereo-histological assays suggest that the EDCxCEM delayed degradation profile supports host wound healing processes including collagen formation, cellular infiltration, and angiogenesis. The use of cross-linked CEM for abdominal wall repair is promising.

Comparative profiling of extractable proteins in extracellular matrices of porcine cholecyst and jejunum intended for preparation of tissue engineering scaffolds.

Scaffolds prepared from cholecyst and jejunum have differential immunological potential, despite similar biocompatibility, when used as subcutaneous grafts. The reason for differential immunogenicity is probably due to differences in the nature of protein composition and biomolecules in the extracellular matrices (ECMs) of source organs that are used for preparation of the scaffolds. Against this background, the present study aims to identify the extractable proteins of ECMs derived from porcine cholecyst and jejunum. The proteins were extracted and identified through a conventional database search following sodium dodecyl sulfate-polyacrylamide gel-electrophoresis separation and mass spectroscopy. The resultant protein profile was analyzed and at least 154 proteins in cholecyst-derived extracellular matrix (CDE) and 186 proteins in jejunum-derived extracellular matrix (JDE) were identified. Both the matrices contained several extracelluar proteins including fibronectin, nidogen, decorin, and lumican that are known to participate in wound healing responses. However, the CDE had fewer cellular proteins than JDE, especially the latter contained class-I and class-II histocompatibility antigens which are incriminated as potent immunogens responsible for graft rejection. The results of the study suggested that the ECMs used for the scaffold preparation need not be "acellular" and differences in the protein composition of the ECMs might have caused the differential wound healing responses. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 489-496, 2017.

Gallbladder agenesis and atrial septal defect: A case report.

Congenital absence of gallbladder and atrial septal defect (ASD) are clinically rare congenital organ malformations, and the simultaneous occurrence of the two is even more rare. The present study reported a case of gallbladder agenesis combined with congenital ASD. A 38-year-old male patient presented with a 3-year history of recurring upper right abdominal pain. The pain had no evident cause and was accompanied by dyspepsia and gasteremphraxis with indigestion. Several color Doppler ultrasonography scans revealed cholecystitis and gallbladder stones. A physical examination revealed cardiac murmur. A color Doppler ultrasonography of the heart was indicative of congenital heart disease. A corrective surgery for ASD was performed. Subsequently, a mini-incision cholecystectomy was performed as explorative surgery. A magnetic resonance cholangiopancreatography scan of the abdomen was performed in order to confirm the diagnosis of gallbladder disorder and cystic duct hypoplasia. A final definite diagnosis of gallbladder agenesis was confirmed. In conclusion, atrophy and gallbladder full of stones are frequently misdiagnosed, and establishing a definitive preoperative diagnosis is difficult. Awareness of this congenital malformation may assist physicians in distinguishing cases with unclear manifestation and avoiding unnecessary surgical interventions.

Fibroblast-loaded cholecyst-derived scaffold induces faster healing of full thickness burn wound in rabbit.

Graft-assisted healing is often proposed for clinical management of large-sized third-degree cutaneous burn wounds. Skin-graft substitutes prepared by loading appropriate cell types on suitable scaffolds have been found successful. We have previously shown that cholecyst-derived scaffold prepared by a non-detergent/enzymatic method can be used as skin-graft substitute for promoting healing of full thickness excision wounds in rabbit. This article examines the use of this scaffold for preparing bio-artificial grafts by loading homologous fibroblasts. The healing potential was evaluated in a rabbit model of full thickness skin-burn wound. The healing process was evaluated by gross morphology evaluation and histomorphology evaluation at 7, 14 and 28 days of healing. Ex vivo imaging of the wounded tissue was performed and it was found that the loaded fibroblasts remained viable at least for 14 days in the healing wound. By the first week, re-epithelialisation was evident in all animals treated with the cell-loaded graft. Histomorphological wound healing parameters such as the quickness of re-epithelialisation, the nature of collagen deposition and the extent of neo-vascularisation indicated that cell-loaded grafts promoted faster healing of the wounds. Results of immunohistochemistry indicated a parallel change in the number of proliferating cells and myofibroblast in the healing tissue. Although the pathophysiology of the healing reaction was not established, the observations suggested that homologus fibroblast-loaded cholecyst-derived scaffold promoted faster healing of third-degree wounds in rabbit model by modulating myofibroblast response. It was concluded that cholecyst-derived scaffold prepared by the non-detergent/enzymatic method is a potential scaffold for fabricating bioartificial skin grafts.

Biocompatibility and Immunophenotypic Characterization of a Porcine Cholecyst-derived Scaffold Implanted in Rats.

Comparative histomorphological assessment of local response to implanted reference biomaterial, also called biocompatibility testing/evaluation, in an appropriate animal model is a widely practiced safety evaluation procedure performed on biomaterials before clinical use. Standardized protocols and procedures, originally designed for testing synthetic materials, available for the testing/evaluation do not account for the immunogenic potential of a candidate biomaterial. Therefore, it is appropriate to supplement the routine biocompatibility test reports with adjunct data that may provide insight into the immunogenic potential of candidate biomaterials, especially when testing biomaterials that are derived from mammalian sources. This article presents expanded safety evaluation data of a porcine cholecyst-derived scaffold (CDS) intended as a xenogeneic graft. The biocompatibility was tested in rat subcutaneous model in comparison with a reference material and the CDS was found biocompatible. However, when studied by immunohistochemistry and real-time reverse transcription polymerase chain reaction for the number and/or polarization of M1 macrophage, M2 macrophage, cytotoxic T-cell, helper T cell, TH1 cell, and TH2 cell, the CDS appeared to induce a differential local immunopathological tissue reaction despite the similarity in biocompatibility with the reference material. The adjunct data collected were useful for objectively assessing the safety of CDS as a xenograft.

Comparative local immunogenic potential of scaffolds prepared from porcine cholecyst, jejunum, and urinary bladder in rat subcutaneous model.

Extracellular matrices isolated from several mammalian organs/tissues have found several clinical uses as xenografts or implants. However, they may cause complications because of adverse immunologic reactions. Scaffolds that promote favorable graft-acceptance reaction are preferred for fabricating xenografts. The objective of this study was to evaluate the immunogenic potential of a porcine cholecyst-derived scaffold (CDS), prepared by a non-detergent/enzymatic method, in comparison with jejunum and urinary bladder-derived scaffolds in a rat subcutaneous model. Key graft-rejection/acceptance reaction was evaluated at the site of implantation by studying the occurrence and/or function of immunocompetent cells in the tissue reaction. There was differential occurrence of M1-macrophage, M2-macrophage, T-helper cells, T-cytotoxic cells, B-cells, and mast cells in the tissue reaction and the CDS attracted few cells compared with other scaffolds. Real-time polymerase chain reaction for evaluating mRNA of functional markers like inducible nitric oxide synthase (M1 macrophage), arginase 1 (M2 macrophage), interferon gamma (TH1 lymphocytes), and interlukin-4 (TH2 lymphocytes) suggested that the CDS, compared with the scaffolds prepared from small intestine and urinary bladder, elicited M2 macrophage and TH2 lymphocyte polarization that are congenial graft-acceptance reactions. The results indicated that CDS has less immunogenic potential compared with the scaffolds prepared from jejunum and urinary bladder when used as subcutaneous graft in rats. It was concluded that CDS is a promising animal-derived xenograft for biomedical application.

Biomaterial properties of cholecyst-derived scaffold recovered by a non-detergent/enzymatic method.

Isolation procedures for the recovery of extracellular matrices (ECMs) from animal organs/tissues that are useful in regenerative medicine involve multiple sequential steps/stages including collection of the source organ at slaughter, their transportation to laboratory, decellularization, decontamination, stabilization, and sterilization. Most of these steps require extensive use of chemicals/reagents/enzymes which may also adversely affect the quality of the scaffold. With an effort to minimize the use of chemicals/reagents/enzymes, while extracting biomaterial-grade ECM from porcine cholecyst (gall bladder), we performed preisolation ex situ incubation of the organ in a stabilizing agent that also caused in situ crosslinking of tissue-components and delaminated the collagen-rich ECM from the tissue-layer beneath the mucosa. The physical, chemical, and biological properties of the isolated scaffolds were similar to that of a commercially available porcine small intestinal submucosa. The cholecyst-derived scaffold not only satisfied preclinical safety-test procedures such as cytotoxicity, local response, and endotoxin load but also showed the potential to promote healing of full-thickness skin wound in a rabbit model. The procedure was also suitable for isolating scaffolds from other hollow organs such as jejunum and urinary bladder. It was concluded that enzyme/detergent treatment may be an avoidable step while isolating biomaterial-grade scaffolds from hollow organs.

Efficacy of crosslinking on tailoring in vivo biodegradability of fibro-porous decellularized extracellular matrix and restoration of native tissue structure: a quantitative study using stereology methods.

Cholecyst-derived extracellular matrix (CEM) is a fibro-porous decellularized serosal layer of porcine gall-bladder. CEM loses 90% of its weight at 48 h of in vitro collagenase digestion, but takes two months to be completely resorbed in vivo. Carbodiimide (EDC) crosslinking helps tailoring CEM's in vitro collagenase susceptibility. Here, the efficacy of EDC crosslinking on tailoring in vivo biodegradability of CEM is reported. CEM crosslinked with 0.0005 and 0.0033 × 10(3) M of EDC/mg that lose 80% and 0% of their weight respectively to in vitro collagenase digestion, were present even after 180 days in vivo. Quantitative histopathology using stereology methods confirmed our qualitative observation that even a tiny degree of crosslinking can significantly prolong the rate of in vivo degradation and removal of CEM.

Porcine cholecyst-derived scaffold promotes full-thickness wound healing in rabbit.

Graft-assisted healing is an important strategy for treating full-thickness skin wounds. This study evaluated the properties of porcine cholecyst-derived scaffold and its use for treating full-thickness skin wound in rabbit. The physical properties of cholecyst-derived scaffold were congenial for skin-graft application. Compared to a commercially available skin-graft substitute made of porcine small intestinal submucosa, the cholecyst-derived scaffold was rich in natural biomolecules like elastin and glycosaminoglycans. When used as a xenograft, it promoted healing with excess cell proliferation at early phases and acceptable collagen deposition in the later remodelling phases.

Analyze the cause of recurrence of cholecystectomy / 中国综合临床

Objective To analyze the cause of the syndrome recurrences of postcholecystectomy.Methods Clinical data of 98 patients with syndrome recurrences of postcholecystectomy were retrospectively reviewed.Results Among 98 cases,95 cases were found with organic lesions.The recurrences included residual or recurrent calculi in extra or intrahepatic bile ducts,stricture of common bile duct,cystic duct remnant,chronic pancreatitis,cholangioduodenal fistula,cancer of biliary ducts,periampullary cancer.Conclusion MRCP and B ultra sound should be conducted before operations to localize the lesion sites.Detailed detection or cholangiography during operation may avoid the injury and incomplete surgery and reduce the recurrence.

Discussion on risk guard in dissection of cholecyst from its bed during laparoscopic cholecystectomy / 中国基层医药

Objective To discuss risk factor and operation guard in dissection of cholecyat from its bed during laparoseopic cholecystectomy.Methods The clinical data of 490 cases of laparoscopic cholecystectomy dissect cholecyst from its bed by traditional method during were retrospectively analyzed and simultaneously perspective study on 500 cases of improved laparoscopic cholecyatectomy dissecting cholecyst from its bed.Results There are 3 cases in hemorrhea due to injuring bed brancha of arteria cystica posterior branch,2 cases in bed brancha of arteria cystica posterior branch haemorrhage,5 cases in postoperative bile leak,2 cases in variant right hepatic portal vein injury,1 case in variant right hepatic duct in the 490 cases of laparoscopic choleeystectomy by traditiorhI method.Using our new technique exposed,and then ligated 39.6%(198/500)bed brancha of arteria cystica posterior branch,11.2% (56/500)bed brancha of venae hepaticae intermediate almost in fight side of cholecyst bed,2.2%(11/500)dilated aberrant bile-duct duct.We separated and then protected 0.6%(3/500)unusual right hepatic duct being exposed,0.4%(2/500)right liver branch of portsl vein.Conclusion There are some larvate risk in isolation of choleeyst from its bed during laparoseopic cholecystectomy.Unexpected injury happen during LC,and it ought tO be open cholecysteetomy The improved method provides a safe,efficiency operative procedure.