Comparison of the therapeutic effects of three minimally invasive approaches for laparoscopic cholecystectomy combined with common bile duct exploration-- a 5-year retrospective analysis.

OBJECTIVE: The aim of this retrospective study was to explore the indications for three minimally invasive approaches-T-tube external drainage, double J-tube internal drainage, and primary closure-in laparoscopic cholecystectomy combined with common bile duct exploration. METHODS: Three hundred eighty-nine patients with common bile duct stones who were treated at the Second People's Hospital of Hefei between February 2018 and January 2023 were retrospectively included. Patients were divided into three groups based on the surgical approach used: the T-tube drainage group, the double J-tube internal drainage group, and the primary closure group. General data, including sex, age, and BMI, were compared among the three groups preoperatively. Surgical time, length of hospital stay, pain scores, and other aspects were compared among the three groups. Differences in liver function, inflammatory factors, and postoperative complications were also compared among the three groups. RESULTS: There were no significant differences among the three groups in terms of sex, age, BMI, or other general data preoperatively (P > 0.05). There were significant differences between the primary closure group and the T-tube drainage group in terms of surgical time and pain scores (P < 0.05). The primary closure group and double J-tube drainage group differed from the T-tube drainage group in terms of length of hospital stay, hospitalization expenses, and time to passage of gas (P <0.05). Among the three groups, there were no statistically significant differences in inflammatory factors or liver function, TBIL, AST, ALP, ALT, GGT, CRP, or IL-6, before surgery or on the third day after surgery (P > 0.05). However, on the third day after surgery, liver function in all three groups was significantly lower than that before surgery (P<0.05). In all three groups, the levels of CRP and IL-6 were significantly lower than their preoperative levels. The primary closure group had significantly lower CRP and IL-6 levels than did the T-tube drainage group (P < 0.05). The primary closure group differed from the T-tube drainage group in terms of the incidences of bile leakage and electrolyte imbalance (P < 0.05). The double J-tube drainage group differed from the T-tube drainage group in terms of the tube dislodgement rate (P < 0.05). CONCLUSION: Although primary closure of the bile ducts has clear advantages in terms of length of hospital stay and hospitalization expenses, it is associated with a higher incidence of postoperative complications, particularly bile leakage. T-tube drainage and double J-tube internal drainage also have their own advantages. The specific surgical approach should be selected based on the preoperative assessment, indications, and other factors to reduce the occurrence of postoperative complications.

A rare case of OHVIRA (obstructed hemivagina and ipsilateral renal anomaly) syndrome: Case report.

Obstructed hemivagina and ipsilateral renal anomaly syndrome (OHVIRA) also known as Herlyn-Werner-Wunderlich syndrome is a rare type of Müllerian duct anomaly with concomitant mesonephric duct anomalies. It is characterized by uterus didelphys, obstructed hemi-vagina, and commonly renal agenesis however; other types of mesonephric duct anomalies such as duplicated kidneys, dysplastic kidneys, rectovesical bands, or crossed fused ectopia have also been reported. We present a case report of a 21-year-old female patient experiencing new-onset vaginal bleeding and pelvic pain over the past month. Subsequent multi-sequence MRI revealed characteristic features indicative of OHVIRA syndrome. Clinical manifestations typically encompass pelvic pain and menstrual abnormalities but mainly depend upon the presence of communication between the hemi-uterus. This article aims to discuss the clinical presentation, types, and diagnostic utility of ultrasound and MRI in OHVIRA syndrome. Additionally, we discuss the possible management plans.

Clinical efficacy of laparoscopic cholecystectomy combined with endoscopic papillary balloon dilation in treatment of gallbladder stones with common bile duct stones: A retrospective study.

BACKGROUND: The incidence of cholelithiasis has been on the rise in recent years, but the choice of procedure is controversial. AIM: To investigate the efficacy of laparoscopic cholecystectomy (LC) combined with endoscopic papillary balloon dilation (EPBD) in patients with gallbladder stones (GS) with common bile duct stones (CBDS). METHODS: The clinical data of 102 patients with GS combined with CBDS were selected for retrospective analysis and divided into either an LC + EPBD group (n = 50) or an LC + endoscopic sphincterotomy (EST) group (n = 52) according to surgical methods. Surgery-related indexes, postoperative recovery, postoperative complications, and expression levels of inflammatory response indexes were compared between the two groups. RESULTS: Total surgical time, stone free rate, rate of conversion to laparotomy, and successful stone extraction rate did not differ significantly between the LC + EPBD group and LC + EST group. Intraoperative hemorrhage, time to ambulation, and length of hospitalization in the LC + EPBD group were lower than those of the LC + EST group (P < 0.05). The rate of total complications of the two groups was 9.80% and 17.65%, respectively, and the difference was not statistically significant. No serious complications occurred in either group. At 48 h postoperatively, the expression levels of interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein, and procalcitonin were lower in the LC + EPBD group than in the LC + EST group (P < 0.05). At 3 d postoperatively, the expression levels of aspartate transaminase, alanine transaminase, and total bilirubin were lower in the LC + EPBD group than in the LC + EST group (P < 0.05). CONCLUSION: LC combined with EPBD and LC combined with EST are both effective procedures for the treatment of GS with CBDS, in which LC combined with EPBD is beneficial to shorten the patient's hospitalization time, reduce the magnitude of elevated inflammatory response indexes, and promote postoperative recovery.

Duct ligation/de-ligation model: exploring mechanisms for salivary gland injury and regeneration.

Sialadenitis and sialadenitis-induced sialopathy are typically caused by obstruction of the salivary gland ducts. Atrophy of the salivary glands in experimental animals caused by duct ligation exhibits a histopathology similar to that of salivary gland sialadenitis. Therefore, a variety of duct ligation/de-ligation models have been commonly employed to study salivary gland injury and regeneration. Duct ligation is mainly characterised by apoptosis and activation of different signaling pathways in parenchymal cells, which eventually leads to gland atrophy and progressive dysfunction. By contrast, duct de-ligation can initiate the recovery of gland structure and function by regenerating the secretory tissue. This review summarizes the animal duct ligation/de-ligation models that have been used for the examination of pathological fundamentals in salivary disorders, in order to unravel the pathological changes and underlying mechanisms involved in salivary gland injury and regeneration. These experimental models have contributed to developing effective and curative strategies for gland dysfunction and providing plausible solutions for overcoming salivary disorders.

Retrograde Transvenous Thoracic Duct Embolization for Tubercular Chylothorax.

This case study documents the clinical profile of a 27-year-old male patient who visited the medical facility two months ago with complaints of dry cough, fatigue, weight loss, and occasional fever. He had been treated for ascites and pleural effusion in the hospital before presentation and returned with an intercostal drain in place. A detailed examination revealed symptoms of respiratory disorders, including fluid in both lungs, fever, and dyspnea. His fluid levels showed multiple deviations from the normal range, according to the report's findings and lab test results. It was determined that the patient had chylothorax, which resulted from hemophagocytic lymphohistiocytosis (HLH) and abdominal tubercular lymphadenopathy. His anti-tubercular treatment (AKT4) was initiated, along with octreotide for his management. Initial management included non-invasive ventilator (NIV) support, intravenous antibiotics, nebulization, and an intercostal chest drain (ICD). Later, the patient underwent retrograde transvenous thoracic duct embolization (TDE) using N-butyl cyanoacrylate (NBCA) glue. The removal of the drainage tube and the patient's stable discharge were made possible through regular monitoring and collaboration between specialists.

Integrated proteomic and metabolomic profiling of lymph after trauma-induced hypercoagulopathy and antithrombotic therapy.

BACKGROUND: Routine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of the interstitial fluid into the lymphatic system and form lymph. SUBJECTIVE: The purpose of this study was to identify the potential lymph biomarkers for TIH. METHODS: Eighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics. RESULTS: A total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group. CONCLUSIONS: This study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.

Biomechanical properties of the capsule and extracellular matrix play a major role during the Wolffian/epididymal duct development.

BACKGROUND: The epididymis is important for sperm maturation and without its proper development, male infertility will result. Biomechanical properties of tissues/organs play key roles during their morphogenesis, including the Wolffian duct. It is hypothesized that structural/bulk stiffness of the capsule and mesenchyme/extracellular matrix that surround the duct is a major biomechanical property that regulates Wolffian duct morphogenesis. These data will provide key information as to the mechanisms that regulate the development of this important organ. OBJECTIVES: To measure the structural/bulk stiffness in Pascals (force/area) of the capsule and the capsule and mesenchyme together that surrounds the Wolffian duct during the development. To examine the relative membrane tension of mesenchymal cells during the Wolffian duct development. Since Ptk7 was previously shown to regulate ECM integrity and Wolffian duct elongation and coiling, the hypothesis that Ptk7 regulates structural/bulk stiffness and mesenchymal cell membrane tension was tested. MATERIALS AND METHODS: Atomic force microscopy and a microsquisher compression apparatus were used to measure the structural stiffness. Biomechanical properties within the membranes of cells within the capsule and mesenchyme were examined using a membrane-tension fluorescent probe. RESULTS AND DISCUSSION: The structural stiffness (Pascals) of the capsule and underlying mesenchyme was relatively constant during development, with a significant increase in the capsule at the later stages. However, this increase may reflect the ECM and associated mesenchyme being close to the capsule because the coiling of the duct pushed or compressed them into that space. Keeping the capsule and mesenchyme/ECM at constant stiffness would ensure that the duct will continue to coil under similar biomechanical forces throughout the development. Cells within the capsule and mesenchyme at different Wolffian duct regions during the development had varying degrees of membrane lipid tension. It is hypothesized that the dynamic changes ensure the duct is kept at a constant stiffness regardless of any external forces. Loss of Ptk7 resulted in an increase in stiffness at E18.5, which was presumable due to the loss of integrity of the ECM within the mesenchyme. CONCLUSION: Biomechanical properties of the capsule and the mesenchyme/extracellular matrix that surround the Wolffian duct play an important role toward Wolffian duct morphogenesis, thereby allowing for the proper development of the epididymis and subsequent male fertility.

True uterus didelphys in she-camel: a case report and review of literature.

Background: Uterus didelphys is a rare congenital anomaly of the female reproductive tract characterized by a divided uterine cervix and body. It occurs due to abnormal development of the paramesonephric (Müllerian) duct. Different forms of uterus didelphys have been reported in several animal species, including bovine, equine, ewe, goat, swine, and bitch. However, there is no previous report that has documented a completely divided female genital tract in she-camel. Moreover, there is a lack of literature regarding this anomaly in animals. Therefore, the present study reports, for the first time, a rare case of a completely divided female genital tract in a she-camel. In addition, the existing relevant literature on uterus didelphys in different animal species is reviewed. Case presentation: A female reproductive tract of she-camel, approximately 10 years old, with a history of previous successful pregnancy, was brought to the anatomy department following the slaughtering of the animal. Initial examination revealed a normal reproductive tract consisting of two ovaries, two fallopian tubes, a uterus, and a vagina. A closer examination revealed a completely divided vagina, with an external os opened into each part of the vagina, as well as a divided uterine body and cervix. Intrauterine infusion of saline through one external os confirmed complete separation of uterine body and cervix. Conclusion: To the authors' knowledge, this is the first reported case of a completely divided female genital tract in a she-camel. This review summarizes the previous reports about uterus didelphys in farm animals.

Case Report: Chronic pancreatitis in children as the cumulative effect of bilio-pancreatic abnormalities and genetic mutations.

Pancreatitis, in general, is a high-morbidity condition. Genetic conditions and anatomic variants are sometimes seen, especially in children, where biliary etiologies and alcohol are less common than in adults. The decision to intervene, the combined operative-endoscopic strategy, and the timing pose unique challenges. We report the case of a 10-year-old boy with PRSS1 mutation and pancreatic duct duplication, discussing the management and reviewing the recent reports in the Literature.

A Novel Zinc-Containing Palatal Stent and Topical Oxygen Therapy for Wound Protection and Healing Following Mucoperiosteal Flap Surgery in the Hard Palate: A Case Report.

In oral surgery, common surgical procedures such as the removal of impacted teeth, the treatment of intraosseous cysts and tumors, and endodontic surgery often require access through a palatal approach. Full-thickness flap surgery in the hard palate region can result in significant post-operative pain, swelling, and hematoma, adversely affecting the patient's function and well-being for several days. Moreover, post-operative infection can delay or compromise healing. Post-surgical traditional palatal stents have been shown to effectively reduce discomfort by minimizing swelling and pain during the early healing phases. Recent advances in materials with the incorporation of bioactive agents have led to the fabrication of a new generation of wound dressings that provide improved conditions for effective wound protection and healing. This case report illustrates the use of a novel, zinc-embedded, thermoplastic surgical polymer for the chairside fabrication of post-operative palatal stents. A 33-year-old female patient, who underwent mucoperiosteal flap surgery for the management of a nasopalatine duct cyst, was provided immediately post-surgery with a customized zinc-containing palatal stent. The bone defect was grafted using a fully resorbable synthetic bone substitute, and an oxygen and lactoferrin-releasing oral gel was provided post-operatively as an adjunct therapy. The innovative stent helped the patient maintain low levels of pain and minimal swelling during the initial post-operative period, resulting in uneventful healing, as documented during the one-week follow-up appointment. Further reviews at four weeks and six months post-surgery revealed successful healing and sensory recovery in the anterior palatal region. As emphasized in this report, the chairside fabrication of zinc-containing palatal stents for post-operative wound protection seems to constitute a valid, simple, time-saving, and cost-effective clinical solution. Moreover, the incorporation of zinc nanoparticles into the stent is of great clinical importance, potentially offering significant benefits in post-operative bacterial control and enhancement of the early-phase palatal soft-tissue healing.

Laparoscopic cholecystectomy for a gallbladder with a short cystic duct draining to the accessory right anterior hepatic duct using indocyanine green fluorescence imaging: A case report.

INTRODUCTION: Gallbladder with a short cystic duct draining to the accessory right anterior hepatic duct is a rare variation. It is frequently associated with bile duct injury during laparoscopic cholecystectomy. We present a case of a gallbladder with this variation safely treated with laparoscopic cholecystectomy using indocyanine green (ICG) fluorescence imaging. PRESENTATION OF CASE: A 57-year-old man had right upper quadrant pain and showed a gallbladder stone on a preoperative computed tomography. Bile duct anomaly was not detected before operation. However, a short cystic duct draining to the accessory right anterior hepatic duct intraoperatively was found using ICG fluorescence imaging. To confirm the exact anatomy, we firstly detached the gallbladder from the liver with a "fundus first technique" and visualized the whole course of the short cystic duct and the accessory right anterior with ICG fluorescence imaging. Laparoscopic cholecystectomy was completed safely. No bile leakage was detected on ICG fluorescence imaging. The patient had no postoperative complication. DISCUSSION: Accessory right hepatic duct is one of the rare variations of bile duct. It can be related to bile duct injury during laparoscopic cholecystectomy. Although it can be injured easily because of its smaller size, we can identify the short cystic duct from it with the aid of ICG fluorescence imaging without injuring the accessory right anterior hepatic duct. CONCLUSION: Laparoscopic cholecystectomy for gallbladder with a short cystic duct draining to the accessory right anterior hepatic duct can be safely performed by identifying biliary anatomy with ICG fluorescence imaging.

Bile duct diffusion-weighted image hyperintensity predicts intrahepatic biliary complications after ABO-incompatible liver transplantation.

OBJECTIVES: We assessed the value of the diffusion-weighted image (DWI) for predicting intrahepatic biliary complications (IHBC) after ABO-incompatible liver transplantation (ABOi-LT), potentially leading to refractory cholangitis. MATERIALS AND METHODS: In this retrospective study at a single center, 56 patients who underwent ABOi-LT from March 2021 to January 2023 were analyzed. All received magnetic resonance cholangiopancreatography (MRCP) and DWI during the postoperative hospitalization. MRCP findings, including bile duct DWI hyperintensity, were assessed. Participants suspected of having a biliary infection or obstructive jaundice underwent endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD) during the follow-up. Non-anastomotic biliary strictures on cholangiography were classified as IHBC, as either perihilar or diffuse form. DWI hyperintensity was compared between groups with and without IHBC. Logistic regression analysis was performed to identify independent risk factors for IHBC. RESULTS: Of the 55 participants (median age 55 years, 39 males), IHBC was diagnosed in eight patients over a median follow-up of 15.9 months (range 5.6-31.1). Bile duct DWI hyperintensity was observed in 18 patients. Those with DWI hyperintensity exhibited a higher IHBC incidence (6/18, 33.3% vs. 2/36, 5.6%; p = 0.01), and more frequently developed the diffuse type IHBC (4/18, 22.2% vs. 1/36, 2.8%; p = 0.04). Regression analysis indicated that bile duct DWI hyperintensity is an independent risk factor for IHBC (odds ratio (OR) 10.1; 95% confidence interval (CI) 1.4, 71.2; p = 0.02) and its diffuse form (OR 15.3; 95% CI 1.2, 187.8; p = 0.03). CONCLUSION: Postoperative DWI hyperintensity of bile ducts can serve as a biomarker predicting IHBC after ABOi-LT. CLINICAL RELEVANCE STATEMENT: Postoperative diffusion-weighted image hyperintensity of the bile duct can be used as a biomarker to predict intrahepatic biliary complications and aid in identifying candidates who may benefit from additional management for antibody-mediated rejection. KEY POINTS: Intrahepatic biliary complications following ABO-incompatible liver transplantation can cause biliary stricture and biloma formation. Bile duct hyperintensity on early postoperative diffusion-weighted imaging was associated with increased intrahepatic biliary complication risk. This marker is an additional method for identifying individuals who require intensive management to prevent complications.

Recombinant collagen coating 3D printed PEGDA hydrogel tube loading with differentiable BMSCs to repair bile duct injury.

Bile duct injury presents a significant clinical challenge following hepatobiliary surgery, necessitating advancements in the repair of damaged bile ducts is a persistent issue in biliary surgery. 3D printed tubular scaffolds have emerged as a promising approach for the repair of ductal tissues, yet the development of scaffolds that balance exceptional mechanical properties with biocompatibility remains an ongoing challenge. This study introduces a novel, bio-fabricated bilayer bile duct scaffold using a 3D printing technique. The scaffold comprises an inner layer of polyethylene glycol diacrylate (PEGDA) to provide high mechanical strength, and an outer layer of biocompatible, methacryloylated recombinant collagen type III (rColMA) loaded with basic fibroblast growth factor (bFGF)-encapsulated liposomes (bFGF@Lip). This design enables the controlled release of bFGF, creating an optimal environment for the growth and differentiation of bone marrow mesenchymal stem cells (BMSCs) into cholangiocyte-like cells. These cells are instrumental in the regeneration of bile duct tissues, evidenced by the pronounced expression of cholangiocyte differentiation markers CK19 and CFTR. The PEGDA//rColMA/bFGF@Lip bilayer bile duct scaffold can well simulate the bile duct structure, and the outer rColMA/bFGF@Lip hydrogel can well promote the growth and differentiation of BMSCs into bile duct epithelial cells. In vivo experiments showed that the scaffold did not cause cholestasis in the body. This new in vitro pre-differentiated active 3D printed scaffold provides new ideas for the study of bile duct tissue replacement.

Intrahepatic distribution of nerves in Suncus murinus by whole-mount immunohistological observation.

BACKGROUND: In recent years, elucidating the actual state of the liver nervous system has attracted attention, owing to clinical needs, such as liver transplantation. Conventional methods for studying the intrahepatic nerve distribution mostly use liver tissue sections, specific markers for immunohistological studies, or anterograde/retrograde tracing in animals. However, knowledge of the three-dimensional structure of intrahepatic innervation is vague or speculative. MATERIALS AND METHODS: In this study, Suncus murinus (Suncus) (n = 10) were perfused and fixed, the livers were excised, and the liver parenchyma was carefully removed, leaving only the intrahepatic vasculature. Specimens were prepared to study the three-dimensional structure of Suncus intrahepatic and hilar innervation by whole-mount immunohistochemical staining using a neurofilament protein antibody. RESULTS: After the nerves running along the intrahepatic arterial system entered the liver parenchyma from the hepatic hilum, they maintained a relatively rich distribution along the interlobular arteries until the distal end. The innervation of the portal system began to decrease after entering the liver parenchyma and decreased significantly after reaching the deep parts. By the time it reached the end of the interlobular vein, there was very little left. The number of nerves running along the intrahepatic bile duct system was significantly reduced after entering the porta hepatis, and innervation was difficult to observe after completely entering the liver parenchyma. CONCLUSIONS: Whole-mount immunohistochemical analyses with an anti-NFP antibody showed that intrahepatic innervation mainly accompanied the hepatic interlobular arteries and extended to their terminal ends. Neuronal regulation is very important in the functional regulation of intrahepatic nutritional vessels. However, there were very few NFP-immunoreactive nerves accompanying the intrahepatic bile duct system, possibly suggesting that the functional regulation of the intrahepatic biliary system mainly relies on hormones and neuropeptides.

Surgical strategies for challenging common bile duct stones in the endoscopic era: A comprehensive review of current evidence.

While endoscopic retrograde cholangiopancreatography (ERCP) remains the primary treatment modality for common bile duct stones (CBDS) or choledocholithiasis due to advancements in instruments, surgical intervention, known as common bile duct exploration (CBDE), is still necessary in cases of difficult CBDS, failed endoscopic treatment, or altered anatomy. Recent evidence also supports CBDE in patients requesting single-step cholecystectomy and bile duct stone removal with comparable outcomes. This review elucidates relevant clinical anatomy, selection indications, and outcomes to enhance surgical understanding. The selection between trans-cystic (TC) vs trans-choledochal (TD) approaches is described, along with stone removal techniques and ductal closure. Detailed surgical techniques and strategies for both the TC and TD approaches, including instrument selection, is also provided. Additionally, this review comprehensively addresses operation-specific complications such as bile leakage, stricture, and entrapment, and focuses on preventive measures and treatment strategies. This review aims to optimize the management of CBDS through laparoscopic CBDE, with the goal of improving patient outcomes and minimizing risks.

New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis.

BACKGROUND: Bone marrow-derived mesenchymal stem cell (BMMSC)-based therapy has become a major focus for treating liver fibrosis/cirrhosis. However, although these cell therapies promote the treatment of this disease, the heterogeneity of BMMSCs, which causes insufficient efficacy during clinical trials, has not been addressed. In this study, we describe a novel Percoll-Plate-Wait procedure (PPWP) for the isolation of an active cell subset from BMMSC cultures that was characterized by the expression of neuroglial antigen 2 (NG2/BMMSCs). METHODS: By using the key method of PPWP and other classical biological techniques we compared NG2/BMMSCs with parental BMMSCs in biological and functional characteristics within a well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhosis injury male C57BL/6 mouse model also in a culture system. Of note, the pathological alterations in the model is quite similar to humans'. RESULTS: The NG2/BMMSCs revealed more advantages compared to parentalBMMSCs. They exhibited greater proliferation potential than parental BMMSCs, as indicated by Ki-67 immunofluorescence (IF) staining. Moreover, higher expression of SSEA-3 (a marker specific for embryonic stem cells) was detected in NG2/BMMSCs than in parental BMMSCs, which suggested that the "stemness" of NG2/BMMSCs was greater than that of parental BMMSCs. In vivo studies revealed that an injection of NG2/BMMSCs into mice with ongoing DEN-induced liver fibrotic/cirrhotic injury enhanced repair and functional recovery to a greater extent than in mice treated with parental BMMSCs. These effects were associated with the ability of NG2/BMMSCs to differentiate into bile duct cells (BDCs). In particular, we discovered for the first time that NG2/BMMSCs exhibit unique characteristics that differ from those of parental BMMSCs in terms of producing liver sinusoidal endothelial cells (LSECs) to reconstruct injured blood vessels and sinusoidal structures in the diseased livers, which are important for initiating hepatocyte regeneration. This unique potential may also suggest that NG2/BMMSCs could be an novel off-liver progenitor of LSECs. Ex vivo studies revealed that the NG2/BMMSCs exhibited a similar trend to that of their in vivo in terms of functional differentiation responding to the DEN-diseased injured liver cues. Additionally, the obvious core role of NG2/BMMSCs in supporting the functions of BMMSCs in bile duct repair and BDC-mediated hepatocyte regeneration might also be a novel finding. CONCLUSIONS: Overall, the PPWP-isolated NG2/BMMSCs could be a novel effective cell subset with increased purity to serve as a new therapeutic tool for enhancing treatment efficacy of BMMSCs and special seed cell source (BDCs, LSECs) also for bioliver engineering.

A Unique Presentation of Acute Biliary Ascites Due to Spontaneous Biliary Duct Perforation With Bowel Obstruction: A Case Report.

Biliary ascites due to spontaneous biliary duct perforation is a rare case presentation usually seen in the paediatric age group of 6-36 months. We are presenting the case of a 14-month-old baby with abdominal distention associated with abdominal pain, vomiting, fever, and a history of no passage of stools. Upon examination, the abdomen was tense and tender. On radiological investigations, gross free fluid was present in the abdominal cavity along with bowel obstruction and partial situs inversus of the spleen and stomach. The bowel obstruction was relieved by rectal stimulation, after which oral feeds were well tolerated. Bilious fluid was found on diagnostic paracentesis, confirming the diagnosis. The patient was managed further by broad-spectrum antibiotics and drainage of the free fluid. The management ranges from conservative treatment to Roux-en-Y anastomosis. A non-surgical diagnosis is uncommonly seen and helps improve the patient's prognosis if detected early. This case report highlights the importance of early diagnosis and non-surgical treatment modality in critical patients.

Insulin receptor orchestrates kidney antibacterial defenses.

Urinary tract infection (UTI) commonly afflicts people with diabetes. This augmented infection risk is partly due to deregulated insulin receptor (IR) signaling in the kidney collecting duct. The collecting duct is composed of intercalated cells (ICs) and principal cells (PCs). Evidence suggests that ICs contribute to UTI defenses. Here, we interrogate how IR deletion in ICs impacts antibacterial defenses against uropathogenic Escherichia coli. We also explore how IR deletion affects immune responses in neighboring PCs with intact IR expression. To accomplish this objective, we profile the transcriptomes of IC and PC populations enriched from kidneys of wild-type and IC-specific IR knock-out mice that have increased UTI susceptibility. Transcriptomic analysis demonstrates that IR deletion suppresses IC-integrated stress responses and innate immune defenses. To define how IR shapes these immune defenses, we employ murine and human kidney cultures. When challenged with bacteria, murine ICs and human kidney cells with deregulated IR signaling cannot engage central components of the integrated stress response-including activating transcriptional factor 4 (ATF4). Silencing ATF4 impairs NFkB activation and promotes infection. In turn, NFkB silencing augments infection and suppresses antimicrobial peptide expression. In diabetic mice and people with diabetes, collecting duct cells show reduced IR expression, impaired integrated stress response engagement, and compromised immunity. Collectively, these translational data illustrate how IR orchestrates collecting duct antibacterial responses and the communication between ICs and PCs.

Dmxl1 Is an Essential Mammalian Gene that Is Required for V-ATPase Assembly and Function In Vivo.

The proton pumping V-ATPase drives essential biological processes, such as acidification of intracellular organelles. Critically, the V-ATPase domains, V1 and VO, must assemble to produce a functional holoenzyme. V-ATPase dysfunction results in cancer, neurodegeneration, and diabetes, as well as systemic acidosis caused by reduced activity of proton-secreting kidney intercalated cells (ICs). However, little is known about the molecular regulation of V-ATPase in mammals. We identified a novel interactor of the mammalian V-ATPase, Drosophila melanogaster X chromosomal gene-like 1 (Dmxl1), aka Rabconnectin-3A. The yeast homologue of Dmxl1, Rav1p, is part of a complex that catalyzes the reversible assembly of the domains. We, therefore,hypothesized that Dmxl1 is a mammalian V-ATPase assembly factor. Here, we generated kidney IC-specific Dmxl1 knockout (KO) mice, which had high urine pH, like B1 V-ATPase KO mice, suggesting impaired V-ATPase function. Western blotting showed decreased B1 expression and B1 (V1) and a4 (VO) subunits were more intracellular and less colocalized in Dmxl1 KO ICs. In parallel, subcellular fractionation revealed less V1 associated B1 in the membrane fraction of KO cells relative to the cytosol. Furthermore, a proximity ligation assay performed using probes against B1 and a4 V-ATPase subunits also revealed decreased association. We propose that loss of Dmxl1 reduces V-ATPase holoenzyme assembly, thereby inhibiting proton pumping function. Dmxl1 may recruit the V1 domain to the membrane and facilitate assembly with the VO domain and in its absence V1 may be targeted for degradation. We conclude that Dmxl1 is a bona fide mammalian V-ATPase assembly factor.