The specialized types and functions of epithelial cells in the adult small intestine have been well elucidated, but remain poorly understood in the embryonic small intestine. Through integrating single-cell RNA sequencing with functional studies using mouse and organoid models, we identify small intestinal sentinel progenitor cells (SISPCs), marked by Lysozyme1 (Lyz1), in the embryonic and neonatal mouse small intestine. Distinct from Lyz1+ Paneth cells, SISPCs exhibit dynamic spatiotemporal patterning and stemness features during intestinal development. Notably, embryonic SISPCs display strong stemness potential in the proximal small intestine, whereas embryonic Lgr5+ cells exhibit greater stem potency in the distal region. In addition, SISPCs play a crucial role in the prenatal intestinal injury repair via the DUSP-p38 signaling axis and contribute to the neonatal antimicrobial defense. Our findings reveal SISPCs play a pivotal role in gut homeostasis and defense during development, and suggest them as potential therapeutic targets for developmental gut disorders.

Mesenteric venous thrombosis (MVT) is an uncommon but potentially fatal complication following major hepatic resection. We report the case of a 62-year-old cirrhotic male with Hepatitis B who underwent an open right hemihepatectomy with Roux-en-Y reconstruction for a suspected Bismuth-Corlette Type 3A Klatskin tumour. On postoperative day (POD) 4, he developed refractory metabolic acidosis with profound hyperlactatemia, prompting urgent CT imaging and exploratory laparotomy which revealed extensive patchy small bowel ischaemia consistent with MVT. Serial laparotomies demonstrated relentless progression to total intestinal infarction despite maximal surgical and intensive care intervention and the patient succumbed to septic shock and multi-organ failure on POD 14. This case illustrates how the convergence of Virchow's triad in the post-hepatectomy cirrhotic patient, namely portal stasis exacerbated by inadequate fluid resuscitation, cirrhosis-mediated hypercoagulability and surgical endothelial injury can precipitate a rapidly fatal thrombotic cascade. It further highlights the dual clinical dilemma of diagnostic elusiveness as early imaging may be falsely negative and therapeutic paralysis where the perceived haemorrhagic risk of anticoagulation in a coagulopathic patient may delay the only intervention capable of halting thrombus propagation. This case underscores the imperative for heightened clinical vigilance, proactive hydration and a low threshold for repeat vascular imaging in cirrhotic patients undergoing major hepatectomy. Early anticoagulation tailored to the individual patient's risk profile should be carefully considered upon clinical suspicion of MVT, even in the setting of apparent coagulopathy.

Ileo-ileal knotting is a rare, life-threatening cause of small bowel strangulation. Preoperative diagnosis is challenging, and hemorrhagic ascites in reproductive-age women may mimic gynecologic emergencies. A 33-year-old Ethiopian female presented with sudden abdominal pain, vomiting, obstipation, and hemorrhagic shock. Ultrasonography showed dilated small bowel loops and echogenic free fluid, suggesting ruptured ovarian cyst. Due to instability, computed tomography was omitted. Emergency laparotomy revealed 2000 ml of hemorrhagic ascites with normal ovaries and no gynecologic bleeding. An ileo-ileal knot with 180 cm of gangrenous bowel was found; hemorrhagic ascites resulted from transmural ischemia with venous congestion. The gangrenous segment was resected, and stoma created. Short bowel syndrome ensued. Staged jejuno-ileal anastomosis was performed 1 week later with good recovery. This case confirms that hemorrhagic ascites in women does not exclude intestinal strangulation. Early surgical exploration is lifesaving when closed-loop obstruction is suspected.

Introduction Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal neoplasms of the gastrointestinal tract, typically originating from the interstitial cells of Cajal. Accurate histopathological assessment and immunohistochemical profiling are pivotal for diagnosis and risk stratification. This study aimed to evaluate the clinicopathological characteristics and immunohistochemical expression patterns of GISTs diagnosed at a tertiary care center. Methods A retrospective analysis was conducted on 30 histologically confirmed cases of GIST over a seven-year period. Formalin-fixed, paraffin-embedded tissue samples were reviewed using hematoxylin and eosin staining and subjected to immunohistochemistry. Parameters assessed included patient demographics, tumor location, histological subtype, mitotic index, and immunoreactivity for CD117, DOG1, and CD34. Results The cohort comprised 19 men and 11 women, with a mean age of 62.1 years. The small intestine had the most number of cases, i.e., eight cases (26%), followed by the stomach, which had seven cases (24%). Spindle cell morphology was predominant (86%), followed by epithelioid and mixed patterns (7% each). Most tumors were low-grade (60%), with a mitotic rate of <5 per 50 high-power fields. Immunohistochemically, DOG1 showed the highest positivity (97%), followed by CD117 (84%) and CD34 (70%). Smooth muscle actin (SMA), desmin, and S-100 showed variable positivity. Conclusion This study highlights a male predominance and a predilection for gastric and small intestinal involvement in GISTs. Spindle cell morphology and low mitotic activity were common histological features. Immunohistochemistry remains indispensable for diagnosis, with DOG1 demonstrating superior sensitivity. These findings reinforce the critical role of integrated histopathological and immunohistochemical evaluation in the accurate diagnosis and management of GISTs.

Intestinal lymphatic vessels are essential for dietary lipid absorption and immune cell trafficking. Villus lymphatic capillaries, lacteals, undergo continuous VEGF-C-dependent renewal to function in a hyperosmolar, inflammatory environment exposed to dietary and microbial by-products. To define mechanisms underlying this adaptation, we integrated new and published single-cell RNA-sequencing datasets of murine small intestinal lymphatic endothelial cells (LECs). Lacteal LECs resembled Ptx3+ immune-interacting LECs and were characterized by high expression of water channel AQP1. LEC-specific Aqp1 deletion reduced lacteal length, impaired lipid uptake, and limited weight gain on a high-fat diet, while mosaic deletion revealed a cell-autonomous requirement for AQP1 in LEC positioning at hyperosmolar tip regions. AQP1 promoted LEC migration under hyperosmotic stress by preserving cytoskeletal and junctional remodeling and alleviating osmotic stress-induced transcriptional programs. AQP1 was upregulated during inflammatory remodeling in lymphedema and lymphatic malformations, but not during embryonic lymphangiogenesis. These findings link lacteal regeneration to inflammatory lymphatic remodeling and highlight tissue osmolarity as a biophysical determinant of postnatal lymphangiogenesis.

An imbalance of macrophage polarization exerts influence over inflammatory bowel disease (IBD) pathogenesis. To investigate how macrophage polarization influences IBD, we engineered a composite system consisting of small intestinal submucosa (SIS) hydrogel combined with bone marrow-derived mesenchymal stem cells (BM-MSCs). The therapeutic potential of this construct was assessed by examining its regulatory effects on macrophage polarization both in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model and in RAW264.7 macrophages in vitro. Clone formation assay was executed to identify the influence of MSC-SIS-conditioned medium on the proliferation of RAW264.7. CD206 and CD86 were measured by flow cytometric. Quantitative real-time PCR (qRT-PCR) was conducted to evaluate cytokine gene expression. Experimental colitis was induced in mice using TNBS. Disease severity was assessed by calculating the clinical disease activity index (CDAI). Colonic tissues were subjected to histological and morphometric analyses, and serum levels of inflammatory cytokines were quantified using enzyme-linked immunosorbent assay (ELISA). Data indicated that the BM-MSCs and SIS hydrogel composite significantly promoted Raw264.7 proliferation. Compared with the lipopolysaccharide (LPS) + MSCs group, treatment with the combined MSCs and SIS hydrogel construct demonstrated a more pronounced inhibitory effect on M1 phenotype the autophagy of LPS-induced RAW264.7 in vitro; what is more, BM-MSCs and SIS hydrogel greatly inhibited cytokine mRNA levels in LPS-stimulated Raw264.7 cells compared with treatment with MSCs solely. In addition, the results implied that the mice in TNBS + MSC + SIS group had alleviated colitis compared with the TNBS + MSCs group, and the interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) levels in the serum also decreased. In conclusion, these results indicate a better wound healing effect of SIS hydrogel on BM-MSCs through promoting cell regeneration and inhibiting macrophage polarization towards the M1 phenotype in a TNBS-induced experimental mouse model.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and aggressive subtype of intestinal T-cell lymphoma with a dismal prognosis. MEITL with aberrant CD20 expression is even rarer. To date, there have been no reported cases of multiple primary malignant tumors (MPMT) composed of concurrent CD20-positive MEITL and solid tumors. We herein present a case of a 59-year-old female with concurrent small intestinal MEITL with aberrant CD20 expression and lung adenocarcinoma. The patient was admitted to hospital for abdominal pain due to intestinal perforation and underwent partial small intestinal resection. Histopathological examination confirmed MEITL with aberrant CD20 expression of the small intestine without lymph node involvement. Meanwhile, two pulmonary ground-glass opacities (GGOs) were identified and histopathological evaluation confirmed the diagnosis of lung adenocarcinoma. The patient received rituximab-based chemotherapy followed by autologous stem cell transplantation, along with surgical resection for lung adenocarcinoma. She has remained alive for more than 24 months without disease progression. Additionally, we conducted a literature review to enhance clinical awareness of this rare concurrent condition of CD20-positive MEITL and lung adenocarcinoma.

A real diagnostic challenge is posed by transfusion-dependent anemia in young patients with obscure gastrointestinal (GI) bleeding. Such a presentation can have many etiologies. Although rare, small intestinal hemangiomas are benign vascular tumors that frequently elude timely diagnosis owing to their intramural growth pattern and deep submucosal sequestration. Recent literature has increasingly shown the benefit of systemic therapies, such as sirolimus, for managing complex vascular anomalies. We report the case of a 17-year-old girl with a history of easy fatigability, melena, and exertional dyspnea, requiring regular red blood cell transfusions for the past six years. Initial laboratory investigations were suggestive of severe iron deficiency anemia, with a hemoglobin level of 6.3 g/dL and a ferritin level of 5.2 ng/mL. The stool occult blood test was positive. However, repeated upper and lower GI endoscopies and imaging were non-contributory. A repeat computed tomography angiography (CTA) of the abdomen was carried out, which showed intramural polypoidal lesions in the distal ileum and descending colon. Diagnostic laparoscopy was confirmatory of multiple small intestinal hemangiomas. In view of the multifocal nature of the lesions and the prohibitive risk of extensive bowel resection, a conservative strategy utilizing systemic mTOR (mechanistic target of rapamycin) inhibition was adopted. The patient achieved transfusion independence within two months, with a sustained normalization of hematological indices and a favorable side-effect profile. This case highlights the diagnostic complexity of small intestinal hemangiomas. It reinforces the role of imaging and laparoscopy, as well as the importance of considering rare causes, in transfusion-dependent anemia with chronic GI bleeding. In multifocal involvement of hemangiomas, sirolimus therapy may be an effective and safer alternative to surgical intervention. This case calls for more research and awareness of such rare vascular anomalies to accelerate diagnosis and management.

Type II diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, is often accompanied by dysregulated bile acid metabolism. Although gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated potential in diabetes management, its therapeutic mechanisms remain incompletely understood. The aim of this study is to investigate the therapeutic effects and potential mechanisms of gastrodin on T2DM mice from the perspective of bile acid metabolism. In this study, we found that gastrodin could not only reduce lipid accumulation, reduce inflammation, improve antioxidant capacity, alleviate oxidative stress, change the composition of intestinal flora, and improve the disorder of flora caused by the disease in T2DM mice, but also target Yin yang 1 (YY1) to reduce the expression level of YY1 in the liver under a high-fat diet condition. At the same time, YY1 negatively regulates the expression level of Farnesoid X Receptor (FXR), which increases the expression level of FXR, inhibits the enzyme activity of Cholesterol-7α-hydroxylase (CYP7A1) through Small Heterodimer Partner (SHP), reduces the production of chenodeoxycholic acid (CDCA) in the liver, and further affects the production of secondary bile acids through liver-intestinal circulation, promoting the secretion of Glucagon-Like Peptide-1 (GLP-1) and insulin, thereby reducing blood glucose. At the same time, combined with the results of HE staining, gastrodin can reduce the pathological damage of the liver and pancreas in type II diabetic mice, repairing their normal morphology and function. It provides a direct pathological basis for the improvement of diabetes and liver complications, provides theoretical support for the subsequent research and development of precision targeted drugs, provides experimental basis for the development of new natural hypoglycemic drugs, and promotes the transformation and application of the modernization of traditional Chinese medicine in the field of metabolic diseases.