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Background: Intestinal-type gastric adenocarcinoma, representing 95 % of gastric malignancies, originates from the malignant transformation of gastric gland cells. Despite its prevalence, existing methods for prognosis evaluation of this cancer subtype are inadequate. This study aims to enhance patient-specific prognosis evaluation by analyzing the clinicopathological characteristics and prognostic risk factors of intestinal-type gastric adenocarcinoma patients using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Methods: We extracted clinical data for patients diagnosed with intestinal-type gastric adenocarcinoma between 2010 and 2015 from the SEER database, selecting 257 cases based on predefined inclusion and exclusion criteria. Independent risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified using a Cox regression model. A nomogram model for predicting OS or CSS was developed from the Cox risk regression analysis and validated through the consistency index (C-index), ROC curve, and calibration curve. Results: Age, primary tumor resection, chemotherapy, lymph node metastasis, and tumor size were identified as independent prognostic factors for OS and CSS (P < 0.05). The nomogram model, constructed from these indicators, demonstrated superior predictive consistency for OS and CSS compared to the AJCC-TNM staging system. ROC curve analysis confirmed the model's higher accuracy, and calibration curve analysis indicated good agreement between the nomogram's predictions and actual observed outcomes. Conclusion: The nomogram model derived from SEER database analyses accurately predicts OS and CSS for patients with intestinal-type gastric adenocarcinoma. This model promises to facilitate more tailored treatments in clinical practice.
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Water collection from atmospheric fog was deemed to be an efficient and sustainable strategy to defuse the freshwater scarcity crisis. Fog harvesting and trapping fibers, therefore, has aroused extensive interest due to their ease of preparation, weave, and use. However, the traditional fibers used in fog collector usually have a low fog collection capacity and efficiency because of their unreasonable morphology and structure design. Herein, we proposed a simple process to construct advanced fibers using a one-step wet spinning of hydrophobic polyvinylidene fluoride (PVDF) and hydrophilic cellulose mixture fiber for fog harvesting. The as-prepared fibers featured a petaloid structure and surface hydrophobic gradient, thus facilitating fog deposition, water droplet formation, and drainage. The unique longitudinal groove structure above enabled the hybrid fiber to achieve an excellent fog collection efficiency of 2750.26 mg/cm2/h per monofilament, which outstripped most of other fiber materials. When woven these fibers were in a longitudinal array network with an interval of 1 mm, and the fog collection efficiency can maintain at 10.30 L/m2/h. Therefore, this work provided a new strategy for further exploration of effective fog collection by cellulose-based fiber materials.
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Purpose: Postoperative cardiac events (PCEs) are among the main adverse events after hip fracture surgery in the elderly. Existing cardiac risk assessment tools have some limitations and are not specifically designed for elderly patients undergoing hip fracture surgery. This study aimed to develop and internally validate a nomogram for prediction of PCEs in these patients. Patients and Methods: We performed a retrospective study of 992 patients aged ≥65 years undergoing hip fracture surgery in our hospital from July 2015 to December 2021. Patients' demographics and clinical data were collected. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select predictors, and multivariate logistic regression was employed to construct a nomogram. Internal validation was performed by bootstrapping. The discriminatory ability of the model was determined by the area under the receiver operating characteristic curve (AUC). The calibration and clinical utility of the model were assessed. The predictive power and clinical benefit of the nomogram were compared with the Revised Cardiac Risk Index (RCRI). Results: The nomogram was constructed including seven variables: general anesthesia, the American Society of Anesthesiologists (ASA) classification, history of heart failure, history of severe arrhythmia, history of coronary artery disease, preoperative platelet count, and serum creatinine. The nomogram had an excellent predictive ability (AUC = 0.875, 95% confidence interval [CI]: 0.828-0.918). Satisfactory calibration was shown by calibration plots and the Hosmer-Lemeshow goodness-of-fit test (P = 0.520). Clinical usefulness was confirmed by decision curve analysis and clinical impact curve. The predictive power and clinical utility of the nomogram were superior to RCRI. Conclusion: We developed an easy-to-use nomogram for prediction of PCEs in elderly hip fracture patients. This prediction model could effectively identify patients at high risk of PCEs and may be useful for perioperative management optimization.
Subject(s)
Coronary Artery Disease , Hip Fractures , Aged , Humans , Anesthesia, General , Hip Fractures/surgery , Nomograms , Retrospective Studies , Postoperative ComplicationsABSTRACT
BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.
Subject(s)
Biliary Atresia , Cholangitis , Jaundice , Child , Humans , Infant , Portoenterostomy, Hepatic/adverse effects , Prospective Studies , Immunoglobulins, Intravenous , Biliary Atresia/surgery , Biliary Atresia/complications , Cholangitis/drug therapy , Cholangitis/etiology , Jaundice/complications , Anti-Bacterial Agents/therapeutic use , Meropenem , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: BAT1706 is a proposed biosimilar of bevacizumab, a vascular endothelial growth factor A (VEGF-A)-targeting biologic used to treat several different cancers, including metastatic colorectal cancer. A comprehensive physicochemical and functional similarity assessment is a key component of demonstrating biosimilarity between a reference biologic and a proposed biosimilar. Here we report the physicochemical and functional similarity of BAT1706 and reference bevacizumab sourced from both the United States (US-bevacizumab) and the European Union (EU-bevacizumab). METHOD: A large range of product attributes, including primary and higher order structure, post-translational modifications, purity, stability, and potency, were characterized for BAT1706 and EU/US-bevacizumab using sensitive state-of-the-art analytical techniques. Up to 18 lots of US- and 29 lots of EU-bevacizumab, and 10 unique drug substance lots of BAT1706, were assessed. RESULT: BAT1706 was shown to have an identical amino acid sequence and an indistinguishable higher-order structure compared with EU/US-bevacizumab. BAT1706 and EU/US-bevacizumab also exhibited similar post-translational modifications, glycan profiles, and charge variants. Potency, assessed using a wide range of bioassays, was also shown to be comparable between BAT1706 and EU/US-bevacizumab, with statistical equivalence demonstrated for VEGF-A binding and neutralizing activity. CONCLUSION: Overall, this extensive comparability exercise demonstrated BAT1706 to match EU/US-bevacizumab in terms of all physicochemical and functional attributes assessed.
Subject(s)
Biosimilar Pharmaceuticals , Vascular Endothelial Growth Factor A , Humans , Bevacizumab/pharmacology , Biosimilar Pharmaceuticals/pharmacology , Biological Assay , PhosphorylationABSTRACT
Splenic abscesses in children are very rare, and multiple splenic abscesses are rarer. These lesions are difficult to diagnose quickly because of their low incidence and the low specificity of the associated clinical and imaging findings. The treatment of splenic abscesses includes conservative treatment, percutaneous drainage, and splenectomy, but the selection criteria for treatment are still unclear. We present a case of a 13-year-old girl with multiple splenic abscesses. Her blood culture report was negative. We eventually confirmed the diagnosis by enhanced magnetic resonance imaging (MRI). The patient underwent a successful laparoscopic total splenectomy, and her symptoms were resolved thereafter.
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OBJECTIVE: To evaluate the accuracy of intraoperative hepatic subcapsular spider-like telangiectasia (HSST) sign for differentiating biliary atresia (BA) from other causes of hepatic cholestasis. METHODS: The data of 69 patients with jaundice treated from January 2019 to December 2021 were retrospectively analyzed. Based on intraoperative cholangiography (IOC), the patients were divided into two groups: the BA group (n = 49) and the non-BA group (n = 20). The biochemistry tests, liver ultrasound, liver stiffness value and HSST sign of the two groups were compared. RESULTS: The incidence of abnormal gallbladder, elevated γ-glutamyl transpeptidase (γ-GGT) > 182.0U/L and abnormal liver stiffness (> 6.4 kPa) in BA group were significantly higher than those in non-BA group (P < 0.001). The HSST sign was present in all BA patients and not found in non-BA group. The area under receiver operating curve of direct bilirubin(DBIL), γ-GGT, abnormal gallbladder, liver stiffness value and HSST sign were 0.53, 0.84, 0.78, 0.96, and 1.00, respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value(NPV) of HSST sign in the diagnosis of BA were all 100%. CONCLUSION: Presence of HSST sign on diagnostic laparoscopy is highly suggestive of BA.It can be used in the differential diagnosis of BA and non-BA. LEVEL OF EVIDENCE: Level III.
Subject(s)
Biliary Atresia , Cholestasis , Liver Diseases , Telangiectasis , Humans , Biliary Atresia/diagnosis , Biliary Atresia/complications , Retrospective Studies , Cholestasis/etiology , Diagnosis, Differential , gamma-Glutamyltransferase , Telangiectasis/complications , Telangiectasis/diagnosisABSTRACT
The objective is to explore the correlation between ultrasonic gallbladder length-width ratio (LTWR) and age, and the value of differential diagnosis between biliary atresia (BA) and other hepatic cholestasis. From January 2016 to June 2022, the data of 183 patients with jaundice who underwent abdominal ultrasound and surgical exploration in the Affiliated Hospital of Zunyi Medical University were analyzed retrospectively. The demographic data, liver function, and ultrasonic parameters were recorded and analyzed. There were statistically significant differences between BA group and non-BA group in maximum length, maximum width and LTWR of gallbladder (P < 0.001). In all age groups (I: ≤ 30 days; II: 31-60 days; III: 61-90 days; IV: 91-120 days; V: ≥ 121 days), in which group III (61-90 days) had the highest area under the curve (AUC) of 0.843, and group V (≥121 days) had the lowest AUC of 0.548. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of gallbladder LTWR > 3.26 for BA in group II (31-60 days) were 78.9%, 75.0%, 75.0%, 78.9% and 76.9%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of gallbladder LTWR > 3.69 for BA in group III (61-90 days) were 76.6%, 84.6%, 92.5%, 59.5% and 78.9%, respectively. Ultrasonography LTWR of gallbladder has certain value in the diagnosis of BA. The diagnostic value of gallbladder LTWR in infants with different ages was quite different, and it was relatively high in infants with 31-90 days.
Subject(s)
Biliary Atresia , Cholestasis , Infant , Humans , Biliary Atresia/diagnostic imaging , Gallbladder/diagnostic imaging , Retrospective Studies , Sensitivity and Specificity , Cholestasis/diagnosis , Ultrasonography , Diagnosis, DifferentialABSTRACT
Objective: Congenital diaphragmatic hernia (CDH) is an uncommon but potentially life-threatening surgical condition in neonates. Surgery can be performed by either open or thoracoscopic techniques. In this study, we compared the clinical efficacy, safety, and effectiveness of thoracoscopic and open CDH repair. Methods: A retrospective review of neonates with CDH who underwent operations at our hospital from 2013 to 2021 was performed. The various perioperative parameters were compared between neonates undergoing thoracoscopic and open surgery. Results: There were 50 neonates in this study (37 in the thoracoscopic group and 13 in the open group). Thoracoscopic surgery was associated with significantly shorter hospital stay (13.32 vs. 18.77 days, p < 0.001); shorter duration of postoperative mechanical ventilation (3.70 vs. 5.98 days, p < 0.001); early feeding (4.34 vs. 7.46 days, p < 0.001); and shorter time to reach optimal feeding (8.21 vs. 13.38 days, p < 0.001). There was one postoperative death in the open group and no death in the thoracoscopic group. The median follow-up time of the two groups was 23.8 months (20.5 months in open group and 25.0 months in thoracoscopic group). Thoracoscopic surgery was associated with lower recurrence rates, but the difference was not statistically significant (2.7% vs. 7.7%, p = 0.456). Conclusion: Thoracoscopy CDH repair, a safe and effective surgical technique for neonates, has better cosmesis, faster postoperative recovery, and a lower recurrence rate than other procedures. It can be considered the first choice for CDH treatment for neonates among experienced surgeons.
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OBJECTIVE: To investigate the expression levels of CD4+ T cells, IL-6, IL-8 and IL-33 in liver tissue of BA, and the relationship with postoperative cholangitis, operative age and early jaundice clearance. METHODS: 45 cases of jaundice treated in the hospital from June 2018 to May 2020 were analyzed retrospectively. The expression and distribution of these factors were detected by HE staining and immunohistochemistry, the total bilirubin level and the incidence of cholangitis were recorded, and the relationship between liver inflammation level and the postoperative incidence of cholangitis, age of operation and early jaundice clearance were compared. RESULTS: Immunohistochemistry showed that the expression of CD4+ T cells, IL-6, IL-8 and IL-33 in the BA group were higher than those in the CBD group. ROC curve analysis showed the AUC of CD4+ T cells, IL-6 and IL-8 were 0.869, 0.886 and 0.838, respectively. The expression level of CD4+ T cells was negatively correlated with the decline rate of TBIL 3 months after operation, and the expressions of IL-8 and IL-33 were negatively correlated with the decline rate of TBIL 1 week after operation. CONCLUSION: The high expression of CD4+ T cells, IL-6, IL-8 and IL-33 in the BA liver tissue may lead to cholangitis and can be used as a predictor of early jaundice clearance. The degree of liver inflammation infiltration had nothing to do with the age of operation and is not a risk factor for postoperative cholangitis.
Subject(s)
Biliary Atresia , Cholangitis , Jaundice , Humans , Infant , Biliary Atresia/complications , Biliary Atresia/surgery , CD4-Positive T-Lymphocytes , Cholangitis/etiology , Inflammation , Interleukin-33 , Interleukin-6 , Interleukin-8 , Jaundice/etiology , Liver/surgery , Portoenterostomy, Hepatic/adverse effects , Prognosis , Retrospective StudiesABSTRACT
The accessory hepatic lobe (AHL) is a rare congenital malformation of the hepatic tissue, among which the giant AHL is the rarest in children. Patients without complications are usually asymptomatic, and most auxiliary examinations cannot provide a definitive preoperative diagnosis. Surgical procedure is the only recommended management for patients who suffered from the complications of AHL. We report the case of a rare pediatric giant AHL torsion combined with left hepatic vein branch thrombosis which was successfully treated by laparoscopic lobectomy followed by excision of AHL.
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Objective: Cystic biliary atresia (CBA) is a rare and peculiar type of biliary atresia (BA) that is easily confused with infantile choledochal cysts (CCs). This study explored information for early CBA diagnosis and treatment. Method: The authors retrospectively analyzed the clinical data of 32 children with hilar cysts from January 2013 to May 2021. According to the diagnosis, they were divided into the CBA (n = 12) and CC (n = 20) groups. Patient features, biochemical indexes, preoperative ultrasound characteristics, cholangiography features, and intraoperative findings were analyzed and compared between the two groups. Results: The alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin levels in the CBA group were higher than in the CCs group (P < 0.05). Additionally, B-mode ultrasound showed a cystic mass in front of the hepatic hilum, and the cyst size was much smaller in the CBA group compared with the CC group (2.2 ± 1.3 cm vs. 6.0 ± 2.2 cm, P < 0.001). Among all of the parameters, cyst width was the most accurate for identifying CBA and CCs. A cutoff value of 2.5 cm (area under the curve, 0.98, P < 0.001) showed 90.9% sensitivity and 95% specificity for cyst size. Conclusion: For children with early-onset severe jaundice, and if the width of the cystic mass was ≤2.5 cm, a diagnosis of CBA was highly likely. Early cholangiography and surgical treatment are necessary for the effective treatment of these infants.
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Objectives: Our institution had modified the Soave pull-through procedure using laparoscopic stepwise gradient muscular cuff cutting (LSGC) for Hirschsprung disease (HSCR). However, we found that a few children still suffered from obstructive symptoms and enterocolitis during the follow-up. Previous studies suggested that these symptoms might be caused by the retained muscular cuff. The purpose of this study was to employ a modified procedure of laparoscopic complete excision of the posterior muscular cuff (LCEPC) for HSCR and compare it with the laparoscopic stepwise gradient cutting muscular cuff (LSGC) procedure. Methods: Our institution records of 83 patients with classic form HSCR who underwent LSGC or LCEPC between August 2014 and July 2018 at the Pediatric Surgery Department of Zunyi Medical University (Zunyi, China) were carefully reviewed (LSGC, n = 52; LCEPC, n = 31). In the present study, we compared the postoperative complications and defecation functions of the two groups. All patients were followed-up (1-5 years, with an average of 2 years). Results: There were no differences regarding the operation time and the length of hospitalization between groups, while the anal dissection time in the LCEPC group (22.4 ± 4.8 min) was shorter than that of the LSGC group (45.5 ± 7.5 min) (p < 0.001). The postoperative complication of soiling was significantly increased in six patients (19.4%) in the LCEPC group compared with two patients (3.8%) in the LSGC group (p = 0.021). However, the total incidence of enterocolitis (two patients, 6.5%) was significantly decreased in the LCEPC group compared with the LSGC group (12 patients, 23.1 %) (p = 0.050). For anastomotic stricture, muscular cuff infection, and constipation, there were no significant differences between the two groups. No patients experienced bladder paralysis and incontinence postoperatively in this study. Anorectal manometries presented that the anorectal resting pressure was significantly lower in the LCEPC group (14.8 ± 2.7 mmHg) than the LSGC group (22.0 ± 3.8 mmHg), (p < 0.001). Conclusion: The laparoscopic complete excision of the posterior muscular cuff method was demonstrated as safe and efficient, with a decrease in the incidence of enterocolitis, although it may increase the number of soiling incidents in the short period post-surgery owing to a dissected partial internal anal sphincter.
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Objective: The purpose of this study was to compare the safety and efficacy of hand-sewn versus stapled anastomosis therapy in intestinal atresia neonatal patients. Materials and Methods: This was a prospective randomized controlled trial in which 90 neonates with intestinal atresia were randomly divided into the hand-sewn group and the stapled group. All patients were assigned to undergo intestinal anastomosis by hand-sewn or stapler. The primary outcome measure was to analyze the anastomotic complications between groups. The secondary outcome measures were operative time, blood loss, length to initial feeds, length to full feeds, length of hospital stay, the incidence of bowel obstruction, reoperation and mortality, and weight and height 1 year after operation. Results: A total of 82 patients were included (43 for hand-sewn and 39 for stapled group) for primary analysis. A total of 16 patients suffered from anastomotic complications in both groups. The incidence rate of anastomotic complications in the stapled group was significantly lower than that of the hand-sewn group (27.9% versus 10.3%, P = .044). There were no differences in anastomotic leak, stricture, and bleeding in the hand-sewn group compared with stapled group. The operative time in the hand-sewn group was longer than the stapled group (P < .001), the length to initial and full feeds in the stapled group was shorter than that of the hand-sewn group (P < .001). The length of hospital stay was significantly shorter in the stapled group than the hand-sewn group (P = .016). The bowel obstruction, reoperation, weight and height, and mortality had no differences between groups during follow-up. Conclusion: Study results demonstrate that stapled anastomosis is safe and effective for intestinal atresia with distal diameter >1 cm, as it can decrease the incidence of anastomotic complications. However, the risk of anastomotic failure should be considered among type III b atresia. Clinical Trial Registration number: NCT03754907.
Subject(s)
Intestinal Atresia , Surgical Stapling , Anastomosis, Surgical/methods , Humans , Infant, Newborn , Intestinal Atresia/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prospective Studies , Surgical Stapling/methods , Suture Techniques/adverse effects , Treatment OutcomeABSTRACT
Rac1 can affect the migration of neural crest cells by regulating the polymerization of actin and the membrane formation process. But the role of the Rac1 signaling pathway in the pathogenesis of Hirschsprung's disease (HSCR) remains unclear. In order to investigate the mechanism of the abnormal protein phosphorylation of Rac1, Lim-kinase 1 (Limk1) and Cofilin involved in the pathogenesis of HSCR. The protein phosphorylation levels of these proteins were detected by Western blot in 30 samples of HSCR narrow segment, 30 samples of transitional segment tissues, and 14 samples of normal intestinal tissues. Subsequently, in the SH-SY5Y human neuroblastoma cell line, a Rac1, Limk1, and Cofilin inhibitor group, a Rac1 overexpression group (PDGF-BB group), a Rac1 overexpression group + a Limk1 inhibitor group (P-B group), a Rac1 overexpression group + a Cofilin inhibitor group (P-C group) were established. The results showed that the expressions of p-Rac1, p-Limk1, and p-Cofilin in HSCR narrow segment and transitional segment were lower than those in normal intestine (p < 0.05). The expression levels of p-Rac1, p-Limk1, and p-Cofilin in the relative inhibitor group were significantly lower than those in the control group (p < 0.05), and the proliferation and migration levels in the control group and Rac1 overexpression group were significantly higher than those in the Rac1, Limk1, and Cofilin inhibitor group (p < 0.05). In conclusion, the decreased phosphorylation of the Rac1/Limk1/Cofilin signaling pathway in HSCR could inhibit the proliferation and migration of SH-SY5Y cells, and this might be associated with the pathogenesis of HSCR.
Subject(s)
Hirschsprung Disease , Lim Kinases , Actin Depolymerizing Factors/metabolism , Hirschsprung Disease/genetics , Humans , Lim Kinases/genetics , Lim Kinases/metabolism , Phosphorylation , Signal Transduction , rac1 GTP-Binding Protein/genetics , rac1 GTP-Binding Protein/metabolismABSTRACT
Hirschsprungassociated enterocolitis (HAEC) is characterized by intestinal mucosal damage and an imbalance in the intestinal microbiota. Recent studies have indicated that the TLR4/pp38/NFκB signaling pathway in the intestine is of great importance to intestinal mucosal integrity. The present study aimed to investigate the role of TLR4/phosphorylated (p)38/NFκB signaling in the pathogenesis of HAEC in E. coli JM83infected endothelin receptor B (Ednrb)/ mice. Ednrb/ mice were infected with E. coli JM83 by oral gavage to establish the HAEC model. Wildtype and Ednrb/ mice were randomly divided into uninfected and E. coli groups. The role of TLR4/pp38/NFκB signaling was further evaluated by in vivo and in vitro analyses. The activation of the TLR4/pp38/NFκB signaling pathway induced by E. coli JM83 resulted in HAEC in Ednrb/ mice, which was evidenced by a significant increase in the expression of TNFα, TGFß and IL10, and a decreased density of Factin protein expression. TLR4 knockdown reduced the severity of enterocolitis and attenuated the expression of IL10, TNFα and TGFß, whilst increasing the density of Factin protein in Ednrb/ mice after E. coli infection. These results indicated that E. coli JM83 activates TLR4/pp38/NFκB signaling in Ednrb/ to promote the development of HAEC. Thus, inhibition of this signaling pathway may benefit the treatment and prevention of HAEC.
Subject(s)
Enterocolitis , NF-kappa B , Animals , Disease Models, Animal , Enterocolitis/genetics , Enterocolitis/metabolism , Escherichia coli/metabolism , Intestinal Mucosa/metabolism , Mice , Mice, Knockout , NF-kappa B/metabolism , Receptor, Endothelin B/metabolism , Receptors, Endothelin/metabolism , Signal Transduction , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolismABSTRACT
Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn's susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.
Subject(s)
Biliary Atresia/immunology , Biliary Atresia/therapy , Cholestasis/metabolism , Gastrointestinal Microbiome , Animals , Animals, Newborn , Bile Ducts/metabolism , Disease Models, Animal , Epithelial Cells/metabolism , Female , Humans , Infant, Newborn , Inflammation/metabolism , Killer Cells, Natural/immunology , Liver/injuries , Liver/metabolism , Liver/pathology , Mice , Mice, Inbred BALB C , PregnancyABSTRACT
Certain patients with anorectal malforma-tions (ARMs) continue to suffer from postoperative dysphoria. The enteric nervous system (ENS) is closely associated with defecation. The purinergic receptor P2Y2 (P2Y2) and Hu antigen D (HuD) proteins contain multiple motifs that enable their activation and direct coupling to integrin and growth factor receptor signaling pathways; thus, they may serve as key points in ENS development. The aim of the present study was to investigate the expression pattern of P2Y2 and HuD proteins during anorectal development in ARM embryos. The embryogenesis of ARM in rats was induced by ethylenethiourea (ETU) on the 10th gestational day. The expression patterns of P2Y2 and HuD proteins were evaluated by immunohistochemistry and western blot analysis in normal, ETU and ARM rat embryos on embryonic days E17, E19 and E21; their mRNA levels were assessed via reverse transcriptionquantitative polymerase chain reaction (RTqPCR) of the distal rectum of fetal rats. Immunohistochemistry of the distal rectum demonstrated that on E17, the expression levels of the two proteins were not different between the three groups. On E19, the expression of HuD was significantly decreased in the ARM group. On E21, the two proteins were significantly decreased in the ARM group. Additionally, the expression levels of the two proteins on E17 were significantly lower than on E21 in the ARM group. Western blotting and RTqPCR also revealed that the P2Y2 and HuD proteins and mRNA expression levels were significantly decreased in the ARM groups when compared with the normal group on E17 and E21 (P<0.01). Thus, the present study demonstrated that downregulation of P2Y2 and HuD may partly be related to the development of the ENS in ARM embryos.
Subject(s)
Anorectal Malformations/embryology , Anorectal Malformations/genetics , Down-Regulation/genetics , ELAV-Like Protein 4/genetics , Enteric Nervous System/embryology , Fetus/metabolism , Gene Expression Regulation, Developmental , Receptors, Purinergic P2Y2/genetics , Animals , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Receptors, Purinergic P2Y2/metabolismABSTRACT
In all existing radical resection procedures available for Hirschprung's disease (HD), the muscular cuff has been retained. In recent years, our study group has modified the procedure using a stepwise gradient muscular cuff cutting pull-through method for the treatment of HD. The objective of the present study was to assess patient prognosis following the use of the transanal endorectal pull-through (TEPT) method or the laparoscopy-assisted pull-through (LPT) method and to provide evidence to assist in clinical decisions. The medical records of 172 patients (age, ≥3 years) who underwent TEPT or LPT for HD between September 2003 and August 2014 at the Pediatric Surgery Department of The Affiliated Hospital of Zunyi Medical College (Zunyi, China) were reviewed (TEPT, n=94; LPT, n=78). Preoperative, intraoperative and post-operative data for the subjects involved were recorded. Each patient's family was interviewed using a uniform 12-item post-pull-through long-term outcome questionnaire, which was scored in order to compare the short and long-term treatment outcomes of patients in each group. Patients in the LPT group had significantly prolonged operating times, reduced intraoperative blood loss and perioperative transfusion rates and shorter anal dissection times. Furthermore, the oral feeding time and length of hospital stay were similar between groups. There were no significant differences in early complications between the groups. No significant differences in late complications, including anastomotic stricture and enterocolitis were observed; however, the soiling and constipation rates were significantly higher in the TEPT group compared with the LPT group. The stool pattern score was not significantly different between groups, while the frequency of bowel movements in the LPT group was significantly higher compared with the TEPT group from 9-24 months post-surgery. The stepwise gradient muscular cuff cutting pull-through method demonstrated a good safety profile and efficacy with regard to the long-term outcomes of patients with HD. These results support the clinical application of LPT as a promising surgical approach for children with HD.
ABSTRACT
Patients with congenital anorectal malformation (ARM) often present with different degrees of defecation dysfunction severity following corrective operations. Therefore, studies on how to improve the postoperative defecation function of patients with ARM are of clinical importance. The present study investigated the expression of the HuD protein in the terminal rectum of ARM embryonic rats and explored the effect of HuD expression on the development of the intestinal nervous system. Pregnant Sprague Dawley rats were randomized into a control or ARM (induced by ethylene thiourea) group. The terminal rectums of the embryonic rats were obtained during pregnancy (20 days). The histological changes of the terminal rectum were observed using hematoxylin and eosin staining. The expression of the HuD protein was assessed by immunohistochemistry and western blot analysis. In the control group, the histological structure of the terminal rectum was welldefined and a large number of submucosal and intermuscular neurons with a rich cytoplasm and strong neuritis were observed. In the ARM group, the histological layers were illdefined and the number of neurons was small. Immunohistochemistry and western blot analysis demonstrated that the concentration of the HuD protein in the ARM group was significantly lower compared with the control group (312.90±53.40:456.40±57.13; 0.24±0.05:0.45±0.06, P<0.05). HuD was abnormally expressed in the terminal rectum of the ARM embryonic rats and may be involved in the development and maturation of the enteric nervous system. The present study may provide a useful theoretical reference for the treatment of postoperative defecation dysfunction in patients with ARM.