Dehydrocholic Acid Ameliorates Sodium Taurocholate-Induced Acute Biliary Pancreatitis in Mice.

Acute biliary pancreatitis (ABP) with a high mortality rate is an incurable digestive system disease induced by abnormal bile acid regurgitation due to the biliary obstruction. Dehydrocholic acid (DA) alleviates the severity of cholestatic hepatitis related to biliary inflammation, suggesting DA is potential to develop for the incurable ABP management. Here we identified DA potency and explored the underlying mechanism in ABP. Our data showed that DA administration not only reduced typically clinicopathological parameters including serum levels of amylase and lipase but also suppressed pancreatic tissue edema, necrosis and trypsin activation in ABP mice. We also found that DA significantly reduced the necrosis of pancreatic acinar cells induced by sodium taurocholate (NaT). Further experimental data showed the significant inhibitions of DA on mitochondrial membrane potential depolarization, ATP exhaustion, calcium overload and reactive oxygen species (ROS) erupted in acinar cells induced by NaT, indicating DA could avert acinar cell death through protecting the mitochondrial function, scavenging excessive oxidative stress and balancing calcium. The comprehensive study found DA elevated the expression of transcription factor EB (TFEB) in vitro thus to increase the functional lysosome content. Indeed, DA decreased the Microtubule-associated protein light chain 3 (LC3) II/I ratio as well as ubiquitin-binding protein p62 and Parkin expressions in vivo and in vitro, revealing autophagy restoration maybe through the improvement of TFEB-mediated lysosome biogenesis. These data indicate that DA improves ABP through the mitochondrial protection, antioxidant ability enhancement and autophagy recovery. In conclusion, our study proposes a potential therapy strategy for the incurable ABP.

Compared outcomes of high-level cryptorchidism managed by Fowler-Stephens orchiopexy versus the Shehata technique: A systematic review and meta-analysis.

BACKGROUND: The surgical approach for high-level intra-abdominal testis (IAT) is variable. While most pediatric urologists prefer staged Fowler-Stephens orchiopexy (FSO), Shehata publicized a novel approach-known as staged laparoscopic traction orchiopexy (SLTO) or the Shehata technique-to better manage IATs. OBJECTIVE: This study compares the overall success rates, atrophy rates, retraction rates, and operation times of the two procedures to assist surgeons with developing procedure strategies. METHODS: Databases were searched for relevant literature involving these two approaches, and studies meeting the eligibility criteria were involved; RevMan 5.4 was used to conduct this meta-analysis. The relative risk (RR), weighted mean difference, 95% confidence interval (CI), p-value, publication bias, and heterogeneity were calculated. RESULTS: The Shehata technique demonstrated better performance than staged FSO regarding the overall success and atrophy rate, while the retraction rate and operation time had no statistical difference. CONCLUSIONS: This study revealed that the Shehata technique may be an alternative to staged FSO for managing high-level IATs. Additional high-quality studies regarding the Shehata technique, as well as a long-term follow-up, are required for further and more credible analysis.

Open transumbilical intussusception reduction in children: A prospective study.

PURPOSE: Manual intussusception reduction can sometimes be accomplished through the existing umbilical incision after a laparoscopic attempt has failed. We compared the safety and efficacy of open transumbilical intussusception reduction (OTIR) and laparoscopic reduction (LAP). METHODS: We prospectively enrolled children diagnosed with intussusception at our hospital from June 2014 to December 2018. Clinically stable patients who failed pneumatic intussusception reduction were randomly assigned to the OTIR or LAP group. We compared reduction rates, complications, operative times, and surgery costs between the two groups. RESULTS: Fifty-one of 451 patients with an intussusception met the study criteria. In the OTIR group (n = 27), 22 intussusceptions were successfully reduced, and 5 required incision extension. The mean operative time was 47.7 ±â€¯10.5 min, and mean surgery cost was 1259.74 ±â€¯46.24 US dollars. In the LAP group (n = 24), 5 patients required conversion to open surgery. Three of the 5 cases were resolved by OTIR, while the other 2 needed incision extension. The mean operative time was 68.63 ±â€¯17.13 min, and mean surgery cost was 1750.63 ±â€¯106.98 US dollars. Severe complications did not occur in either group. CONCLUSIONS: OTIR was as safe and effective as LAP and had a shorter operative time and lower surgery cost. OTIR is a good option for intussusception reduction in children. TYPE OF STUDY: Treatment study. LEVELS OF EVIDENCE: Level I.

Piezo1 initiates platelet hyperreactivity and accelerates thrombosis in hypertension.

BACKGROUND: Thrombosis is the pathological basis of cardiovascular and cerebrovascular diseases, which seriously threaten human life and health. Among them, nearly half of cardiovascular disease patients suffer from severe hypertension complications. Hypertension is thought to cause abnormal platelet activation and increases the risk of thrombosis, but the related mechanism is still vague. OBJECTIVES: This study hypothesized that the abnormal hemodynamics of blood under hypertension might affect platelet function and accelerate thrombosis by activating mechanoreceptor Piezo1. METHODS: To assess the activation effect of hypertension on mechanoreceptor Piezo1, we injected Piezo1 agonist Yoda1 and antagonist GsMTx-4 through the tail vein, then examined the platelet activation status and thrombosis. RESULTS: Our results displayed that antagonist GsMTx-4 effectively inhibited calcium influx caused by hypertension and agonist Yoda1. Antithrombotic studies proved that the inhibition of Piezo1 effectively inhibited arterial thrombosis and reduced the infarct size of stroke in hypertensive mice. CONCLUSIONS: Our study explains the activation of mechanoreceptor Piezo1 under hypertension is the key to abnormal platelet activation and thrombosis while providing novel platelet intervention strategies to prevent thrombosis.

Vitamin B12 Attenuates Acute Pancreatitis by Suppressing Oxidative Stress and Improving Mitochondria Dysfunction via CBS/SIRT1 Pathway.

Acute pancreatitis is an inflammatory disorder of the pancreas associated with substantial morbidity and mortality, which is characterized by a rapid depletion of glutathione (GSH). Cysthionine-ß-synthase (CBS) is a key coenzyme in GSH synthesis, and its deficiency is related to a variety of clinical diseases. However, whether CBS is involved in the pathogenesis of acute pancreatitis remains unclear. First, we found that CBS was downregulated in both in vivo and in vitro AP models. The pancreatic damage and acinar cell necrosis related to CBS deficiency were significantly improved by VB 12, which stimulated clearance of reactive oxygen species (ROS) by conserving GSH. Furthermore, EX-527 (a specific inhibitor of SIRT1) exposure counteracted the protective effect of VB 12 by promoting oxidative stress and aggravating mitochondrial damage without influencing CBS, indicating that vitamin B12 regulates SIRT1 to improve pancreatical damage by activating CBS. In conclusion, we found that VB 12 protected acute pancreatitis associated with oxidative stress via CBS/SIRT1 pathway.

Tumor angiogenesis and its clinical significance in pediatric malignant liver tumor.

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD) count in pediatric malignant liver tumor and their clinical significances. METHODS: Fourteen children with malignant liver tumors including seven hepatocellular carcinomas (HCCs), five hepatoblastomas, one malignant mesenchymoma and one rhabdomyosarcoma were studied. Twelve adult HCC samples served as control group. All samples were examined with streptavidin-biotin peroxidase (SP) immunohistochemical staining for VEGF expression and MVD count. RESULTS: VEGF positive expression in all pediatric malignant liver tumors was significantly higher than that in adult HCC (0.4971+/-0.14 vs 0.4027+/-0.03, P<0.05). VEGF expression in pediatric HCC group was also markedly higher than that in adult HCC group (0.5665+/-0.10 vs 0.4027+/-0.03, P<0.01) and pediatric non-HCC group (0.5665+/-0.10 vs 0.4276+/-0.15, P<0.05). The mean value of MVD in pediatric malignant liver tumors was significantly higher than that in adult HCC (33.66+/-12.24 vs 26.52+/-4.38, P<0.05). Furthermore, MVD in pediatric HCC group was significantly higher compared to that in adult HCC group (36.94+/-9.28 vs 26.52+/-4.38, P<0.05), but there was no significant difference compared to the pediatric non-HCC group (36.94+/-9.28 vs 30.37+/-14.61, P>0.05). All 7 children in HCC group died within 2 years, whereas the prognosis in pediatric non-HCC group was better, in which two patients survived more than 5 years. CONCLUSION: Children with malignant liver tumors, especially with HCC, may have extensive angiogenesis that induces a rapid tumor growth and leads to a poor prognosis.

The mechanism underlying dibutyl phthalate induced shortened anogenital distance and hypospadias in rats.

PURPOSE: The purpose of this study was to investigate the mechanism of dibutyl phthalate (DBP) induced hypospadias and shortened anogenital distance (AGD). METHODS: AGD, hypospadias, and cryptorchidism incidence was observed in male offspring of DBP treated pregnant Wistar rats. Testicular development and testosterone levels of normal and DBP-treated rat embryos were compared. RESULTS: Male offspring of 300mg and 900mg DBP-treated pregnant Wistar rats exhibited shortened average AGD compared with the control group. A 22.7% hypospadias incidence was observed in the 300mg group, but no offspring with cryptorchidism were identified. In the 900mg group, hypospadias and cryptorchidism incidence reached 43.5% and 17.4%, respectively. Between E15.5 and E17.5, the 300mg group exhibited delayed testicular development and testosterone secretion. However, testicular development and testosterone secretion subsequently recovered. The 300mg treated and control groups had similar measures after E19.5. Contrastingly, testicular development and testosterone secretion were significantly diminished throughout development in the 900mg group. Exogenous testosterone partially counteracted DBP-induced changes in the reproductive organs of male offspring of DBP-treated rats. CONCLUSIONS: High-dose DBP exposure may induce testicular dysgenesis in rat embryos. Additionally, low-dose DBP may delay testicular development and testosterone secretion during urethral development. This disruption may result in hypospadias.

Ceftriaxone and acute renal failure in children.

OBJECTIVE: Our aim was to evaluate the clinical profile, treatment, and outcome of ceftriaxone-associated postrenal acute renal failure (PARF) in children. METHODS: We retrospectively studied 31 consecutive cases from 2003 to 2012 for PARF after ceftriaxone treatment. There was no past history of urolithiasis or nephropathy in these children. RESULTS: The average time of ceftriaxone administration before PARF was 5.2 days. The major symptoms apart from anuria included flank pain (>3 years old, 25/25), excessive crying (<3 years, 6/6), and vomiting (19/33). Ultrasound showed mild hydronephrosis (25/31) and ureteric calculi (11/31). Nine children recovered after 1 to 4 days of pharmacotherapy. Twenty-one children who were resistant to pharmacotherapy underwent retrograde ureteral catheterization. After catheterization of their ureters, normal urine flow was observed, and the symptoms subsided immediately. Catheter insertion failed in 1 child who subsequently underwent 3 sessions of hemodialysis before normal urination was restored. Ceftriaxone was verified to be the main component of the calculi in 4 children by tandem mass spectrometric analysis. The recovery was complete in all cases. CONCLUSIONS: Ceftriaxone therapy in children may cause PARF. Early diagnosis and prompt pharmacological therapy are important in relieving the condition. Retrograde ureteral catheterization is an effective treatment of those who fail to respond to pharmacotherapy.

Multi-incisional transumbilical laparoscopic surgery for nonpalpable undescended testes: a report of 126 cases.

PURPOSE: The aim of this study was to evaluate the feasibility of multi-incisional transumbilical laparoscopic surgery for the management of nonpalpable undescended testes. MATERIAL AND METHODS: A series of 126 patients with 162 nonpalpable undescended testes underwent transumbilical laparoscopic surgery. Their mean age was 1.8 years (range, 1.1-6.5 years). Of the 126 cases, 73 were left-sided, 17 were right-sided, and 36 had bilateral cryptorchidism. Primary orchidopexy and the Fowler-Stephens procedure were used to mobilize the testes. RESULTS: All the operations were successfully performed without intraoperative complications. No additional ports or any conversions to an open procedure were required. Of the 162 nonpalpable undescended testes, 21 were absent or atrophied. One-hundred thirteen testes underwent primary orchidopexy, and 28 cases underwent a Fowler-Stephens orchidopexy. Patients were followed-up for 6-15 months. Only one case of testicular retraction was observed, and all others maintained a good size and the correct position. The scars were hidden within the umbilicus. CONCLUSION: Transumbilical laparoscopic surgery is safe and feasible for nonpalpable undescended testes, and leaves no obvious abdominal or inguinal scar.

Complicated appendicitis in children: is laparoscopic appendectomy appropriate? A comparative study with the open appendectomy--our experience.

PURPOSE: Good outcomes have been reported with laparoscopic appendectomy (LA) for uncomplicated appendicitis in children, but the use of laparoscopy for complicated appendicitis in children is more controversial. This is related to a higher incidence of postoperative abdominal and wound infections. The purpose of this trial was to retrospectively compare LA and open appendectomy (OA) for complicated appendicitis and evaluate the efficacy of LA in children with complicated appendicitis. METHODS: The outcome of 128 patients with complicated appendicitis in children was retrospectively analyzed. There were 80 children in the LA group and 48 in the OA group. The appendectomies were performed by a single senior surgeon and his surgical trainees. There was no selection of cases for LA. Data collection included demographics, operative time, resumption of diet, infectious complications (wound infection and intraabdominal abscess), length of hospitalization, and duration of antibiotic use. RESULTS: There were no cases of LA that required conversion to OA. The operative time for LA (88.5 +/- 28.8 minutes for LA vs 71.8 +/- 30.6 minutes for OA; t = 3.10; P = .002) was longer. Patients in the LA group returned to oral intake earlier (1.8 +/- 0.6 days for LA vs 2.8 +/- 0.8 days for OA; t = -8.04; P < .01) and had a shorter length of hospital stay (6.5 +/- 2.2 days for LA vs 7.8 +/- 2.9 days for OA; t = -2.87; P = .005). The incidence of wound infection (1/80 [1.3%] for LA vs 6/48 [12.5%] for OA; P < .05) and postoperative intraabdominal abscess (2/80 [2.5%] for LA vs 7/48 [14.6%] for OA; P < .05) in LA group was lower. No significant difference was found in the duration of antibiotic administration between the 2 groups (5.8 +/- 1.8 days for LA vs 6.3 +/- 2.3 days for OA; t = -1.37; P = .174). No mortality was observed in either group. CONCLUSIONS: The minimally invasive laparoscopic technique is feasible, safe, and efficacious for children with complicated appendicitis. Laparoscopic appendectomy should be the initial procedure of choice for most cases of complicated appendicitis in children.

Factors affecting the long-term results of hypospadias repairs.

PURPOSE: The aim of this study was to explore the relationships between the short- and long-term results of hypospadias repair and identify the factors that could affect the long-term results of hypospadias repair. MATERIALS AND METHODS: Between 1982 and 1988, 142 patients were operated for hypospadias and completed their treatment at Tongji Hospital (Wuhan, China). Their records were analyzed retrospectively, and a detailed questionnaire was mailed to them. RESULTS: One hundred two patients returned the questionnaire. Patients in the proximal hypospadias group, those using Denis-Browne technique, and those with early complications were markedly dissatisfied with the overall results of hypospadias repair and penile appearance. Moreover, their dissatisfaction grew with the number of operations they had. Thirty-nine (95.1%) of 41 patients using the Denis-Browne technique had voiding problems. Forty-nine (48%) of 102 patients felt inhibited in seeking girlfriends or sexual contacts. Moreover, there was a positive correlation between the level of sexual inhibition and operation times. A highly positive correlation was found between the age at the time hypospadias surgery was completed and the extent of being sexually inhibited. The patients in proximal hypospadias group had more erection and ejaculation problems. CONCLUSIONS: The short-term results of hypospadias repair could affect the long-term results significantly, and good short-term results also predict long-term ones. The types of hypospadias, procedures, and complications have significant influences on predicting the long-term results of hypospadias repairs.

Rare causes of gastric outlet obstruction in children.

Gastric outlet obstruction (GOO) presenting beyond the newborn period is a relatively rare condition, when infantile hypertrophic pyloric stenosis (IHPS) is excluded. This report describes the clinical features, evaluation and management of 18 patients with GOO which was not caused by IHPS. The sex, age, and main presenting features were recorded on admission. Hemoglobin estimation, serum chemistry and blood gas analysis were also assessed in these patients. The diagnosis was confirmed with gastrointestinal barium, B ultrasound, gastroscopy, or at surgery. Some of them underwent gastroscopy with biopsy sampling for rapid urease test or histologic examination with Giemsa stains for Helicobacter pylori. Thirteen patients had peptic ulcer disease, of which six were successfully treated with medications. While the other seven needed operative management which included Heineke-Mikulicz pyloroplasty, gastroduodenostomy or gastrojejunostomy, respectively. All the patients who had Heineke-Mikulicz pyloroplasty or gastrojejunostomy developed bile reflux gastritis that could be alleviated with omeprazol. None of the patients developed dumping syndrome, failing to thrive, or anemia. Three children with antral diaphragm recovered without any complications by diaphragm excision with Heineke-Mikulicz pyloroplasty. The pylorus was compressed by fibrotic band in one 30-month boy, and he recovered uneventfully with Heineke-Mikulicz pyloroplasty during 10-year follow-up. Gastric outlet obstruction secondary to ingestion of sulfuric acid was noted in one patient, and he was successfully treated with gastroduodenostomy. Our data suggests that the satisfactory results could be expected in children with GOO with different therapeutic modalities based on the specific cause and degree of obstruction.

Acute phlegmonous gastritis in an infant.

The authors present a case of acute phlegmonous gastritis occurring in an 11-month-old infant in whom the diagnosis was made by microscopic examination after surgery for perforation of the stomach. The patient recovered uneventfully. The pathogenesis, diagnosis, and treatment in this inflammatory process are discussed.

[Reoperation for postoperative constipation recurrences of Hirschsprung disease].

OBJECTIVE: To summarize the causes and treatment experiences of postoperative constipation recurrences of Hirschsprung disease. METHODS: Clinical data of 37 cases receiving operation again for postoperative constipation recurrences of Hirschsprung disease were collected. The recurrent causes, reoperation procedures and therapeutic efficacy were analyzed. RESULTS: Among 37 cases, the recurrent causes included insufficient resection of the intestine in 14 cases, co-existent intestinal neural hypogenesis in 6, gate syndrome in 5, and others in 12 cases. There was no postoperative death. Thirty-one cases (83.8%) were followed-up from 6 months to 11 years. The defecation frequency was 1-2 times per day in 15 cases, one times per two days in 7, one times per three days in 6 cases. Two cases could defecate with the help of laxative purgatives. Nobody had incontinence. CONCLUSION: The main cause of postoperative constipation recurrences of Hirschsprung disease is insufficient resection of the intestine,and reoperation can get better results.

The treatment of high and intermediate anorectal malformations: one stage or three procedures?

BACKGROUND/PURPOSE: The aim of this study was to examine the safety, feasibility, and the long-term outcome of complete 1-stage repair of high and intermediate anorectal malformation using posterior sagittal anorectoplasty (PSARP) in a neonate. METHODS: One hundred thirteen patients with high-type and intermediate-type anorectal malformations (ARM) underwent follow-up. Of 113 cases, 48 cases entailed a divided colostomy, definitive operation, and colostomy closure (group I); the other 65 patients underwent 1-stage PSARP (group II). Anorectal function was measured by the modified Wingspread scoring, including "excellent," "good," "fair," and "poor." In barium enema studies, anorectal angulation was judged as "clear," "unclear," and "not present," and leakage of barium was observed in the meantime. For anorectal manometric studies, anal resting pressure (ARP), anal squeezing pressure (ASP), and positive anorectal reflex (PAR) were measured. RESULTS: In group I, the rate of excellent and good scores was 58.3% (28 of 48). In the barium enema examination, 85.4% (41 of 48) was clear and 14.6%(7 of 48) unclear or not present. The rate of barium leakage was 10.4% (5 of 48). In group II, the rate of excellent and good was 53.8% (35 of 65). Anorectal angulations were clear in 83.1% of patients (54 of 65). Barium leakage happened in 7.69% of patients (5 of 65). Early operative complications occurred in 56.3% (27 of 48) of patients in group I and 29.2% (19 of 65) in group II. The incidence of colostomy complications in group I was 39.6% (19 of 48). Soiling and constipation were the major complications after the PSARP operation. The respective rates of constipation in the 2 groups were 47.9% (23 of 48) and 44.6% (29 of 65), and the respective rates of soiling were 47.9% (23 of 48) and 50.8% (33 of 65). There was no significant difference in the mean ARP between the 2 groups. CONCLUSIONS: The 1-stage PSARP procedure in the neonate not only achieves the same long-term outcome as the conventional PSARP procedure but also involves fewer short-term complications. Complete 1-stage repair using the PSARP to treat high-type and intermediate-type anorectal malformations is safe and feasible.