Indocyanine green fluorescence imaging-assisted laparoscopy resection of retroperitoneal tumors in children: case report and literature review.

This study examined the applicability of indocyanine green (ICG) fluorescence imaging to assist the laparoscopic resection of retroperitoneal tumors in pediatric patients via an abdominal approach. Conducted prospectively at the Guangzhou Women and Children's Medical Center from May to September 2023, the research included three pediatric cases, for whom laparoscopic retroperitoneal tumor resections were performed utilizing ICG fluorescence imaging. In each case, ICG was intravenously administered (0.3 mg/kg) prior to surgery, enabling the visualization of vital vascular structures through real-time fluorescence imaging. The trocar's placement was guided by a "four-hole" technique from the healthy side in a 70-degree lateral decubitus position. The operations were accomplished successfully without any complications. Pathological analysis of the patients identified one case of Wilms tumor of the embryonal type, one ganglioneuroblastoma of the mature type without N-MYC gene amplification, and one mature cystic teratoma. The findings suggest that with careful patient selection and skilled surgical execution, the utilization of ICG fluorescence imaging in the laparoscopic resection of retroperitoneal tumors is both safe and effective in children. This approach significantly improves the visualization of critical blood vessels, thus enhancing surgical safety.

Inherited KDM6AA649T facilitates tumor-immune escape and exacerbates colorectal signet-ring cell carcinoma outcomes.

Childhood onset of colorectal signet-ring cell carcinoma (CR-SRCC) is extremely rare and featured as highly malignant with poor prognosis. Here we reported a CR-SRCC case of 11-year-old boy with a novel inherited X-linked KDM6AA694T mutation. The H3K27me3 demethylase KDM6A was frequently mutated in varieties of tumors and acts as a tumor suppressor. In vivo H3K27me3 demethylation assay demonstrated that KDM6AA694T had dampened H3K27me3 demethylase activity. Overexpression of KDM6AA694T in SRCC cell line KATO3 promoted cell proliferation, invasion and migration, which were further confirmed in vivo by constructing orthotopic tumor growth and lung metastasis model. Besides, expression of KDM6AA694T in immune cells suppresses inflammatory macrophage response and effector T cell response. In conclusion, we characterized a novel inherited KDM6AA694T mutant from a childhood-onset SRCC case and demonstrated that the mutant with impaired H3K27me3 demethylase activity could potentiate tumor malignancy and suppress antitumor immunity.

Associations of Fish and Fish Oil Consumption With Incident Inflammatory Bowel Disease: A Population-Based Prospective Cohort Study.

BACKGROUND: We examined the associations of fish and fish oil consumption with inflammatory bowel disease (IBD) incidence. PATIENTS AND METHODS: We conducted a longitudinal analysis based on the UK Biobank, a population-based prospective cohort. Dietary consumption of fish and fish oil was collected by questionnaire. IBD incident cases were identified through links to National Health Services datasets. Cox proportional hazards regression models were used to assess the associations between oily fish, nonoily fish, and fish oil intake and IBD incidence with adjustment for various confounding factors. RESULTS: A total of 265 839 participants free of IBD at baseline were included, and 1554 incident IBD cases were identified during an average follow-up of 11.8 years. In fully adjusted models, we found that compared with participants who never ate oily fish, those having <1 serving/wk, 1 serving/wk, and >1 serving/wk had 9% (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.77-1.08), 19% (HR, 0.81; 95% CI, 0.69-0.96), and 12% (HR, 0.88; 95% CI, 0.73-1.06) lower risks of IBD, respectively, albeit not all statistically significant. A significant association was found between fish oil intake and a reduced risk of IBD (HR, 0.84; 95% CI, 0.75-0.93). We found no significant associations for nonoily fish. In a subsample (n = 105 714) of participants with multiple subsequent dietary reviews, we also found a negative association between the frequency of fish oil intake over time and incident IBD (P trend < .05). CONCLUSIONS: Our findings indicate that oily fish and fish oil supplements might be protective factors against IBD.

Individuals who regularly consumed oily fish had a reduced risk of inflammatory bowel disease (IBD). Fish oil supplementation was also linked with a reduced risk of IBD. By contrast, no significant association was observed between nonoily fish intake and IBD.

The association of immune-related genes and the potential role of IL10 with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a severe immune-related disease that is characterized by biliary obstruction and cholestasis. The etiology of BA is unclear, our aim was to explore the relationship between biliary tract inflammation and immune-related genes. METHODS: We selected 14 SNPs in 13 immune-related genes and investigated their associations with BA by using a large case‒control cohort with a total of 503 cases and 1473 controls from southern China. RESULTS: SNP rs1518111 in interleukin10 (IL10) was identified as associated with BA (P = 5.79E-03; OR: 0.80; 95% CI: 0.68-0.94). The epistatic effects of the following pairwise interactions among these SNPs were associated with BA: signal transducer and activator of transcription 4 (STAT4) and chemokine (C-X-C motif) ligand 3 (CXCL3); STAT4 and damage-regulated autophagy modulator1 (DRAM1); CXCL3 and RAD51 paralog B (RAD51B); and interferon gamma (IFNG) and interleukin26 (IL26). Furthermore, we explored the potential role of IL-10 in the pathogenesis of the neonatal mouse model of BA. IL-10 effectively prevented biliary epithelial cell injury and biliary obstruction in murine BA as well as inhibit the activation of BA-related immune cells. CONCLUSIONS: In conclusion, this study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. IMPACT: This study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. This study could infer that IL-10 may play a protective role in BA mouse model. We found that four SNPs (rs7574865, rs352038, rs4622329, and rs4902562) have genetic interactions.

Mitochondria-associated gene expression perturbation predicts clinical outcomes and shows potential for targeted therapy in neuroblastoma.

Background: Mitochondria have long been considered a potential target in cancer therapy because malignant cells are known for their altered energy production. However, there is a lack of comprehensive research on the involvement of mitochondria-associated proteins (MAPs) in neuroblastoma (NB), and their potential as therapeutic targets is yet to be fully explored. Methods: MAP genes were defined based on the protein-coding genes with mitochondrial localization. The mRNA expression patterns and dynamics of MAP genes associated with NB were investigated by integrating publicly available transcriptional profiles at the cellular and tissue levels. Multivariate Cox regression analysis was conducted to reveal the association of MAP genes with the overall survival (OS) and clinical subgroups of NB patients. The single-cell RNA-seq dataset and gene dependency screening datasets were analyzed to reveal the therapeutic potential of targeting MAP genes. Results: We compiled a total of 1,712 MAP genes. We found the global and cell type-specific mRNA expression changes of the MAP genes associated with NB status and survival. Our analyses revealed a group of MAP gene signatures independent of MYCN-amplification status associated with NB outcome. We provided computational evidence with selected MAP genes showing good performance in predicting long-term prognosis. By analyzing gene dependency of the MAP genes in NB cell lines and ex vivo human primary T cells, we demonstrated the therapeutic potential of targeting several MAP genes in NB tumors. Conclusions: Collectively, our study provides evidence for the MAP genes as extended candidates in NB tumor stratification and staging, prognostic prediction, and targeted drug development.

MiR-100 rs1834306 A>G Increases Biliary Atresia Risk in Southern Han Chinese Children.

Background: Biliary atresia (BA) is a type of severe cholestatic childhood disease that may have a genetic component. miR-100 plays a key role in regulating cell apoptosis, proliferation, and inflammatory reactions. A single-nucleotide polymorphism in miR-100 has been proven to modulate susceptibility to various diseases. Methods: We conducted a case-control retrospective study to explore the correlation between miR-100 gene polymorphism (rs1834306 A>G) and biliary atresia susceptibility in 484 Chinese patients and 1445 matched control subjects. Results: Our results showed that rs1834306 A>G was correlated with a significantly increased risk for BA (GG vs. AA: adjusted odds ratio (OR) = 1.44, 95%confidence interval (CI) = 1.02-2.03, p = 0.041; and GG vs. AA/AG: adjusted OR = 1.39, 95%CI = 1.02-1.89, p = 0.036). Conclusions: Our results showed that the rs1834306 A>G polymorphism is associated with an increased risk for BA and contributes to BA susceptibility.

Empirical dynamic modeling of the association between ambient PM2.5 and under-five mortality across 2851 counties in Mainland China, 1999-2012.

BACKGROUND: Ambient fine particulate matter (PM2.5) pollution has been associated with mortality from various diseases, however, its association with under-five mortality rate (U5MR) has remained largely unknown. METHODS: Based on the U5MR data across 2851 counties in Mainland China from 1999 to 2012, we employed approximate Bayesian latent Gaussian models to assess the association between ambient PM2.5 and U5MR at the county level for the whole nation and sub-regions. GDP growth rate, normalized difference vegetation index (NDVI), temperature, and night-time light were included as covariates using a smoothing function. We further implemented an empirical dynamic model (EDM) to explore the potential causal relationship between PM2.5 and U5MR. RESULTS: We observed a declining trend in U5MR in most counties throughout the study period. Spatial heterogeneity in U5MR was observed. Nationwide analysis suggested that each 10 µg/m3 increase in annual concentration of PM2.5 was associated with an increase of 1.2 (95% CI: 1.0 - 1.3) per 1000 live births in U5MR. Regional analyses showed that the strongest positive association was located in the Northeastern part of China [1.8 (95% CI: 1.4 - 2.1)]. The EDM showed a significant causal association between PM2.5 and U5MR, with an embedding dimension of 5 and 7, and nonlinear values θ of 4 and 6, respectively. CONCLUSION: China exhibited a downward trend in U5MR from 1999 to 2012, with spatial heterogeneity observed across the country. Our analysis reveals a positive association between PM2.5 and U5MR, which may support a causal relationship.

Diagnosis and treatment of traumatic duodenal rupture in children.

BACKGROUND: The purpose of this study was to investigate the diagnosis and treatment experience of traumatic duodenal ruptures in children. METHODS: Clinical data were collected from four children suffering from a traumatic duodenal rupture who were admitted to and treated by our hospital from January 2012 to December 2020. The early diagnosis and treatment, surgical plan, postoperative management, complications, and prognosis of each child were analyzed. The key points and difficulties of the diagnosis and treatment for this type of injury are summarized. RESULTS: One child had an extreme infection caused by drug-resistant bacteria, which resulted in severe complications, including wound infection, dehiscence, and an intestinal fistula. One child developed an anastomotic stenosis after the duodenostomy, which improved following an endoscopic balloon dilatation. The other two children had no relevant complications after their operations. All four patients were cured and discharged from hospital. The average hospital stay was 48.25 ± 26.89 days. The follow-up period was 0.5 to 1 year. No other complications occurred, and all children had a positive prognosis. CONCLUSIONS: The early identification of a duodenal rupture is essential, and surgical exploration should be carried out proactively. The principles of damage-control surgery should be followed as much as possible during the operation. Multidisciplinary cooperation and management are both important to reduce the occurrence of postoperative complications and improve cure rates.

Prenatal diagnosis and postnatal management of congenital mesoblastic nephroma: Experience at a single center in China.

OBJECTIVE: To review the prenatal and postnatal clinical characteristics and pathological subtypes, as well as the surgical outcome for congenital mesoblastic nephroma (CMN) cases. METHOD: A retrospective review was performed in 11 cases with CMN prenatally diagnosed at a single center between 2015 and 2019. The clinical characteristics, surgical outcome, histopathology, and follow-up were retrospectively obtained and reviewed. RESULTS: The median gestational age at which the sonographic diagnosis was made was 35 weeks. Polyhydramnios was found in four (36.4%) cases, and all resulted in a preterm birth. Nine infants had hypertension. Ten cases underwent radical nephrectomy, and one underwent radical nephrectomy and partial adrenalectomy. The pathological results showed that six tumors were classical variants, four mixed variants, and one was a cellular variant. Three cases presented as a stage I, eight as stage II, and no stage III or IV cases were diagnosed. All patients are alive so far. At a median follow-up of 14 months, no local recurrence, or remote metastases were found. CONCLUSION: The prognosis of prenatal CMN cases is excellent after early surgery.

Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia.

Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1+effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology.

Total versus conventional laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy in children with choledochal cysts: a case-control study.

BACKGROUND: To compare the efficacy of total and conventional laparoscopic hepaticojejunostomy (TLH and CLH) in children with choledochal cysts (CDCs). METHODS: Data from patients undergoing TLH and CLH between August 2017 and December 2018 were retrospectively analyzed. Intraoperative blood loss, time for jejunum-cojejunum anastomosis, time to oral intake, postoperative hospital stay, hospitalization expenses, and postoperative complications were compared. RESULTS: All 55 patients (TLH = 30, CLH = 25) were successfully treated without conversion to open surgery. In the TLH and CLH groups, the time to oral intake was 3.57 ± 0.19 d and 4.56 ± 0.27 d, respectively (t = 3.07, P < 0.01), the postoperative hospital stay was 5.50 ± 0.28 d and 7.00 ± 0.74 d (t = 2.03, P < 0.05), and the hospitalization expenses were CNY 40,085 ± 2447 and CNY 26,084 ± 2776 (t = 3.79, P < 0.001). There were no significant differences in intraoperative blood loss (9.57 ± 3.28 ml vs 8.2 ± 1.13 ml, t = 0.37, P = 0.72) or time for jejunum-cojejunum anastomosis (80.5 ± 2.46 min vs 75.00 ± 2.04 min, t = 1.68, P = 0.10). The median follow-up periods of the TLH and CLH groups were 17 and 16 months, respectively. Overall complication rates were comparable between the two groups (10% vs 8%, χ2 = 0.07, P = 0.79). CONCLUSIONS: TLH in children with CDCs has the advantages of rapid gastrointestinal functional recovery and a short hospitalization. However, hospitalization is relatively expensive.

Nitrite Accumulation Is Required for Microbial Anaerobic Iron Oxidation, but Not for Arsenite Oxidation, in Two Heterotrophic Denitrifiers.

Phylogenetically diverse species of bacteria can mediate anaerobic oxidation of ferrous iron [Fe(II)] and/or arsenite [As(III)] coupled to nitrate reduction, impacting the biogeochemical cycles of Fe and As. However, the mechanisms for nitrate-dependent anaerobic oxidation of Fe(II) and As(III) remain unclear. In this study, we isolated two bacterial strains from arsenic-contaminated paddy soils, Ensifer sp. ST2 and Paracoccus sp. QY30. Both strains were capable of anaerobic As(III) oxidation, but only QY30 could oxidize Fe(II) under nitrate-reducing conditions. Both strains contain the As(III) oxidase gene aioA, whose expression was induced greatly by As(III) exposure. Both strains contain the whole suite of genes for complete denitrification, but the nitrite reductase gene nirK was not expressed in QY30 and nitrite accumulated under nitrate-reducing conditions. When the functional nirK gene was knocked out in strain ST2, its nitrite reduction ability was completely abolished and nitrite accumulated in the medium. Moreover, the ST2ΔnirK mutant gained the ability to oxidize Fe(II). When nirK gene from ST2 was introduced to QY30, the recombinant strain QY30::nirK gained the ability to reduce nitrite but lost the ability to oxidize Fe(II). These genetic manipulations did not affect the ability of both strains to oxidize As(III). Our results indicate that nitrite accumulation is required for anaerobic oxidation of Fe(II) but not for As(III) oxidation in these strains. The results suggest that anaerobic Fe(II) oxidation in the two bacterial strains is primarily driven by abiotic reaction of Fe(II) with nitrite, while reduction of nitrate to nitrite is sufficient for redox coupling with anaerobic As(III) oxidation catalyzed by Aio. Deletion of nirK gene in denitrifiers can enhance anaerobic Fe(II) oxidation.

HMGB1-promoted and TLR2/4-dependent NK cell maturation and activation take part in rotavirus-induced murine biliary atresia.

Recent studies show that NK cells play important roles in murine biliary atresia (BA), and a temporary immunological gap exists in this disease. In this study, we found high-mobility group box-1 (HMGB1) and TLRs were overexpressed in human and rotavirus-induced murine BA. The overexpressed HMGB1 released from the nuclei of rotavirus-infected cholangiocytes, as well as macrophages, activated hepatic NK cells via HMGB1-TLRs-MAPK signaling pathways. Immature NK cells had low cytotoxicity on rotavirus-injured cholangiocytes due to low expression of TLRs, which caused persistent rotavirus infection in bile ducts. HMGB1 up-regulated the levels of TLRs of NK cells and promoted NK cell activation in an age-dependent fashion. As NK cells gained increasing activation as mice aged, they gained increasing cytotoxicity on rotavirus-infected cholangiocytes, which finally caused BA. Adult NK cells eliminated rotavirus-infected cholangiocytes shortly after infection, which prevented persistent rotavirus infection in bile ducts. Moreover, adoptive transfer of mature NK cells prior to rotavirus infection decreased the incidence of BA in newborn mice. Thus, the dysfunction of newborn NK cells may, in part, participate in the immunological gap in the development of rotavirus induced murine BA.

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.

Silencing of the rotavirus NSP4 protein decreases the incidence of biliary atresia in murine model.

Biliary atresia is a common disease in neonates which causes obstructive jaundice and progressive hepatic fibrosis. Our previous studies indicate that rotavirus infection is an initiator in the pathogenesis of experimental biliary atresia (BA) through the induction of increased nuclear factor-kappaB and abnormal activation of the osteopontin inflammation pathway. In the setting of rotavirus infection, rotavirus nonstructural protein 4 (NSP4) serves as an important immunogen, viral protein 7 (VP7) is necessary in rotavirus maturity and viral protein 4 (VP4) is a virulence determiner. The purpose of the current study is to clarify the roles of NSP4, VP7 and VP4 in the pathogenesis of experimental BA. Primary cultured extrahepatic biliary epithelia were infected with Rotavirus (mmu18006). Small interfering RNA targeting NSP4, VP7 or VP4 was transfected before rotavirus infection both in vitro and in vivo. We analyzed the incidence of BA, morphological change, morphogenesis of viral particles and viral mRNA and protein expression. The in vitro experiments showed NSP4 silencing decreased the levels of VP7 and VP4, reduced viral particles and decreased cytopathic effect. NSP4-positive cells had strongly positive expression of integrin subunit α2. Silencing of VP7 or VP4 partially decreased epithelial injury. Animal experiments indicated after NSP4 silencing, mouse pups had lower incidence of BA than after VP7 or VP4 silencing. However, 33.3% of VP4-silenced pups (N = 6) suffered BA and 50% of pups (N = 6) suffered biliary injury after VP7 silencing. Hepatic injury was decreased after NSP4 or VP4 silencing. Neither VP4 nor VP7 were detected in the biliary ducts after NSP4. All together, NSP4 silencing down-regulates VP7 and VP4, resulting in decreased incidence of BA.

A novel method for establishment and characterization of extrahepatic bile duct epithelial cells from mice.

Culture of extrahepatic bile duct epithelial cells is a useful model to investigate physiology of extrahepatic bile duct epithelia and hepatobiliary disease mechanisms. The aim of this work was to establish and characterize a primary murine extrahepatic bile duct epithelial cell culture. Epithelial cells were isolated from extrahepatic bile ducts of BALB/c mice that were intraperitoneally injected with newborn bovine serum to induce the proliferation of extrahepatic bile ducts' epithelial cells and cultured on rat tail type I collagen-coated plastic culture flask containing DMEM/HamF12 with 10% FBS and 10 ng/ml epidermal growth factor at 37°C in an incubator with 5% humidified CO(2). The cells showed typical morphologic characteristics of epithelial phenotypes with cobblestone appearance in monolayer within 5-6 d after culture; they were positive against anticytokeratin-19 immunostaining. Transmission electron microscopy showed typical bile duct epithelia with microvilli on the cytomembrane, Golgi complex, massive mitochondria, and rough endoplasmic reticulum in the cytoplasmic. The growth curve of the epithelial cells was determined by a MTT assay which showed a normal sigmoidal growth curve. This culture technique might be a reliable method for isolation, purification, and primary culture of extrahepatic bile duct epithelial cells that can serve as a model for in vitro studies on the pathophysiology of hepatobiliary diseases as well as pharmacological and toxicological targets relevant to hepatobiliary diseases.