Comprehensive Insights Into Renal Perivascular Epithelioid Cell Neoplasms: From Molecular Mechanisms to Clinical Practice.

Perivascular epithelioid cell neoplasms (PEComas) are a rare category of mesenchymal tissue tumors, manifesting across various tissues and organs such as the kidneys, liver, lungs, pancreas, uterus, ovaries, and gastrointestinal tract. They predominantly affect females more than males. PEComas characteristically express both melanocytic and smooth muscle markers, making immunohistochemistry vital for their diagnosis. Renal angiomyolipoma (AML) represents a common variant of PEComas, typically marked by favorable prognoses. Nonetheless, only a small fraction of subtypes, especially epithelioid AML, possess the capacity to be malignant. Renal PEComas usually appear as asymptomatic masses accompanied by vague imaging characteristics. The main methods for diagnosis are histopathological analysis and the application of immunohistochemical stains. Presently, a uniform treatment plan for renal PEComas is absent. Strategies for management include active surveillance, selective arterial embolization, surgical procedures, and drug-based treatments. The focus of this review is on renal PEComas, shedding light on their pathogenesis, pathological characteristics, clinical presentations, diagnosis, and treatment modalities, and incorporating a clinical case study.

An end-to-end multi-scale airway segmentation framework based on pulmonary CT image.

Objective. Automatic and accurate airway segmentation is necessary for lung disease diagnosis. The complex tree-like structures leads to gaps in the different generations of the airway tree, and thus airway segmentation is also considered to be a multi-scale problem. In recent years, convolutional neural networks have facilitated the development of medical image segmentation. In particular, 2D CNNs and 3D CNNs can extract different scale features. Hence, we propose a two-stage and 2D + 3D framework for multi-scale airway tree segmentation.Approach. In stage 1, we use a 2D full airway SegNet(2D FA-SegNet) to segment the complete airway tree. Multi-scale atros spatial pyramid and Atros Residual Skip connection modules are inserted to extract different scales feature. We designed a hard sample selection strategy to increase the proportion of intrapulmonary airway samples in stage 2. 3D airway RefineNet (3D ARNet) as stage 2 takes the results of stage 1 asa prioriinformation. Spatial information extracted by 3D convolutional kernel compensates for the loss of in 2D FA-SegNet. Furthermore, we added false positive losses and false negative losses to improve the segmentation performance of airway branches within the lungs.Main results. We performed data enhancement on the publicly available dataset of ISICDM 2020 Challenge 3, and on which evaluated our method. Comprehensive experiments show that the proposed method has the highest dice similarity coefficient (DSC) of 0.931, and IoU of 0.871 for the whole airway tree and DSC of 0.699, and IoU of 0.543 for the intrapulmonary bronchi tree. In addition, 3D ARNet proposed in this paper cascaded with other state-of-the-art methods to increase detected tree length rate by up to 46.33% and detected tree branch rate by up to 42.97%.Significance. The quantitative and qualitative evaluation results show that our proposed method performs well in segmenting the airway at different scales.

Long-term mortality in patients with end-stage renal disease undergoing hemodialysis and peritoneal dialysis: a propensity score matching retrospective study.

BACKGROUND: Hemodialysis (HD) and peritoneal dialysis (PD) are effective ways to treat end-stage renal disease (ERSD). This study aimed to investigate the differences in survival and the factors that influence it in patients with end-stage renal disease treated with HD or PD. METHODS: We retrospectively analyzed factors related to all-cause death with renal replacement therapy and compared the long-term mortality between HD and PD strategies in patients with ESRD who started HD or PD treatment in our renal HD center between January 1, 2008, and December 1, 2021. RESULTS: Overall, 1,319 patients were included, comprising 690 and 629 patients in the HD and PD groups, respectively, according to the inclusion criteria. After propensity matching, 922 patients remained, with 461 (50%) patients each in the two groups. There were no significant differences in the 1-, 2-, 3-, and 4-year mortality rates between the HD and PD groups (all p > .05). However, the 5- and 10-year mortality rates of the matched patients were 15.8%. 17.6% in the HD group and 21.0%. 27.3% in the PD group, respectively. The 5- and 10-year mortality rates were significantly lower in the HD group (all p < .05) as compared to the PD group. After matching, Kaplan-Meier curve analysis with log-rank test was performed, which showed a significant difference in the survival rates between the two groups (p = .001). Logistic multifactor regression analysis revealed that age, weight, hypertension, serum creatinine, and combined neoplasms influenced the survival rate of patients with ESRD (p < .05). In contrast, age, hypertension, parathyroid hormone (PTH), serum creatinine, and peripheral vascular diseases (PVD) influenced the survival rate of patients in the HD group (p < .05), and age and weight influenced the survival rate of patients in the PD group (p < .05). CONCLUSIONS: This study found that long-term mortality rates were higher in the PD group than that in the HD group, indicating that HD may be superior to PD.

Bacillus subtilis JATP-3 Improves Nitrogen Metabolism by Regulating Intestinal Flora and AKG in Weaned Piglets.

Recently, it has been reported that oral probiotics improve the apparent digestibility of nitrogen in weaned piglets; however, the underlying mechanism is unclear. A total of 12 crossbred piglets (Yorkshire × Landrace; 28 days old) were randomly divided into two groups. The control (Con) group was fed with a basic diet + Luria-Bertani (LB; sterile; 10 mL), whereas the subject (Sub) group was fed with a basic diet + B. subtilis JATP-3 (1 × 109 CFU/mL; 10 mL). The results showed that feeding B. subtilis JATP-3 increased the final body weight and nitrogen deposition rate of weaned piglets (P < 0.05); while the daily weight gain showed an upward trend (P < 0.1). The abundance of Pedicoccus, Collinella, Turiciator, Veillonella, Clostridium, and Escherichia were significantly increased in the jejunum (P < 0.05). The abundance of Olsenella and Pediococcus were significantly increased in the ileum (P < 0.05). The metabolomics analysis showed that the levels of l-lactic acid and Alpha-ketoglutaric acid (AKG) in portal vein plasma were significantly increased (P < 0.05). In addition, the content of AKG in muscle and liver increased significantly (P < 0.01). The metagenomics analysis showed that Veillonella encoded the functional genes of 2-oxoglutarate synthase and promoted AKG production. The protein expression of eIF4E-binding protein 1 (4EBP1) phosphorylated in the skeletal muscle increased (P < 0.05). In summary, B. subtilis JATP-3 promotes dietary nitrogen metabolism and skeletal muscle synthesis by modulating the intestinal microbiota and its metabolites, in which AKG may be one of the main mediators of the therapeutic effects of B. subtilis JATP-3.

Lactobacillus rhamnosus GG ATCC53103 and Lactobacillus plantarum JL01 improved nitrogen metabolism in weaned piglets by regulating the intestinal flora structure and portal vein metabolites.

At present, most studies have shown that probiotics have a positive regulatory effect on the nutritional metabolism of the body, but the mechanism is still unclear. Here, 48 piglets were divided into four groups. The control group was not fed probiotics, the Lac group was fed L. Rhamnosus GG ATCC53103, the Rha group was fed L. Plantarum JL01, and the mix group was fed two types of probiotics. Nitrogen metabolism and mRNA levels of mTOR and S6K in skeletal muscle were observed in each group. Then, metagenome and non-targeted metabonomics were used to observe the changes of intestinal microorganisms and plasma metabolites in portal channels after probiotics feeding. Finally, we combined the results of omics analysis to reveal the mechanism of probiotics on nitrogen metabolism in weaned piglets. The results showed that L. Rhmnosus GG ATCC53103 and L. Plantarum JL01 increased nitrogen apparent digestibility, nitrogen deposition rate, and nitrogen utilization rate of weaned piglets (P < 0.05); the relative expression of mTOR and SK6 mRNA in skeletal muscle increased significantly (P < 0.05). When L. rhamnosus GG ATCC53103 and L. plantarum JL01 were combined, we found that Clostridium and Prevotella significantly increased in the jejunum (P < 0.05). The relative abundance of Lactobacillus, Ruminococcus, Streptococcus, and Prevotella in the ileum increased significantly (P < 0.05). Compared with the control group, L-Tryptophan, 3-Phosphonyloxypyruvate, cis-Aconitate, and Carbamoyl phosphate were significantly increased in the mixed group portal vein. The result of the combinatorial analysis showed that the significantly increased microorganisms could encode the enzyme genes for the synthesis of L-Tryptophan, 3-Phosphonooxypyruvate, cis-Aconitate, and Carbamoyl phosphate. In summary, our results demonstrated that L. Rhamnosus GG ATCC53103 and L. Plantarum JL01 could stimulate the expression of skeletal muscle protein synthesis genes of weaned piglets by modulating the structure of the gut microbiota and its metabolites, thereby improving nitrogen metabolism in weaned piglets.

Types of Neurons in the Human Colonic Myenteric Plexus Identified by Multilayer Immunohistochemical Coding.

BACKGROUND AND AIMS: Gut functions including motility, secretion, and blood flow are largely controlled by the enteric nervous system. Characterizing the different classes of enteric neurons in the human gut is an important step to understand how its circuitry is organized and how it is affected by disease. METHODS: Using multiplexed immunohistochemistry, 12 discriminating antisera were applied to distinguish different classes of myenteric neurons in the human colon (2596 neurons, 12 patients) according to their chemical coding. All antisera were applied to every neuron, in multiple layers, separated by elutions. RESULTS: A total of 164 combinations of immunohistochemical markers were present among the 2596 neurons, which could be divided into 20 classes, with statistical validation. Putative functions were ascribed for 4 classes of putative excitatory motor neurons (EMN1-4), 4 inhibitory motor neurons (IMN1-4), 3 ascending interneurons (AIN1-3), 6 descending interneurons (DIN1-6), 2 classes of multiaxonal sensory neurons (SN1-2), and a small, miscellaneous group (1.8% of total). Soma-dendritic morphology was analyzed, revealing 5 common shapes distributed differentially between the 20 classes. Distinctive baskets of axonal varicosities surrounded 45% of myenteric nerve cell bodies and were associated with close appositions, suggesting possible connectivity. Baskets of cholinergic terminals and several other types of baskets selectively targeted ascending interneurons and excitatory motor neurons but were significantly sparser around inhibitory motor neurons. CONCLUSIONS: Using a simple immunohistochemical method, human myenteric neurons were shown to comprise multiple classes based on chemical coding and morphology and dense clusters of axonal varicosities were selectively associated with some classes.

The apoptotic effects of soybean agglutinin were induced through three different signal pathways by down-regulating cytoskeleton proteins in IPEC-J2 cells.

Soybean agglutinin (SBA) is a main anti-nutritional factor in soybean. SBA exhibits its anti-nutritional functions by binding to intestinal epithelial cells. Keratin8 (KRT8), Keratin18 (KRT18) and Actin (ACTA) are the representative SBA-specific binding proteins. Such cytoskeletal proteins act a crucial role in different cell activities. However, limited reports reveal what the signal transduction pathway of apoptosis caused by SBA when binding to KRT8, KRT18 and ACTA. We aimed to evaluate the effects of SBA on cell apoptosis and the expression of the cytoskeletal protein (KRT8, KRT18 and ACTA), reveal the roles of these cytoskeletal proteins or their combinations on SBA-induced cell apoptosis in IPEC-J2 cell line, evaluate the influences of SBA on the mitochondria, endoplasmic reticulum stress and death receptor-mediated apoptosis signal pathway and to show the roles of KRT8, KRT18 and ACTA in different apoptosis signal pathways induced by SBA. The results showed that SBA induced the IPEC-J2 cell apoptosis and decreased the mRNA expression of KRT8, KRT18 and ACTA (p < 0.05). The degree of effect of three cytoskeleton proteins on cell apoptosis was ACTA > KRT8 > KRT18. The roles of these three cytoskeletal proteins on IPEC-J2 apoptotic rates had a certain accumulation effect. SBA up-regulated mitochondrial fission variant protein (FIS1) and fusion protein (Mfn2) promoted CytC and AIF in mitochondria to enter the cytoplasm, activated caspase-9 and caspase-3, damaged or declined mitochondrial function and reduced ATP synthesis (p < 0.05). Also, SBA up-regulated the expression of GRP78, XBP-1, eIF2α, p-eIF2α and CHOP (p < 0.05), down-regulated the expression level of ASK1 protein (p < 0.05). SBA led to the recruitment of FADD to the cytoplasmic membrane and increased the expression of FasL, resulting in caspase-8 processing. SBA up-regulated the expression level of Bax protein and decreased cytosolic Bcl-2 and Bid (p < 0.05). In addition, there was a significant negative correlation between the gene expression of cytoskeleton proteins and apoptosis, as well as the expression of key proteins of apoptosis-related signal transduction pathways. In conclusion, SBA induced the activation of the mitochondria, endoplasmic reticulum stress and the death receptor-mediated apoptosis signal pathway and the crosstalk between them. The effect of SBA on these three pathways was mainly exhibited via down-regulation of the mRNA expression of the three cytoskeletal expressions. This study elucidates the molecular mechanism and signaling pathway of SBA that lead to apoptosis from the perspective of cell biology and molecular biology and provides a new perspective on the toxicity mechanism of other food-derived anti-nutrients, medical gastrointestinal health and related cancer treatment.

Degradation of Antibiotic Resistance Genes by VADER with CRISPR-Cas Immunity.

The evolution and dissemination of antibiotic resistance genes (ARGs) are prompting severe health and environmental issues. While environmental processes, e.g., biological wastewater treatment, are key barriers to prevent the spread of ARGs, they are often sources of ARGs at the same time, requiring upgraded biotechnology. Here, we present VADER, a synthetic biology system for the degradation of ARGs based on CRISPR-Cas immunity, an archaeal and bacterial immune system for eliminating invading foreign DNAs, to be implemented for wastewater treatment processes. Navigated by programmable guide RNAs, VADER targets and degrades ARGs depending on their DNA sequences, and by employing an artificial conjugation machinery, IncP, it can be delivered via conjugation. The system was evaluated by degrading plasmid-borne ARGs in Escherichia coli and further demonstrated via the elimination of ARGs on the environmentally relevant RP4 plasmid in Pseudomonas aeruginosa. Next, a prototype conjugation reactor at a 10-mL scale was devised, and 100% of the target ARG was eliminated in the transconjugants receiving VADER, giving a proof of principle for the implementation of VADER in bioprocesses. By generating a nexus of synthetic biology and environmental biotechnology, we believe that our work is not only an enterprise for tackling ARG problems but also a potential solution for managing undesired genetic materials in general in the future. IMPORTANCE Antibiotic resistance has been causing severe health problems and has led to millions of deaths in recent years. Environmental processes, especially those of the wastewater treatment sector, are an important barrier to the spread of antibiotic resistance from the pharmaceutical industry, hospitals, or civil sewage. However, they have been identified as a nonnegligible source of antibiotic resistance at the same time, as antibiotic resistance with its main cause, antibiotic resistance genes (ARGs), may accumulate in biological treatment units. Here, we transplanted the CRISPR-Cas system, an immune system via programmable DNA cleavage, to tackle the antibiotic resistance problem raised in wastewater treatment processes, and we propose a new sector specialized in ARG removal with a conjugation reactor to implement the CRISPR-Cas system. Our study provides a new angle for resolving public health issues via the implementation of synthetic biology in environmental contexts at the process level.

Electrophysiological and morphological features of myenteric neurons of human colon revealed by intracellular recording and dye fills.

BACKGROUND: Ex vivo intracellular recordings and dye fills, combined with immunohistochemistry, are a powerful way to analyze the enteric nervous system of laboratory animals. METHODS: Myenteric neurons were recorded in isolated specimens of human colon. A key determinant of successful recording was near-complete removal of circular muscle from the surface of ganglia. KEY RESULTS: Treatment with a collagenase/neutral protease mix before dissection significantly improved recording success and reduced damage to the plexus. Carboxyfluorescein in microelectrodes allowed recorded neurons to be routinely labeled, analyzed, and subjected to multi-layer immunohistochemistry. Carboxyfluorescein revealed morphological details that were not detected by immunohistochemical methods. Of 54 dye-filled myenteric neurons (n = 22), 45 were uni-axonal and eight were multi-axonal. There was a significant bias toward recordings from large neural somata. The close association between morphology and electrophysiology (long after-hyperpolarizations and fast EPSPs) seen in mice and guinea pigs did not hold for human myenteric neuron recordings. No slow EPSPs were recorded; however, disruption to the myenteric plexus during dissection may have led the proportion of cells receiving synaptic potentials to be underestimated. Neurons immunoreactive for nitric oxide synthase were more excitable than non-immunoreactive neurons. Distinctive grooves were observed on the serosal and/or mucosal faces of myenteric neurons in 3D reconstructions. These had varicose axons running through them and may represent a preferential site of synaptic inputs. CONCLUSIONS: Human enteric neurons share many features with laboratory animals, but the combinations of features in individual cells appear more variable.

Fructo-oligosaccharides Ameliorate Intestinal Mechanical Barrier Injury in Piglets Induced by Soybean Antigen in vitro and in vivo.

BACKGROUND: Fructose oligosaccharides (FOS) have been shown to reduce soybean antigeninduced hypersensitivity in piglets, but their effects on intestinal epithelial barrier function have not been characterized. Therefore, this study aimed to determine the effects of FOS on intestinal barrier injury induced by soybean antigen in piglets in vitro and in vivo. METHODS: We studied the protective effects of FOS against mechanical barrier dysfunction induced using ß-conglycinin or glycinin in porcine intestinal epithelial cells (IPEC-J2), and measured the serum concentrations of diamine oxidase (DAO), D-lactic acid, and endotoxin, and the expression of tight junction (TJ) proteins, in piglets. RESULTS: We found that FOS concentration dependently increases cell activity, trans-epithelial electrical resistance, and TJ protein expression (P < 0.05) and reduces alkaline phosphatase (AP) activity (P < 0.05) in vitro. In addition, the serum DAO, D-lactic acid, and endotoxin concentrations were reduced by FOS administration in piglets (P < 0.05). Both in vitro and in vivo, the expression levels of TJ proteins (zona occludens 1 and occludin) were increased significantly by FOS (P < 0.05). CONCLUSION: Therefore, FOS protect against intestinal injury induced by soybean antigen in piglets, which may provide a basis for the prevention of allergy.

Preparation of Cellulose Nanofibers from Corn Stalks by Fenton Reaction: A New Insight into the Mechanism by an Experimental and Theoretical Study.

Agricultural biomass wastes are an abundant feedstock for biorefineries. However, most of these wastes are not treated in the right way. Here, corn stalks (CSs) were assigned as the raw material to produce cellulose nanofibers (CNFs) via in situ Fenton oxidation treatment. In order to probe the formation mechanism of an in situ Fenton reactor, the bonding interaction of hydrated Fe2+ ions and fiber has been systemically studied based on adsorption experiments, IR spectroscopy, density functional theory (DFT) calculations, and Raman spectroscopy. The results indicate that the coordination of the hydrated Fe2+ ion to the fiber generates a quasi-octahedral-coordinated sphere around the Fe center. The Jahn-Teller distortion effect of the Fe center promotes the Fe-O2H2 bonding interaction via reduction of the energy gap of the dz2 orbital of the Fe center and π2py/π2pz orbitals of the H2O2 molecule. The oxidation treatment of the pretreated CS by the in situ Fenton process shows the formation of a new carboxyl group on the fiber surface. The scanning electron microscopy image shows that the Fenton-treated fiber was scattered into the nanosized CNFs with a diameter of up to 50 nm. Both experimental and theoretical studies show that the pseudo-first-order kinetic reaction could describe the in situ Fenton kinetics well. Moreover, the proposed catalytic cycle shows that the large thermodynamic barrier is the cleavage of the O-O bond of H2O2 to generate the •OH radical, and the whole catalytic cycle is found to be spontaneous at room temperature.

Effects of diets with different amino acid release characteristics on the gut microbiota and barrier function of weaned pigs.

BACKGROUND: The absorption and utilization of proteins by animals is affected by the amino acid (AA) release characteristics of their diets. In the present study, we aimed to determine the effects of diets with various amino acid release characteristics on the intestinal barrier function and diversity of gut microbiota of weaned pigs. RESULTS: Forty-eight pigs (7.45 ± 0.58 kg) were fed with diets having different amino acid release characteristics during a period of 28 days. We used a 2 × 3 full-factor (two protein levels and three protein sources with differing amino acid release characteristics) experimental design, with normal (standard terminal ileal digestibility of 17.5%) or low (standard terminal ileal digestibility of 14.9%) protein levels as the first factor. Casein (CAS), corn gluten meal (CGM) and a MIX diet were used as protein sources. Due to the more balanced release of amino acids, the diamine oxidase (DAO) concentrations in the CAS and MIX groups were significantly lower than those in the CGM group (P < 0.05); Reducing the dietary protein content from 17.5% to 14.9% had no significant effects on the levels of serum DAO or D-lactic acid. By contrast, it increased the microbial diversity (chao1 and ACE values) and the number of Lactobacillus in the jejunum (P < 0.05). The CAS-containing diet and the MIX diet resulted in significantly higher microbial diversity (Simpson and Shannon) than the CGM-containing diet in the jejunum. CONCLUSION: The balanced release of amino acids in CAS and MIX diets maintained intestinal barrier function and increased gut microbiota diversity. These findings could potentially provide a scientific reference for the rational preparation of piglet feed.

Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity.

Inflammatory and functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and obstructive bowel disorder (OBD) underlie the most prevalent forms of visceral pain. Although visceral pain can be generally provoked by mechanical distension/stretch, the mechanisms that underlie visceral mechanosensitivity in colon-innervating visceral afferents remain elusive. Here, we show that virally mediated ablation of colon-innervating TRPV1-expressing nociceptors markedly reduces colorectal distention (CRD)-evoked visceromotor response (VMR) in mice. Selective ablation of the stretch-activated Piezo2 channels from TRPV1 lineage neurons substantially reduces mechanically evoked visceral afferent action potential firing and CRD-induced VMR under physiological conditions, as well as in mouse models of zymosan-induced IBS and partial colon obstruction (PCO). Collectively, our results demonstrate that mechanosensitive Piezo2 channels expressed by TRPV1-lineage nociceptors powerfully contribute to visceral mechanosensitivity and nociception under physiological conditions and visceral hypersensitivity under pathological conditions in mice, uncovering potential therapeutic targets for the treatment of visceral pain.

Wi-Breath: A WiFi-Based Contactless and Real-Time Respiration Monitoring Scheme for Remote Healthcare.

Respiration rate is an important healthcare indicator, and it has become a popular research topic in remote healthcare applications with Internet of Things. Existing respiration monitoring systems have limitations in terms of convenience, comfort, and privacy, etc. This paper presents a contactless and real-time respiration monitoring system, the so-called Wi-Breath, based on off-the-shelf WiFi devices. The system monitors respiration with both the amplitude and phase difference of the WiFi channel state information (CSI), which is sensitive to human body micro movement. The phase information of the CSI signal is considered and both the amplitude and phase difference are used. For better respiration detection accuracy, a signal selection method is proposed to select an appropriate signal from the amplitude and phase difference based on a support vector machine (SVM) algorithm. Experimental results demonstrate that the Wi-Breath achieves an accuracy of 91.2% for respiration detection, and has a 17.0% reduction in average error in comparison with state-of-the-art counterparts.

miR-378a-3p promotes renal cell carcinoma proliferation, migration, and invasion by targeting TOB2.

PURPOSE: Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system, which has high metastasis. MicroRNAs (miRNAs) have been reported to participate in RCC progression. The present study aimed to understand the biological role and mechanism of miR-378a-3p in RCC. METHODS: RT-qPCR assay was used to assess miR-378a-3p and transducer of ERBB2 (TOB2) expression in RCC tissues and cell lines. CCK-8, clone formation, scratch, and transwell assays were carried out to evaluate cell proliferation, migration, and invasion. Furthermore, the target genes of miR-378a-3p were predicted by the online bioinformatics databases. Dual-luciferase reporter assay was used to validate the relationship between miR-378a-3p and TOB2. RESULTS: miR-378a-3p was highly expressed in RCC tissues and RCC cell lines. Besides, miR-378a-3p accelerated the progression of RCC by mediating cell proliferation, migration and invasion. More importantly, TOB2 was confirmed as a potential target gene of miR-378a-3p. The results of loss-of-function experiments showed that inhibition of TOB2 reversed the inhibitory roles of miR-378a-3p inhibitor on RCC progression. CONCLUSIONS: miR-378a-3p promoted cell proliferation, migration and invasion through regulating TOB2 in RCC, which indicated a promising target for the treatment of RCC.

Characterization of viscerofugal neurons in human colon by retrograde tracing and multi-layer immunohistochemistry.

Background and Aims: Viscerofugal neurons (VFNs) have cell bodies in the myenteric plexus and axons that project to sympathetic prevertebral ganglia. In animals they activate sympathetic motility reflexes and may modulate glucose metabolism and feeding. We used rapid retrograde tracing from colonic nerves to identify VFNs in human colon for the first time, using ex vivo preparations with multi-layer immunohistochemistry. Methods: Colonic nerves were identified in isolated preparations of human colon and set up for axonal tracing with biotinamide. After fixation, labeled VFN cell bodies were subjected to multiplexed immunohistochemistry for 12 established nerve cell body markers. Results: Biotinamide tracing filled 903 viscerofugal nerve cell bodies (n = 23), most of which (85%) had axons projecting orally before entering colonic nerves. Morphologically, 97% of VFNs were uni-axonal. Of 215 VFNs studied in detail, 89% expressed ChAT, 13% NOS, 13% calbindin, 9% enkephalin, 7% substance P and 0 of 123 VFNs expressed CART. Few VFNs contained calretinin, VIP, 5HT, CGRP, or NPY. VFNs were often surrounded by dense baskets of axonal varicosities, probably reflecting patterns of connectivity; VAChT+ (cholinergic), SP+ and ENK+ varicosities were most abundant around them. Human VFNs were diverse; showing 27 combinations of immunohistochemical markers, 4 morphological types and a wide range of cell body sizes. However, 69% showed chemical coding, axonal projections, soma-dendritic morphology and connectivity similar to enteric excitatory motor neurons. Conclusion: Viscerofugal neurons are present in human colon and show very diverse combinations of features. High proportions express ChAT, consistent with cholinergic synaptic outputs onto postganglionic sympathetic neurons in prevertebral ganglia.

Bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap technique for nonsyndromic unilateral coronal synostosis.

Background: The goals of operative treatment for unilateral coronal synostosis (UCS) are to improve appearance and allow unrestricted brain growth. However, for severe unilateral premature closure of the coronal suture, existing methods do not address the compression of the brain or expand the volume of the skull cavity. We report our retrospective experience with bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap (CVR + FFBF) technique and the resulting changes in the anterior cranial vault asymmetry index (ACVAI) and intracranial volume. Methods: Twenty patients with UCS who underwent bilateral fronto-orbital advancement combined with CVR + FFBF technique from April 2014 to May 2019 were included. Surgical efficacy was evaluated by the ACVAI and intracranial volume before the operation, 1 week after the operation, and at the last follow-up (average 19.8 months; range, 12 to 40 months). The measurement data are presented as the mean ± standard deviation and were statistically analyzed by t-test. Results: The ACVAI was 9.07%±3.55% before the operation, 3.56%±3.42% 1 week after the operation, and 3.13%±2.41% at the last follow-up. The ACVAI 1 week after the operation was significantly lower than that before the operation (t=4.827, P<0.001). There was no significant difference between the ACVAI 1 week after the operation and at the last follow-up (t=0.660, P=0.517). The intracranial volume was 1,027.85±112.25 mL in patients before the operation and 1,131.92±161.71 mL in the normal control group, which was a statistically significant difference (t=2.364, P=0.023). The intracranial volume significantly increased 1 week after surgery: 1,081.62±111.10 mL (t=8.703, P<0.001), and this trend continued at the last follow-up (1,386.90±119.30 mL) similarly to the normal control group (1,438.22±89.28 mL). At the last follow-up, there was no significant difference between the two groups (t=1.540, P=0.132). Conclusions: For the treatment of UCS, bilateral fronto-orbital advancement combined with CVR + FFBF technique offers functional and cosmetic outcomes in terms of intracranial volume expansion and fronto-orbital symmetry.

Segmentation and volume quantification of epicardial adipose tissue in computed tomography images.

BACKGROUND: Many cardiovascular diseases are closely related to the composition of epicardial adipose tissue (EAT). Accurate segmentation of EAT can provide a reliable reference for doctors to diagnose the disease. The distribution and composition of EAT often have significant individual differences, and the traditional segmentation methods are not effective. In recent years, deep learning method has been gradually introduced into EAT segmentation task. PURPOSE: The existing EAT segmentation methods based on deep learning have a large amount of computation and the segmentation accuracy needs to be improved. Therefore, the purpose of this paper is to develop a lightweight EAT segmentation network, which can obtain higher segmentation accuracy with less computation and further alleviate the problem of false-positive segmentation. METHODS: First, the obtained computed tomography was preprocessed. That is, the threshold range of EAT was determined to be -190, -30 HU according to prior knowledge, and the non-adipose pixels were excluded by threshold segmentation to reduce the difficulty of training. Second, the image obtained after thresholding was input into the lightweight RDU-Net network to perform the training, validating, and testing process. RDU-Net uses a residual multi-scale dilated convolution block in order to extract a wider range of information without changing the current resolution. At the same time, the form of residual connection is adopted to avoid the problem of gradient expansion or gradient explosion caused by too deep network, which also makes the learning easier. In order to optimize the training process, this paper proposes PNDiceLoss, which takes both positive and negative pixels as learning targets, fully considers the class imbalance problem, and appropriately highlights the status of positive pixels. RESULTS: In this paper, 50 CCTA images were randomly selected from the hospital, and the commonly used Dice similarity coefficient (DSC), Jaccard similarity, accuracy (ACC), specificity (SP), precision (PC), and Pearson correlation coefficient are used as evaluation metrics. Bland-Altman analysis results show that the extracted EAT volume is consistent with the actual volume. Compared with the existing methods, the segmentation results show that the proposed method achieves better performance on these metrics, achieving the DSC of 0.9262. The number of false-positive pixels has been reduced by more than half. Pearson correlation coefficient reached 0.992, and linear regression coefficient reached 0.977 when measuring the volume of EAT obtained. In order to verify the effectiveness of the proposed method, experiments are carried out in the cardiac fat database of VisualLab. On this database, the proposed method also achieved good results, and the DSC value reached 0.927 in the case of only 878 slices. CONCLUSIONS: A new method to segment and quantify EAT is proposed. Comprehensive experiments show that compared with some classical segmentation algorithms, the proposed method has the advantages of shorter time-consuming, less memory required for operations, and higher segmentation accuracy. The code is available at https://github.com/lvanlee/EAT_Seg/tree/main/EAT_seg.

Analysis of clinical features of neonates with congenital heart disease who develop necrotizing enterocolitis: a retrospective case-control study.

Background: Infants with congenital heart disease (CHD) are known to have higher rates of necrotizing enterocolitis (NEC). Although the etiology is recognized as distinct from the premature neonatal population, there is not a universal consensus regarding etiology or specific risk factors. To analyze the clinical features of neonates with CHD who develop NEC. Methods: A retrospective study of neonates with CHD in the cardiac intensive care unit (ICU) between 2015 and 2018 was performed, and modified Bell's criteria were used to diagnose NEC. Patients were divided into 2 groups according to ductal-dependent (DD) lesions, and were further stratified by Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) score and Aristotle score, to compare the differences. Results: Among 412 patients with CHD, 69 (16%) developed NEC. The incidence of NEC was notably higher among DD patients than among non-DD (nDD) patients (18.7% vs. 11.1%; P=0.04). Patients with RACHS-1 >2 also had a higher rate of NEC than did those with RACHS-1 ≤2 (19.49% vs. 9.29%; P=0.01). nDD patients who developed NEC were younger, had a lower gestational age (36.25±1.88 vs. 38.10±1.28 weeks; P=0.00), a lower weight (2.86±0.85 vs. 3.33±0.55 kg; P=0.01), and a lower birth weight (2.79±0.79 vs. 3.26±0.55; P=0.01) compared to the DD group. All nDD patients developed NEC after congenital heart surgery, while only 38 cases (76%), NEC occurred after heart surgery in the DD group. Four patients needed surgery for NEC in the DD group and RACHS-1 >2 group. Presence of NEC was not associated with an increased risk of mortality in any group. Conclusions: NEC is a common complication in neonates with CHD and can occur both before and after CHD operations. Likely there are varying mechanism for NEC in different forms of CHD. While NEC is more common in patients with DD CHD and those with more complex forms of CHD, there was no significant difference observed in weight-for-age Z-score (WAZ) between the DD group during follow-up.

Permanent Visual Impairment due to Delayed Diagnosis of Shunt Malfunction in Case of Lack of Typical Features of Increased Intracranial Pressure and Unchanged Ventricular Size.

OBJECTIVE: We present the clinical features, imaging, and management of 5 cases of visual impairment as the primary manifestation ventriculoperitoneal (V-P) shunt malfunction. METHODS: We retrospectively reviewed the medical records of 126 patients of V-P shunt malfunction in Shanghai Children's Medical Center between 2015 and 2020. Medical records including all hospital admissions were reviewed and follow-up data were collected. RESULTS: Five children (3.97%) had visual impairment as the primary manifestation of V-P shunt malfunction, with a mild or no headache. Four broken distal shunt catheters and one proximal catheter blockage were confirmed intraoperatively and cured by surgery. None of the patients had a definite improvement in ophthalmic examinations after 4-52 months of follow-up. CONCLUSION: Visual impairment as the primary manifestation of V-P shunt malfunction was uncommon and could be easily missed or misdiagnosed as the only problem for lack of typical features of increased intracranial pressure and unchanged ventricular size. Earlier definitive diagnosis and surgical intervention could prevent a further development of the visual loss caused by V-P shunt malfunction.