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The British Journal of Dermatology Apr 2024
PubMed: 38623710
DOI: 10.1093/bjd/ljae167 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Feb 2024This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen...
This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1β, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1β, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500_29_marine_group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1β level had a significantly positive correlation with Acinetobacter and CL500_29_marine_group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.
Topics: Humans; Mice; Animals; Spleen; Tumor Necrosis Factor-alpha; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Interleukin-2; Serotonin; Immunoglobulin A
PubMed: 38621910
DOI: 10.19540/j.cnki.cjcmm.20231013.701 -
Journal of Neurosurgery. Case Lessons Apr 2024Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies, and/or scoliosis (CLOVES) syndrome is the most recently described...
BACKGROUND
Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies, and/or scoliosis (CLOVES) syndrome is the most recently described combined vascular anomaly characterized by congenital excessive growth of adipose tissue, vascular malformations, epidermal nevi, and skeletal deformities. This condition exhibits a significant variability in clinical manifestations and a tendency for rapid progression and affects extensive anatomical regions. Information regarding the association of epidural lipomatosis with low-flow venous lymphatic malformations is rare, with few reports in the literature.
OBSERVATIONS
The authors present a case of a 6-year-old girl who was admitted to the emergency department complaining of rapidly progressing weakness in her lower extremities and partial loss of sensation in the inguinal area. Radiologically, an extradural mass was identified at the T2-6 level, causing acute spinal cord compression. Urgent decompression and partial resection of the mass were performed. Despite satisfactory intraoperative hemo- and lymphostasis, postoperative lymphorrhea/seroma leakage was encountered as a delayed complication and was managed conservatively.
LESSONS
CLOVES syndrome is characterized by the combination of various clinical symptoms, not all of which are included in the abbreviation, as well as a progressively deteriorating course, the emergence of new symptoms, and complications throughout the patient's life. This necessitates ongoing monitoring of such patients.
PubMed: 38621301
DOI: 10.3171/CASE23772 -
International Journal of Molecular... Mar 2024Beckwith-Wiedemann Syndrome (BWS) is an imprinting disorder characterized by overgrowth, stemming from various genetic and epigenetic changes. This study delves into the...
Beckwith-Wiedemann Syndrome (BWS) is an imprinting disorder characterized by overgrowth, stemming from various genetic and epigenetic changes. This study delves into the role of upregulation in BWS, focusing on insulin-like growth factor pathways, which are poorly known in this syndrome. We examined the IGF2R, the primary receptor of IGF2, WNT, and autophagy/lysosomal pathways in BWS patient-derived lymphoblastoid cell lines, showing different genetic and epigenetic defects. The findings reveal a decreased expression and mislocalization of IGF2R protein, suggesting receptor dysfunction. Additionally, our results point to a dysregulation in the AKT/GSK-3/mTOR pathway, along with imbalances in autophagy and the WNT pathway. In conclusion, BWS cells, regardless of the genetic/epigenetic profiles, are characterized by alteration of the IGF2R pathway that is associated with the perturbation of the autophagy and lysosome processes. These alterations seem to be a key point of the molecular pathogenesis of BWS and potentially contribute to BWS's characteristic overgrowth and cancer susceptibility. Our study also uncovers alterations in the WNT pathway across all BWS cell lines, consistent with its role in growth regulation and cancer development.
Topics: Humans; Autophagy; Beckwith-Wiedemann Syndrome; Cell Line; Glycogen Synthase Kinase 3; Neoplasms
PubMed: 38612397
DOI: 10.3390/ijms25073586 -
Neurogastroenterology and Motility Jun 2024Glucose breath test (GBT) is used for the diagnosis of small intestine bacterial overgrowth. A restrictive diet without fibers and/or fermentable food is recommended on...
BACKGROUND
Glucose breath test (GBT) is used for the diagnosis of small intestine bacterial overgrowth. A restrictive diet without fibers and/or fermentable food is recommended on the day before the test. The aim of our retrospective study was to evaluate the impact of two different restrictive diets on the results of GBT.
METHODS
A change of the pretest restrictive diet was applied in our lab on September 1, 2020. The recommended diet was a fiber-free diet before this date, and a fiber-free diet plus restriction of all fermentable food afterward. We thus compared the results of GBT performed before (group A) and after (group B) this pretest diet modification. Demographics, reasons to perform GBT, digestive symptoms, and hydrogen and methane baseline values and variations after glucose ingestion were compared between the two groups.
KEY RESULTS
269 patients underwent GBT in group A, and 316 patients in group B. The two groups were comparable in terms of demographics. Methane and hydrogen baseline values were significantly higher in group A (respectively 14 [18] vs. 8 [14] ppm, p < 0.01 and 11 [14] vs. 6 [8] ppm, p < 0.01). The percentage of positive tests was higher in group A for methane (43% vs. 28%, p < 0.05), and for hydrogen (18% vs. 12%, p = 0.03).
CONCLUSION & INFERENCES
This retrospective study suggests the importance of the restrictive diet prior to GBT. A strict limitation of fibers and fermentable food decreased hydrogen and methane baseline values, and the prevalence of positive GBT. Thus a strict restrictive diet should be recommended on the day before the test, in order to limit the impact of food on hydrogen and methane breath levels, and possibly improve the diagnosis quality of GBT.
Topics: Humans; Breath Tests; Female; Male; Retrospective Studies; Intestine, Small; Middle Aged; Glucose; Adult; Aged; Blind Loop Syndrome; Diet; Methane; Hydrogen
PubMed: 38606691
DOI: 10.1111/nmo.14801 -
Fetal and Pediatric Pathology 2024Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder that exhibits etiologic genomic imprinting characterized by molecular heterogeneity and phenotypic...
Novel Autopsy Findings in Premature Infant With Beckwith-Wiedemann Syndrome Uniparental Disomy: Multifocal Developmental Dysplastic Chrondromatous Lesions and Cortical Neuronal Heterotopias.
BACKGROUND
Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder that exhibits etiologic genomic imprinting characterized by molecular heterogeneity and phenotypic variability. Associations with localized developmental dysplastic chondromatous lesions and cortical neuronal heterotopias have not previously been described.
CASE PRESENTATION
A 33-week gestational age female had an omphalocele and intractable hypoglycemia at birth. The placenta demonstrated placental mesenchymal dysplasia. Detection of hypermethylation of IC1 and hypomethylation of IC2 confirmed Beckwith-Wiedemann syndrome, most likely due to uniparental disomy. Additional findings included right mid-tibial and right 5-8th developmental dysplastic chondromatous lesions, absent corpus callosum and numerous right-sided cortical neuronal heterotopias, right hemihypertrophy, multiple cystic hepatic mesenchymal hamartomas and hepatic infantile hemangiomas, nisidioblastosis and cystic pancreatic lesions. The infant died with multi-organ failure and anasarca at 7 weeks of life.
CONCLUSION
Beckwith-Wiedemann syndrome anomalies may include multifocal developmental dysplastic chondromatous lesions and cerebral neuronal heterotopias, lateralized, and corpus callosum aplasia.
Topics: Humans; Beckwith-Wiedemann Syndrome; Female; Infant, Newborn; Uniparental Disomy; Infant, Premature; Autopsy; Pregnancy; Fatal Outcome
PubMed: 38587479
DOI: 10.1080/15513815.2024.2337639 -
Molecular Syndromology Mar 2024Weaver syndrome (WS) is a rare autosomal dominant disorder characterized by distinctive facial features, pre- and post-natal overgrowth, macrocephaly, and variable...
INTRODUCTION
Weaver syndrome (WS) is a rare autosomal dominant disorder characterized by distinctive facial features, pre- and post-natal overgrowth, macrocephaly, and variable developmental delay. The characteristic facial features are ocular hypertelorism, a broad forehead, almond-shaped palpebral fissures and, in early childhood, large, fleshy ears, a pointed "stuck-on" chin with horizontal skin creases, and retrognathia. Heterozygous pathogenic/likely pathogenic variants in the enhancer of zeste homolog 2 () gene are responsible for WS.
CASE PRESENTATION
Here, we report a male patient with a heterozygous likely pathogenic variant in EZH2 gene who has tall stature, distinctive facial features, mild development delay, hypoxic-ischemic encephalopathy with a MRI finding of periventricular leukomalacia, gingival hypertrophy, and early onset high hypermetropia.
CONCLUSION
This case demonstrates the importance of reporting detailed molecular and clinical findings in patients to expand the genotypic and phenotypic findings of this rare syndrome.
PubMed: 38585548
DOI: 10.1159/000533733 -
Frontiers in Pediatrics 2024Fetal Wilms tumor (WT) is extremely rare, but with advances in fetal imaging, more cases are being reported. The management of these cases remains challenging. Herein,...
Fetal Wilms tumor (WT) is extremely rare, but with advances in fetal imaging, more cases are being reported. The management of these cases remains challenging. Herein, we present the case of a full-term female infant diagnosed antenatally at 32 weeks of gestation with a right solid renal mass detected on routine prenatal ultrasound without polyhydramnios. At birth, the infant was healthy, with no evidence of dysmorphic features or abnormal laboratory tests to suggest a predisposition syndrome. Her family history was also unremarkable. A successful radical right nephrectomy was performed on day 2 of life revealing a classic WT. She received vincristine as adjuvant chemotherapy without any complications. At the age of 1 month, the infant developed isolated lateralized overgrowth of the right lower limb suspicious of Beckwith-Wiedemann syndrome. At the latest follow-up of 4 years, the child is healthy and disease-free with conserved asymmetry of lower limbs. The case provides insights into the challenging diagnosis and treatment of fetal WT. A review of the literature suggests that the presence of polyhydramnios is a worse prognostic factor while the combination of best supportive care and surgery remains the best management. Fetal WT can be associated with predisposition syndromes; however, their first manifestations can develop after the diagnosis of cancer has been made, as in our patient. We propose starting active surveillance programs and genetic testing for any case of fetal WT.
PubMed: 38562132
DOI: 10.3389/fped.2024.1334544 -
HCA Healthcare Journal of Medicine 2024Gastric bypass surgery is an effective surgical intervention for morbid obesity. However, it is not without risk. Gastric bypass surgery may produce malabsorptive or...
INTRODUCTION
Gastric bypass surgery is an effective surgical intervention for morbid obesity. However, it is not without risk. Gastric bypass surgery may produce malabsorptive or surgical complications, which can result in nutritional deficiencies as well as syndromes related to bacterial overgrowth in the blind loops of the bowel.
CASE PRESENTATION
Severe nutritional deficiencies may occur due to patient noncompliance with the prescribed regimen, or arise secondary to malabsorptive or mechanical surgical complications. We describe a case of a 37-year-old female who underwent gastric bypass surgery and experienced a recalcitrant eczematous eruption with sporadic subcutaneous, purulent nodules which completely resolved after the reversal of her bariatric procedure.
CONCLUSION
Since 2001, the number of morbidly obese patients who have undergone bariatric surgery has been increasing. As a result, clinicians can expect to more frequently encounter complications that can result from these procedures.
PubMed: 38560393
DOI: 10.36518/2689-0216.1468 -
Life (Basel, Switzerland) Feb 2024The PI3K enzymes modify phospholipids to regulate cell growth and differentiation. Somatic variants in PI3K are recurrent in cancer and drive a proliferative phenotype....
The PI3K enzymes modify phospholipids to regulate cell growth and differentiation. Somatic variants in PI3K are recurrent in cancer and drive a proliferative phenotype. Somatic mosaicism of and are associated with vascular anomalies and overgrowth syndromes. Germline variants are associated with varying phenotypes, including immunodeficiency or facial dysmorphism with growth delay, lipoatrophy, and insulin resistance associated with SHORT syndrome. There has been limited study of the molecular mechanism to unify our understanding of how variants in drive both undergrowth and overgrowth phenotypes. Thus, we compiled genomic variants from cancer and rare vascular anomalies and sought to interpret their effects using an unbiased physics-based simulation approach for the protein complex. We applied molecular dynamics simulations to mechanistically understand how genetic variants affect PIK3R1 and its interactions with PIK3CA. Notably, iSH2 genetic variants associated with undergrowth destabilize molecular interactions with the PIK3CA receptor binding domain in simulations, which is expected to decrease activity. On the other hand, overgrowth and cancer variants lead to loss of inhibitory interactions in simulations, which is expected to increase activity. We find that all disease variants display dysfunctions on either structural characteristics or intermolecular interaction energy. Thus, this comprehensive characterization of novel mosaic somatic variants associated with two opposing phenotypes has mechanistic importance and biomedical relevance and may aid in future therapeutic developments.
PubMed: 38541623
DOI: 10.3390/life14030297