Case report: A rare case of desmoid-type fibromatosis originating in the small intestine.

Background: Desmoid-type fibromatosis (DF) is characterized by a rare monoclonal fibroblast proliferation that exhibits variable and unpredictable clinical presentation. DF can be classified into sporadic and hereditary types. Despite extensive research efforts, the exact etiology of DF remains elusive. Case description: A 31-year-old male patient presented to the hospital with a progressively growing mass in the right lower abdomen, accompanied by abdominal discomfort. Symptoms are discovered 1 week before admission. Enteroscopy revealed no evidence of colonic abnormalities, and blood tests did not indicate any abnormalities. Due to the indeterminate nature of the mass during surgery, a partial resection of the ileum and cecum was performed, followed by ileocolonic end-to-end anastomosis, with no postoperative complications. The final pathological diagnosis confirmed primary desmoid-type fibromatosis of the distal ileum (invasive fibromatosis). To effectively manage DF, we recommend a follow-up schedule for patients. This includes appointments every 3 months in the first year following surgery, followed by appointments every 6 months up to the fifth year, and then once a year thereafter. The follow-up examinations should include collection of the patient's medical history, physical examination, blood tests, ultrasounds, CT scans, and other relevant assessments. During the first year of the follow-up period, no further treatment was administered, and the patient remained disease-free. Conclusion: Desmoid-type fibromatosis (DF) originating from the small intestine is an extremely rare condition that exhibits local invasiveness and can be life-threatening. Despite its benign histology, DF has a high local recurrence rate and lacks metastatic potential. Diagnosis of DF remains challenging, especially in cases where surgical intervention is not feasible due to asymptomatic patients or partial organ impairment. In such cases, a "watchful waiting" approach is recommended as the initial treatment strategy. However, when preoperative diagnosis is difficult, surgery is typically considered the best option. Given the potential for local recurrence and the uncertain long-term prognosis, regular follow-up is necessary.

KIAA1429 promotes infantile hemangioma regression by facilitating the stemness of hemangioma endothelial cells.

Infantile hemangiomas are common vascular tumors with a specific natural history. The proliferation and regression mechanism of infantile hemangiomas may be related to the multilineage differentiation ability of hemangioma stem cells, but the specific mechanism is not well elucidated. KIAA1429 is an N6 -methyladenosine methylation-related protein that can also exert its role in a methylation-independent manner. This study aims to explore the function of KIAA1429 in infantile hemangiomas. qRT-PCR, western blotting, and immunostaining were performed to verify the expression of KIAA1429. The endothelial and fibroblast-like phenotypes of hemangioma endothelial cells were detected after KIAA1429 knockdown and overexpression. The stemness properties of hemangioma endothelial cells and the underlying mechanism of KIAA1429 in hemangiomas were also investigated. Nude mouse models of infantile hemangiomas were conducted to ascertain the effects of KIAA1429 in vivo. The results showed that KIAA1429 was highly expressed in infantile hemangiomas, particularly in involuting hemangiomas. In vitro experiments confirmed that KIAA1429 inhibited the endothelial phenotype, enhanced the differentiation ability, and promoted the fibroblast-like phenotype of hemangioma endothelial cells by inducing endothelial cell transition to facultative stem cells. However, the effect of KIAA1429 on the potential target was shown to be independent of N6 -methyladenosine methylation modification. Mouse models further revealed that KIAA1429 could inhibit the proliferation and promote the regression of hemangiomas. In conclusion, this study found that KIAA1429 played an important role in the regression of infantile hemangiomas by enhancing the stemness of hemangioma endothelial cells and could be a potential treatment target for infantile hemangiomas.

The value of a risk model combining specific risk factors for predicting postoperative severe morbidity in biliary tract cancer.

Purpose: Several surgical risk models are widely utilized in general surgery to predict postoperative morbidity. However, no studies have been undertaken to examine the predictive efficacy of these models in biliary tract cancer patients, and other perioperative variables can also influence morbidity. As a result, the study's goal was to examine these models alone, as well as risk models combined with disease-specific factors, in predicting severe complications. Methods: A retrospective study of 129 patients was carried out. Data on demographics, surgery, and outcomes were gathered. These model equations were used to determine the morbidity risks. Severe morbidity was defined as the complication comprehensive index ≥ 40. Results: Severe morbidity was observed in 25% (32/129) patients. Multivariate analysis demonstrated that four parameters [comprehensive risk score ≥1, T stage, albumin decrease value, and international normalized ratio (INR)] had a significant influence on the probability of major complications. The area under the curve (AUC) of combining the four parameters was assessed as having strong predictive value and was superior to the Estimation of Physiologic Ability and Surgical Stress System (E-PASS) alone (the AUC value was 0.858 vs. 0.724, p = 0.0375). The AUC for the modified E-PASS (mE-PASS) and Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) in patients over the age of 70 was classified as no predictive value (p = 0.217 and p = 0.063, respectively). Conclusion: The mE-PASS and POSSUM models are ineffective in predicting postoperative morbidity in patients above the age of 70. In biliary tract cancer (BTC) patients undergoing radical operation, a combination of E-PASS and perioperative parameters generates a reasonable prediction value for severe complications.

Quantitative Study on Human Error in Emergency Activities of Road Transportation Leakage Accidents of Hazardous Chemicals.

The emergency rescue process of road transportation leakage accidents involving hazardous chemicals is complex and includes various emergency activities. A quantitative study of human errors in emergency activities is conducive to seeking the focus of the emergency rescue process. To quantitatively analyze human error in emergency activities during the emergency rescue process of road transportation leakage accidents of hazardous chemicals, sequentially timed events plotting (STEP) and the cognitive reliability and error analysis method (CREAM), were used. First, STEP was used to analyze six laws, regulations and standards, as well as 54 accident cases, to derive 24 emergency activities in the emergency rescue process. Then, CREAM was used to analyze and obtain the probability of human error for each emergency activity. Two high error level emergency activities, five medium error level emergency activities, and seventeen low error level emergency activities were identified after the human error levels of the emergency activities were classified. The results show that two emergency activities, the initial handling of the accident, and cleanup of the leakage site, should be prioritized in the emergency rescue process of road transportation leakage accidents of hazardous chemicals.

Long-term explant culture: an improved method for consistently harvesting homogeneous populations of keloid fibroblasts.

Explant culture is a more suitable method than enzyme digestion for the isolation of keloid fibroblasts (KFs), but it has a longer isolation period. In this study, we propose a long-term explant culture method. Unlike in the conventional explant culture method, we continued culturing explants to isolate KFs rather than discarding them during passage. We demonstrated that keloid explants could be cultured for more than 4 months to continuously yield enriched KFs, and the KFs from the repeatedly cultured explants had shorter isolation times. The biological behavior and fibrotic phenotypic characteristics of the KFs from the explants cultured long term were investigated, and no statistical differences were found compared with the KFs from the original explants. In conclusion, the long-term explant culture method was shown to be efficient for harvesting a large, homogeneous population of KFs. The high efficiency as well as ease of operation and sample saving make this method convenient for researchers working with KFs.

Analysis of Human Factors Relationship in Hazardous Chemical Storage Accidents.

Human factors are important causes of hazardous chemical storage accidents, and clarifying the relationship between human factors can help to identify the logical chain between unsafe behaviors and influential factors in accidents. Therefore, the human factor relationship of hazardous chemical storage accidents was studied in this paper. First, the human factors analysis and classification system (HFACS), which originated from accident analysis in the aviation field, was introduced. Since some items were designed for aviation accident analysis, such as the item "Crew Resource Management", it is not fully applicable to the analysis of hazardous chemical storage accidents. Therefore, this article introduced some modifications and changes to make the HFACS model suitable for the analysis of hazardous chemical storage accidents. Based on the improved HFACS model, 42 hazardous chemicals storage accidents were analyzed, and the causes were classified. After analysis, we found that under the HFACS framework, the most frequent cause of accidents is resource management, followed by violations and inadequate supervision, and finally the organizational process and technological environment. Finally, according to the statistical results for the various causes of accidents obtained from the improved HFACS analysis, the chi-square test and odds ratio analysis were used to further explore the relevance of human factors in hazardous chemical storage accidents. The 16 groups of significant causal relationships among the four levels of factors include resource management and inadequate supervision, planned inappropriate operations and technological environment, inadequate supervision and physical/mental limitations, and technological environment and skill-based errors, among others.

Unveiling the transcriptome alteration of POMC neuron in diet-induced obesity.

Loss of neuron homeostasis in the arcuate nucleus (ARC) is responsible for diet-induced-obesity (DIO). We previously reported that loss of Rb1 gene compromised the homeostasis of anorexigenic POMC neurons in ARC and induced obesity in mice. To evaluate the development of DIO, we propose to analyze the transcriptomic alteration of POMC neurons in mice following high fat diet (HFD) feeding. We isolated these neurons from established DIO mice and performed transcriptomic profiling using RNA-seq. In total, 1066 genes (628 upregulated and 438 downregulated) were identified as differentially expressed genes (DEGs). Pathway enrichment analysis with these DEGs further revealed that "cell cycle," "apoptosis," "chemokine signaling," and "sphingolipid metabolism" pathways were correlated with DIO development. Moreover, we validated that the pRb protein, a key regulator of "cell cycle pathway," was inactivated by phosphorylation in POMC neurons by HFD feeding. Importantly, the reversal of deregulated cell cycle by stereotaxic delivering of the unphosphorylated pRbΔP in ARC significantly meliorated the DIO. Collectively, our study provides insights into the mechanisms related to the loss of homeostasis of POMC neurons in DIO, and suggests pRb phosphorylation as a potential intervention target to treat DIO.

[Advances in the correlation between loss of neural homeostasis and diet-induced obesity].

The social problems and medical burdens caused by obesity have become more serious in recent years. Obesity is mainly caused by the imbalance of energy intake and consumption in the body. The central nervous system and related neurons regulate the balance of energy metabolism. The hypothalamic arcuate nucleus (ARC) contains anorexigenic proopiomelanocortin (POMC) neurons and orexigenic neuropeptid Y(NPY)/agouti-related protein (AgRP) neurons that regulate the feeding behavior of body. High-fat diet induces phosphorylation of Rb protein in POMC neurons, and inactivation of Rb phosphorylation leads to re-entry of POMC neurons from the resting-state into the cell cycle, which rapidly shifts to apoptosis. High-fat diet also causes the inhibition of neuronal regeneration, induces inflammation and neuronal damage, loss of neuronal homeostasis, leptin resistance, and ultimately leads to obesity. This review discusses the relationship between loss of neuronal homeostasis and dietary obesity, as well as the underlying mechanisms, which might provide the evidence for prevention and treatment of these diseases.

Maintenance of dimer conformation by the dengue virus core protein α4-α4' helix pair is critical for nucleocapsid formation and virus production.

The virion of dengue virus (DENV) is composed of a viral envelope covering a nucleocapsid formed by a complex of viral genomic RNA and core protein (CP). DENV CP forms a dimer via the internal α2 and α4 helices of each monomer. Pairing of α2-α2' creates a continuous hydrophobic surface, while the α4-α4' helix pair joins the homodimer via side-chain interactions of the inner-edge residues. However, the importance of dimer conformation and the α4 helix of DENV CP in relation to its function are poorly understood. Loss of association between CP and lipid droplets (LDs) due to mutation suggests that the CP hydrophobic surface was not exposed, offering a possible explanation for the absence of dimers. Further assays suggest the connection between CP folding and protein stability. Attenuation of full-length RNA-derived virus production is associated with CP mutation, since no significant defects were detected in virus translation and replication. The in vitro characterization assays further highlighted that the α4-α4' helix pair conformation is critical in preserving the overall α-helical content, thermostability, and dimer formation ability of CP, features correlated with the efficiency of nucleocapsid formation. Addition of Tween 20 improves in vitro nucleocapsid-like particle formation, suggesting the role of the LD in nucleocapsid formation in vivo. This study provides the first direct link between the α4-α4' helix pair interaction and the CP dimer conformation that is the basis of CP function, particularly in nucleocapsid formation during virion production. Importance: Structure-based mutagenesis study of the dengue virus core protein (CP) reveals that the α4-α4' helix pair is the key to maintaining its dimer conformation, which is the basis of CP function in nucleocapsid formation and virus production. Attenuation of full-length RNA-derived virus production is associated with CP mutation, since no significant defects in virus translation and replication were detected. In vitro inefficiency and size of nucleocapsid-like particle (NLP) formation offer a possible explanation for in vivo virus production inefficiency upon CP mutation. Further, the transition of NLP morphology from an incomplete state to an intact particle shown by α4-α4' helix pair mutants in the presence of a nonionic detergent suggests the regulatory role of the intracellular lipid droplet (LD) in CP-LD interaction and in promoting nucleocapsid formation. This study provides the first direct link between the α4-α4' helix pair interaction and CP dimer conformation that is the fundamental requirement of CP function, particularly in nucleocapsid formation during virion production.

A novel dengue virus inhibitor, BP13944, discovered by high-throughput screening with dengue virus replicon cells selects for resistance in the viral NS2B/NS3 protease.

Dengue virus (DENV) causes disease globally, resulting in an estimated 25 to 100 million new infections per year. No effective DENV vaccine is available, and the current treatment is only supportive. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease. In the present study, we identified a potential small-molecule inhibitor, BP13944, via high-throughput screening (HTS) of 60,000 compounds using a stable cell line harboring an efficient luciferase replicon of DENV serotype 2 (DENV-2). BP13944 reduced the expression of the DENV replicon reporter in cells, showing a 50% effective concentration (EC50) of 1.03 ± 0.09 µM. Without detectable cytotoxicity, the compound inhibited replication or viral RNA synthesis in all four serotypes of DENV but not in Japanese encephalitis virus (JEV). Sequencing analyses of several individual clones derived from BP13944-resistant RNAs purified from cells harboring the DENV-2 replicon revealed a consensus amino acid substitution (E66G) in the region of the NS3 protease domain. Introduction of E66G into the DENV replicon, an infectious DENV cDNA clone, and recombinant NS2B/NS3 protease constructs conferred 15.2-, 17.2-, and 3.1-fold resistance to BP13944, respectively. Our results identify an effective small-molecule inhibitor, BP13944, which likely targets the DENV NS3 protease. BP13944 could be considered part of a more effective treatment regime for inhibiting DENV in the future.

RNA binding property and RNA chaperone activity of dengue virus core protein and other viral RNA-interacting proteins.

In this study we showed that the dengue virus (DENV) core protein forms a dimer with an α-helix-rich structure, binds RNA and facilitates the strand annealing process. To assess the RNA chaperone activity of this core protein and other dengue viral RNA-interacting proteins, such as NS3 helicase and NS5 proteins, we engineered cis- and trans-cleavage hammerhead ribozyme constructs carrying DENV genomic RNA elements. Our results indicate that DENV core protein facilitates typical hammerhead structure formation by acting as an RNA chaperone and DENV NS5 has a weak RNA chaperone activity, while DENV NS3 helicase failed to refold RNA with a complex secondary structure.

HCV NS3 protein helicase domain assists RNA structure conversion.

NS3H, the helicase domain of HCV NS3, possesses RNA-stimulated ATPase and ATP hydrolysis-dependent dsRNA unwinding activities. Here, the ability of NS3H to facilitate RNA structural rearrangement is studied using relatively long RNA strands as the model substrates. NS3H promotes intermolecular annealing, resolves three-stranded RNA duplexes, and assists dsRNA and ssRNA inter-conversions to establish a steady state among RNA structures. NS3H facilitates RNA structure conversions in a mode distinct from an ATP-independent RNA chaperone. These findings expand the known function of HCV NS3 helicase and reveal a role for viral helicase in assisting RNA structure conversions during virus life cycle.

Analysis of the nucleoside triphosphatase, RNA triphosphatase, and unwinding activities of the helicase domain of dengue virus NS3 protein.

The helicase domain of dengue virus NS3 protein (DENV NS3H) contains RNA-stimulated nucleoside triphosphatase (NTPase), ATPase/helicase, and RNA 5'-triphosphatase (RTPase) activities that are essential for viral RNA replication and capping. Here, we show that DENV NS3H unwinds 3'-tailed duplex with an RNA but not a DNA loading strand, and the helicase activity is poorly processive. The substrate of the divalent cation-dependent RTPase activity is not restricted to viral RNA 5'-terminus, a protruding 5'-terminus made the RNA 5'-triphosphate readily accessible to DENV NS3H. DENV NS3H preferentially binds RNA to DNA, and the functional interaction with RNA is sensitive to ionic strength.

Characterization and application of the selective strand annealing activity of the N terminal domain of hepatitis delta antigen.

We used synthetic DNA oligos to investigate the nucleic acid chaperone properties of the N terminal domain of hepatitis delta antigen (NdAg). We found that NdAg possessed a bona fide chaperone activity. NdAg could distinguish subtle differences in the thermal stability of the base pairing region, and enabled DNA oligos to form a more stable duplex among competing sequences through facilitating strand annealing selectively, stimulating duplex conversion selectively, and stabilizing the more stable duplex. The property of NdAg identified in this study could be applied to improve the efficiency and specificity of dot blot hybridization under conditions of low stringency.

Nucleic acid binding properties of the nucleic acid chaperone domain of hepatitis delta antigen.

The N terminal region of hepatitis delta antigen (HDAg), referred to here as NdAg, has a nucleic acid chaperone activity that modulates the ribozyme activity of hepatitis delta virus (HDV) RNA and stimulates hammerhead ribozyme catalysis. We characterized the nucleic acid binding properties of NdAg, identified the structural and sequence domains important for nucleic acid binding, and studied the correlation between the nucleic acid binding ability and the nucleic acid chaperone activity. NdAg does not recognize the catalytic core of HDV ribozyme specifically. Instead, NdAg interacts with a variety of nucleic acids and has higher affinities to longer nucleic acids. The studies with RNA homopolymers reveal that the binding site size of NdAg is around nine nucleotides long. The extreme N terminal portion of NdAg, the following coiled-coil domain and the basic amino acid clusters in these regions are important for nucleic acid binding. The nucleic acid-NdAg complex is stabilized largely by electrostatic interactions. The formation of RNA-protein complex appears to be a prerequisite for facilitating hammerhead ribozyme catalysis of NdAg and its derivatives. Mutations that reduce the RNA binding activity or high ionic strength that destabilizes the RNA-protein complex, reduce the nucleic acid chaperone activity of NdAg.

Selective strand annealing and selective strand exchange promoted by the N-terminal domain of hepatitis delta antigen.

We have previously shown that the N-terminal domain of hepatitis delta virus (NdAg) has an RNA chaperone activity in vitro (Huang, Z. S., and Wu, H. N. (1998) J. Biol. Chem. 273, 26455-26461). Here we investigate further the basis of the stimulatory effect of NdAg on RNA structural rearrangement: mainly the formation and breakage of base pairs. Duplex dissociation, strand annealing, and exchange of complementary RNA oligonucleotides; the hybridization of yeast U4 and U6 small nuclear RNAs and of hammerhead ribozymes and cognate substrates; and the cis-cleavage reaction of hepatitis delta ribozymes were used to determine directly the role of NdAg in RNA-mediated processes. The results showed that NdAg could accelerate the annealing of complementary sequences in a selective fashion and promote strand exchange for the formation of a more extended duplex. These activities would prohibit NdAg from modifying the structure of a stable RNA, but allow NdAg to facilitate a trans-acting hammerhead ribozyme to find a more extensively matched target in cognate substrate. These and other results suggest that hepatitis delta antigen may have a biological role as an RNA chaperone, modulating the folding of viral RNA for replication and transcription.