Search

Abstract Objective According to the diagnosis-related group (DRG) requirement, issues of diagnosis and procedure coding in the gastroenterology department of our hospital were analyzed and improvement plans were proposed to lay the foundation for effective implementation of DRGs. Methods The title page of case-history of 1600 patients admitted to the Department of Gastroenterology of this hospital from January 1, 2021 to December 31, 2021 was sampled as a data source, and the primary and other diagnostic codes, operation or procedure codes involved in the title page of case-history were categorized and statistically analyzed. Results Of the 531 cases treated with gastrointestinal endoscopy in our hospital in 2021, coding errors were identified in 66 cases and unsuccessful DRG enrollment in 35 cases, including 14 cases with incorrect coding of the primary diagnosis (8 cases with unsuccessful DRG enrollment), 37 cases with incorrect coding of the primary operation (23 cases with unsuccessful DRG enrollment), and 8 cases with incorrect coding of both the primary diagnosis and the primary operation (4 cases with unsuccessful DRG enrollment). Analysis of 66 inpatient cases with coding problems showed a total of 167 deficiencies, including 36 deficiencies in major diagnoses, 84 deficiencies in other diagnoses, and 47 deficiencies in surgery or operation coding. Conclusion The accuracy of coding of disease diagnosis and surgical operation is the basis for the smooth implementation of DRGs. The medical staff of this hospital has poor cognition of DRGs coding and fails to recognize the important role of the title page of case-history quality to DRGs system, and their attention to DRGs and knowledge base of disease classification coding should be improved. In addition, the high incidence of coding errors, especially the omission of disease diagnosis, requires increased training of physicians and nurses on clinical knowledge and requirements for DRGs medical records, thereby improving the quality of medical cases and ensuring the accuracy of DRGs information.

Amidst the mounting global challenges associated with climate change and resource depletion, achieving sustainable development is paramount. Focusing on cities as vital scenarios for pursuing sustainability, this research measured urban sustainability and identified its obstacles. Employing the DPSIR (Driver–Pressure–State–Impact–Response) framework, we establish a metric system with 25 indicators to assess the urban sustainability of six innovation zones in China and identify their developmental impediments to sustainability with an obstacle model. The core findings of the study are as follows: First, over the five-year period, all six cities demonstrated a consistent increase in their urban sustainability levels except for Shenzhen, which experienced a decline from its top position among these cities due to a decrease in its score from 0.44296 to 0.36942 in 2017. Second, there was consistent urban sustainability progress in five cities, with the exception of Shenzhen, from 2016 to 2020. Third, inadequate government response emerges as a primary obstacle across all six cities, marked by shortcomings in public expenditure, R&D investment, and healthcare. Every year, all six cities experienced more than 60% obstacle degrees in terms of response, with the exception of Shenzhen in 2016. The urban sustainability pursuit model we developed bridges urban sustainability theory with practical interventions, promoting adaptive governance. In addition, this study provides scholars and policymakers with a comprehensive approach to gauging urban sustainability, recognizing obstacles, and designing strategies for a sustainable urban future.

EAAT2 is an amino acid transporter implicated in glutamate homeostasis in brain and therapy resistance of cancer cells. Here, the authors report cryo-EM structures and reveal inhibitory mechanisms via selective inhibitor WAY213613.

Abstract Glial cells play crucial roles in brain homeostasis and pathogenesis of central nervous system (CNS) injuries and diseases. However, the roles of these cells and the molecular mechanisms toward regeneration in the CNS have not been fully understood, especially the capacity of them toward demyelinating diseases. Therefore, there are still very limited therapeutic strategies to restore the function of adult CNS in diseases such as multiple sclerosis (MS). Remyelination, a spontaneous regeneration process in the CNS, requires the involvement of multiple cellular and extracellular components. Promoting remyelination by therapeutic interventions is a promising novel approach to restore the CNS function. Herein, we review the role of glial cells in CNS diseases and injuries. Particularly, we discuss the roles of glia and their functional interactions and regulatory mechanisms in remyelination, as well as the current therapeutic strategies for MS.

BackgroundHuman papillomavirus (HPV) infection is the leading cause of cervical cancer. More and more studies discovered that cervical microbiota (CM) composition correlated with HPV infection and the development of cervical cancer. However, more studies need to be implemented to clarify the complex interaction between microbiota and the mechanism of disease development, especially in a specific area of China.Materials and methodsIn this study, 16S rDNA sequencing was applied on 276 Thin-prep Cytologic Test (TCT) samples of patients from the Sanmenxia area. Systematical analysis of the microbiota structure, diversity, group, and functional differences between different HPV infection groups and age groups, and co-occurrence relationships of the microbiota was carried out.ResultsThe major microbiota compositions of all patients include Lactobacillus iners, Escherichia coli, Enterococcus faecalis, and Atopobium vaginae at species level, and Staphylococcus, Lactobacillus, Gardnerella, Bosea, Streptococcus, and Sneathia in genus level. Microbiota diversity was found significantly different between HPV-positive (Chao1 index: 98.8869, p < 0.01), unique-268 infected (infections with one of the HPV genotype 52, 56, or 58, 107.3885, p < 0.01), multi-268 infected (infections with two or more of HPV genotype 52, 56, and 58, 97.5337, p = 0.1012), other1 (94.9619, p < 0.05) groups and HPV-negative group (83.5299). Women older than 60 years old have higher microbiota diversity (108.8851, p < 0.01, n = 255) than younger women (87.0171, n = 21). The abundance of Gardnerella and Atopobium vaginae was significantly higher in the HPV-positive group than in the HPV-negative group, while Burkholderiaceae and Mycoplasma were more abundant in the unique-268 group compared to the negative group. Gamma-proteobacteria and Pseudomonas were found more abundant in older than 60 patients than younger groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) analysis revealed the effects on metabolism by microbiota that the metabolism of cells, proteins, and genetic information-related pathways significantly differed between HPV-negative and positive groups. In contrast, lipid metabolism, signal transduction, and cell cycle metabolism pathway significantly differed between multi-268 and negative groups.ConclusionThe HPV infection status and age of women were related to CM’s diversity and function pathways. The complex CM co-occurrent relationships and their mechanism in disease development need to be further investigated.

Abstract Background Tumor angiogenesis is regarded as a rational anti-cancer target. The efficacy and indications of anti-angiogenic therapies in clinical practice, however, are relatively limited. Therefore, there still exists a demand for revealing the distinct characteristics of tumor endothelium that is crucial for the pathological angiogenesis. L-type amino acid transporter 1 (LAT1) is well known to be highly and broadly upregulated in tumor cells to support their growth and proliferation. In this study, we aimed to establish the upregulation of LAT1 as a novel general characteristic of tumor-associated endothelial cells as well, and to explore the functional relevance in tumor angiogenesis. Methods Expression of LAT1 in tumor-associated endothelial cells was immunohistologically investigated in human pancreatic ductal adenocarcinoma (PDA) and xenograft- and syngeneic mouse tumor models. The effects of pharmacological and genetic ablation of endothelial LAT1 were examined in aortic ring assay, Matrigel plug assay, and mouse tumor models. The effects of LAT1 inhibitors and gene knockdown on cell proliferation, regulation of translation, as well as on the VEGF-A-dependent angiogenic processes and intracellular signaling were investigated in in vitro by using human umbilical vein endothelial cells. Results LAT1 was highly expressed in vascular endothelial cells of human PDA but not in normal pancreas. Similarly, high endothelial LAT1 expression was observed in mouse tumor models. The angiogenesis in ex/in vivo assays was suppressed by abrogating the function or expression of LAT1. Tumor growth in mice was significantly impaired through the inhibition of angiogenesis by targeting endothelial LAT1. LAT1-mediated amino acid transport was fundamental to support endothelial cell proliferation and translation initiation in vitro. Furthermore, LAT1 was required for the VEGF-A-dependent migration, invasion, tube formation, and activation of mTORC1, suggesting a novel cross-talk between pro-angiogenic signaling and nutrient-sensing in endothelial cells. Conclusions These results demonstrate that the endothelial LAT1 is a novel key player in tumor angiogenesis, which regulates proliferation, translation, and pro-angiogenic VEGF-A signaling. This study furthermore indicates a new insight into the dual functioning of LAT1 in tumor progression both in tumor cells and stromal endothelium. Therapeutic inhibition of LAT1 may offer an ideal option to potentiate anti-angiogenic therapies.

Boron neutron capture therapy (BNCT) is a radiotherapy utilizing the neutron capture and nuclear fission reaction of 10B taken up into tumor cells. The most commonly used boron agent in BNCT, p-borono-l-phenylalanine (BPA), is accumulated in tumors by amino acid transporters upregulated in tumor cells. Here, by using dipeptides of BPA and tyrosine (BPA-Tyr and Tyr-BPA), we propose a novel strategy of selective boron delivery into tumor cells via oligopeptide transporter PEPT1 upregulated in various cancers. Kinetic analyses indicated that BPA-Tyr and Tyr-BPA are transported by oligopeptide transporters, PEPT1 and PEPT2. The intrinsic oligopeptide transport activity in tumor cells clearly correlated with PEPT1 protein expression level but not with PEPT2, suggesting that PEPT1 is the predominant oligopeptide transporter at least in tumor cell lines. Furthermore, using BPA-Tyr and Tyr-BPA, boron was successfully delivered into PEPT1-expressing pancreatic cancer AsPC-1 cells via a PEPT1-mediated mechanism. Intravenous administration of BPA-Tyr into the mice bearing AsPC-1 xenograft tumors resulted in significant boron accumulation in the tumors. It is proposed that the oligopeptide transporters, especially PEPT1, are promising candidates for molecular targets of boron delivery in BNCT. The BPA-containing dipeptides would have a potential for the development of novel boron carriers targeting PEPT1. Keywords: Boron delivery, Boron neutron capture therapy, p-Borono-l-phenylalanine-containing dipeptide, Oligopeptide transporter, PEPT1

[This corrects the article DOI: 10.1371/journal.pone.0241869.].

Chronic enteropathy associated with SLCO2A1 gene (CEAS) is caused by loss-of-function mutations in SLCO2A1, which encodes a prostaglandin (PG) transporter. In this study, we report a sibling case of CEAS with a novel pathogenic variant of the SLCO2A1 gene. Compound heterozygous variants in SLCO2A1 were identified in an 8-year-old boy and 12-year-old girl, and multiple chronic nonspecific ulcers were observed in the patients using capsule endoscopy. The splice site mutation (c.940 + 1G>A) of the paternal allele was previously reported to be pathogenic, whereas the missense variant (c.1688T>C) of the maternal allele was novel and had not yet been reported. The affected residue (p.Leu563Pro) is located in the 11th transmembrane domain (helix 11) of SLCO2A1. Because SLCO2A1 mediates the uptake and clearance of PGs, the urinary PG metabolites were measured by liquid chromatography coupled to tandem mass spectrometry. The urinary tetranor-prostaglandin E metabolite levels in the patients were significantly higher than those in unaffected individuals. We established cell lines with doxycycline-inducible expression of wild type SLCO2A1 (WT-SLCO2A1) and the L563P mutant. Immunofluorescence staining showed that WT-SLCO2A1 and the L563P mutant were dominantly expressed on the plasma membranes of these cells. Cells expressing WT-SLCO2A1 exhibited time- and dose-dependent uptake of PGE2, while the mutant did not show any uptake activity. Residue L563 is very close to the putative substrate-binding site in SLCO2A1, R561 in helix 11. However, in a molecular model of SLCO2A1, the side chain of L563 projected outside of helix 11, indicating that L563 is likely not directly involved in substrate binding. Instead, the substitution of Pro may twist the helix and impair the transporter function. In summary, we identified a novel pathogenic variant of SLCO2A1 that caused loss-of-function and induced CEAS.

Injuries to the central nervous system (CNS) can cause severe neurological deficits. Axonal regrowth is a fundamental process for the reconstruction of compensatory neuronal networks after injury; however, it is extremely limited in the adult mammalian CNS. In this study, we conducted a loss-of-function genetic screen in cortical neurons, combined with a Web resource-based phenotypic screen, and identified synaptotagmin 4 (Syt4) as a novel regulator of axon elongation. Silencing Syt4 in primary cultured cortical neurons inhibits neurite elongation, with changes in gene expression involved in signaling pathways related to neuronal development. In a spinal cord injury model, inhibition of Syt4 expression in cortical neurons prevented axonal sprouting of the corticospinal tract, as well as neurological recovery after injury. These results provide a novel therapeutic approach to CNS injury by modulating Syt4 function. [ABSTRACT FROM AUTHOR]