Evaluating the Performance of Different Large Language Models on Health Consultation and Patient Education in Urolithiasis.

OBJECTIVES: To evaluate the effectiveness of four large language models (LLMs) (Claude, Bard, ChatGPT4, and New Bing) that have large user bases and significant social attention, in the context of medical consultation and patient education in urolithiasis. MATERIALS AND METHODS: In this study, we developed a questionnaire consisting of 21 questions and 2 clinical scenarios related to urolithiasis. Subsequently, clinical consultations were simulated for each of the four models to assess their responses to the questions. Urolithiasis experts then evaluated the model responses in terms of accuracy, comprehensiveness, ease of understanding, human care, and clinical case analysis ability based on a predesigned 5-point Likert scale. Visualization and statistical analyses were then employed to compare the four models and evaluate their performance. RESULTS: All models yielded satisfying performance, except for Bard, who failed to provide a valid response to Question 13. Claude consistently scored the highest in all dimensions compared with the other three models. ChatGPT4 ranked second in accuracy, with a relatively stable output across multiple tests, but shortcomings were observed in empathy and human caring. Bard exhibited the lowest accuracy and overall performance. Claude and ChatGPT4 both had a high capacity to analyze clinical cases of urolithiasis. Overall, Claude emerged as the best performer in urolithiasis consultations and education. CONCLUSION: Claude demonstrated superior performance compared with the other three in urolithiasis consultation and education. This study highlights the remarkable potential of LLMs in medical health consultations and patient education, although professional review, further evaluation, and modifications are still required.

LncRNA DGCR5 Isoform-1 Silencing Suppresses the Malignant Phenotype of Clear Cell Renal Cell Carcinoma via miR-211-5p/Snail Signal Axis.

Long non-coding RNAs (lncRNAs) play important roles during the initiation and progression of cancer. We identified DiGeorge Syndrome Critical Region Gene 5 (DGCR5) as a clear cell renal cell carcinoma (ccRCC) cancer- and lineage-specific lncRNA. Agarose gel electrophoresis analysis and sanger sequencing verified two main isoforms of DGCR5 in ccRCC patient tissues and cell lines. Quantitative polymerase chain reaction further demonstrated that the expression level of DGCR5 major isoform (isoform-1) was higher in ccRCC tissues than that in papillary/chromophobe RCC and other multiple solid malignant tumors. We investigate the biological functions of DGCR5 isoform-1 in ccRCC and show that DGCR5 isoform-1 exerts a tumor-promoting effect in ccRCC. DGCR5 isoform-1 is localized in cytoplasm and shares the same binding sequence to the tumor-suppressive miR-211-5p with the epithelial-to-mesenchymal transition key component SNAI. Furthermore, cellular and molecular experiments demonstrate that DGCR5 isoform-1 could sequester miR-211-5p, leading to the elevation of Snail protein and downregulation of its downstream targets and further promoting ccRCC cell proliferation and migration. Thus, our study indicates that DGCR5 isoform-1 could contribute to ccRCC progression by sponging miR-211-5p through regulating the expression of Snail protein and could serve as a reliable diagnostic biomarker in ccRCC.

HP-1 inhibits the progression of ccRCC and enhances sunitinib therapeutic effects by suppressing EMT.

Trametes robiniophila Murr (Huaier) has been used for many years as an adjuvant treatment for tumors. Sunitinib is the first-line therapy for end-stage renal cancer, but its side effects and drug resistance limit its clinical application. Cell counting kit- 8 (CCK-8), colony formation, scratch, and Transwell assays showed that Huaier polysaccharide (HP-1) reduced tumor progression. Its combination with sunitinib elicited stronger antitumor effects, including induction of apoptosis and cycle arrest. HP-1-induced effects depended on CIP2A downregulation and suppression of the EMT process. Moreover, qPCR and western blotting experiments showed that CIP2A downregulation was particularly pronounced after treatment with the combination therapy and was associated with EMT suppression. In addition, the HP-1/sunitinib combination inhibited the PI3K/Akt/VEGFR pathway, reducing the expression of pathway-related proteins. The HP-1-induced enhancement of sunitinib effects on tumor growth were also observed in vivo in a xenograft mouse model. Overall, these results indicated that HP-1 exerted antitumor effects against clear cell renal cell carcinoma (ccRCC) and enhanced the therapeutic efficacy of sunitinib.

Hypoxia-regulated lncRNA CRPAT4 promotes cell migration via regulating AVL9 in clear cell renal cell carcinomas.

INTRODUCTION: Long noncoding RNAs (lncRNAs) are proven to be key regulators in cancer biology. Our screening effort for clear cell renal cell carcinoma (ccRCC) prognosis-associated lncRNAs identified a novel lncRNA, ccRCC prognosis-associated transcript 4 (CRPAT4), as one of the top candidates that was previously uncharacterized. The aim of this study was to verify the clinical significance of CRPAT4 in ccRCC patients and to explore its biological role as well as the underlying mechanisms, in ccRCC cell lines. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (PCR) was performed to demonstrate that CRPAT4 was differentially expressed between ccRCC and the normal controls and that high CRPAT4 expression significantly associated with advanced Fuhrman nuclear grades. RESULTS: Kaplan-Meier survival analysis with The Cancer Genome Atlas KIRC RNA sequencing data indicated that high CRPAT4 expression was significantly associated with poor overall survival and progression-free survival. Functional studies indicated that CRPAT4 was an HIF-1α regulated gene, and CRPAT4 knockdown significantly inhibited cell migration and proliferation in the absence of HIF-1α. In addition, a mechanistic study revealed that CRPAT4 could regulate the expression of the migration-associated protein AVL9. CONCLUSION: Collectively, our study first identified CRPAT4 as a hypoxia-regulated lncRNA, acting as an oncogene in ccRCC progression via regulating AVL9 protein, thus expanding our knowledge on the hypoxia pathway in ccRCC biology from a noncoding perspective. Moreover, CRPAT4 has the potential to be a prognostic marker in ccRCC patients.

Chemokine (C­C motif) ligand 21/C­C chemokine receptor type 7 triggers migration and invasion of human lung cancer cells by epithelial­mesenchymal transition via the extracellular signal­regulated kinase signaling pathway.

C-C chemokine receptor type 7 (CCR7) has been implicated in lymph node metastasis of various cancers. Previous studies have revealed that epithelial­mesenchymal transition (EMT) is involved in the chemotactic process mediated by CCR7 and its ligands in various types of carcinoma. However, the underlying mechanism of this process remains to be fully elucidated. The present study investigated whether chemokine (C­C motif) ligand 21 (CCL21)/CCR7 may activate EMT of lung cancer cells and their associated signaling pathways. A549 and H520 lung cancer cell lines were examined in vitro in the present study. The results indicated that A549 and H520 expressed CCR7, but reduced levels of CCL21. Following stimulation of lung cancer cell lines with CCL21, the expression of the epithelial marker E­cadherin was downregulated, and the mesenchymal markers Vimentin/Slug and extracellular signal­regulated kinase (ERK) were upregulated. In addition, the ERK inhibitor PD98059 may inhibit EMT caused by CCL21, and decreased cell migration and invasion initiated by CCL21. Furthermore, lung adenocarcinoma tissues from 50 patients who underwent lung cancer operations were investigated by immunohistochemistry. The findings revealed that CCR7, Slug and Vimentin were highly expressed in lung carcinoma tissues, and were significantly associated with lymph node metastasis and clinical pathological stages, respectively. CCR7 expression was correlated positively with expression levels of Slug and Vimentin. CCL21 was expressed positively in the endothelium of lymphatic vessels adjacent to cancer cells, and weakly in lung cancer cells. Collectively, these results demonstrated that CCL21/CCR7 may activate EMT in lung cancer cells via the ERK1/2 signaling pathway. The current study provides evidence that a close interaction exists between CCL21/CCR7chemotaxis and EMT procedures in lung cancer metastasis, providing a basis for the development of therapeutic targets.

Fault detection for discrete-time switched systems with sensor stuck faults and servo inputs.

This paper addresses the fault detection problem of switched systems with servo inputs and sensor stuck faults. The attention is focused on designing a switching law and its associated fault detection filters (FDFs). The proposed switching law uses only the current states of FDFs, which guarantees the residuals are sensitive to the servo inputs with known frequency ranges in faulty cases and robust against them in fault-free case. Thus, the arbitrarily small sensor stuck faults, including outage faults can be detected in finite-frequency domain. The levels of sensitivity and robustness are measured in terms of the finite-frequency H- index and l2-gain. Finally, the switching law and FDFs are obtained by the solution of a convex optimization problem.

Anatomic study on mental canal and incisive nerve canal in interforaminal region in Chinese population.

PURPOSE: This study was aimed to detect the positions of mental canal and incisive nerve canal as well as the prolongation of mandibular canal in interforaminal region in Chinese population to supply the reference data of the surgical safe zone in chin for clinicians. MATERIALS AND METHODS: A total of 80 formalin-fixed semi-mandibles of Chinese adult cadavers were dissected, the positions and courses of mental canal and incisive nerve canal as well as the prolongation of mandibular canal in interforaminal region were measured. RESULTS: The mental foramina were present in all cases (100 %), and most of them were located below 2nd premolar (58.75 %). Accessory mental foramina were observed in 5 %. The anterior end of mandibular canal, extending along the course of 7.37 ± 1.10 mm above the lower border of mandible to interforaminal region about 3.54 ± 0.70 mm medial to the mental foramen, most often ended below between the two premolars (73.75 %), where it continued as the incisive nerve canal (100 %) and the mental canal (96.25 %). Mental canal, with the wall formed by compact bone, being 2.60 ± 0.60 mm in diameter and 4.01 ± 1.20 mm in length, opened into mental foramen. Incisive nerve canal, with the wall formed by thin compact bone and/or partly or completely by spongy bone, being 1.76 ± 0.27 mm in diameter and 24.87 ± 2.23 mm in length, extended to the incisor region along the course of 9.53 ± 1.43 mm above the lower border of mandible, and most often ended below the lateral incisor (70.00 %). CONCLUSION: This research recommended for chin operations in Chinese population: the surgical safe zone could be set in the region about over 4 mm anterior to the mental foramen, and over 12 mm above inferior border of mandible for anterior alveolar surgery, or within 9 mm above inferior border of mandible for genioplasty.

CCL21/CCR7 axis activating chemotaxis accompanied with epithelial-mesenchymal transition in human breast carcinoma.

Secondary lymphoid tissue chemokine (SLC/CCL21) and its receptor CCR7 have been implicated in lymph node metastasis, whereas the mechanism of which remains unclear. Epithelial-mesenchymal transition (EMT) plays an important role in invasion and migration of cancer cells. We presumed that CCL21/CCR7 axis activates EMT process to induce cancer cell invasion and metastasis. Firstly, the expressions of CCR7 and EMT markers were examined by immunohistochemical staining in the primary breast carcinoma tissues from 60 patients who underwent radical mastectomy. Then, we investigated whether CCL21/CCR7 induces EMT process during mediating cancer cell invasion or migration in vitro. By immunohistolochemistry, high expressions of CCR7, Slug and N-cadherin were seen in 60, 65, and 76.67 % of tumors, respectively, and significantly associated with lymph node metastases as well as clinical pathological stage. Furthermore, the CCR7 expression was significantly correlated to Slug and N-cadherin. In vitro, stimulating breast cancer cell lines 1428, MCF-7 and MDA-MB-231 with CCL21, the invasion and migration of tumor cells were promoted, and simultaneously, EMT phenotype of tumor cells was enhanced, including down-regulation of E-cadherin, up-regulation of Slug, Vimentin and N-cadherin at both protein and mRNA levels. Inversely, knockdown of CCR7 by shRNA suppressed tumor cell invasion, migration and EMT phenotype induced by CCL21. These results indicated that CCL21/CCR7 axis could activate EMT process during chemotaxis of breast carcinoma cells.