OBJECTIVE To investigate the protective effect and mechanism of saikosaponin C （SSC） on acute liver injury （ALI） in mice induced by carbon tetrachloride （CCl4） based on serum metabolomics. METHODS Forty mice were divided into blank group （water）， model group （water）， positive control drug group （Biphenyl diester drop pills， 150 mg/kg）， and SSC low- and high-dose groups （2.5， 10 mg/kg） using the random number table method， with 8 mice in each group. They were given water/ relevant drugs， once a day， for 7 consecutive days. One hour after the last administration， all mice were intraperitoneally injected with 0.2% CCl4 olive oil to induce ALI model， except for the blank group. After 17 hours of the modeling， the liver index of mice was calculated. The levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in serum of mice were detected. The histopathological changes of liver tissue were observed. Meanwhile， the serum metabolomics of mice were analyzed by liquid chromatography-mass spectrometry. RESULTS Compared with the blank group， the levels of liver index， ALT， AST， LDH， TNF-α， IL-6， and IL-1β in the model group were significantly increased （P＜0.01）. Hepatocytes were edema， vacuolar degeneration， more necrosis， and a large number of inflammatory cells were infiltrated. Compared with the model group， liver index and serum index levels of mice were significantly decreased （P＜0.05 or P＜0.01）， accompanied by marked improvement in histopathological damage to the liver tissue. The metabolomics results showed that compared with the model group， there were 63 up-regulated and 256 down-regulated differential metabolites in the serum of mice in the SSC high-dose group， including prostaglandin B2， 20-hydroxy-leukotriene B4， 5- hydroxy-L-tryptophan， 7α -hydroxycholesterol， etc.； these metabolites were primarily involved in metabolic pathways such as arachidonic acid metabolism， 5-hydroxytryptamine synapse， primary bile acid biosynthesis. CONCLUSIONS SSC exerts a protective effect against CCl4-induced ALI by down-regulating the level of key metabolites such as prostaglandin B2 and 20-hydroxy-leukotriene B4， and then ruducing metabolic pathways such as arachidonic acid metabolism， 5- hydroxytryptamine synapse， and primary bile acid biosynthesis.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Objective:To explore the correlation between ferroptosis-related proteins SLC7A11, GPX4, ACSL4 and the radiosensitivity and prognosis of nasopharyngeal carcinoma. And to investigate the potential of these proteins as molecular markers for predicting the radiosensitivity of nasopharyngeal carcinoma. Methods: A retrospective analysis was conducted on 52 cases of nasopharyngeal carcinoma （nasopharyngeal carcinoma group） and 20 cases of chronic nasopharyngiti s（control group）. The relevant clinical data were reviewed, and paraffin-embedded tissue blocks were collected for study. The expressions of SLC7A11, GPX4, and ACSL4 in pathological specimens were detected by immunohistochemical staining. The expression differences of ferroptosis-related proteins between the nasopharyngeal carcinoma group and the control group were analyzed. The nasopharyngeal carcinoma group was further divided based on the protein expression levels into high and low expression subgroups for SLC7A11, GPX4, and ACSL4. Subsequently, a differential analysis of clinical data and survival analysis was conducted for each of these subgroups. Finally, logistic regression analysis was performed to identify the factors influencing radiotherapy resistance in nasopharyngeal carcinoma. Results:①The differential analysis revealed that, compared to the control group, the nasopharyngeal carcinoma group exhibited significantly higher expression of SLC7A11 and GPX4, and lower expression of ACSL4 （P<0.05）. ②Notably, the proportion of patients displaying radioresistance was higher in the SLC7A11 and GPX4 high expression groups compared to their respective low expression groups （P<0.05）. However, the proportion of radioresistance in the ACSL4 high expression group was lower than that in the ACSL4 low expression group （P<0.05）. Survival analysis indicated that the 5-year overall survival rate was lower in the SLC7A11 and GPX4 high expression groups compared to their respective low expression groups（P<0.05）. However, the 5-year overall survival rate of the ACSL4 high expression group was higher than that of the ACSL4 low expression group（P<0.05）. ③logistic regression analysis showed that SLC7A11 and GPX4 was an independent risk factor for radioresistance in patients with nasopharyngeal carcinoma（P<0.05）. Conclusion:Nasopharyngeal carcinoma tissues over-express SLC7A11, GPX4, and under-express ACSL4. Over-expression of SLC7A11 and GPX4 are independent risk factors for radioresistance in patients with nasopharyngeal carcinoma. The inhibition of ferroptosis may be related to the occurrence, progression and radioresistance of nasopharyngeal carcinoma. Detection of the expression of SLC7A11, GPX4, and ACSL4 has guiding significance for the evaluation of radiosensitivity and prognosis of patients with nasopharyngeal carcinoma.
Humans ; Nasopharyngeal Carcinoma/radiotherapy* ; Nasopharyngeal Neoplasms/pathology* ; Coenzyme A Ligases/metabolism* ; Radiation Tolerance ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Amino Acid Transport System y+/metabolism* ; Prognosis ; Long-Chain-Fatty-Acid-CoA Ligase ; Retrospective Studies ; Ferroptosis ; Male ; Female ; Middle Aged

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Currently, the application rate of virtual reality technology in the fields of medical education and medical treatment is relatively low. In this study, based on the structure of the human stomach, virtual reality technology, sensing technology, big data technology, and cloud computing technology were integrated. A new form of medical education was established to include the online website platform for data storage and analysis and the offline VR glasses for the physical operation. Through the use of 3d Max technology, Unity3D technology, and C# language, we constructed a three-dimensional model of the human stomach to present the stomach in three dimensions. This enables the users to immerse in it to achieve true human-computer interactive learning. This study updates the concept of medical education, effectively improves the quality and efficiency of medical education, and facilitates the development of surgical programs and reduction in the risk of surgery, as well as provides experimental materials for scientific research. In the future, it can be further developed to include the three-dimensional structures of the circulatory system and other major systems in the human body.