四川大学学报(医学版)最新文献

{"title":"[Characteristics of Aurora Kinase A-Mediated Tumor Microenvironment in Colorectal Cancer and Mining of Active Compounds From Chinese Herbs].","authors":"Mengyao Li, Dongming Hua, Zhiyan Wang, Zhiyi Liu, Hangjun Gong, Yunchuan Sun, Xueqing Hu, Yan Wang","doi":"10.12182/20250160104","DOIUrl":"10.12182/20250160104","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effects of Aurora kinase A (AURKA) on the tumor microenvironment of colorectal cancer (CRC) and to predict the active compounds in Chinese herbs that can target AURKA.</p><p><strong>Methods: </strong>Based on the transcriptomic data and clinical information from 380 CRC tissues and 51 paracancerous tissues in The Cancer Genome Atlas (TCGA) database, the infiltration of different cells in the tumor tissues was analyzed using xCell and the binding of active compounds of Chinese herbs with AURKA was predicted through molecular docking.</p><p><strong>Results: </strong>The expression of AURKA was significantly upregulated in CRC tissues compared with that in paracancerous tissues (<i>P</i> < 0.05), and CRC patients with high AURKA expression had shorter overall survival. Compared with the AURKA low-expression group, the abundance of macrophages, monocytes, and effector memory CD4⁺ and CD8⁺ T cells was significantly downregulated in the AURKA high-expression group (<i>P</i> < 0.05). In addition, the cytotoxicity of T cells was significantly reduced (<i>P</i> < 0.05). Further analysis revealed that AURKA expression was positively correlated with the abundance of myeloid-derived suppressor cells (MDSCs) and the expression levels of their chemokines CXCL2 and CXCL5 (<i>P</i> < 0.05). Genes that were differentially expressed between the AURKA high- and low-expression groups were mainly enriched in monocyte migration, chemokine-induced cellular responses, and other related processes. Chinese herbal compounds, including hesperidin, aristololactam A Ⅱa, anacardic acid, coumestrol, and 17β -estradiol, all showed binding energies to AURKA lower than -1.2 kcal/mol, indicating a certain level of binding stability. Among these Chinese herbal compounds, 17β-estradiol exhibited the best binding stability to AURKA-3UOL.</p><p><strong>Conclusion: </strong>The high expression of AURKA in CRC tissues suggests a poor clinical prognosis. AURKA can promote the development of a suppressive immune microenvironment in CRC, and 17β-estradiol, an active compound from Chinese herbs, is a potential therapeutic agent targeting AURKA.</p>","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"59-67"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Effects of Inhibiting the NKCC1/AQP4 Pathway on Neurological Injury Improvement in a Rat Model of High-Altitude Cerebral Edema].","authors":"Huali Geng, Baichuan Li, Xu Song, Yilin Xia, Xiangyang Zhou, Jing Gao, Lei Chen","doi":"10.12182/20250160204","DOIUrl":"10.12182/20250160204","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the pathogenesis of high-altitude cerebral edema (HACE) and develop new therapeutic strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Male Sprague-Dawley (SD) rats of 6 weeks old were selected and placed in a hypobaric chamber. The rats were exposed to the high-altitude environment of 7000 m above sea level for 3 days for HACE modeling. Whether the HACE model was successfully established in the rats was evaluated by measuring brain water content, the degree of disruption to the blood-brain barrier (BBB), and brain tissue Nissl staining. The experimental animals were divided into four groups, with 28 rats in each group. The blank control group was exposed to a normobaric and normoxic environment simulating the conditions at 500 m above sea level for 3 d. The other groups, including a model group (the HACE group), a bumetanide group (the positive control group), and a XH-6003 treatment group, were placed at an altitude of 7000 m above sea level and were injected with normal saline, bumetanide, and XH-6003, a new type of Na-K-2Cl cotransporter 1 (NKCC1) inhibitor, via the tail vein, respectively, twice daily for 3 d. The experimental animals were taken out of the hypobaric chamber for testing after 3 d. The primary outcome measures included brain water content, BBB permeability, changes in brain tissue morphology, and the expression levels of aquaporin-4 (AQP4) and NKCC1. The secondary outcome measures included behavioral changes, apoptosis, and oxidative stress markers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The HACE rat model was successfully established. The model group exhibited increased brain water content (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), BBB disruption (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), impairment in learning skills and memory (&lt;i&gt;P&lt;/i&gt; &lt; 0.001), and anxiety/depression-like behaviors (&lt;i&gt;P&lt;/i&gt; &lt; 0.01). qPCR results showed significantly increased expression of &lt;i&gt;NKCC1&lt;/i&gt; and &lt;i&gt;AQP4&lt;/i&gt; in the brain tissue of the model group (&lt;i&gt;P&lt;/i&gt; &lt; 0.01). Pathology examination revealed neuronal and glial cell damage in the hippocampus of the model group (&lt;i&gt;P&lt;/i&gt; &lt; 0.01). Treatment with XH-6003, the NKCC1 inhibitor, reversed brain water content, BBB disruption, and neuronal and glial cell damage to a certain degree (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), decreased the expression of &lt;i&gt;NKCC1&lt;/i&gt; and &lt;i&gt;AQP4&lt;/i&gt; in the brain tissue (&lt;i&gt;P&lt;/i&gt; &lt; 0.01), and inhibited apoptosis-related proteins. Among the oxidative stress indices, only glutathione (GSH) showed improvement (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). Rats treated with XH-6003 showed functional improvement only in the time spent exploring novel objects, while other behavioral outcomes remained unchanged.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;HACE is associated with the activation of the NKCC1/AQP4 pathway. Inhibition of this pathway alleviates brain edema, BBB disruption, and neuronal and glial cell damage. These findings suggest that XH-6003 holds potential as a therapeutic strategy for HACE at the cellular and molecular levels, but i","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"156-165"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Investigation and Analysis of Deacclimatization in Tibetan College Students Upon First Visit to Low-Altitude Regions].","authors":"Weihua Zhang, Kezhen Han, Li Shao, Chao Yang, Kexin Zhao, Zhao Jiang","doi":"10.12182/20250160509","DOIUrl":"10.12182/20250160509","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the correlation between changes in physiological indicators and altitude, age, and sex among ethnic Tibetan college students living in Xizang on long-term basis upon their first ever visit to a low-altitude region, thereby providing health guidance for long-term residents of high-altitude regions when they visit low-altitude environments for the first time.</p><p><strong>Methods: </strong>A cluster random sampling method was used to select 170 healthy first-year college students of Tibetan ethnicity (85 males and 85 females), from Xizang Minzu University. The participants did not have any respiratory, circulatory, or nervous system diseases, nor any family history of such conditions. Based on their responses to questionnaires and the monitoring data of their physiological indicators, an analysis was conducted to assess the incidence and duration of deacclimatization symptoms among these Tibetan college students during the first month after their arrival at a low-altitude region. In addition, the R programming language and the SPSS software were used to analyze the correlation between changes in blood pressure, heart rate, and body weight and the participants' age, sex, and the altitude of their long-term residence in Xizang before and after their arrival at a low-altitude region.</p><p><strong>Results: </strong>Statistical analysis revealed that Tibetan college students experienced deacclimatization symptoms within the first week of their first ever visit to a low-altitude region, primarily characterized by dizziness, fatigue, and drowsiness. The incidence was 41.9% among female students and 22.5% among male students. Furthermore, after arriving at low-altitude region, the participants experience an initial decrease followed by a recovery in both blood pressure and heart rate. They gained an average of 1.5 kg in body mass compared with their initial measurements upon arrival in a low-altitude region. Significant differences in blood pressure, heart rate, and body mass were observed among Tibetan students of different sexes and altitudes of their long-term residence in Xizang after their arrival in a low-altitude region.</p><p><strong>Conclusion: </strong>After arriving at a low-altitude region, Tibetan college students exhibit marked changes in physiological indicators, showing strong correlations between systolic blood pressure, body mass, etc., and sex, altitude, and other parameters.</p>","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"254-261"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Establishment and Evaluation of a Nucleic Acid Amplification Test for Spectinomycin-Resistant <i>Neisseria gonorrhoeae</i>].","authors":"Guiqin Yang, Menghuan Li, Youwei Wang, Gang Yong, Hongren Wang, Mingjiang Bie","doi":"10.12182/20250160402","DOIUrl":"10.12182/20250160402","url":null,"abstract":"<p><strong>Objective: </strong>To develop and evaluate a nucleic acid amplification test for spectinomycin-resistant <i>Neisseria gonorrhoeae</i> (<i>N. gonorrhoeae</i>).</p><p><strong>Methods: </strong><i>N. gonorrhoeae</i>-specific primers NG1/NG2 and primers specific to the N. gonorrhoeae <i>rpsE</i> gene mutation (80_82 delTTA) were designed. Genomic nucleic acids of spectinomycin-sensitive and resistant <i>N. gonorrhoeae</i>, <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, and <i>Salmonella typhi</i> were used as templates to be amplified by PCR and quantitative real-time PCR (qPCR). The sensitivity and specificity of the method were evaluated accordingly.</p><p><strong>Results: </strong>The NG1/NG2 primers could effectively amplify specific fragments of <i>N. gonorrhoeae</i>, yielding negative results for the nucleic acid amplification test of the other types of bacteria tested. E64/E175R and E-87/E95R could effectively differentiate the wild type and mutant (80_82 delTTA) <i>rpsE</i> genes. In PCR reactions, the minimum limits of NG1/NG2, E64/E175R, and E87/E95R for the target genes were 414.8 copies, 414.8 copies, and 4.1 copies /μL, respectively, while those for qPCR reactions were 41.5, 41.5, and 4.1×10^－2 copies /μL, respectively.</p><p><strong>Conclusion: </strong>A nucleic acid amplification test for spectinomycin-resistant <i>N. gonorrhoeae</i> with high specificity and sensitivity was successfully established in this study, which is expected to provide support for the rapid diagnosis of <i>N. gonorrhoeae</i> infection and treatment decision-making in clinical settings.</p>","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"262-267"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Nafamostat Mesylate Alleviates Renal Ischemia-Reperfusion Injury in a Rat Model Through HMGB1 Modulation: An Omics Analysis -Based Study of the Protective Effect and the Mechanisms Involved].","authors":"Yuxuan Wu, Hongqian Li, Linfeng Liu, Yu Wang, Bo Chen, Jiang Liu, Jianhua Qin, Santao Ou, Weihua Wu","doi":"10.12182/20250160506","DOIUrl":"10.12182/20250160506","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the organ protective role and the underlying mechanism of nafamostat mesylate (NM) in a renal ischemia-reperfusion injury (RIRI) model.</p><p><strong>Methods: </strong>A total of 21 healthy male Sprague-Dawley (SD) rats were randomly assigned to 3 groups (<i>n</i> = 7 in each group), including the sham operation group (Sham group), the RIRI group, and the NM intervention group (NM group). The RIRI and NM groups underwent ischemia-reperfusion injury (IRI) modeling. The NM group was given an intraperitoneal injection of NM at 0.75 mg/kg before modeling. Venous blood and renal tissue samples were then collected from the rats 24 hours after modeling. The levels of serum creatinine, cystatin C, and serum inflammatory factors were determined using the serum samples. Hematoxylin-eosin (HE) staining and TUNEL stainings were performed on the renal tissues to evaluate the damage of the renal tissues. The localization and expression of HMGB1 were analyzed by immunofluorescence and Western blotting, respectively. Single-cell RNA sequencing of the nuclei was performed to obtain the single-cell transcriptome of the kidneys from the rats in the RIRI and the NM groups and to acquire the RIRI cell profile. The cells were annotated according to the cell marker genes to explore the cell type composition in the disease model and the functional status of immune cells between the groups.</p><p><strong>Results: </strong>1) Compared with those of the Sham group, the levels of cystatin C, creatinine, and inflammatory factors in the RIRI and NM groups were significantly increased, and the expression levels in the NM group were lower than those in the RIRI group (<i>P</i> < 0.05). Compared with those of the RIRI group, the tubular injury score and apoptosis rate in the NM group were significantly decreased (<i>P</i> < 0.05), but those of both the NM and RIRI groups were higher than those of the sham group. Compared with that in the RIRI group, the expression of HMGB1 in the NM group was significantly decreased (<i>P</i> < 0.05), but the expression levels in both the RIRI and NM groups were higher than that in the sham group. Immunofluorescence showed that there was increased cytoplasmic expression of HMGB1 in both the NM and RIRI groups, with the increase being more prominent in the RIRI group. 2) A total of 13 major cell populations were identified through the single-nucleus sequencing results. The proportion of tubular cells in the NM group was higher, with the HMGB1 gene being highly expressed in the damaged proximal convoluted tubular cells. The proportion of the polarized Macro3 cell subpopulation in the macrophages in the NM group was lower compared to that in the RIRI group.</p><p><strong>Conclusion: </strong>NM may play a protective role in a rat model of RIRI, and its underlying mechanisms may be related to the regulation of the functional abnormalities of HMGB1-mediated macrophages.</p>","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"175-182"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Legal Risk Assessment and Prevention in Artificial Intelligence-Assisted Health Care].","authors":"Jinming Yang, Na Wang, Yexun Hu, Wei Zhang","doi":"10.12182/20250160301","DOIUrl":"10.12182/20250160301","url":null,"abstract":"<p><p>With the wide application of new technologies such as large language models and generative artificial intelligence (AI) in the health care sector, artificial intelligence-assisted health care is confronted with new forms of legal risks. The algorithmic bias and data security issues in AI-assisted health care have given rise to risks of infringement on general personality rights and specific personality rights. The handling of health care data and the distribution of profits from health care data have spawned disputes over data property rights. Moreover, there will also be risks of uncertainties in the attribution of liability for medical harms once AI technology becomes deeply embedded in health care. Based on the emerging changes in the legal risks associated with AI-assisted health care, it is necessary to establish a corresponding algorithm review mechanism to eliminate algorithm biases, improve the data management system through a whole-life cycle approach to ensure data security, define hierarchical data property rights and establish authorization rules to resolve property rights disputes, and reasonably assign tort liability for medical harms based on specific faults.</p>","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"143-148"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Value of Blood Uric Acid/Creatinine Ratio and Osteoporosis Self-Assessment Tool for Asians for Predicting Osteoporosis in Middle-Aged, Older, and Elderly Adult Tibetan Populations in Xizang].","authors":"Kangzhi Ding, Peng Wang, Jing Zhang, Yufei Zhang, Hai Xiong","doi":"10.12182/20250160508","DOIUrl":"10.12182/20250160508","url":null,"abstract":"<p><strong>Objective: </strong>To explore the predictive value of the blood uric acid/creatinine ratio (SUA/Cr) and the Osteoporosis Self-Assessment Tool for Asians (OSTA) for osteoporosis (OP) in middle-aged, older, and elderly adult Tibetan populations in Xizang.</p><p><strong>Methods: </strong>A total of 1058 middle-aged and older adult ethnic Tibetans who underwent physical examination in Xizang between June 2020 and December 2023 were selected for the study. Fasting venous blood samples were collected for laboratory analysis. The bone mineral density (BMD) of the radius of the participants was measured using dual-energy X-ray absorptiometry. Based on the BMD measurement results and OP diagnostic criteria, participants were divided into the OP group (<i>n</i> = 759) and the non-OP group (<i>n</i> = 299). Multivariate logistic stepwise regression analysis was used to further identify independent predictors associated with OP risk in the middle-aged and older adult Tibetan population. The predictive value of SUA/Cr and OSTA for OP was evaluated using the receiver operating characteristic (ROC) curve.</p><p><strong>Results: </strong>1) The OP prevalence among the middle-aged and older adult Tibetan populations was 28.3% (299 people), including 209 females (69.9%) and 90 males (30.1%). Significant differences between the two groups were found in terms of age (OP group: 62 [54, 69] vs non-OP group: 56 [51, 62]), SUA/Cr (OP group: 6.86 [5.06, 10.23] vs non-OP group: 5.36 [4.36, 6.52]), and OSTA (OP group: [－1.27 ± 3.06] vs non-OP group: [1.25 ± 2.68]) (<i>P</i> < 0.05). 2) SUA/Cr (OR: 1.592, 95% CI: 1.469-1.726) was identified as a risk factor for OP, while OSTA (OR: 0.706, 95% CI: 0.662-0.752) was a protective factor for OP (<i>P</i> < 0.05). 3) For gender-based group analysis, the combined use of SUA/Cr and OSTA showed better diagnostic performance for OP, with AUCs of 0.807 (95% CI: 0.751-0.863) for males and 0.820 (95% CI: 0.782-0.857) for females. For age-based group analysis, the combined diagnosis of OP using SUA/Cr and OSTA provided the best performance, with the optimal cutoff value increasing with age. 4) In the middle-aged group and the older adult male group, the combined use of SUA/Cr and OSTA for OP diagnosis was more effective than using SUA/Cr or OSTA alone (<i>P</i> < 0.001). In the elderly adult male group, the AUC for SUA/Cr was 0.954 (95% CI: 0.858-1.000), with a sensitivity of 88.9% and specificity of 100.0%, indicating excellent predictive performance. In females, the diagnostic effectiveness of OSTA and the combined use of SUA/Cr and OSTA increased with age across different age groups.</p><p><strong>Conclusion: </strong>The predictive performance of SUA/Cr and OSTA for OP varies across different sex and age groups in the Tibetan population. Both SUA/Cr and OSTA can be used to predict OP in middle-aged and older adult Tibetan populations, with the combined use of SUA/Cr and OSTA providing better predictive performance.</p>","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"247-253"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Gandou Bushen Decoction Ameliorates Cognitive Impairment in Wilson Disease Model TX Mice by Regulating Melatonin Synthesis via the SIRT3/FOXO3α Pathway].","authors":"Luyao Wang, Limin Wu, Tingting Wang, Xinru Fang, Zhenzhen Jiang, Yike Yue, Dan Zhao, Qianzhuo Liu, Hui Han","doi":"10.12182/20250160602","DOIUrl":"10.12182/20250160602","url":null,"abstract":"<p><strong>Objective: </strong>Melatonin has been shown to have neuroprotective effects. This study is aimed at observing the effects of copper deposition on cognitive function in a toxic milk (TX) mouse model of Wilson disease (WD), and investigating the effects and mechanisms of action of Gandou Bushen Decoction (GDBSD) on melatonin synthesis and pineal function in the WD model mice.</p><p><strong>Methods: </strong>A total of 30 homozygous TX mice were randomly assigned to 3 groups (<i>n</i> = 10 in each group), including a WD group, a GDBSD group, and a dimercaptosuccinic acid (DMSA) group. A total of 10 DL mice were included in the normal control (NC) group. The structure and copper content of pineal gland tissues, oxidative stress and apoptosis-related markers, and serum melatonin levels were evaluated using hematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and Western blot.</p><p><strong>Results: </strong>Compared with the NC group, the WD group exhibited decreased learning and cognitive abilities (<i>P</i> < 0.05), damaged pineal gland structure, increased copper content, reactive oxygen species (ROS) levels, and mitochondrial damage rate in the pineal gland (<i>P</i> < 0.01), altered levels of melatonin and oxidative stress-related markers (<i>P</i> < 0.05), upregulated expression levels of pro-apoptotic proteins Bax and Caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2 (<i>P</i> < 0.01). After treatment with GDBSD and DMSA, the SIRT3/FOXO3α signaling pathway was activated, the copper content in the pineal gland was reduced, and oxidative stress and apoptosis-related damages were improved, leading to an improvement in learning and memory abilities (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>GDBSD can alleviate cognitive impairments in WD mice caused by pineal gland copper deposition by inhibiting oxidative stress and apoptosis in the pineal gland. The underlying molecular mechanism is associated with the regulation of the SIRT3/FOXO3α signaling pathway.</p>","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"102-111"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Preparation of Trop2-Targeted CAR-T Cells Based on Nanobodies and Their Antitumor Effects Against Non-Small Cell Lung Cancer].","authors":"Jing Wen, Xin Li","doi":"10.12182/20250160107","DOIUrl":"10.12182/20250160107","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether chimeric antigen receptor (CAR) T cells constructed with nanobodies based on trophoblast cell-surface antigen 2 (Trop2) can be used to treat Trop2-positive non-small cell lung cancer.</p><p><strong>Methods: </strong>A Trop2-specific phage display nanobody library was constructed to screen for Trop2-specific nanobodies. The antigen-binding capacities of three Trop2 nanobodies (8^#, 14^#, and 48^#) were assessed using indirect enzyme-linked immunosorbent assay (ELISA), and their binding affinities were analyzed through surface plasmon resonance (SPR) analysis. CAR-T cells were constructed with Trop2-specific nanobodies and were then co-cultured with the Trop2-positive NCI-H292 cell line expressing luciferase and the Trop2-negative A549 cell line. Luciferase values at effector-to-target ratios of 4∶1, 2∶1, 1∶1, and 1∶2 were measured using a multifunctional microplate reader to assess the killing efficiency. The levels of interleukin (IL)-2, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) cytokines in the supernatant at an effector-to-target ratio of 4∶1 were measured using the ELISA method. We also established in this study an NCI-H292 xenograft model in NCG immunodeficient mice, which were divided into three groups, a phosphate-buffered saline (PBS) control group, a Mock-T group, and a Trop2 CAR-T group (<i>n</i> = 5). A total of 1×10⁷ Trop2 CAR-T cells were administered via tail vein injection. Throughout the experimental period, the growth and survival status of the mice were observed daily, and tumor sizes were measured once every three days to analyze the survival time.</p><p><strong>Results: </strong>A Trop2-specific nanobody was successfully screened from the nanobody library, and indirect ELISA initially indicated that nanobody 48^# had the strongest affinity. Subsequently, surface plasmon resonance analysis revealed that nanobody 48^# exhibited an affinity in the range of 2.49×10^－8 M, indicating that it was a high-affinity antibody. Based on this nanobody, Trop2 CAR-T cells were successfully constructed. Furthermore, <i>in vitro</i> experiments demonstrated that Trop2 CAR-T cells killed Trop2-positive NCI-H292 non-small cell lung cancer cells in a dose-dependent manner. ELISA showed a significant increase in the secretion of cytokines (IL-2, IFN-γ, and TNF-α) in the co-culture system, further validating their antitumor activity. In the NCI-H292 xenograft mouse model, the Trop2 CAR-T group exhibited reduced tumor size (<i>P</i> < 0.001) and prolonged survival time of tumor-bearing mice (<i>P</i> < 0.05) compared to the PBS and Mock-T groups.</p><p><strong>Conclusion: </strong>These findings demonstrate that CAR T cells constructed with Trop2 nanobodies can effectively treat Trop2-positive non-small cell lung cancer.</p>","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"198-205"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Effects and Efficacy of Wenyang Huayin Yangxin Prescription on the Traditional Chinese Medicine Syndromes of Patients With Chronic Heart Failure Combined With Diuretic Resistance].","authors":"Jiali Wu, Dan Xiao, Tao Zhan, Yi Yuan, Yun Zhan, Hong Liu","doi":"10.12182/20250160109","DOIUrl":"10.12182/20250160109","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To study the traditional Chinese medicine (TCM) syndromes of patients with chronic heart failure (CHF) combined with diuretic resistance by using the Wenyang Huayin Yangxin Prescription, and to observe its therapeutic efficacy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 68 CHF patients complicated with diuretic resistance and who had Yangqi deficiency and presenting blood stasis syndrome combined with Tanyin were randomly assigned to a control group and an observation group. The control group was given intravenous furosemide (≥ 80 mg/d) via infusion pump in addition to standard Western medical treatment, while the observation group was given intravenous furosemide (&lt; 80 mg/d) via infusion pump along with the Wenyang Huayin Yangxin Prescription (30 g Astragalus, 15 g Poria, 15 g Baizhu, 15 g Chuanxiong, 10 g Danfu tablet, 10 g Cassia, 10 g Alisma, and 10 g Zhimu). The quantitative index of diuretic resistance was used as the primary outcome measure. In addition, the differences between the two groups in TCM syndromes, cardiac function-related indicators, incidence of endpoint events, and readmission rate were compared.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After 2 weeks of treatment, the filtration sodium excretion fraction (FENa) in the observation group was (0.18 ± 0.04)%, while that of the control group was (0.16 ± 0.03)%, showing a statistically significant difference (&lt;i&gt;P&lt;/i&gt; = 0.037). The 24-hour urine volume and urine Na&lt;sup&gt;+&lt;/sup&gt;/K&lt;sup&gt;+&lt;/sup&gt; ratio in the observation group increased significantly from baseline levels and were higher than those in the control group (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). The differences in the changes of 24-hour urine volume, urine sodium, FENa, and urine Na&lt;sup&gt;+&lt;/sup&gt;/K&lt;sup&gt;+&lt;/sup&gt; ratio between the two groups were statistically significant (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). The TCM syndrome scores decreased in both groups after 2 weeks of treatment, with the observation group showing a significantly greater reduction compared with the control group (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). The differences in the changes of TCM syndrome scores between the two groups were statistically significant (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). After 2 weeks of treatment, the observation group showed significant improvements in palpitations, shortness of breath, facial and limb edema, spontaneous sweating, chest tightness (pain), asthma, and oliguria compared with the baseline data (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), while the control group showed improvements only in facial and limb edema, asthma, and oliguria (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Except for the asthma syndrome after 2 weeks of treatment, the observation group showed better outcomes in spontaneous sweating, chest tightness (pain), asthma, and oliguria at various time points after treatment compared with the control group (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). After 2 weeks of treatment, the observation group had significantly better cardiac output (CO) and stroke volume (SV) compared with those of the control group (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). The differences ","PeriodicalId":39321,"journal":{"name":"四川大学学报(医学版)","volume":"56 1","pages":"94-101"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}