四川大学学报(医学版)最新文献

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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.

Objective: To develop and evaluate a nucleic acid amplification test for spectinomycin-resistant Neisseria gonorrhoeae (N. gonorrhoeae).

Methods: N. gonorrhoeae-specific primers NG1/NG2 and primers specific to the N. gonorrhoeae rpsE gene mutation (80_82 delTTA) were designed. Genomic nucleic acids of spectinomycin-sensitive and resistant N. gonorrhoeae, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi 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.

Results: The NG1/NG2 primers could effectively amplify specific fragments of N. gonorrhoeae, 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) rpsE 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.

Conclusion: A nucleic acid amplification test for spectinomycin-resistant N. gonorrhoeae with high specificity and sensitivity was successfully established in this study, which is expected to provide support for the rapid diagnosis of N. gonorrhoeae infection and treatment decision-making in clinical settings.

In recent years, a growing body of research has demonstrated that acupuncture can be used to effectively treat a diverse range of diseases, including functional gastrointestinal disorders, cardiovascular diseases, as well as anxiety and depression, through the modulation of the paraventricular hypothalamic nucleus (PVN). Acupuncture may exert its therapeutic effect either by modulating specific neurons within the PVN, such as corticotropin releasing hormone (CRH) neurons, or by regulating the release of hormones, such as oxytocin (OXT) and vasopressin (VP), and the activity of neural circuits associated with the PVN. This review summarizes the mechanisms by which PVN is involved in acupuncture treatment, including its regulatory mechanisms in gastrointestinal diseases, cardiovascular diseases, and negative emotions and pain. Future research should be conducted to further explore the precise mechanisms by which acupuncture regulates PVN to treat diseases, focusing on clarifying the specific processes of signaling pathway transduction, and exploring the specific effects of acupunture of different acupoint combinations and stimulation frequencies and intensity on PVN.

Objective: To investigate the organ protective role and the underlying mechanism of nafamostat mesylate (NM) in a renal ischemia-reperfusion injury (RIRI) model.

Methods: A total of 21 healthy male Sprague-Dawley (SD) rats were randomly assigned to 3 groups (n = 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.

Results: 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 (P < 0.05). Compared with those of the RIRI group, the tubular injury score and apoptosis rate in the NM group were significantly decreased (P < 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 (P < 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.

Conclusion: 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.

Objective: To investigate the mechanisms by which Porphyromonas gingivalis (P. gingivalis) promotes the malignant progression of oral squamous cell carcinoma (OSCC) through the recruitment of chemokine receptor 6-positive (CCR6⁺) regulatory T cells (Treg) in the tumor microenvironment (TME).

Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the correlation between chemokine ligand 20 (CCL20), CCR6, and Treg. The Treg enrichment index and the expression levels of interleukin (IL)-10 and tumor necrosis factor β1 (TGF-β1) were assessed in the high CCR6 expression group of OSCC patients. C57BL/6 mice were randomly assigned to a control group and an experimental group (n = 6 in each group). The control group received a single injection of 100 μL SCC7, a mice head and neck squamous carcinoma cell line, while the experimental group received a single injection of 100 μL mixture of SCC7 cells and P. gingivalis in the cheek. After two weeks, the mice were sacrificed, and immunohistochemistry was performed to assess the expression levels of CCR6 and forkhead box protein 3 (FOXP3) in OSCC. Flow cytometry was performed to analyze the effects of P. gingivalis on OSCC malignant biological behavior, CCR6⁺ Treg cells, and the immune microenvironment.

Results: Bioinformatics analysis revealed a correlation between CCL20, CCR6, and Treg (r = 0.373, P < 0.000 1). OSCC patients with high CCR6 expression showed higher Treg enrichment scores and increased IL-10 expression. Animal experiments showed that P. gingivalis promoted the increase in the tumor volume (mm³) (0.294 ± 0.105 in the control group and 0.526 ± 0.101 in the experimental group, P < 0.01) and mass (mg) (206.200 ± 53.950 in the control group and 376.000 ± 119.200 in the experimental group, P < 0.01) in mice with OSCC. Immunohistochemistry confirmed a correlation between CCR6 and FOXP3 (r = 0.659, P < 0.05), and P. gingivalis promoted the expression of CCR6 and FOXP3. Flow cytometry analysis showed that P. gingivalis increased the proportion of CCR6⁺ Treg (%) (13.780 ± 1.506 in the control group and 18.260 ± 2.257 in the experimental group, P < 0.01) and decreased the proportion of CD8⁺ T cells (%) (27.120 ± 1.647 in the control group and 21.060 ± 3.148 in the experimental group, P < 0.01) in OSCC, thereby promoting the formation of a immunosuppressive microenvironment.

Conclusion: P. gingivalis promotes the malignant progression of OSCC by recruiting CCR6⁺ Treg cells to form an immunosuppressive TME.

Objective: 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.

Methods: 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.

Results: The expression of AURKA was significantly upregulated in CRC tissues compared with that in paracancerous tissues (P < 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 (P < 0.05). In addition, the cytotoxicity of T cells was significantly reduced (P < 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 (P < 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.

Conclusion: 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.