OBJECTIVES:Kidney transplant recipients are highly susceptible to respiratory tract infections (RTIs), and short-term exposure to ambient air pollution may aggravate their clinical outcomes. However, evidence regarding the effects of specific pollutants on hospitalization burden in this population remains limited. This study aims to investigate the effects of pollutants such as PM2.5 on hospitalization burden after RTIs in kidney transplant recipients. METHODS:This retrospective time-series study included 874 kidney transplant recipients who were hospitalized for RTIs at the Third Xiangya Hospital of Central South University between 2017 and 2023. High-resolution environmental data were used to assess daily exposure to 6 ambient air pollutants, namely PM2.5, PM10, SO2, NO2, CO, and O3, within the 7 days before the onset of RTI symptoms. Distributed lag non-linear models (DLNMs) were applied to evaluate pollutant-specific lagged and cumulative associations between the 6 ambient air pollutants and hospitalization costs and length of hospital stay, with adjustment for meteorological conditions and individual-level variables. RESULTS:PM2.5 showed the most significant association with hospitalization burden. At a cumulative exposure level of 160 µg/m3, hospitalization costs increased by 9 544.5 yuan (95% CI 2 548.8 to 21 637.7). When PM2.5 exposure reached 200 µg/m3 on lag day 0, it was associated with prolonged hospital stay and increased hospitalization costs. PM10 showed a trend toward dose-dependent cumulative effect on length of hospital stay, with a relative risk of 1.63 at 300 µg/m3 (95% CI 0.18 to 15.94). SO₂ levels above 75 µg/m3 were also associated with increased hospitalization burden. In contrast, no consistent or significant associations were observed for CO, NO2, or O3. CONCLUSIONS:Short-term exposure to higher levels of PM2.5, PM10, and SO2 significantly increases the clinical and economic burden of RTIs in kidney transplant recipients. These findings highlight the importance of developing targeted air pollution prevention and control strategies to protect susceptible patient populations.
OBJECTIVES:THAP domain-containing protein 6 (THAP6) is a member of the THAP family and contains a conserved THAP zinc-finger domain, allowing it to regulate gene expression as a transcription factor. Previous studies have shown that THAP6 may be involved in macrophage activation and transcriptional regulation related to social stimuli; however, whether THAP6 affects emotional behavior and brain tissue structure has not yet been reported. This study aims to clarify the effects of Thap6 gene deletion on emotional behaviors in mice, preliminarily explore the effects of Thap6 gene knockout on mouse brain tissue, and provide experimental evidence for revealing the potential role of THAP6 in neuropsychiatric disorders. METHODS:A whole-body Thap6 knockout mouse model was generated using CRISPR/Cas9 technology. Genotyping was performed to select heterozygous Thap6 knockout (Thap6+/-; n=8) and wild-type (WT; n=10) male C57BL/6J mice as study subjects. After the mice reached adulthood, motor and balance abilities were assessed using the rotarod test; general locomotor activity and exploratory ability were evaluated using the open-field test; depression-like behaviors were assessed using the sucrose preference test and tail suspension test; anxiety-like behavior was evaluated using the elevated plus-maze test; and social behavior was assessed using the three-chamber social test. After behavioral assessments, mouse brain tissues were collected, and hematoxylin and eosin (HE) staining and Nissl staining were used to observe changes in brain microstructure and neuronal number. RESULTS:Behavioral results showed that, compared with WT mice, Thap6+/- mice had a significantly lower percentage of entries into the open arms in the elevated plus maze test (t=2.516, P=0.024) and a significantly higher average movement speed in the open arms (t=3.045, P=0.013). In the three-chamber social test, the sociability index (t=4.350, P<0.001) and social preference index (t=2.732, P=0.014) of Thap6+/- mice were significantly lower than those of WT mice. No statistically significant differences were observed between the 2 groups in other behavioral indicators (all P>0.05). HE staining of brain tissues showed scattered abnormal cell morphology, loose cytoplasm, and blurred nuclei in the cortex of Thap6⁺/⁻ mice; loosely arranged neurons, enlarged intercellular spaces, and extensive vacuole formation in the amygdala; disordered arrangement of cerebellar Purkinje cells, unclear boundaries, swelling and dissolution of some nuclei, and cell loss; and loss of neuronal nucleoli and partial cellular pyknosis in the substantia nigra. In the hippocampus of Thap6⁺/⁻ mice, neurons were orderly arranged, with relatively good cell morphology, a larger number of cells, and compact arrangement. Nissl staining showed that the number of neurons in the hippocampal dentate gyrus region was significantly increased in Thap6⁺/⁻ mice (U=0, P=0.029), whereas morphological abnormalities and reduced neuronal numbers were observed in the cortex, amygdala, cerebellum, and substantia nigra (all U=0, P=0.029). CONCLUSIONS:Thap6 gene knockout leads to anxiety-like behavior and social behavioral deficits in mice. It also causes structural abnormalities and reductions in neuronal number across multiple brain regions. This study systematically reveals, for the first time, the important role of THAP6 in the regulation of emotional and social behaviors, provides new evidence for understanding the functional differentiation of THAP family proteins in the central nervous system, and suggests that Thap6 knockout mice may serve as a novel animal model for studying neuropsychiatric disorders related to anxiety and social deficits.
OBJECTIVES:In the context of prenatal counseling, the factors influencing pregnancy decision-making among parents of fetuses with congenital heart disease (CHD) remain unclear. This study aims to investigate the factors influencing pregnancy decision-making among parents of fetuses with CHD, with a particular focus on the roles of non-medical factors such as psychological status, socioeconomic status, and the degree of fetal expectation. METHODS:A prospective cohort study design was adopted. Expectant parents whose fetuses were prenatally diagnosed with CHD at the Second Xiangya Hospital of Central South University and Hunan Provincial Maternal and Child Health Care Hospital from July 2021 to December 2025, and who received multidisciplinary counseling led by CHD specialists, were enrolled. According to the prognostic risk scoring system, the fetuses were classified into a mild group (0-3 points), a moderate group (4-6 points), and a severe group (7-9 points).Information on the fetuses and parents was collected through questionnaires, and follow-up files were established. Standardized follow-up was conducted at 1 week after counseling, 1 to 2 weeks before the expected date of delivery, and 2 weeks after the expected date of delivery to record the pregnancy outcomes. Multivariate Logistic regression analysis was used to identify independent factors influencing pregnancy decision-making. RESULTS:A total of 834 families with fetuses prenatally diagnosed with CHD were included. Among them, 522 families (62.6%) chose to continue the pregnancy, whereas 312 families (37.4%) chose to terminate the pregnancy. The severity of fetal disease was the strongest predictor of pregnancy termination. Compared with the mild group, the risk of pregnancy termination in the moderate group increased by 6-fold [adjusted odds ratio (aOR)=6.04, 95% confidence interval (CI) 3.98 to 9.15, P<0.01], and the risk in the severe group increased by 53-fold (aOR=52.97, 95% CI 14.73 to 190.44, P<0.01). Multivariate Logistic regression analysis showed that, after controlling for disease severity, earlier gestational age at diagnosis (aOR=0.76, 95% CI 0.72 to 0.81, P<0.01), older maternal age (aOR=0.96, 95% CI 0.92 to 0.99, P=0.039), multiple pregnancy (aOR=0.24, 95% CI 0.09 to 0.65, P=0.005), higher annual household income (≥200 000 yuan; aOR=0.05, 95% CI 0.01 to 0.21, P<0.01), and a higher degree of fetal expectation (aOR=0.66, 95% CI 0.47 to 0.94, P=0.019) were independent protective factors for continuing pregnancy. CONCLUSIONS:Pregnancy decision-making among parents of fetuses with CHD is a complex process jointly influenced by fetal medical factors, family socioeconomic status, and psychosocial factors. In addition to disease severity, family economic status, and par ental expectations regarding the fetus have important effects on decision-making.
OBJECTIVES:The prevalence of non-alcoholic fatty liver disease (NAFLD) in obese children has been increasing year by year. Its pathogenesis involves the joint effects of genes and gut microbiota, but their interaction effects remain unclear. This study aims to investigate the associations of gene polymorphisms, gut microbiota, and their interactions with NAFLD in obese children, thereby providing new clues for research on the pathogenesis of NAFLD in this population. METHODS:A case-control study was conducted. A total of 87 obese children with NAFLD who visited Hunan Children's Hospital from January 2020 to September 2021 were selected as a case group, and 50 obese children without NAFLD who visited the hospital during the same period were selected as a control group. Polymorphisms in 52 candidate genes were detected using multiplex polymerase chain reaction and high-throughput sequencing, and the composition of the gut microbiota was analyzed using 16S ribosomal DNA (16S rDNA) sequencing. Logistic regression was used to analyze the associations between candidate gene polymorphisms and NAFLD in obese children, and the Benjamini-Hochberg method was applied for false discovery rate (FDR) correction in multiple comparisons, with an expected FDR of 0.05. Linear discriminant analysis effect size (LEfSe) analysis was used to compare the relative abundance of gut microbiota at the genus level. Logistic regression models, crossover analysis, and generalized multifactor dimensionality reduction (GMDR) were used to explore two-factor gene-microbiota interactions and the associations of higher-order multifactor interactions with the risk of NAFLD in obese children. RESULTS:After adjustment for sex, age, and body mass index, PRKAB1 rs6490265 and IL32 rs28372698 were both significantly associated with NAFLD in obese children (both P<0.05). IL32 rs28372698 remained statistically significant after FDR correction, under both the dominant and additive models (Padj=0.035), whereas PRKAB1 rs6490265 showed no significant differences in any model after FDR correction. Compared with the control group, Escherichia-Shigella, Enterobacter, Bacteroides, Klebsiella, Dialister, and Erysipelotrichaceae_UCG_003 were significantly enriched in the NAFLD group (all P<0.05). Compared with the NAFLD group, Intestinibacter, Coprococcus, Ralstonia, Ligilactobacillus, Fusicatenibacter, Sarcina, Eubacterium_eligens_group, and Pseudomonas were significantly enriched in the control group (all P<0.05). Multiplicative interaction analysis showed that the interaction terms between PRKAB1 rs6490265 and Bacteroides, between PRKAB1 rs6490265 and Intestinibacter, and between IL32 rs28372698 and Ligilactobacillus were statistically significant (all P<0.05). GMDR higher-order interaction analysis showed that the interaction among IL32 rs28372698, Ligilactobacillus, and Intestinibacter was the best model. CONCLUSIONS:Polymorphisms in PRKAB1 and IL32 may be potentially associated with the risk of NAFLD in obese children. The antagonistic interaction effects between PRKAB1 rs6490265 and the abundance of Bacteroides and Enterobacter, as well as the synergistic interaction effect between IL32 rs28372698 and the abundance of Ligilactobacillus, may jointly influence the risk of NAFLD in obese children.
Circadian rhythm is an intrinsic 24-hour physiological rhythm of the human body,and its disruption is closely associated with obesity and chronic inflammation.Circadian clock genes not only regulate metabolic processes but also participate in the regulation of inflammatory responses.Circadian clock disruption can lead to a vicious cycle involving rhythm disturbance,obesity,and inflammation.Regular exercise can serve as an effective zeitgeber,helping to realign disrupted biological rhythms and reduce obesity-related inflammation.The effects of exercise may be influenced by factors such as exercise timing and intensity;for example,exercise performed at different times of the day may have different effects on improving blood glucose and sleep.However,it remains unclear whether there is a universally applicable"optimal"exercise time for individuals whose biological clocks are already disrupted.Systematically reviewing and summarizing the mechanisms underlying the interactions among circadian rhythm,obesity,and inflammation,and revealing the potential value of exercise in regulating the biological clock and reducing inflammation,are of great significance for developing exercise intervention strategies.Future studies may further explore the formulation of personalized exercise prescriptions,particularly for high-risk populations such as shift workers,to promote the application of chronomedicine in metabolic health management.
OBJECTIVES:Patients with acute ischemic stroke remain at risk of hemorrhagic transformation after mechanical thrombectomy, which may lead to neurological deterioration and adversely affect clinical outcomes. Early identification of related risk factors is therefore important for optimizing perioperative management. This study aimed to investigate the clinical factors associated with hemorrhagic transformation (HT) after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS), and to further evaluate the value of these factors in combination for predicting the risk of HT after MT, thereby providing a reference for early identification of high-risk patients, optimization of perioperative management, and development of individualized follow-up strategies. METHODS:This was a single-center, prospective, observational cohort study. A total of 268 patients with AIS who underwent MT and had complete clinical data at the Stroke Center of Beijing Hospital between May 2020 and December 2024 were consecutively enrolled. All patients met the diagnostic criteria for AIS and the indications for vascular recanalization therapy. Patients were excluded if they had a pre-stroke Modified Rankin Scale score ≥3, hemorrhagic disorders or a clear bleeding tendency, onset-to-treatment time ≥24 h, large-area cerebral infarction, severe cardiac, pulmonary, hepatic, or renal disease, end-stage malignant tumors, loss to follow-up, or unwillingness to participate in follow-up. HT was determined according to cranial computed tomography (CT) or magnetic resonance imaging (MRI) findings within 14 days after MT, and the patients were divided into an HT group and a non-HT group. Data were collected using standardized case report forms, including demographic characteristics, previous stroke risk factors, use of antiplatelet drugs, unhealthy lifestyle factors, onset-to-thrombectomy time, baseline National Institutes of Health Stroke Scale (NIHSS) score, preoperative blood pressure, emergency laboratory test results, stroke etiological classification, infarct location, intravenous thrombolysis, thrombectomy method, and vascular recanalization status. The t test, Mann-Whitney U test, and chi-square test were used to compare clinical characteristics between the two groups. Variables with statistically significant differences in univariate analysis, together with variables considered clinically relevant or previously reported to be associated with HT, were included in multivariate Logistic regression analysis to identify independent factors associated with HT after MT in AIS patients. Individual predicted probabilities were calculated based on the final Logistic regression model, and receiver operating characteristic (ROC) curve analysis was performed. The area under the curve (AUC) was used to evaluate the discriminative ability of the model for HT after MT. RESULTS:A total of 268 AIS patients were included in this study, including 156 males and 112 females, with a mean age of (72.6±12.9) years. HT occurred in 92 patients after MT, with an incidence of 34.3%. Among them, 29 patients had hemorrhagic infarction type 1 (HI-1), 24 had hemorrhagic infarction type 2 (HI-2), 16 had parenchymal hematoma type 1 (PH-1), and 23 had parenchymal hematoma type 2 (PH-2). Symptomatic intracranial hemorrhage (sICH) occurred in 15 patients, with an incidence of 5.6%. Compared with the non-HT group, the HT group had a higher proportion of patients with a history of coronary heart disease, a lower proportion of patients with a history of stroke, higher baseline NIHSS scores, a higher proportion of patients with NIHSS score ≥12, a lower proportion of posterior circulation infarction, and a lower rate of favorable outcome at 3 months (all P<0.05). In terms of laboratory indicators, platelet count and fibrinogen level were lower in the HT group than in the non-HT group (both P<0.05). There were no statistically significant differences between the 2 groups in age, sex, history of hypertension, history of diabetes mellitus, atrial fibrillation, hyperlipidemia, smoking, alcohol consumption, use of antiplatelet drugs, onset-to-thrombectomy time, trial of Org 10172 in acute stroke treatment (TOAST) classification, intravenous thrombolysis before MT, stent retriever thrombectomy, aspiration thrombectomy, vascular recanalization status, or mortality (all P>0.05). Multivariate Logistic regression analysis showed that baseline NIHSS score ≥12 [odds ratio (OR)=2.271, 95% confidence interval (CI) 1.266 to 4.076, P<0.01] and history of coronary heart disease (OR=2.144, 95% CI 1.141 to 4.026, P<0.05) were independent risk factors for HT after MT in AIS patients. Patients with NIHSS score ≥12 had an increased risk of HT, and those with a history of coronary heart disease also had a significantly higher risk of HT. A higher fibrinogen level (OR=0.651, 95% CI 0.467 to 0.909, P<0.05) was independently associated with a lower risk of HT. After further adjustment for the use of antiplatelet drugs, history of coronary heart disease remained independently associated with HT, whereas antiplatelet drug use itself showed no independent association. The multivariate Logistic regression prediction model constructed using NIHSS score ≥12, history of coronary heart disease, fibrinogen level, and antiplatelet drug use had an AUC of 0.680. CONCLUSIONS:The incidence of HT after MT is relatively high in patients with AIS. A baseline NIHSS score ≥12 and a history of coronary heart disease were identified as independent risk factors for HT, whereas a higher fibrinogen level was an independent protective factor. The predictive model developed in this study may facilitate early identification of HT risk; however, further optimization through the incorporation of additional imaging and perioperative variables, as well as validation in multicenter studies, is warranted.
OBJECTIVES:The Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) is widely used to measure health-related quality of life and common symptoms, but it has not yet been validated in patients receiving kidney replacement therapy (KRT). This study aims to evaluate the psychometric properties of the Chinese version of PROMIS-29 in patients receiving KRT. METHODS:A cross-sectional survey was conducted from November 2023 to January 2024 among adult patients receiving KRT. Participants completed a clinical information questionnaire, PROMIS-29, and conventional measurement questionnaires through an online survey platform. Evaluation indicators included internal consistency, ceiling and floor effects, structural validity, convergent and discriminant validity, and criterion validity, and measurement invariance. Item characteristic curves and item information curves were also plotted. RESULTS:A total of 500 participants were included, with a age of (48.76±12.59) years. Cronbach's α coefficients for the 7 domains of PROMIS-29 ranged from 0.75 to 0.96. Confirmatory factor analysis demonstrated good model fit: Comparative fit index (CFI)=0.975, Tucker-Lewis index (TLI)=0.971, root mean square error of approximation (RMSEA)=0.046, and standardized root mean square residual (SRMR)=0.056. All dimensions met the assumption of unidimensionality. No differential item functioning was detected for the majority of items across subgroups, indicating good measurement invariance. Most items showed ideal item characteristic curves and acceptable item information curves. CONCLUSIONS:The Chinese version of PROMIS-29 has good reliability, validity, and measurement invariance among Chinese patients receiving KRT and can be used to assess health-related quality of life and symptoms in this population.
OBJECTIVES:Hypertensive retinopathy is a microvascular complication caused by systemic hypertension and can lead to severe visual impairment. At present, the molecular mechanisms of this disease remain incompletely understood, particularly the global expression profiles and regulatory networks of non-coding RNA (ncRNA). This study aims to comprehensively analyze the genome-wide differential expression profiles of messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) in retinal tissues from a spontaneously hypertensive rat (SHR) model of hypertensive retinopathy, and to observe transcriptomic changes after treatment with the calcium channel blocker lacidipine, thereby revealing their potential roles in disease pathogenesis and identifying possible therapeutic targets. METHODS:SHRs were used as a model of hypertensive retinopathy, and normotensive Wistar-Kyoto (WKY) rats were used as controls. Rats were divided into 3 groups: A control group (WKY), a model group (SHR), and a treatment group (SHR+lacidipine). Rats in the treatment group received lacidipine by gavage at 0.5 mg/(kg·d) for 8 consecutive weeks. At the end of the experiment, retinal tissues were collected for histopathological examination by hematoxylin and eosin (HE) staining and for high-throughput sequencing. The lncRNA library was used to analyze mRNA, lncRNA, and circRNA expression profiles, and the small RNA (sRNA) library was used to analyze miRNA expression profiles. Differential expression analysis was performed using DESeq2. The screening criteria were |log2 fold change (FC)|≥1 and false discovery rate (FDR) significance criteria for mRNAs and lncRNAs, and |log2FC|≥1 and P<0.05 for miRNAs and circRNAs as exploratory candidates. Differentially expressed RNAs were subjected to Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Competing endogenous RNA (ceRNA) regulatory networks involving lncRNA/circRNA-miRNA-mRNA were constructed through target prediction and co‑expression analysis. Ten mRNAs whose expression changes were reversed after treatment were selected for validation by real-time reverse transcription polymerase chain reaction (real-time RT-PCR; n=6 per group). Comparisons among multiple groups were performed using one-way analysis of variance and post hoc multiple-comparison tests. RESULTS:1) Verification of the animal model: Blood pressure was significantly higher in the model group than in the control group. The model group exhibited edema of the retinal nerve fiber layer, dilation of vascular lumens, and increased retinal thickness. Lacidipine treatment reduced blood pressure and alleviated these pathological changes. 2) Differential expression of mRNAs: Compared with the control group, 870 mRNAs were significantly downregulated and 1 018 mRNAs were significantly upregulated in the model group. Compared with the model group, 2 644 mRNAs were significantly downregulated and 186 mRNAs were significantly upregulated in the treatment group. GO analysis showed that upregulated mRNAs in the model group were enriched in immune-inflammatory processes, such as leukocyte activation, chemotaxis, defense response, and regulation of tumor necrosis factor (TNF) production, whereas downregulated mRNAs were enriched in G protein-coupled receptor (GPCR) signaling, glycoprotein synthesis, ion channel activity, and related processes. KEGG analysis revealed that upregulated mRNAs in the model group were enriched in interleukin-17 (IL-17), TNF, oxidative stress, and lipid inflammatory mediator metabolic pathways, whereas downregulated mRNAs were enriched in phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling, vascular smooth muscle contraction, extracellular matrix (ECM)-receptor interaction, and related pathways. In the treatment group, the downregulated mRNAs were mainly enriched in pathways related to immune-inflammatory activation, such as mast cell degranulation and leukocyte degranulation. 3) Treatment-reversed mRNAs: A total of 67 genes that were upregulated in the model group and downregulated after treatment were identified; these genes were mainly enriched in endoplasmic reticulum stress-associated apoptotic signaling, mitophagy, ubiquitin ligase activity, and related processes. In addition, 54 genes that were downregulated in the model group and upregulated after treatment were identified; these genes were mainly enriched in amino acid transport, integrin complex, focal adhesion, glutamate transport activity, and related processes. Real-time RT-PCR validated the expression changes of Med22, Rmt1, Sytl3, Itgb7, and Slc1a3 which were decreased in the model group and increased after treatment, as well as Rnf183, Lrrc29, Lat2, Hist1h4m, and Dpm3, which were increased in the model group and decreased after treatment. These findings were consistent with the sequencing results. 4) Differential expression of miRNAs: Compared with the control group, 30 miRNAs were downregulated and 26 miRNAs were upregulated in the model group. Compared with the model group, 14 miRNAs were downregulated and 53 miRNAs were upregulated in the treatment group. Treatment-reversed miRNAs were identified: Rno-miR-1-3p, novel_miR_1203, and novel_miR_1417 were upregulated in the model group and downregulated after treatment, whereas novel_miR_107 and novel_miR_905 were downregulated in the model group and upregulated after treatment. Their target genes were enriched in regulation of retinal cone/rod cell differentiation, ECM remodeling, the Notch pathway, fatty acid synthesis, and related processes. 5) Differential expression of lncRNAs: Compared with the control group, 786 lncRNAs were downregulated and 764 lncRNAs were upregulated in the model group. Compared with the model group, 217 lncRNAs were downregulated and 230 lncRNAs were upregulated in the treatment group. A total of 55 lncRNAs that were upregulated in the model group and downregulated after treatment, and 76 lncRNAs that were downregulated in the model group and upregulated after treatment, were identified. Their target genes were enriched in immune regulation, wound healing, vascular remodeling, retinol metabolism related to rod-mediated scotopic vision, glutamatergic neuron differentiation, the forkhead box O (FoxO) pathway, retinoic acid-inducible gene I (RIG-I)-like receptor signaling, and related processes. 6) Differential expression of circRNAs: Compared with the control group, 45 circRNAs were downregulated and 47 circRNAs were upregulated in the model group. Compared with the model group, 25 circRNAs were downregulated and 22 circRNAs were upregulated in the treatment group. Eleven circRNAs that were downregulated in the model group and upregulated after treatment, and 10 circRNAs that were upregulated in the model group and downregulated after treatment, were identified. Their host genes were enriched in regulation of synaptic neural signaling, second messenger transmission, calcium signaling, and vascular endothelial growth factor (VEGF) signaling pathways. 7) Construction of ceRNA networks: Based on expression patterns and target prediction, multiple lncRNA/circRNA-miRNA-mRNA regulatory networks were constructed. For example, the networks composed of rno_circ_Rims2_10, rno-miR-1-3p, and related mRNAs, such as Mmp14 and Fasn, as well as the novel_miR_1417 related network, may be involved in retinal stress responses, inflammatory regulation, and neurovascular remodeling. CONCLUSIONS:This study is the first to integrate and analyze retinal transcriptomic profiles of mRNAs, miRNAs, lncRNAs, and circRNAs in an SHR model of hypertensive retinopathy, and it reveals RNA expression changes associated with lacidipine treatment. The results suggest that immune-inflammatory activation, neurovascular dysfunction, and ncRNA-mediated ceRNA regulatory networks may participate in the pathogenesis of hypertensive retinopathy. The identified differentially expressed molecules and predicted regulatory axes provide a candidate molecular basis for further mechanistic validation and screening of potential therapeutic targets.
Ovarian cancer is the most lethal malignancy of the female reproductive system worldwide.Chemoresistance,particularly platinum resistance,is a major factor limiting improvement in prognosis,and its underlying mechanisms involve complex regulation of and escape from multiple programmed cell death pathways in cancer cells.Disulfidptosis is triggered by high expression of solute carrier family 7 member 11(SLC7A11)under glucose starvation and shares upstream regulatory nodes with ferroptosis.Necrosis by sodium overload is driven by sodium ion overload mediated by transient receptor potential cation channel subfamily M member 4(TRPM4),but its role remains to be further investigated.Other programmed cell death pathways are interwoven into a dynamic regulatory network through key regulatory molecules such as tumor protein p53,the caspase family,cysteine-aspartic proteases,and glutathione.Autophagy can inhibit pyroptosis;ferroptosis and pyroptosis can synergistically amplify cell-killing effects through the reactive oxygen species/NOD-like receptor thermal protein domain-associated protein 3 axis;ferroptosis and cuproptosis share the glutathione metabolic axis;and the interaction between ferroptosis and disulfidptosis can shift from antagonism to synergy under specific metabolic stress.Ferroptosis and necrosis by sodium overload mutually promote each other through cascades involving adenosine triphosphate depletion,reactive oxygen species accumulation,and mitochondrial damage.PANoptosis can overcome cancer-cell resistance to a single mode of cell death through the simultaneous activation of multiple cell death pathways.A comprehensive review of the roles and interactive networks of various programmed cell death modalities,including disulfidptosis,necrosis by sodium overload,apoptosis,autophagy,necroptosis,pyroptosis,ferroptosis,cuproptosis,and PANoptosis,in platinum resistance in ovarian cancer is expected to provide a solid theoretical basis and potential translational directions for reversing platinum resistance and optimizing clinical treatment strategies.
OBJECTIVES:Colorectal cancer is a common gastrointestinal malignancy worldwide. KRAS gene mutation is an important molecular feature of colorectal cancer, but the clinical significance of different mutation sites remains unclear. This study aims to investigate the distribution characteristics of specific KRAS gene mutation sites and analyze their associations with clinicopathological parameters and survival outcomes in patients with colorectal cancer, thereby providing a basis for precise stratified diagnosis and treatment. METHODS:A total of 550 patients with colorectal cancer who underwent surgical treatment at the Affiliated Cancer Hospital of Zhengzhou University from May 2018 to January 2020 were retrospectively included, and tumor tissue specimens were retained from all patients. Polymerase chain reaction (PCR) was first used to screen all specimens for KRAS gene mutations, and the overall mutation rate was calculated. High-throughput sequencing was then performed on 210 of these specimens using the Illumina Nova sequencing platform to determine the specific mutation types at codons 12 and 13 of exon 2 of the KRAS gene. Clinicopathological data, including age, sex, tumor stage, lymph node metastasis status, and primary lesion diameter, were collected. Survival data were obtained through outpatient follow-up and telephone follow-up, with the follow-up cutoff date of December 29, 2023. Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors affecting prognosis. Variables were included based on a univariate analysis threshold of P<0.10 and clinically recognized key variables, such as tumor stage and lymph node metastasis. RESULTS:Among the 550 specimens, KRAS gene mutations were detected in 232 cases, with an overall mutation rate of 42.18%. Among the 210 specimens subjected to high-throughput sequencing, mutations were detected in 155 cases, with a mutation rate of 73.81%. Seven mutation types were identified. G12D was the most common mutation site (19.52%), followed by G12V (12.86%), G13D (12.86%), G12S (10.95%), G12A (8.57%), G12C (8.10%), and double mutations, including G12D+G12V and G12V+G13D, each accounting for 0.48%. Analysis of associations with clinical features showed that the proportion of patients with lymph node metastasis at initial diagnosis was 73.17% (30/41) among patients with the G12D mutation, which was significantly higher than that in patients with wild-type KRAS [38.18% (21/55), P<0.05]. However, the proportion of patients with a primary lesion diameter ≥4 cm was 36.59% in the G12D mutation group, which did not differ significantly from that in the wild-type group (25.45%, P>0.05). The proportions of patients with a primary lesion diameter ≥4 cm were 66.67%, 76.47%, 78.26%, and 66.67% among patients with G12A, G12C, G12S, and G13D mutations, respectively, all of which were significantly higher than that in the wild-type group (all P<0.05). However, the proportions of lymph node metastasis in these mutation groups did not differ significantly from that in the wild-type group (P>0.05). Cox proportional hazards regression analysis demonstrated that tumor stage Ⅲ-Ⅳ (HR=1.820, 95% CI 1.194 to 2.774, P=0.005), G12C mutation (HR=2.014, 95% CI 1.321 to 3.069, P=0.001), G12D mutation (HR=1.857, 95% CI 1.218 to 2.930, P=0.004), and G12V mutation (HR=1.751, 95% CI 1.149 to 2.669, P=0.009) were independent risk factors for death in patients with colorectal cancer. CONCLUSIONS:Different KRAS gene mutation sites are specifically associated with clinical features of colorectal cancer. The G12D mutation is associated with a high risk of lymph node metastasis, whereas G12A, G12C, G12S, and G13D mutations are associated with increased primary tumor size. G12C, G12D, and G12V mutations are independent prognostic risk factors and may serve as potential molecular markers for risk stratification and individualized treatment.
OBJECTIVES:Spinal tuberculosis commonly involves the thoracic and lumbar vertebrae, but its clinical differential diagnosis remains challenging. This study included patients with imaging findings suggestive of thoracic or lumbar spinal infection and aims to establish a diagnostic model based on routine laboratory indicators to assist in differentiating thoracolumbar spinal tuberculosis from non-tuberculous spinal infections. METHODS:Clinical data were consecutively collected from patients whose imaging findings suggested thoracic or lumbar spinal infection. Patients were divided into a thoracolumbar spinal tuberculosis group and a non-tuberculous spinal infection group according to the final diagnosis. Candidate variables included 40 routine clinical laboratory indicators. First, the Boruta algorithm was used to screen all candidate variables. All cases were then randomly divided into a training set and a validation set at a ratio of 7꞉3, with 70% of cases used for model construction and 30% for model validation. In the training set, the variables selected by the Boruta method were further analyzed using logistic regression to identify independent diagnostic variables with statistical significance and clinical interpretability. An auxiliary differential diagnostic model for thoracolumbar spinal tuberculosis was then constructed based on the final variables included in the model. A nomogram was further developed to visually present the contribution of each predictor to the diagnostic outcome in the form of scores. Receiver operating characteristic curves and the area under the curve were used to evaluate the discriminative ability of the model in the training and validation sets, and the diagnostic performance of the model was internally validated using the validation set. Calibration analysis and decision curve analysis were also performed to evaluate the consistency between predicted probabilities and actual diagnostic results, as well as the potential clinical net benefit of the model. RESULTS:A total of 275 patients with thoracolumbar spinal infection were included, comprising 104 patients in the tuberculosis group and 171 patients in the non-tuberculous group. The Boruta method selected 11 variables from the 40 candidate variables: Interferon-γ release assay, Mycobacterium tuberculosis antibody, red blood cell count, hemoglobin, lymphocyte count, monocyte percentage, high-density lipoprotein, D-dimer, C-reactive protein, erythrocyte sedimentation rate, and activated partial thromboplastin time. A model was then established using Logistic regression. Five variables with significant differences, namely high-density lipoprotein, tuberculosis antibody, monocyte percentage, lymphocyte count, and interferon-γ release assay, were used to construct the nomogram. Each variable can be converted into a corresponding score according to its value, and the total score can be used to estimate the predicted probability of thoracolumbar spinal tuberculosis. The model showed good discriminative ability in the training set, with an area under the receiver operating characteristic curve of 0.877. It maintained stable diagnostic performance in the validation set, with an area under the curve of 0.875, suggesting good internal validation performance and certain generalizability. Calibration analysis showed good agreement between the predicted probabilities and actual diagnostic results. Decision curve analysis demonstrated that, within a certain range of threshold probabilities, the model provided higher clinical net benefit than the simple assumption that all patients had thoracolumbar spinal tuberculosis or that all patients had non-tuberculous spinal infection, indicating its incremental value for clinical differential diagnosis. CONCLUSIONS:Five routine laboratory indicators, namely high-density lipoprotein, tuberculosis antibody, monocyte percentage, lymphocyte count, and interferon-γ release assay, can be used to construct an auxiliary differential diagnostic model for thoracolumbar spinal tuberculosis. This model has significant net benefit and good ability to distinguish thoracolumbar spinal tuberculosis from non-tuberculous spinal infection. It has potential application value as an auxiliary differential diagnostic model before etiological results become available.
OBJECTIVES:Drug-resistant tuberculosis is one of the major challenges currently faced in tuberculosis prevention and control. Regional studies on drug resistance profiles and their influencing factors are of great significance for understanding epidemiological patterns and developing precise prevention and control strategies. This study aims to analyze the drug resistance characteristics and trends of pulmonary tuberculosis in Changsha from 2018 to 2025, and to explore the factors associated with rifampicin (RFP) resistance, so as to provide scientific evidence for precise prevention and control of drug-resistant tuberculosis. METHODS:Data from 21 351 bacteriologically confirmed pulmonary tuberculosis patients registered in Changsha from 2018 to 2025 were collected from the "China Disease Prevention and Control Information System". The completion of drug resistance screening, mycobacterial species distribution, drug resistance spectrum characteristics, and resistance trends of 5 anti-tuberculosis drugs were analyzed. The Cochran-Armitage trend test was used to compare annual changes, and multivariate Logistic regression analysis was used to identify influencing factors of rifampicin resistance. RESULTS:From 2018 to 2025, the average drug resistance screening rate among bacteriologically confirmed pulmonary tuberculosis patients in Changsha was 90.82%, showing a significant increasing trend (P<0.001). A total of 17 439 isolates underwent mycobacterial species identification, of which 17 034 (97.68%) were identified as Mycobacterium tuberculosis complex. The proportion of non-tuberculous mycobacteria showed a decreasing trend (P<0.001). The overall drug resistance rate was 10.27%, including mono-resistance 7.25%, poly-resistance 0.71%, RFP resistance 4.31%, multidrug resistance 2.31%, pre-extensively drug-resistant tuberculosis rate was 0.29%, and extensive drug-resistant tuberculosis rate was 0.04%. The overall drug resistance rate, mono-resistance rate, and pre-extensively drug-resistant rate showed slight decreasing trends (all P<0.05). The resistance rates to 5 drugs ranked as follows: Isoniazid (INH; 8.84%), rifampicin (4.31%), ofloxacin (OFX; 2.54%), ethambutol (EMB; 1.87%), and kanamycin (KM; 0.52%). The isoniazid resistance rate showed a significant increasing trend (average annual increase of 1.47%, P<0.001). The drug resistance spectrum was dominated by mono-resistance (7.28%), and the most common multidrug resistance combination was RFP+INH (1.29%). Multivariate Logistic regression analysis showed that patients aged 25-44 years (OR=1.23, 95% CI 1.05 to 1.43) and previously treated patients (OR=1.76, 95% CI 1.61 to 1.94) had a higher risk of rifampicin resistance, while patients aged ≥65 years had a lower risk (OR=0.72, 95% CI 0.61 to 0.85). CONCLUSIONS:The drug resistance level of pulmonary tuberculosis in Changsha from 2018 to 2025 was generally stable. However, the RFP resistance rate among new patients was higher than the global and national levels, and the continuous increase in INH resistance rate requires heightened attention. Young and middle-aged adults aged 25-44 years and previously treated patients are high-risk populations for RFP resistance and should be prioritized for drug resistance monitoring and precise intervention.
Pulmonary infection caused by Mycobacterium abscessus is rare in children without underlying pulmonary disease,especially in infants.A 3-month-old female infant was admitted to the Third Xiangya Hospital of Central South University on July 29,2023.Cough was her only clinical manifestation,and chest computed tomography revealed multiple patchy and mass-like high-density opacities in both lungs.Metagenomic next-generation sequencing of bronchoalveolar lavage fluid confirmed the diagnosis of Mycobacterium abscessus pulmonary disease.Further evaluation for immunodeficiency and whole-exome sequencing revealed no abnormalities.The patient improved after combination therapy with amikacin,cefoxitin,linezolid,and azithromycin,without adverse reactions.For rare pulmonary infections in infants with atypical clinical manifestations and a low positivity rate of conventional etiological tests,metagenomic next-generation sequencing may facilitate early diagnosis.
OBJECTIVES:Osteosarcoma (OS) is a malignant bone tumor that predominantly affects adolescents. Due to its early metastatic tendency and chemoresistance, long-term survival rates in patients have not shown significant improvement over time, highlighting the urgent need for novel molecular targets and therapeutic strategies. Ferroptosis, a form of programmed cell death driven by iron-dependent lipid peroxidation, offers a promising avenue for overcoming drug-resistant tumors. ATP-binding cassette subfamily B member 6 (ABCB6) belongs to the ATP-binding cassette (ABC) transporter superfamily and is mainly localised to the outer mitochondrial membrane, where it participates in haem synthesis and intracellular iron transport. Recent studies have indicated that ABCB6 is aberrantly expressed in various malignancies and regulates tumor progression, yet its role and mechanism in OS remain unexplored. The present study aims to systematically characterise the expression pattern, clinical prognostic significance, and biological functions of ABCB6 in OS, and to dissect the molecular mechanism by which ABCB6 governs ferroptosis in OS cells, thereby providing a theoretical foundation for ABCB6-targeted therapy. METHODS:Human OS cell lines (HOS and 143B) and human bone marrow mesenchymal stem cells (BMSCs) were used as research subjects. Stable ABCB6-knockdown OS cell lines were established via lentivirus-mediated RNA interference, and rescue experiments were performed using lentiviral overexpression of hypoxia-inducible factor 1-alpha (HIF1A). Cell proliferation was assessed by cell counting kit-8 (CCK-8) and colony formation assays; migration was evaluated by Transwell and scratch wound-healing assays; apoptosis was detected by flow cytometry. Ferroptosis-related phenotypic assays were employed to determine the impact of ABCB6 expression on ferroptosis. Transcriptome sequencing was conducted to analyse differentially expressed genes and enriched pathways; chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were applied to verify the direct binding of HIF1A to the promoter of glutathione peroxidase 4 (GPX4) and its transcriptional regulation. Iron chelator and proteasome inhibitor interventions were used to validate the regulation of HIF1A protein stability by Fe2+. In vivo, ABCB6-knockdown and control 143B cells were injected subcutaneously into nude mice to establish a xenograft tumor model, and tumor growth was monitored. RESULTS:Both messenger RNA (mRNA) and protein levels of ABCB6 were significantly higher in OS cell lines than in BMSCs (both P<0.05), and analysis of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-OS cohort revealed that patients with high ABCB6 expression had markedly worse overall survival than those with low expression [hazard ratio (HR)=2.94, 95% confidence interval (CI) 1.36 to 6.36, P<0.05]. ABCB6 knockdown significantly suppressed OS cell proliferation and colony formation, reduced migratory capacity, and increased the apoptosis rate, accompanied by downregulation of N-cadherin and upregulation of E-cadherin and cleaved caspase-3 (all P<0.05). ABCB6 silencing markedly elevated the proportion of Liperfluo-positive cells and dihydroethidium (DHE) oxidation levels, increased intracellular Fe2+ concentration, decreased the glutathione (GSH)/oxidized glutathione (GSSG) ratio, reduced mitochondrial membrane potential, and induced typical ferroptotic mitochondrial morphological changes (shrinkage and cristae reduction) as observed by transmission electron microscope (all P<0.05); these oxidative alterations were reversed by the ferroptosis inhibitors. ABCB6 knockdown downregulated GPX4 at both protein and mRNA levels, whereas solute carrier family 7 member 11 (SLC7A11) expression remained unchanged (P>0.05). Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed significant enrichment of the HIF-1 signalling pathway in the control group (P<0.001); ABCB6 knockdown decreased HIF1A protein expression, and treatment with an iron chelator or a proteasome inhibitor reversed this degradation through Fe2+ chelation or inhibition of the ubiquitin-proteasome pathway, respectively (all P<0.05). Chromatin immunoprecipitation followed by quantitative polymerase chain reaction (ChIP-qPCR) and dual-luciferase reporter assays confirmed that HIF1A directly binds to the GPX4 promoter and activates its transcription. Overexpression of HIF1A in ABCB6-knockdown cells restored GPX4 expression and significantly rescued the proliferation inhibition, migration impairment, and apoptosis increase caused by ABCB6 silencing, while also restoring mitochondrial membrane potential (all P<0.05). In the xenograft model, tumors from the ABCB6-knockdown group exhibited significantly reduced volume and weight compared with the control group (all P<0.05); immunohistochemistry confirmed downregulation of HIF1A and GPX4, reduced Ki-67 and N-cadherin positivity, and increased cleaved caspase-3 and E-cadherin positivity in the knockdown group (all P<0.05). CONCLUSIONS:This study systematically uncovers, for the first time, the oncogenic role and prognostic value of ABCB6 in OS, and delineates the complete "ABCB6/Fe2+/HIF1A/GPX4" axis that governs ferroptosis in OS cells. These findings not only provide a novel biomarker for molecular subtyping and prognostic evaluation of OS, but also establish a theoretical basis for therapeutic strategies that target the ABCB6/HIF1A/GPX4 axis to induce ferroptosis. Future investigations may explore the upstream regulators of ABCB6 and its potential utility in reversing chemoresistance in OS.
Triggering receptor expressed on myeloid cells 2(TREM2)is a key transmembrane immune receptor that is specifically highly expressed in myeloid cells,particularly macrophages,within atherosclerosis(AS)plaques.Advances in single-cell sequencing technology have clearly defined TREM2-high macrophages as a distinct subpopulation known as lipid-associated macrophages.TREM2 exhibits stage-specific bidirectional regulatory effects during the progression of AS.In the early stage of the disease,TREM2 promotes cholesterol uptake by upregulating the scavenger receptor CD36,thereby accelerating foam cell formation and lesion expansion.In the advanced stage,however,its protective effects become prominent:TREM2 enhances macrophage survival,drives reverse cholesterol transport,and improves efferocytosis efficiency,thereby effectively inhibiting necrotic core expansion and maintaining plaque stability.At the molecular level,the TREM2-DAP12 complex upregulates CD36-mediated lipid uptake through the p38 mitogen-activated protein kinase/peroxisome proliferator-activated receptor gamma(PPARγ)axis,whereas deficiency of liver X receptor(LXR)can weaken its protective effects.Mitochondrial reactive oxygen species(mtROS)drive the transition of macrophages toward a pro-inflammatory foam cell phenotype through signal transducer and activator of transcription 5(STAT5).In addition,ferroptosis-related mitochondrial dysfunction promotes the death of advanced foam macrophages and aggravates plaque instability.In terms of clinical translation,soluble TREM2(sTREM2)levels are associated with the risk of coronary heart disease and adverse cardiovascular events,suggesting that sTREM2 may serve as a potential biomarker reflecting plaque inflammation and cellular injury and may provide incremental predictive value beyond high-sensitivity C-reactive protein.TREM2 agonists,such as AL002a,can reprogram foam macrophages and enhance efferocytosis and necrotic core clearance,thereby improving plaque stability and showing potential for precision intervention.In summary,TREM2 shows a"double-edged sword"role at different stages of AS,and precise stage-specific modulation of TREM2 may represent a new direction for immunotherapy in AS.
OBJECTIVES:Adolescence is a critical period with a high incidence of psychological problems. Anxiety, depression, and non-suicidal self-injury (NSSI) are relatively common among adolescents and can affect their physical and mental health. This study aims to investigate the dynamic temporal interactions among anxiety, depression, NSSI, and distress tolerance in adolescents using three waves of longitudinal follow-up data and cross-lagged network analysis. This study also aims to quantify the relative importance of each variable in the network and its cross-time predictive effects, thereby providing empirical evidence for early prevention and precision intervention in adolescent mental health. METHODS:Cluster sampling was used to recruit first-year students from 3 public junior high schools and first-year students from 3 public senior high schools in Yiyang, Hunan Province. Three follow-up surveys were conducted at T1, T2, and T3, with 6-month intervals between assessments. A total of 1 621 adolescents who completed all 3 surveys with valid responses were included. The assessment tools included the simplified Chinese version of the Depression Anxiety Stress Scale-21, the Tolerance for Mental Pain Scale (TMPS)-10, and the Ottawa Self-Injury Inventory. RESULTS:Repeated-measures analysis of variance showed that from T1 to T2, the total score of distress tolerance and scores for tolerating distress and managing distress significantly decreased, whereas the scores for anxiety, depression, and NSSI thoughts and behaviors in the past month significantly increased. From T2 to T3, the total score of distress tolerance and the score for tolerating distress significantly decreased, while the scores for anxiety and NSSI thoughts in the past month significantly decreased (all P<0.05). Cross-lagged network analysis revealed that in the T1→T2 network, managing distress had the highest out-expected influence (out-EI=-2.01) and showed strong negative predictive effects on both anxiety and depression. In the T2→T3 network, managing distress still had the highest out-expected influence (out-EI=-1.67) and continued to negatively predict anxiety and depression, while NSSI behavior in the past month positively predicted anxiety and depression. CONCLUSIONS:The relationships among anxiety, depression, NSSI, and distress tolerance in adolescents are dynamic and stage-specific. The ability to manage distress is a protective factor against anxiety and depression in adolescents, although its predictive effect weakens over time. In contrast, NSSI behavior gradually becomes a risk factor for depression at later stages. Therefore, improving adolescents' ability to manage distress, especially at an early stage, and intervening in NSSI behavior may effectively reduce anxiety and depression levels.
OBJECTIVES:Non-alcoholic fatty liver disease (NAFLD) is a globally prevalent chronic liver disease, and its progression is closely associated with Kupffer cells (KCs). This study aims to characterize C-X-C motif chemokine ligand 9꞉secreted phosphoprotein 1 (CS) polarization in KCs and investigate its intercellular communication with endothelial cells (ECs) in NAFLD. METHODS:Single-cell RNA sequencing data of liver tissues from 3 NAFLD mice and 3 control mice were obtained from the Gene Expression Omnibus (GEO) dataset GSE129516. Seurat was used for data integration, quality control, clustering, and annotation. KCs and ECs were divided into subgroups, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A mouse liver single-cell dataset (GSE270583) was further included for cross-validation of CS polarization. CellChat was used to infer intercellular communication networks between KC and EC subgroups. Twenty male C57BL/6J mice were assigned to a control group (n=10) and a high-fat diet (HFD) group (n=10). Body weight was measured weekly. At 20 weeks of feeding, glucose tolerance and insulin tolerance were assessed, after which the mice were sacrificed, and serum and liver tissues were collected for subsequent experiments. Hematoxylin and eosin (HE) staining and Oil Red O staining were used to observe pathological changes in the liver. Immunofluorescence staining of liver tissues was performed to validate the characteristics of CS polarization and M1/M2 polarization. RESULTS:A total of 29 cell clusters belonging to 8 cell types were identified. Compared with the control group, the proportion of KCs was increased and the proportion of ECs was decreased in the NAFLD group. Under M1/M2 and CS polarization frameworks, subgroups including CD80+ KCs, CD206+ KCs, S100A4+ KCs, secreted phosphoprotein 1 (SPP1)+ KCs, and C-X-C motif chemokine ligand 9 (CXCL9)+ KCs were identified. Among these, CD80+ KCs and SPP1+ KCs were significantly expanded, and their characteristic genes were mainly enriched in nuclear factor-kappa B (NF-κB) and tumor necrosis factor (TNF) signaling pathways. Peroxiredoxin 3 (PRDX3) was upregulated in CD80+ KCs and downregulated in CD206+ KCs. ECs were divided into 3 subgroups: Apoa2+ ECs, PRDX3+ ECs, and Col4a1+ ECs. In the NAFLD group, the PRDX3+ EC subgroup was abnormally active, accompanied by high expression of PRDX1 and downregulation of glutathione peroxidase 4 (GPX4). Further external validation using the single-cell dataset GSE270583 showed that SPP1+ KCs and CXCL9+ KCs could be clearly separated, and the proportion of SPP1+ KCs was increased in the NAFLD group, supporting the cross-cohort reproducibility of CS polarization in NAFLD. CellChat analysis suggested activation of the TNF receptor superfamily member 1A (TNFRSF1A) signaling pathway from CD80+ KCs and SPP1+ KCs to PRDX3+ ECs. After 20-week HFD feeding, mice displayed significant weight gain, impaired glucose tolerance, and reduced insulin sensitivity compared with controls (all P<0.05). The levels of alanine aminotransferase (ALT), aspartate transferase (AST), total cholesterol (TC), and triglyceride (TG) were significantly higher in the HFD group than in the control group (all P<0.05). HE staining and Oil Red O staining showed marked disordered hepatic architecture, lipid vacuoles, and lipid deposition in the livers of HFD mice. Immunofluorescence staining showed increased expression of PRDX3 and CD80 in liver tissues of the HFD group. Compared with the control group, SPP1 expression was increased, whereas CXCL9 expression was decreased, in hepatic KCs of the HFD group. These results were consistent with the single-cell transcriptome sequencing findings. CONCLUSIONS:KCs in NAFLD exhibit characteristics of CS polarization, with increased proportions of SPP1+ KCs and CD80+ KCs, as well as enhanced TNF-TNFRSF1A communication with PRDX3+ ECs. Changes in the expression of SPP1, CXCL9, CD80, and PRDX3 in the liver tissues of HFD mice were generally consistent with the single-cell analysis results. CS polarization may participate in alterations of the hepatic inflammatory microenvironment in NAFLD and may provide a new research direction for understanding the inflammation-fibrosis progression of NAFLD.
OBJECTIVES:Chronic heart failure (CHF) is characterized by high prevalence, high mortality, and high readmission rates. Optimized combination pharmacotherapy is the main approach to controlling clinical symptoms and reducing mortality and readmission rates. Ensuring medication safety is a top priority in disease management for patients with CHF, and adequate medication literacy is essential for medication safety. At present, there is a lack of disease-specific tools for assessing medication literacy in patients with CHF. This study aims to develop a Medication Literacy Scale for patients with CHF and to test its reliability and validity, thereby providing a reference for medication use in patients with CHF. METHODS:An initial item pool was established through literature analysis and group discussion. Items were optimized using qualitative methods, including Delphi expert consultation and cognitive interviews, and quantitative methods, including item analysis and exploratory factor analysis. Reliability was then evaluated using the Kuder-Richardson formula 20 (KR-20), split-half reliability, and test-retest reliability. Validity was assessed in terms of content validity, criterion-related validity, and construct validity. RESULTS:The Medication Literacy Scale for patients with CHF consisted of 4 dimensions and 13 items, including 4 items for functional literacy and 3 items each for communicative literacy, critical literacy, and numeracy. A dichotomous scoring method was used, with a total score of 13; higher scores indicated higher levels of medication literacy among patients with CHF. The KR-20 coefficient of the total scale was 0.794, the split-half reliability was 0.701, and the test-retest reliability was 0.842. The item-level content validity index ranged from 0.90 to 1.00, the scale-level content validity index was 0.92, and the criterion-related validity coefficient was 0.739. The chi-square/degrees of freedom ratio was 1.472, the root mean square residual was 0.009, the root mean square error of approximation was 0.049, the goodness-of-fit index was 0.942, the adjusted goodness-of-fit index was 0.908, and both the comparative fit index and incremental fit index approached 0.9. CONCLUSIONS:The Medication Literacy Scale for patients with CHF has a scientific theoretical basis, a standardized development process, and good reliability and validity. It can be used to assess medication literacy in patients with CHF. Clinical practitioners may use this scale to evaluate the overall level of medication literacy and the levels of each dimension among patients with CHF, thereby providing targeted medication guidance and ensuring medication safety in this population.
Autoimmune diseases are a group of disorders caused by dysregulated immune function,in which the immune system mistakenly attacks the host's own healthy cells,tissues,and organs.Genetic factors are one of the important foundations for the development of autoimmune diseases.Human leukocyte antigen(HLA)is closely related to immune function in the human body,and HLA-encoding genes are highly polymorphic,making them important susceptibility factors for autoimmune diseases.HLA genetic variants are closely associated with a variety of autoimmune diseases,and they mediate the occurrence and development of these diseases through multiple mechanisms,such as molecular mimicry and self-antigen presentation.They have also been importantly applied in clinical disease prevention,diagnosis,and treatment.An in-depth understanding of the relationship between HLA genetic variants and autoimmune diseases is of great significance for discovering biomarkers related to disease prevention,diagnosis,treatment,and prognosis,elucidating disease pathogenesis,and developing new therapeutic strategies.However,substantial challenges remain in the basic research and clinical translation of autoimmune disease-associated HLA variants.Multi-omics technologies have important application prospects and significance in the field of HLA-related autoimmune diseases and may provide new directions for mechanistic research and clinical application of HLA genetic variants in autoimmune diseases.
OBJECTIVES:The prevention and treatment of stroke in China remain challenging, and long-term standardized use of secondary prevention medications is of great significance. Overall medication adherence among patients with ischemic stroke is suboptimal and shows a gradual decline after discharge, indicating an urgent need for improvement. This study aims to identify the categories and predictors of developmental trajectories of medication adherence in patients with ischemic stroke, thereby providing a reference for developing precision intervention programs. METHODS:A total of 373 patients with ischemic stroke admitted to the Third Xiangya Hospital of Central South University from January to December 2024 were selected using purposive sampling. Baseline data were collected during hospitalization using a general information questionnaire, the Brief Illness Perception Questionnaire (BIPQ), the Self-efficacy for Appropriate Medication Use Scale (SEAMS), the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version (FACES Ⅱ-CV), and the Connor-Davidson Resilience Scale (CD-RISC). Medication adherence was assessed at 2 weeks, 1 month, 3 months, and 6 months after discharge using the 8-item Morisky Medication Adherence Scale (MMAS-8). A latent growth mixture model (LGMM) was used to identify developmental trajectories of medication adherence in patients with ischemic stroke, and multivariate Logistic regression analysis was used to analyze predictors of different trajectory classes. RESULTS:Four developmental trajectory classes of medication adherence were identified among patients with ischemic stroke: the sustained moderate-adherence group (22.8%), the low-adherence declining group (17.2%), the low-adherence improving group (26.2%), and the moderate-adherence declining group (33.8%). Multivariate Logistic regression analysis showed that, with the low-adherence declining group as the reference, each 1-point increase in SEAMS score increased the odds of being classified into the sustained moderate-adherence group, moderate-adherence declining group, and low-adherence improving group by 48.3%, 33.9%, and 36.5%, respectively (all P<0.05). Each 1-point increase in FACES Ⅱ-CV score increased these odds by 9.2%, 4.3%, and 5.6%, respectively (all P<0.05). Each 1-point increase in BIPQ score decreased these odds by 18.9%, 15.7%, and 16.3%, respectively (all P<0.05). Each 1-point increase in CD-RISC score increased the odds of being classified into the sustained moderate-adherence group and low-adherence improving group by 9.1% and 6.2%, respectively (both P<0.05). Patients aged 18-59 years were 3.537 and 4.032 times more likely than those aged ≥60 years to be classified into the sustained moderate-adherence group and low-adherence improving group, respectively (both P<0.05). Patients taking 1-5 medications were 5.405 and 3.010 times more likely than those taking >5 medications to be classified into the sustained moderate-adherence group and low-adherence improving group, respectively (both P<0.05). With the sustained moderate-adherence group as the reference, each 1-point increase in SEAMS, FACES Ⅱ-CV, and CD-RISC scores, taking 1-5 medications, and being aged 18-59 years reduced the odds of being classified into the moderate-adherence declining group by 9.7%, 4.5%, 9.1%, 77.5%, and 55.8%, respectively (all P<0.05). CONCLUSIONS:The developmental trajectories of medication adherence in patients with ischemic stroke show significant population heterogeneity. Healthcare professionals should actively identify the trajectory types of medication adherence in patients with ischemic stroke and implement stratified intervention strategies based on predictive factors to reverse unfavorable adherence trends.
