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.
