ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

Objective : To explore the mediating effect of self-efficacy on family health and health literacy among middle-aged and elderly chronic diseases patients in rural areas, so as to provide a basis for developing targeted health literacy improvement strategies. Methods: Based on the publicly available 2021 "Survey of Chinese Residents' Psychology and Behavior" database, rural chronic diseases patients aged >45 years were selected as the study subjects. Data on demographic information, family type, and chronic diseases comorbidities were collected. The Chinese simplified Family Health Scale, General Self-Efficacy Scale, and Health Literacy Scale were used to assess family health, self-efficacy, and health literacy, respectively. Correlation analysis was employed to explore the relationships between variables, and the 4.1 Process program was used to analyze the mediating effect of self-efficacy on family health and health literacy. The Bootstrap method was applied to test the significance of the mediating effect. Results: A total of 449 participants were included, of whom 241 were male (53.67%) and 208 were female (46.33%). The majority (205 cases, 45.66%) were aged 60-<76 years. There were 168 cases (37.42%) with chronic disease comorbidities. The total score for family health was (37.96±6.25) points. The self-efficacy score was (27.28±5.40) points, the health literacy index was (27.72±8.08) points, and the health literacy proficiency rate was only 14.90% (67 patierts). Mediating effect analysis showed that family health could directly and positively influence health literacy, with a direct effect value of 0.090 (95%CI: 0.001-0.179). It could also indirectly and positively influence health literacy through self-efficacy, with a mediating effect value of 0.164 (95%CI: 0.099-0.234). The mediating effect accounted for 64.31% of the total effect. Conclusion Self-efficacy plays a positive mediating role between family health and health literacy among middle-aged and elderly chronic diseases patients in rural areas.

Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Objective Currently, there is no commercially available quantitative detection kit for the main Felis domestic allergen (Fel d 1) in China. To establish a rapid detection method for Fel d 1, this study aims to prepare monoclonal antibodies against Fel d 1 protein. Methods The codon preference of Escherichia coli was utilized to optimize and synthesize the Fel d 1 gene. The prokaryotic expression plasmid pET-28a-Fel d 1 was constructed and used to express and purify the recombinant Fel d 1 protein. Subsequently, the recombinant protein was immunized into BALB/c mice and monoclonal antibodies (mAbs) were prepared by the hybridoma technique. An indirect ELISA was established using the recombinant Fel d 1 as the coating antigen, and hybridoma cell lines were screened for positive clones. The specificity and antigenic epitopes of the mAbs were confirmed by Western blot analysis. Finally, the selected hybridoma cells were injected into the peritoneal cavities of BALB/c mice for large-scale monoclonal antibody production. Results The recombinant plasmid pET-28a-Fel d 1 was successfully constructed, and soluble Fel d 1 protein was obtained after optimizing the expression conditions. Western blot and antibody titer assays confirmed the successful isolation of two hybridoma cell lines, 7D11 and 5H4, which stably secreted mAbs specific to Fel d 1. Antibody characterization revealed that the 5H4 mAb was of the IgG2a subtype and could recognize the amino acid region 105-163 of Fel d 1, while the 7D11 mAb was the IgG1 subtype and could recognize the amino acid region 1-59. Conclusion The high-purity recombinant Fel d 1 protein produced in this study provides a promising alternative for clinical immunotherapy of cat allergies. Furthermore, the monoclonal antibody prepared in this experiment lays a material foundation for the in-depth study of the biological function of Fel d 1 and the development of ELISA detection.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice, Inbred BALB C ; Cats ; Mice ; Allergens/genetics* ; Glycoproteins/genetics* ; Enzyme-Linked Immunosorbent Assay ; Hybridomas/immunology* ; Recombinant Proteins/genetics* ; Female ; Antibody Specificity

Ferroptosis is a regulated form of cell death, with its core mechanism being intracellular iron overload-induced lipid peroxidation, leading to cellular dysfunction and mitochondrial structural abnormalities. Ferroptosis is closely related to various diseases including neurodegenerative disorders, tumors, and ischemia-reperfusion organ damage, and has become a potential therapeutic target. Iron is essential for life but can also cause cell death. Despite continuous progress in iron-related biomedical research, many questions remain unanswered. Advances in high-throughput technologies, genomics and proteomics are expected to reveal the cellular iron regulatory mechanism and open up new therapeutic approaches for ferroptosis-related diseases. This article reviews the research progress on iron in terms of its biology, metabolism, regulation, and related diseases, aiming to provide clues and references for developing new ferroptosis-targeted therapeutic strategies and facilitating more in-depth molecular studies from multiple perspectives.
Humans ; Ferroptosis/physiology* ; Iron/metabolism* ; Animals ; Neoplasms/metabolism* ; Neurodegenerative Diseases/metabolism*

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare autosomal dominant hereditary disorder characterized by hyperuricemia, gout, impaired urinary concentration, and progressive renal failure. It is primarily caused by mutations in uromodulin (UMOD) gene. This study reports a family with ADTKD in which whole-exome sequencing and Sanger sequencing identified a missense mutation in the UMOD gene, c.761A>C (p.H254P), present in both the proband and affected relatives. According to American College of Medical Genetics and Genomics (ACMG) guidelines, this variant is classified as likely pathogenic. The mutation results in an amino acid substitution that may impair UMOD protein folding and intracellular trafficking. UMOD gene mutations are associated with ADTKD, and genetic testing plays a vital role in the early diagnosis and treatment of this condition, highlighting its importance in the diagnosis of rare kidney diseases.
Adult ; Humans ; Male ; Exome Sequencing ; Mutation ; Mutation, Missense ; Nephritis, Interstitial/genetics* ; Pedigree ; Uromodulin/genetics*

Dent disease is a rare X-linked recessive inherited renal tubular disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and other clinical features, and can lead to progressive renal failure. It is primarily caused by mutations in the CLCN5 gene. This article reports the case of a 10-year-old male patient of Chinese descent who was incidentally found to have asymptomatic proteinuria during a routine health examination. Comprehensive biochemical testing and clinical evaluation revealed significant LMWP and hypercalciuria, while renal biopsy showed mesangial cell and matrix proliferation. Whole exome sequencing identified a novel deletion mutation in the CLCN5 gene (NM_001127899.4, c.1158delC, p.F387Lfs*42) causing a frameshift and premature termination, which is likely to disrupt its role in chloride/hydrogen ion exchange and endosomal acidification. Bioinformatic analysis indicated the variant is pathogenic. Genetic testing plays an important role in diagnosing rare kidney diseases. Early identification of pathogenic mutations is essential for facilitating timely intervention and appropriate management, potentially enhancing patient outcomes. This report expands the CLCN5 mutation spectrum and contributes to understanding the genetic and molecular mechanisms of Dent disease.
Humans ; Chloride Channels/genetics* ; Dent Disease/genetics* ; Male ; Child ; Computational Biology ; Mutation ; Proteinuria/genetics* ; Hypercalciuria/genetics*

Dendrobium moniliforme (D. moniliforme) is a traditional medicinal herb widely cultivated in Asia. Flavonoids, one of the largest groups of secondary metabolites in plants, are significant medicinal components in Dendrobium species. Several subgroups of R2R3-MYB proteins have been validated to directly regulate flavonoid biosynthesis. Using PacBio sequencing technology, we assembled a high-quality chromosome-level D. moniliforme genome with a total length of 1.20 Gb and a contig N50 of 3.97 Mb. The BUSCO assessment of genome annotation was 91.4%. By integrating the genome and transcriptome, we identified biosynthesis pathway enzyme genes related to flavonoids, polysaccharides, carotenoids, and alkaloids. A total of 90 R2R3-MYBs were identified in D. moniliforme and classified into 21 subgroups. Studies on the functions of R2R3-MYB transcription factors revealed that R2R3-MYB in SG6 can up-regulate flavonoid biosynthesis. Various validation experiments, including subcellular localization, transient overexpression, UPLC-MS/MS, HPLC, yeast one-hybrid, and dual-luciferase assays, demonstrated that DMYB69 directly up-regulates the expression of enzyme genes involved in flavonoid biosynthesis, increasing the content of flavonoids such as anthocyanin, flavone, and flavonol. Additionally, DMYB44 was shown to directly up-regulate the expression of carotenoid biosynthesis enzyme genes, thereby increasing carotenoid content. This study provides an essential genome resource and theoretical basis for molecular breeding research in D. moniliforme.