ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a major cause of chronic kidney disease and kidney failure. IgAN exhibits marked heterogeneity in clinical presentation, histopathology, and pathogenic mechanisms, contributing to variable treatment responses and prognosisamong patients. Precise risk assessment and individualized intervention are therefore of critical importance. This review systematically traces the evolution of IgAN management from traditional risk stratification toward biomarker-driven precision medicine. We first review the clinical utility and limitations of established risk stratification tools, including the KDIGO guidelines, the Oxford MEST-C classification, and the International IgAN Prediction Tool. We then discuss emerging biomarkers closely linked to disease pathogenesis, including galactose-deficient IgA1 (Gd-IgA1), anti-Gd-IgA1 autoantibodies, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and complement components, as well as the targeted therapies they have informed. In addition, urinary biomarkers and multi-omics approaches show promise for dynamic disease monitoring and individualized risk stratification.

[Objective] To explore the influencing factors of quality monitoring index on the nucleic acid pooling detection mode and continuously improve the detection quality of nucleic acid laboratory. [Methods] The quality monitoring indicators (NAT reactive rate, NAT resolution reactive rate, NAT invalid batch rate, NAT invalid result rate, equipment failure rate) and causes of invalidity in our laboratory from January 1, 2020 to December 31, 2022 were retrospectively analyzed. The quality monitoring indicators of the laboratory during 2020 to 2022 were compared longitudinally. The quality monitoring indicators of the laboratory in 2022 were compared horizontally with the overall level in Shandong for the same period to find the differences. [Results] From 2020 to 2022, a total of 218 686 samples were detected, the NAT reactive rate was 0.15‰ (32 samples in total), the resolution reactive rate was 39.02%, the invalid batch rate was 1.06%, the invalid result rate was 1.18%, and the equipment failure rate was 3.58%. There were no differences in the NAT reactive rate, NAT resolution reactive rate and NAT invalid batch rate among different years (P>0.05), but there were differences in the invalid result rate (P<0.05). Equipment failure was the main cause of invalid results (56.53%). Compared with other laboratories in Shandong, there were differences in the NAT reactive rate and invalid result rate (P<0.05). There were differences in the reaction rate, resolution rate and invalid result rate among different reagents (P<0.05). Compared with other two laboratories using the same manufacturer's reagent, there were differences in the reactive rate and invalid result rate (P<0.05), but no difference in the resolution rate and invalid batch rate (P>0.05). [Conclusion] Establishing quality indexes for process control and regular analysis can timely detect potential risks in laboratory operation. The use of quality indicators to implement self-comparison and inter-laboratory comparison can help the laboratory systematically and scientifically evaluate its own operating status and formulate corresponding quality management strategies, thereby improving the laboratory's testing capacity and ensure the safety of blood use.

To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

OBJECTIVES: This study aims to compare the effects of two orthodontic treatment modalities for skeletal class Ⅲ malocclusion on specific changes in airway volume, morphology, palatal angle, mandibular rotation, and bone displacement. Results provide scientific evidence for the selection of orthodontic treatment plans and reduce the risk of developing obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Thirty-six patients diagnosed with skeletal class Ⅲ malocclusion at the Department of Orthodontics, the Affiliated Stomatological Hospital of Nanjing Medical University from September 2018 to December 2023 were divided into two groups: orthodontic-orthognathic treatment group (18 patients) and camouflage orthodontic treatment group (18 patients). Changes in airway volume, cross-sectional area, palatal angle, mandibular, and tongue positions were observed through pre- and post-operative cone beam computed tomography and 3D cephalometric measurements. RESULTS: In the camouflage orthodontic treatment group, nasopharyngeal volume and oropharyngeal volume statistically increased after treatment (P<0.05). In the orthodontic-orthognathic treatment group, changes in nasopharyngeal volume, nasopharyngeal airway, distance from posterior tongue to pharyngeal wall, palatal angle, mandibular rotation, and hyoid bone displacement were statistically significant after surgery (P<0.05). In the comparison between the two groups after treatment, changes in the distance from posterior tongue to pharyngeal wall, palatal angle, and distance from hyoid bone to sella turcica point were statistically significant (P<0.05). CONCLUSIONS Patients in the orthodontic-orthognathic treatment group showed significantly greater changes in oropharyngeal cross-sectional area, palate angle, and tongue position compared with patients in the camouflage orthodontic treatment group. As individuals susceptible to OSAHS often exhibit mandibular retrusion and decreased minimum airway cross-sectional area, special attention should be paid to airway morphology changes when adopting orthodontic-orthognathic treatment to avoid adverse consequences.
Humans ; Hyoid Bone/diagnostic imaging* ; Malocclusion, Angle Class III/therapy* ; Male ; Female ; Cone-Beam Computed Tomography ; Cephalometry ; Orthodontics, Corrective/methods* ; Adult ; Mandible ; Pharynx/diagnostic imaging* ; Sleep Apnea, Obstructive/etiology* ; Orthognathic Surgical Procedures

OBJECTIVES: This study aims to analyze the clinical symptoms and imaging manifestations in patients with temporomandibular disorder syndrome (TMD), who are sensitive to sudden temperature drop. METHODS: One hundred and nineteen patients with TMD who attended the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital from December 2022 to December 2023 were included, including 44 males and 75 females, with a mean age of 32.4±13.7 years.The questionnaire was used to determine whether they were sensitive to temperature drop, and the TMD patients were divided into a temperature plunge-sensitive group and a temperature drop insensitive group. The clinical symptoms and imaging manifestations of patients in the two groups were observed. SPSS 25.0 was used for statistical analysis. RESULTS: There was no statistically significant difference between the gender and age of patients in the temperature plunge-sensitive group (50 patients) and the insensitivity group (69 patients) (P>0.05). The percentage of patients with pain was slightly higher in the temperature plunge-sensitive group [86.0% (43/50)] than in the insensitive group [68.1% (47/69)], and the difference was statistically significant (χ²=5.031, P=0.025), while the differences in joint murmur and mouth opening limitation between the two groups were not statistically significant. A total of 238 lateral joints were detected in both groups, the percentage of osteoarthropathic imaging changes was significantly higher in the temperature plunge-sensitive group [82.0% (82/100)] than in the insensitive group [53.6% (74/138)] (χ²=20.675, P<0.001). Magnetic imaging showed that the percentage of joint effusion was higher in patients in the temperature plunge-sensitive group [66.0% (33/50)] than in the insensitive group [42.0% (29/69)], and the difference was statistically significant (χ²=5.602, P=0.018). CONCLUSIONS TMD patients with maxillofacial pain symptoms, joint effusions, and abnormal imaging of osteoarticular structures are more likely to be sensitive to sudden temperature drops.
Humans ; Male ; Female ; Adult ; Temporomandibular Joint Disorders/diagnosis* ; Surveys and Questionnaires ; Middle Aged ; Young Adult ; Temperature ; Adolescent

ObjectiveThis study aims to explore the potential mechanism of the Xiezhuo Jiedu formula in regulating pyroptosis for the treatment of ulcerative colitis （UC） using bioinformatics and in vivo animal experiments. MethodsDifferentially expressed genes （DEGs） in colon tissues of UC patients were retrieved from the Gene Expression Omnibus （GEO） database. Pyroptosis-related genes were obtained from the GEO and GeneCards databases. The intersection of these datasets yielded pyroptosis-related DEGs （Pyro-DEGs）. Pyro-DEGs were subjected to Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using the Metascape database. A protein-protein interaction （PPI） network was constructed using the STRING database. Least absolute shrinkage and selection operator （LASSO） prediction model and receiver operating characteristic （ROC） analysis were conducted to identify core Pyro-DEGs with diagnostic and therapeutic potential. Immune infiltration analysis of the UC datasets was performed using the deconvolution method （CIBERSORT）， along with correlation analysis with core Pyro-DEGs. Sixty male Sprague-Dawley （SD） rats were randomly divided into a control group， a model group， high-， medium-， and low-dose groups of Xiezhuo Jiedu formula （26.64， 13.32， 6.66 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. UC was established by intrarectal administration of 3，5-trinitrobenzenesulfonic acid （TNBS） dissolved in ethanol. The control and model groups were given distilled water by gavage， while the treatment groups were administered the corresponding drugs for 7 consecutive days. Hematoxylin-eosin （HE） staining was used to observe the colon histopathology. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors such as interleukin-1β （IL-1β）， IL-10， IL-18， and transforming growth factor-β （TGF-β）. Immunohistochemistry （IHC） and Western blot were applied to detect the expression of Caspase-1， gap junction alpha-1 protein （GJA1）， peroxisome proliferator-activated receptor gamma （PPARG）， and S100 calcium-binding protein A8 （S100A8）. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure mRNA expression of Caspase-1， GJA1， PPARG， and S100A8. Western blot was performed to assess protein expression levels of Caspase-1， GJA1， PPARG， and S100A8. ResultsGEO datasets GSE87466 and GSE87473 yielded 64 Pyro-DEGs. KEGG analysis indicated that these genes were enriched in the NOD-like receptor signaling pathway， tumor necrosis factor （TNF） signaling pathway， and hypoxia-inducible factor 1 （HIF-1） signaling pathway. Four core Pyro-DEGs （Caspase-1， GJA1， PPARG， and S100A8） were identified. Immune infiltration analysis showed that expression of these genes was positively correlated with mast cells， neutrophils， M0 macrophages， M1 macrophages， and dendritic cells. Animal experimental results indicated that compared with the control group， the model group had significantly increased levels of IL-1β and IL-18， significantly decreased levels of IL-10 and TGF-β. The model group showed enhanced Caspase-1， GJA1， and S100A8 staining， and significantly increased mRNA and protein expression of Caspase-1， GJA1， and S100A8 （P<0.01）. In contrast， the expression of PPARG was reduced in the model group （P<0.01）. After treatment， all dosage groups showed varying degrees of improvement （P<0.05， P<0.01）， with the high-dose group showing the most significant improvement （P<0.01）. ConclusionCaspase-1， GJA1， PPARG， and S100A8 are core Pyro-DEGs closely associated with the pathogenesis of UC. These genes may collaborate with immune cells such as mast cells， neutrophils， and M0 macrophages to mediate disease development. The Xiezhuo Jiedu formula may regulate the expression of core Pyro-DEGs through the NOD-like receptor， TNF， and HIF-1 core signaling pathways， thereby modulating immune homeostasis in UC rats and effectively alleviating UC.