To investigate the risk factors for acute kidney injury (AKI) following the use of amphotericin B deoxycholate and to develop a predictive model to guide clinical monitoring and intervention.

Traditional Chinese medicine and its bioactive components have garnered increasing attention as potential therapeutic options for allergic asthma. By targeting the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, these natural compounds exhibit unique advantages in multilevel immunomodulation and inflammation suppression compared with single-target synthetic drugs. Accumulating pharmacological evidence supports their capacity to restore pathway homeostasis, positioning them as promising candidates for complementary strategies in asthma management. Allergic asthma, a heterogeneous respiratory disorder affecting approximately 150 million individuals worldwide, arises from a complex interplay of genetic predisposition, environmental exposures, and lifestyle factors. Its pathological progression is marked by aberrant activation of the PI3K/AKT signaling cascade, with the mechanistic target of rapamycin serving as a key downstream regulatory node. This evolutionarily conserved pathway orchestrates fundamental cellular processes that contribute to three hallmark pathological features of allergic asthma: chronic airway inflammation, structural remodeling of the bronchial architecture, and airway hyperresponsiveness. This review has 3 primary objectives: (1) to evaluate the role of the PI3K/AKT pathway in allergic asthma pathogenesis, (2) to analyze the molecular mechanisms of representative traditional Chinese medicine preparations and their active ingredients, and (3) to identify novel bioactive inhibitors derived from natural products. Collectively, these investigations provide a conceptual framework for the development of next-generation targeted therapies and for optimizing clinical management strategies for allergic asthma.

BACKGROUND:The reasonable implantation range of femoral prosthesis in unicompartmental knee arthroplasty in patients with osteoporosis has not been investigated,and previous studies have often been based on unicompartmental knee arthroplasty models in normal bone,with fewer mechanical studies in models with non-normal bone.Complications after unicompartmental knee arthroplasty have been shown to be highly associated with osteoporosis. OBJECTIVE:To analyze the biomechanical effects of the coronal inclination of the Sled fixed platform femoral prosthesis on unicompartmental knee arthroplasty in patients with osteoporosis and to find the correlation between osteoporosis and mid-and long-term complications after unicompartmental knee arthroplasty. METHODS:Based on the digital imaging technology to obtain the data of the knee joint and prosthesis,a normal bone knee model is then created by using specialized software such as Mimics and Geomagic studio.Based on a validated normal bone knee model,an osteoporotic knee model was created by changing the material parameters.Totally 14 unicompartmental knee arthroplasty finite element models were created using Sled fixed platform femoral prosthesis:standard position(0°),varus and valgus angles:3°,6°,9° in the normal bone and osteoporosis groups.Stress changes on the surface of polyethylene liner,cancellous bone under tibial prosthesis,and cortical bone were calculated and analyzed in all unicompartmental knee arthroplasty models. RESULTS AND CONCLUSION:(1)In the osteoporotic models,the high stress values of the polyethylene liner surface and the cancellous bone under the tibial prosthesis increased with the increase of the tilt angle of the femoral prosthesis,and the high stress values of the cortical bone surface under the tibial prosthesis increased with the increase of the prosthesis valgus angles and decreased with the increase of the varus angles.(2)For the polyethylene liner surface as well as the subcortical bone surface of the tibial prosthesis,the high stress values of the models for each inclination angle in the osteoporosis group were greater than those of the corresponding models in the normal bone group.For the surface of the cancellous bone under the tibial prosthesis,the high stress values of the tilt angle models of the osteoporosis groups were smaller than those of the normal bone groups.(3)Osteoporosis may cause biomechanical abnormalities in the internal structures of the knee after unicondylar replacement,increasing the potential risk of postoperative aseptic loosening of the prosthesis and periprosthetic fractures.Varus and valgus of the femoral prosthesis in the coronal plane should be avoided as much as possible when performing medial unicompartmental knee arthroplasty with a Sled fixation platform in osteoporotic knees.

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective To confirm the effects of hemolysis,chylemia and repeated freeze-thawing of human serum immunized with pneumococcal vaccine on ELISA for the detection of specific IgG antibody against pneumococcal capsular polysaccharide,and to promote the continuous development and improvement of the evaluation methods for clinical serum IgG antibody content of pneumococcal vaccine.Methods The same batch of reconstituted laboratory internal quality control serum 09CS was aliquoted into different volumes and subjected to 1 to 12 freeze-thaw cycles.The IgG antibodies of 24 types were detected respectively with the serum after single freeze-thaw and the repeated freeze-thaw serum.The ELISA test for detecting the content of IgG antibodies specific to pneumococcal capsular polysaccharides was carried out,and the test results were systematically analyzed.The laboratory internal quality control serum 09CS was respectively mixed with hemolyzed and chylous serum after immunization in different volume fractions to prepare hemolyzed and chylous serum,and the IgG antibodies of 24 types were detected respectively.The test was repeated three times,and the recovery rate was calculated.Results The repeated freeze-thaw serum and single freeze-thaw serum were detected for 24 types respectively,and the detection results showed good linear relationship with R~2> 0.99.The detection results were analyzed by Lin's concordance correlation coefficient(r_c),and the r_c was 0.992 3(95% CI:0.990 2-0.993 9),indicating that the test results of single freeze-thaw serum and repeated freeze-thaw serum were highly consistent.The accuracy of serum recovery rate was74.65% for hemolyzed serum and 70.48% for chylous serum,both in line with the acceptance range of accuracy±40%.Conclusion During the ELISA test for the specific IgG antibody content against pneumococcal capsular polysaccharide,hemolyzed and chylous serum and repeated freeze-thawing of serum for 12 times have no effect on the detection,which can satisfy the detection requirements for clinical serum antibody evaluation of pneumococcal vaccine.

Objective:A GC method was established for the determination of three potential genotoxic impuri-ties methyl ethanesulfonate,ethyl ethanesulfonate and isopropyl ethanesulfonate in baritinib raw materials.Methods:The chromatography was performed on Agilent J&W DB-1701(30 m×0.25 mm,1.0 μm)col-umn.The heating procedure was the initial temperature of 100℃,maintained for 3 min,at the rate of 5℃per minute to 180℃,maintained for 2 min,and then at the rate of 30℃per minute to 240℃,maintained for 5 min.The temperature of the injector was 240℃.The shunt ratio was 1∶10.The carrier gas was helium with a flow rate of 2.0 mL per minute.The temperature of the detector was 260℃and the injection volume was 2 μL.Results:The specificity,linearity and range,limit of quantification and detection,accuracy,pre-cision,repeatability and stability of the method meet the requirements.Conclusion:The analytical method is simple,accurate,sensitive and reproducible,and can be used for quality control of three potential genotoxic impurities in baritinib.

Objective:To evaluate spinal-pelvic mobility and sagittal spinal-pelvic alignment characteristics in patients with developmental dysplasia of the hip (DDH), and to investigate differences in sagittal spinal-pelvic parameters between patients with DDH and those with osteonecrosis of the femoral head (ONFH).Methods:A total of 55 patients with DDH who underwent primary total hip arthroplasty (THA) at the Affiliated Hospital of Xuzhou Medical University between April 2021 and March 2024 were retrospectively analyzed. The cohort included 8 males and 47 females, with a mean age of 56.16±10.82 years (range: 26-76 years). Among them, 18 patients had bilateral DDH and 37 had unilateral DDH. Fifty-five age- and sex-matched patients with ONFH were selected as the control group. Unilateral DDH cases were classified according to the Hartofilakidis classification: 18 cases of type A, 13 cases of type B, and 6 cases of type C. Lateral spinal-pelvic radiographs were used to measure pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and lumbar lordosis (LL) in both standing and sitting positions. Changes in sagittal spinal-pelvic parameters between standing and sitting positions were analyzed to assess spinal-pelvic mobility. Spinal-pelvic mobility was considered abnormal if △SS was outside the range of 10°-30°. Abnormal mobility was further categorized as stiffness (△SS<10°) or hypermobility (△SS>30°).Results:The PI (52.37°±12.43°), standing PT (12.13°±9.50°), and sitting PT (36.49°±13.43°) of DDH patients were significantly higher than those of ONFH patients (44.88°±11.38°, 7.80°±11.36°, and 28.91°±11.38°, respectively), with statistically significant differences ( P<0.05). Abnormal spinal-pelvic mobility, including both stiffness and hypermobility, was observed in 53% of DDH patients, with stiffness accounting for 20%. These proportions were significantly higher than those in ONFH patients, which were 24% and 6%, respectively ( P<0.05). The prevalence of abnormal spinal-pelvic mobility in Hartofilakidis type C DDH patients was 83%, significantly higher than the 30.8% observed in type B patients (χ 2=4.550, P=0.033). The standing LL (54.37°±11.59°) and sitting LL (28.56°±15.51°) in unilateral DDH patients were significantly greater than those in bilateral DDH patients (46.88°±15.30° and 20.42°±9.77°, respectively), with statistically significant differences ( P< 0.05). Conclusions:Compared with patients with ONFH, those with DDH demonstrate a higher prevalence of abnormal spinal-pelvic mobility, particularly a greater incidence of spinal stiffness. Among DDH subtypes, Hartofilakidis type C patients exhibit a higher proportion of abnormal mobility compared to types A and B. Additionally, patients with unilateral DDH present with greater lumbar lordosis than those with bilateral involvement.