Juvenile idiopathic arthritis (JIA) is the most common condition of chronic rheumatic disease in children. JIA is an autoimmune or autoinflammatory disease, with unclear mechanism and limited treatment efficacy. Recent studies have found a number of alterations in gut microbiota and its metabolites in children with JIA, which are related to the development and progression of JIA. This review focuses on the influence of the gut microbiota and its metabolites on immune function and the intestinal mucosal barrier and discuss the key role of the gut-joint axis in the pathogenesis of JIA and emerging treatment methods based on gut microbiota and its metabolites. This review could help elucidate the pathogenesis of JIA and identify the potential therapeutic targets for the prevention and treatment of JIA.
Humans ; Arthritis, Juvenile/physiopathology* ; Gastrointestinal Microbiome/physiology* ; Child ; Intestinal Mucosa

This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ) in improving osteoporosis by combining network pharmacology and proteomics technologies. The SD rats were randomly divided into a blank control group and a 700 mg·kg~(-1) YRJ group. The rats were subjected to gavage administration with the corresponding drugs, and the blank serum, drug-containing serum, and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) to analyze the main components absorbed into blood. Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis, and Venn diagrams were used to identify the intersection of drug action targets and disease targets. The STRING database was used for protein-protein interaction(PPI) network analysis of potential target proteins to construct a PPI network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ. Ovariectomy(OVX) was performed to establish a rat model of osteoporosis, and the rats were divided into a sham group, a model group, and a 700 mg·kg~(-1) YRJ group. The rats were given the corresponding drugs by gavage. The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins. With the help of network pharmacology and proteomics results, the mechanism by which YRJ improves osteoporosis was predicted. The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ, and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF), tumor protein p53(TP53), protein kinase(AKT1), and matrix metalloproteinase 9(MMP9). These targets are mainly involved in osteoclast differentiation, estrogen signaling pathways, and nuclear factor-kappa B(NF-κB) signaling pathways. Additionally, the proteomics analysis highlighted important pathways such as peroxisome proliferator-activated receptor(PPAR) signaling pathways, mitogen-activated protein kinase(MAPK) signaling pathways, and β-alanine metabolism. The combined approaches of network pharmacology and proteomics have revealed that the mechanism by which YRJ improves osteoporosis may be closely related to the regulation of inflammation, osteoblast, and osteoclast metabolic pathways. The main pathways involved include the NF-κB signaling pathways, MAPK signaling pathways, and PPAR signaling pathways, among others.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Osteoporosis/metabolism* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Female ; Protein Interaction Maps/drug effects* ; Capsules ; Humans ; Signal Transduction/drug effects*

Aconitum kusnezoffii is a perennial herbaceous medicinal plant of the family Ranunculaceae, with unique medicinal value. Damping off is one of the most important seedling diseases affecting A. kusnezoffii, occurring widely and often causing large-scale seedling death in the field. To clarify the species of the pathogen causing damping off in A. kusnezoffii and to formulate an effective control strategy, this study conducted pathogen identification, research on biological characteristics, and evaluation of fungicide inhibitory activity. Through morphological characteristics, cultural traits, and phylogenetic tree analysis, the pathogen causing damping off in A. kusnezoffii was identified as Rhizoctonia solani, belonging to the AG5 anastomosis group. The optimal temperature for mycelial growth of the pathogen was 25-30 ℃, with OA medium as the most suitable medium, pH 8 as the optimal pH, and sucrose and yeast as the best carbon and nitrogen sources, respectively. The effect of light on mycelial growth was not significant. In evaluating the inhibitory activity of 45 chemical fungicides, including 30% hymexazol, and 4 biogenic fungicides, including 0.3% eugenol, it was found that 30% thifluzamide and 50% fludioxonil had significantly better inhibitory effects on R. solani than other tested agents, with EC_(50) values of 0.129 6,0.220 6 μg·mL~(-1), respectively. Among the biogenic fungicides, 0.3% eugenol also showed an ideal inhibitory effect on the pathogen, with an EC_(50) of 1.668 9 μg·mL~(-1). To prevent the development of resistance in the pathogen and to reduce the use of chemical fungicides, it is recommended that the three fungicides above be used in rotation during production. These findings provide a theoretical basis for the accurate diagnosis and effective control strategy for R. solani causing damping off in A. kusnezoffii.
Fungicides, Industrial/pharmacology* ; Plant Diseases/microbiology* ; Rhizoctonia/growth & development* ; Aconitum/microbiology* ; Phylogeny ; Mycelium/growth & development*

The evaluation of blood compatibility of biomaterials is crucial for ensuring the clinical safety of implantable medical devices. To address the limitations of traditional testing methods in real-time monitoring and electrical property analysis, this study developed a portable electrical impedance tomography (EIT) system. The system uses a 16-electrode design, operates within a frequency range of 1 to 500 kHz, achieves a signal to noise ratio (SNR) of 69.54 dB at 50 kHz, and has a data collection speed of 20 frames per second. Experimental results show that the EIT system developed in this study is highly consistent with a microplate reader ( R ²=0.97) in detecting the hemolytic behavior of industrial-grade titanium (TA3) and titanium alloy-titanium 6 aluminum 4 vanadium (TC4) in anticoagulated bovine blood. Additionally, with the support of a multimodal image fusion Gauss-Newton one-step iterative algorithm, the system can accurately locate and monitor in real-time the dynamic changes in blood permeation and coagulation caused by TC4 in vivo. In conclusion, the EIT system developed in this study provides a new and effective method for evaluating the blood compatibility of biomaterials.
Electric Impedance ; Animals ; Tomography/instrumentation* ; Biocompatible Materials ; Materials Testing/instrumentation* ; Cattle ; Titanium ; Alloys ; Prostheses and Implants

OBJECTIVE: To investigate the short-term effectiveness of uni-portal non-coaxial spinal endoscopic surgery (UNSES) via crossing midline approach (CMA) in the treatment of free lumbar disc herniation (FLDH). METHODS: Between March 2024 and June 2024, 16 patients with FLDH were admitted and treated with UNSES via CMA. There were 9 males and 7 females with an average age of 55.1 years (range, 47-62 years). The disease duration was 8-30 months (mean, 15.6 months). The pathological segments was L _{3, 4} in 4 cases, L _{4, 5} in 5 cases, and L ₅, S ₁ in 7 cases. The preoperative pain visual analogue scale (VAS) score was 6.9±0.9 and the Oswestry disability index (ODI) was 57.22%±4.16%. The operation time, intraoperative bleeding volume, postoperative hospital stay, and incidence of complications were recorded. The spinal pain and functional status were evaluated by VAS score and ODI, and effectiveness was evaluated according to the modified MacNab criteria. CT and MRI were used to evaluate the effect of nerve decompression. RESULTS: All 16 patients underwent operation successfully without any complications. The operation time was 63-81 minutes (mean, 71.0 minutes). The intraoperative bleeding volume was 47.3-59.0 mL (mean, 55.0 mL). The length of hospital stay after operation was 3-4 days (mean, 3.5 days). All patients were followed up 1-3 months, with 15 cases followed up for 2 months and 14 cases for 3 months. The VAS score and ODI gradually decreased over time after operation, and there were significant differences between different time points ( P<0.05). At 3 months after operation, the effectiveness was rated as excellent in 12 cases and good in 2 cases according to the modified MacNab criteria, with an excellent and good rate of 100%. CT and MRI during follow-up showed a significant increase in the diameter and cross-sectional area of the spinal canal, indicating effective decompression of the canal. CONCLUSION When using UNSES to treat FLDH, choosing CMA for nerve decompression has the advantages of wide decompression range, large operating space, and freedom of operation. It can maximize the preservation of the articular process, avoid fracture and breakage of the isthmus, clearly display the exiting and traversing nerve root, and achieve good short-term effectiveness.
Humans ; Male ; Intervertebral Disc Displacement/diagnostic imaging* ; Middle Aged ; Female ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Treatment Outcome ; Operative Time ; Pain Measurement ; Length of Stay

OBJECTIVE: To assess the effectiveness of bone acupuncture in improving pain and function in degenerative lumbar spinal stenosis (DLSS) and compare it with Jiaji acupuncture. METHODS: From January to December 2023, 80 DLSS patients were treated with acupuncture and divided into bone acupuncture and Jiaji acupuncture groups. Among them, 40 patients in the bone acupuncture group included 15 males and 25 females, with a mean age of (60.60±6.98) years old;anthor 40 patients in the Jiaji acupuncture group included 16 males and 24 females, with a mean age of (61.48±9.55) years old. The Roland Morris disability questionnaire(RMDQ), walking distance, visual analogue scale(VAS), and the MOS item short from health survey(SF-36) of two groups at baseline, 2 weeks, 4 weeks, and 12 weeks post-treatment were compared. RESULTS: Eighty patients were followed up for 3 to 5 months with an average of (3.62±0.59) months. There was no significant differences in general data and the scores before treatment between two groups(P>0.05). The RMDQ scores in both groups decreased significantly at 2, 4 and 12 weeks after treatment compared with before treatment(P<0.05), at each time point after treatment, the decrease was more significant in the bone acupuncture group than in the Jiaji acupuncture group(P<0.05). The VAS of waist and leg in both groups was significantly lower at 2, 4 and 12 weeks after treatment that before treatment(P<0.05). At all time points after treatment, the waist VAS in the bone acupuncture group was reduced more significant than in the Jiaji acupuncture group(P<0.05);there was no significant difference in leg VAS at 2 and 12 weeks after treatment between two groups(P>0.05), the improvement was more significant in the bone acupuncture group in the 4 weeks after treatment than in the Jiaji acupuncture group. The SF-36 scores in both groups were significantly higher at 2, 4, and 12 weeks after treatment than before treatment(P<0.05);the SF-36 score raised more significant in the bone acupuncture group than in the Jiaji acupunture group(P<0.05). No significant difference in the walking distance between two groups at 2 weeks after treatment(P>0.05);the walking distance in the bone acupuncture group was significantly higher than that in the Jiaji acupuncture group at 4 and 12 weeks after treatment(P<0.05). CONCLUSION Bone-penetrating acupuncture moderately improves functional impairment, pain, and quality of life in patients with DLSS, showing better efficacy than Jiaji acupuncture.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/methods* ; Spinal Stenosis/physiopathology* ; Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management

OBJECTIVE: To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping. METHODS: A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety. RESULTS: All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001). CONCLUSION Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans ; Female ; Male ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae/physiopathology* ; Cupping Therapy/methods* ; Pressure ; Aged ; Treatment Outcome

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*