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Abstract Background Intervertebral disc degeneration (IVDD) is an age‐related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes. Methods We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co‐expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein–protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT‐PCR. Additionally, we predicted miRNAs involved in hub gene co‐regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs. Results We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT‐PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co‐regulation of the hub genes using miRNet prediction: mir‐191‐5p, mir‐20a‐5p, mir‐155‐5p, and mir‐124‐3p. Using limma difference analysis, we discovered that mir‐191‐5p, mir‐20a‐5p, and mir‐155‐5p were all down‐regulated and expressed in IVDD samples, but mir‐124‐3p showed no significant change. Conclusion JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.

Abstract Background This study aimed to apply the backpropagation neural network (BPNN) to develop a model for predicting multidrug-resistant organism (MDRO) infection in critically ill patients. Methods This study collected patient information admitted to the intensive care unit (ICU) of the Affiliated Hospital of Qingdao University from August 2021 to January 2022. All patients enrolled were divided randomly into a training set (80%) and a test set (20%). The least absolute shrinkage and selection operator and stepwise regression analysis were used to determine the independent risk factors for MDRO infection. A BPNN model was constructed based on these factors. Then, we externally validated this model in patients from May 2022 to July 2022 over the same center. The model performance was evaluated by the calibration curve, the area under the curve (AUC), sensitivity, specificity, and accuracy. Results In the primary cohort, 688 patients were enrolled, including 109 (15.84%) MDRO infection patients. Risk factors for MDRO infection, as determined by the primary cohort, included length of hospitalization, length of ICU stay, long-term bed rest, antibiotics use before ICU, acute physiology and chronic health evaluation II, invasive operation before ICU, quantity of antibiotics, chronic lung disease, and hypoproteinemia. There were 238 patients in the validation set, including 31 (13.03%) MDRO infection patients. This BPNN model yielded good calibration. The AUC of the training set, the test set and the validation set were 0.889 (95% CI 0.852–0.925), 0.919 (95% CI 0.856–0.983), and 0.811 (95% CI 0.731–0.891), respectively. Conclusions This study confirmed nine independent risk factors for MDRO infection. The BPNN model performed well and was potentially used to predict MDRO infection in ICU patients.

Bone nonunion is a common and serious orthopedic disorder, the occurrence of which is associated with a disruption of the dynamic balance between osteoblasts and osteoclasts during bone repair. However, the critical molecular mechanisms affecting this homeostasis are not well understood, and it is essential to investigate the specific components of this mechanism and to restore the balance between osteoblasts and osteoclasts to promote bone repair. First, we defined this complex local environmental factor as the “bone nonunion microenvironment” and identified the importance of the “struggle” between osteoblasts and osteoclasts, which is the most essential element in determining the process of repair. On this basis, we also explored the cellular factors that influence osteogenesis and the molecular signals that influence the balance between osteoclast and osteoblasts, which are important for restoring homeostasis. Further, we explored other factors involved in osteogenesis, such as the biomechanical environment, the nutritional environment, the acid-base environment, and the temperature environment, which are important players in osteogenesis. In conclusion, we found that the balance between osteoblasts and osteoclasts is the essence of bone healing, which is based on the “bone nonunion microenvironment”. Therefore, investigating the role of the bone nonunion microenvironment in the system of osteoblast-osteoclast “struggle” provides an important basis for further understanding of the mechanism of nonunion and the development of new therapeutic approaches.

Abstract Intervertebral disc degeneration (IVDD) has become a serious public health problem, placing a heavy burden on society and the healthcare system. Its pathogenesis is not completely clear and may be closely related to mechanical damage, inflammatory factors, oxidative stress and death of nucleus pulposus cells (NPCs). The treatment of IVDD mainly includes conservative treatment and surgery. Conservative treatment is based on hormonal and anti-inflammatory drugs and massage techniques, which can relieve the pain symptoms to a certain extent, but cannot solve the problem from the root cause. Surgical treatment is mainly by removing the herniated nucleus pulposus, but it is more traumatic for IVDD patients, expensive and not suitable for all patients. Therefore, it is extremely important to clarify the pathogenesis of IVDD, to find an effective and convenient treatment and to further elaborate its mechanism of action. The effectiveness of traditional Chinese medicine in the treatment of IVDD has been well demonstrated in clinical medical research. We have been working on the Chinese herbal formula Duhuo Jisheng Decoction, which is a common formula for the treatment of degenerative disc disease. Not only does it have significant clinical effects, but it also has few adverse effects. At present, we found that its mechanism of action mainly involves regulation of inflammatory factors, reduction of apoptosis and pyroptosis of NPCs, inhibition of extracellular matrix degradation, improvement of intestinal flora, etc. However, a few relevant articles have yet comprehensively and systematically summarized the mechanisms by which they exert their effect. Therefore, this paper will comprehensively and systematically explain on it. This is of great clinical significance and social value for elucidating the pathogenesis of IVDD and improving the symptoms of patients, and will provide a theoretical basis and scientific basis for the treatment of IVDD with traditional Chinese medicine.