Cancer, a common malignant disease, is one of the predominant causes of diseases that lead to death. Additionally, cancer is often detected in advanced stages and cannot be radically cured. Consequently, there is an urgent need for reliable and easily detectable markers to identify and monitor cancer onset and progression as early as possible. Our aim was to systematically review the relevant roles of cathepsin K (CTSK) in various possible cancers in existing studies. CTSK, a well-known key enzyme in the bone resorption process and most studied for its roles in the effective degradation of the bone extracellular matrix, is expressed in various organs. Nowadays, CTSK has been involved in various cancers such as prostate cancer, breast cancer, bone cancer, renal carcinoma, lung cancer and other cancers. In addition, CTSK can promote tumor cells proliferation, invasion and migration, and its mechanism may be related to RANK/RANKL, TGF-β, mTOR and the Wnt/β-catenin signaling pathway. Clinically, some progress has been made with the use of cathepsin K inhibitors in the treatment of certain cancers. This paper reviewed our current understanding of the possible roles of CTSK in various cancers and discussed its potential as a biomarker and/or novel molecular target for various cancers.

Purpose: Percutaneous endoscopic lumbar discectomy for the treatment of far-migrated lumbar disc herniation (LDH) is clinically challenging. The aim of this study was to compare the efficacy and safety of interlaminar endoscopic lumbar discectomy (IELD) and interlaminar microscopic lumbar discectomy (IMLD) for the treatment of far-migrated LDH. Materials and Methods: We retrospectively analyzed 50 consecutive cases of far-migrated LDH treated by IELD or IMLD. Clinical data and outcomes were assessed before the operation and 1 day and 3, 12, and 24 months after the surgery using the visual analog scale (VAS) and Oswestry disability index (ODI). Modified MacNab criteria were used to evaluate patient satisfaction at the 24-month follow-up. Results: A significant reduction in leg pain and improvement in ODI (P< 0.01) were observed in both groups after surgery. Lower back pain (LBP) was reduced at 24 months postsurgery in the IELD group (P< 0.05) but not in the IMLD group (P> 0.05). There were significant intergroup differences in VAS LBP score at 1 day and 24 months postsurgery (p=0.01 and 0.02, respectively) and in ODI at 24 months (p=0.03). The rate of excellent or good outcome was 90.32% with IELD and 78.95% with IMLD (p=0.55). Hospital stay and time to ambulation were shorter in the IELD group than in the IMLD group, but the former had a longer operative time (p< 0.01). Low and comparable complication rates were reported in the IELD (16.13%) and IMLD (10.53%) groups (p=0.70). Conclusion: Both IELD and IMLD achieve favorable clinical results in the treatment of far-migrated LDH, with only minor complications. Compared to IMLD, LBP was significantly reduced with IELD presumably because it involved less trauma.

Purpose: Although lumbar spinal stenosis (LSS) is the most common spinal disease in the elderly, there is still a confusion about the appropriate surgical treatment strategy. The aim of this study was to compare the safety and efficacy of full-endoscopic and microscopic unilateral laminotomy for bilateral decompression (ULBD) for LSS in elderly patients. Patients and Methods: A retrospective analysis of 61 consecutive elderly patients with LSS who underwent either full-endoscopic (FE group) or microscopic (Micro group) unilateral laminotomy for bilateral decompression was performed. Clinical data were assessed before 2 weeks, 3 months, 6 months and 12 months after surgery using the Visual Analog Scale (VAS), the Oswestry Disability Index (ODI) and the modified MacNab criteria. Results: There are no significant differences in VAS (back and leg) and ODI between the two groups. However, the VAS back pain in the FE group was significantly improved compared to the Micro group at 2 weeks. The rate of excellent or good outcomes was 87.88% and 85.71% in the FE and Micro group, respectively (P>0.05). The hospital stay and early ambulation in FE group were shorter than those in Micro group, but the operation time was longer (P0.05). Conclusion: Both full-endoscopic and microscopic decompression have achieved favorable clinical results in treating elderly lumbar spinal stenosis, and the complications are minor. Full-endoscopic decompression has the advantages of small incision and rapid recovery, which can be used as an alternative for the treatment of lumbar spinal stenosis, especially the elderly with comorbidities.

Intervertebral disc degeneration (IVDD) is a prevalent condition contributing to various spinal disorders, posing a significant global health burden. Mitophagy plays a crucial role in maintaining mitochondrial quantity and quality and is closely associated with the onset and progression of IVDD. Well-documented region-specific mitophagy mechanisms in IVDD are guiding the development of therapeutic strategies. In the nucleus pulposus (NP), impaired mitochondria lead to apoptosis, oxidative stress, senescence, extracellular matrix degradation and synthesis, excessive autophagy, inflammation, mitochondrial instability, and pyroptosis, with key regulatory targets including AMPK, PGC-1α, SIRT1, SIRT3, Progerin, p65, Mfn2, FOXO3, NDUFA4L2, SLC39A7, ITGα5/β1, Nrf2, and NLRP3 inflammasome. In the annulus fibrosus (AF), mitochondrial damage induces apoptosis and oxidative stress mediated by PGC-1α, while in the cartilage endplate (CEP), mitochondrial dysfunction similarly triggers apoptosis and oxidative stress. These mechanistic insights highlight therapeutic strategies such as activating Parkin-dependent and Ub-independent mitophagy pathways for NP, enhancing Parkin-dependent mitophagy for AF, and targeting Parkin-mediated mitophagy for CEP. These strategies include the use of natural ingredients, hormonal modulation, gene editing technologies, targeted compounds, and manipulation of related proteins. This review summarizes the mechanisms of mitophagy in different regions of the intervertebral disc and highlights therapeutic approaches using mitophagy modulators to ameliorate IVDD. It discusses the complex mechanisms of mitophagy and underscores its potential as a therapeutic target. The objective is to provide valuable insights and a scientific basis for the development of mitochondrial-targeted drugs for anti-IVDD.

Backgroud: Alzheimer’s disease (AD) is a typical neurodegenerative disease, which occurs in the elderly population. Alpiniae oxyphyllae Fructus (AOF) is a traditional Chinese medicine that has potential therapeutic effect on AD, but the mechanism behind it is unclear.Methods: Firstly, the main chemical components of AOF were identified by LC-MS, while the main active ingredients and targets were screened by TCMSP database. At the same time, AD-related target proteins were obtained using Genecards and OMIM databases. PPI was constructed by cross-linking AOF and AD targets, and GO enrichment analysis and KEGG pathway enrichment analysis were performed to identify the relevant biological processes and signaling pathways. Finally, based on the H₂O₂-stimulated PC12 cell, flow cytometry, WB and immunofluorescence experiments were performed to verify the protective effect of AOF on AD.Results: We identified 38 active ingredients with 662 non-repetitive targets in AOF, of which 49 were potential therapeutic AD targets of AOF. According to the GO and KEGG analysis, these potential targets are mainly related to oxidative stress and apoptosis. The role of AOF in the treatment of AD is mainly related to the PI3K/AKT signaling pathway. Protocatechuic acid and nootkatone might be the main active ingredients of AOF. In subsequent experiments, the results of CCK-8 showed that AOF mitigated PC12 cell damage induced by H₂O₂. Kits, flow cytometry, and laser confocal microscopy indicated that AOF could decrease ROS and increase the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), while AOF could also increase mitochondrial membrane potential (MMP), thereby inhibiting apoptosis. Finally, immunofluorescence and WB results showed that AOF inhibited the expression of BAX and caspase-3 in PC12 cells, and promoted the expression of Bcl-2. At the same time, the phosphorylation levels of PI3K and Akt proteins were also significantly increased.Conclusion: This study suggests that AOF had the potential to treat AD by suppressing apoptosis induced by oxidative stress via the PI3K/Akt pathway.

Background and objectives: Diabetes mellitus is a serious metabolic disease that causes a serious economic burden worldwide. Gut flora is a major component of diabetes research, and the aim of this study was to understand the trends and major components of research related to diabetes and gut flora in the last 11 years.Methods: We searched the Web of Science Core Collection database for articles on diabetes and gut flora related research from 2011-2021 on July 2, 2022. The literature data were analyzed for country, institution, author, steward, journal, and highly cited literature using Citespace.5.8.R3 and Vosviewer1.6.17.Results: Finally 4834 articles that met the requirements were included. The overall trend of articles published in the last 11 years is increasing, and the trend of articles published after 2019 is increasing significantly. In total, 109 countries, 4820 institutions, and 23365 authors were involved in the field of research. The highest number of publications was 1262 articles from the United States, the institution with the most publications was the University of Copenhagen with 134 articles, and the author with the most publications was PATRICE D CANI with 52 articles.Conclusion: The number of studies related to diabetes and intestinal flora is increasing and more and more researchers are involved in this field. Intestinal flora provides a key research direction for the treatment of diabetes. In the future, gut flora will remain the focus of the diabetes field.